ID Author Year Title Journal Volume Issue Pages Abstract URL Incl(1)/Excl(0) 1 R. L. Whistler and W. C. Lake 1972 Inhibition of cellular transport processes by 5-thio-D-glucopyranose Biochem.J. 130 4 919-925 "5-Thio-d-glucopyranose, the nearest analogue of normal d-glucose, which is proving a useful tool in examinations of d-glucose biochemistry, affects active and facilitated-diffusion transport processes. 5-Thio-d-glucose is readily transported in rabbit kidney-cortex slices and reaches a tissue/medium ratio of 6.5 within 40min. The sulphur analogue shows typical saturation kinetics with a K(m) value of 2.4mm and V(max.) value of 70mumol/h per g of cell water. Uptake of 5-thio-d-glucose is phlorrhizin-sensitive, Na(+)-dependent and energy-dependent. d-Galactose and methyl alpha-d-glucopyranoside transport is competitively inhibited by 5-thio-d-glucose with K(i) values of 4.8 and 9.7mm respectively. 5-Thio-d-glucose thus shows all of the characteristics of active transport in kidney cortex. Transport of neutral amino acids in rat kidney cortex is inhibited by 5-thio-d-glucose. Thus 5.6mm-5-thio-d-glucose causes a 25-30% inhibition of the transport of glycine and the non-metabolized amino acids cycloleucine and alpha-aminoisobutyric acid. 5-Thio-d-glucose is freely taken up by the facilitated-diffusion transport system in rat diaphragm muscle. The sulphur analogue inhibits the transport of d-xylose in this tissue but has no effect on the uptake of d-arabinose. It is concluded that the ring heteroatom is not an effector of binding in the transport processes examined and causes no important alteration in the conformation of the sugar. The diabetogenic action produced by 5-thio-d-glucose is due, in part, to the ability of the analogue to interfere with cellular transport processes that use d-glucose" http://www.ncbi.nlm.nih.gov/pubmed/4656804 0 2 G. B. Koval'skii 1984 [Age-related characteristics of structural support for ovarian function] Biull.Eksp.Biol.Med. 98 12 759-761 "Histoenzymological assay was used to investigate various structures of the ovaries of rats of two groups aged 3-4 and 12-14 months during estral cycle. The activity of 3 beta-, 17 beta- and 20 alpha-steroid dehydrogenases, glucose-6-phosphate dehydrogenase, NAD and NADP-diaphorases, esterase, acid and alkaline phosphatases was studied. It has been shown that transport alterations in the microcirculation including the hematofollicular barrier play, the leading part in age-dependent depression of reproductive and endocrine functions. Ageing rats demonstrated no linkage between endothelial, thecal and granular cells, which points to the injury of the histophysiological mechanisms of the follicular system integration" http://www.ncbi.nlm.nih.gov/pubmed/6542443 0 3 "D. Pavlinac, R. Langer, L. Lenhard and L. Deftos" 1979 Magnesium in affective disorders "Biological Psychiatry.14 (4) ()(pp 657-661), 1979.Date of Publication: 1979." 4 657-661 "This investigation suggests that lithium and magnesium exert different effects on plasma calcium. Since increased calcium concentrations are associated with depression, and decreases in calcium are associated with the relief of depression, the following emerges as a possible explanation for lithium's mode of action. Lithium administration may increase plasma magnesium and calcium. The increase in magnesium alone or in both of these ions may specifically exert an antimanic effect. Secondarily, magnesium may decrease plasma calcium, exerting an antidepressant effect" 0 4 "J. W. Quintino-dos-Santos, C. J. Muller, A. M. Santos, S. Tufik, C. A. Rosa and L. C. Schenberg" 2014 Long-lasting marked inhibition of periaqueductal gray-evoked defensive behaviors in inescapably-shocked rats Eur.J.Neurosci. 39 2 275-286 "Clinical evidence suggests that depression and trauma predispose the subject to panic. Accordingly, here we examined the late effects of uncontrollable stress, a presumptive model of depression and/or traumatic disorder, on panic-like behaviors evoked by electrical stimulation of the dorsal periaqueductal gray (DPAG). Changes in anxiety and depression were also assessed in the elevated plus-maze (EPM) and forced-swimming test (FST), respectively. Rats with electrodes in the DPAG were subjected to a 7-day shuttle-box one-way escape yoked training with foot-shocks either escapable (ES) or inescapable (IS). The day after the end of one-way escape training, rats were trained in a two-way escape novel task (test-session) to ascertain the effectiveness of uncontrollable stress. DPAG stimulations were carried out in an open field, both before the escape training and 2 and 7 days after it, and EPM and FST were performed on the 8th and 10th days afterwards, respectively. Controls were either trained with fictive shocks (FS) or subjected to intracranial stimulations only. Although the ES rats performed significantly better than the IS group in the two-way escape task, groups did not differ with respect to either the anxiety or depression scores. Unexpectedly, however, IS rats showed a marked attenuation of DPAG-evoked freezing and flight behaviors relative to both the ES and FS groups, 2 and 7 days after one-way escape training. The conjoint inhibition of passive (freezing) and active (flight) defensive behaviors suggests that IS inhibits a DPAG in-built motivational system that may be implicated in depressed patients' difficulties in coping with daily-life stress" http://www.ncbi.nlm.nih.gov/pubmed/24188077 1 5 "S. Yang, D. J. Koo, I. H. Chaudry and P. Wang" 2001 Glycine attenuates hepatocellular depression during early sepsis and reduces sepsis-induced mortality Crit Care Med. 29 6 1201-1206 "OBJECTIVES: To determine whether administration of glycine, a nonessential amino acid, early after the onset of polymicrobial sepsis has any beneficial effects on hepatocellular function and the survivability of septic animals and, if so, whether the beneficial effects of glycine are associated with down-regulation of proinflammatory cytokine tumor necrosis factor-alpha production. DESIGN: Prospective, controlled, and randomized animal study. SETTING: A university research laboratory. SUBJECTS: Male adult rats were subjected to polymicrobial sepsis by cecal ligation and puncture or sham operation followed by the administration of normal saline solution. MEASUREMENTS AND MAIN RESULTS: At 1 hr after cecal ligation and puncture, glycine (0.6 mmol/kg) or vehicle (normal saline solution) was administered intravenously over 15 mins. At 5 hrs after cecal ligation and puncture (i.e., early stage of sepsis), hepatocellular function (i.e., the maximal velocity and efficiency of in vivo indocyanine green clearance) was determined and hepatocyte injury was assessed by measuring plasma concentrations of alpha-gluthathione S-transferase. Serum tumor necrosis factor-alpha was measured by enzyme-linked immunosorbent assay. In additional animals, the necrotic cecum was excised at 20 hrs after cecal ligation and puncture, the peritoneal cavity was irrigated with saline, and the midline incision was closed in layers. Mortality was monitored for 10 days thereafter. The results indicate that hepatocellular function was depressed in the early stage of sepsis (i.e., 5 hrs after cecal ligation and puncture) as indicated by significant decreases in both maximal velocity and transport efficiency of in vivo indocyanine green clearance. Plasma concentrations of alpha-gluthathione S-transferase and tumor necrosis factor-alpha were elevated significantly at that interval after cecal ligation and puncture. Administration of glycine 1 hr after cecal ligation and puncture, however, increased maximal velocity and maximal efficiency by 60% and 101% (p <.05), respectively. Glycine administration in septic animals decreased alpha-gluthathione S-transferase and tumor necrosis factor-alpha by 43% and 80% (p <.05). In addition, glycine treatment decreased the mortality rate from 50% to 0% (p <.05) at 10 days after cecal ligation and puncture and cecal excision. CONCLUSIONS: It appears that the beneficial effect of glycine on hepatocyte function and integrity in sepsis may be mediated via down-regulation of tumor necrosis factor-alpha. Because administration of glycine attenuated hepatocellular depression and injury during early sepsis and decreased sepsis-induced mortality rates, this amino acid appears to be a useful adjunct for maintaining cellular functions and preventing lethality from polymicrobial sepsis" http://www.ncbi.nlm.nih.gov/pubmed/11395604 0 6 "W. Zhang, J. Li, J. Zhu, Z. Shi, Y. Wang and L. Kong" 2004 Chinese medicine Banxia-houpu decoction regulates c-fos expression in the brain regions in chronic mild stress model in rats Phytother.Res. 18 3 200-203 "Banxia-houpu decoction is a safe and effective traditional Chinese medicinal formula used in the treatment of mild and manic-depressive disorders for centuries. There has been increasing interest in its therapeutic application in depression. However, the mechanisms behind behavioural changes are still poorly understood. Chronic mild stress (CMS)-induced preference behaviour change has been used as a model to predict the clinical efficacy of many types of antidepressant treatment. Both EtOH and water extracts (AE and WE) of Banxia-houpu decoction exhibited a significantly increased sucrose intake in the CMS model in rats, but there was no effect in unstressed animals. In the present study, it was found that the c-fos expression in cerebral cortex, hippocampus and striatum corpora were very high in the CMS model in rats. WE and AE at a dose of 130 mg/kg exhibited a significantly decreased c-fos expression in the cerebral regions in CMS model in rats, respectively. The former was more potent than the latter. However, no significant changes in the c-fos expression were observed in unstressed rats treated with the decoction. Fluoxetine not only significantly reduced c-fos expression in all regions in the CMS model in rats, but only showed a marked decrease in c-fos expression in the hippocampus in unstressed animals. A different molecular mechanism of Banxia-houpu decoction and fluoxetine may be implied. The cerebral cortex, hippocampus and striatum conpora might be important structural substrates in the central nervous system mediating the section of the Banxia-houpu decoction on preference behaviour in CMS-induced rats, and fos protein might be the common substrate of the signal transduction process of the decoction" http://www.ncbi.nlm.nih.gov/pubmed/15103665 1 7 "G. Ossowska, G. Nowa, R. Kata, B. Klenk-Majewska, Z. Danilczuk and I. Zebrowska-Lupina" 2001 Brain monoamine receptors in a chronic unpredictable stress model in rats J.Neural Transm.(Vienna.) 108 3 311-319 "Antidepressant drugs are devoid of mood-elevating effects in normal (non-depressed) human subjects, thus, it is necessary to evaluate the antidepressant property of compounds (drugs) in animal models of depression. Several animal models of depression have been introduced, however, only a few have been extensively validated. In the present study we report the results of investigations into monoaminergic receptors in the brain of rats subjected to chronic unpredictable stress (CUS) procedure (one of the well validated animal models of depression). We have examined the dopaminergic (D-1, D-2), adrenergic (alpha-1, beta-1) and serotonergic (5HT-1A, 5HT-2A) receptors in different brain regions by a saturation radioligand binding method in rats subjected to CUS paradigm and control animals. CUS procedure resulted in a significant 29% increase in the D-1 receptor density in the limbic system and 52% increase of the density of 5HT-2A receptors in the cerebral cortex. The present data indicate that the increase of the density of brain D-1 and 5HT-2A receptors of rats subjected to CUS might be involved in the pathophysiology of ""animal depression"" (since chronic antidepressant treatment produced opposite changes i.e. decrease in the density of these receptors) and thus in pathophysiology of human depression" http://www.ncbi.nlm.nih.gov/pubmed/11341483 1 8 D. Dhingra and R. Valecha 2014 Behavioural and neuroendocrine effects of aqueous extract of Boerhaavia diffusa Linn. in mice using tail suspension and forced swim tests - A preliminary study "Indian Journal of Experimental Biology.52 (1) ()(pp 53-59), 2014.Date of Publication: January 2014." 1 53-59 "The present study was done to evaluate the effect of aqueous extract of B. diffusa on depression in mice using behavioral models such as tail suspension test (TST) and forced swim test (FST). The extract (50, 100 and 200 mg/kg, po) was administered for 14 successive days to Swiss young albino mice. On 14th day, 60 min after administration, mice were subjected to TST and FST. The administration of aqueous extract of B. diffusa (50, 100 and 200 mg/kg, po) significantly decreased immobility period in both TST and FST, indicating significant antidepressant-like activity. The lowest dose (50 mg/kg) of the extract decreased the immobility period most significantly in FST, showing most potent antidepressant-like action. The efficacy of the extract (50 mg/kg) was comparable to fluoxetine (20 mg/kg). The extract did not show any significant effect on locomotor activity. The extract showed significant monoamine oxidase -A inhibitory activity. There was no significant effect of the extract on plasma corticosterone levels. Prazosin (alpha1-adrenoceptor antagonist), sulpiride (selective D2-receptor antagonist), baclofen (GABAB agonist), and p-CPA (tryptophan hydroxylase inhibitor) significantly attenuated the extract-induced antidepressant-like effect, when tested in TST. The extract might produce antidepressant-like effect by interaction with alpha1-adrenoceptors, dopamine-D2 receptors, serotonergic, and GABAB receptors. Thus, aqueous extract of B. diffusa showed significant antidepressant-like activity in mice probably through involvement of monoaminergic and GABAergic systems" 1 9 M. Vornanen and J. Haverinen 2011 Seasonality of glycogen phosphorylase activity in crucian carp (Carassius carassius L.) J.Comp Physiol B 181 7 917-926 "Seasonal changes in the activity of glycogen phosphorylase (GP), a rate-limiting enzyme of glycogen degradation, were examined in an anoxia-tolerant fish species, the crucian carp (Carassius carassius L.). In muscle and brain, the activity of GP remained constant throughout the year when tested at 25 degrees C. In contrast, the activities of liver and heart GP displayed striking increases in summer. When seasonal temperature changes are taken into account, the activity of GP during the anoxic mid-winter is only 4-6% of its summer time activity in the muscle, heart and liver, and 13% in brain. In winter-acclimatized fish, experimental anoxia (1-6 weeks) caused sustained depression of the GP activity in heart and gills. In liver and muscle, a transient depression of GP activity occurred during the first week of anoxia but later GP activity recovered back to the normoxic level. GP of the brain was completely resistant to anoxia. In all studied tissues, the constitutive activity of GP is more than sufficient to degrade glycogen deposits during winter anoxia without anoxia-induced activation of GP. The seemingly paradoxical summer-time increase in the activity of liver and heart GP could be related to active life-style of the summer-acclimatized fish (growth, reproduction), the increased demand of energy and molecular precursors of anabolic metabolism being satisfied by preferential degradation of glycogen. The high glycogen content of winter-acclimatized crucian carp is not associated with the elevated GP activity or anoxic activation of GP" http://www.ncbi.nlm.nih.gov/pubmed/21512743 0 10 "E. S. Mitema, F. W. Oehme and L. Penumarthy" 1980 "Effect of chronic lead on the haematology, blood glutathione and bone marrow non-haeme iron of dogs" Acta Pharmacol.Toxicol.(Copenh) 46 4 250-256 "Ten clinically normal male beagle dogs were used in the study. Two dogs served as control, 4 received 2 mg lead/kg daily and 4 received 5 mg lead/kg/daily. Lead was administered for 13 weeks, after which one-half of each experimental group was treated with calcium ethylene diaminetetraacetate (CaEDTA) for 5 days. All animals were then monitored for another 4 weeks. Blood lead levels, haematology, blood glutathione concentration, and the number of bone marrow cells with stainable iron granules were measured weekly during the 18-week experimental period. Clinical signs of poisoning were observed only in one dog in the high dose group after 6 weeks. The signed included emaciation, anorexia, muscular weakness, evidence of abdominal pain and depression. These signs were reversed with cessation of lead dosing and CaEDTA treatment. Blood lead levels and the number of marrow cells with non-haeme iron increased in both lead-dosed groups; nucleated red blood cells increased only in high lead dosed group. There was a trend for an increased packed cell volume in all groups; however, the high lead dosed group did not increase as fast. No significant changes were observed in blood glutathione concentration and in other haematologic parameters. There were no differences in the parameters studied between the dogs treated with CaEDTA and those not so treated. Blood lead levels and the number of nucleated red blood cells decreased after cessation of lead administration and the number of marrow cells with iron also tended to decrease after lead removal" http://www.ncbi.nlm.nih.gov/pubmed/6768221 0 11 "P. S. Pagel, J. P. Kampine, W. T. Schmeling and D. C. Warltier" 1990 Effects of nitrous oxide on myocardial contractility as evaluated by the preload recruitable stroke work relationship in chronically instrumented dogs Anesthesiology 73 6 1148-1157 "Assessment of the effects of nitrous oxide on myocardial contractile function in vivo has been complicated by lack of a reliable, easily quantified, load-independent index of contractility and by the presence of intact autonomic nervous system reflexes. Although several previous investigations in humans and experimental animals have demonstrated that nitrous oxide possesses direct negative inotropic effects, this conclusion remains controversial. This investigation reexamined the effect of nitrous oxide on myocardial contractile function when this agent was combined with baseline isoflurane or sufentanil anesthesia in chronically instrumented dogs. Contractility was evaluated with the use of the regional preload recruitable stroke work (PRSW)-end-diastolic segment length relationship, a method that provides an accurate, relatively afterload-independent assessment of inotropic state in conscious and anesthetized dogs. Because autonomic nervous system tone may influence the response of systemic hemodynamics to anesthesia in vivo, experiments were performed in the presence of pharmacologic blockade of the autonomic nervous system. Two groups of experiments, consisting of a total of 15 experiments, were performed with 12 dogs. Dogs, chronically instrumented for measurement of systemic hemodynamics, including left ventricular pressure and subendocardial segment length, were anesthetized with isoflurane or sufentanil. Thirty percent and 70% nitrous oxide were then administered in a random fashion. Left ventricular pressure-segment length loops were generated after 30 min of equilibration after each anesthetic intervention with the use of preload reduction by partial inferior vena caval constriction, and regional PRSW was calculated. Regional PRSW versus end-diastolic length slope reflected decreases in contractile state when nitrous oxide was added to isoflurane (50 +/- 5 for isoflurane alone to 28 +/- 2 erg.cm-2 x 10(-3).min-1 with 70% added nitrous oxide) or sufentanil (73 +/- 8 for sufentanil alone to 52 +/- 5 erg.cm-2 x 10(-3).mm-1 with 70% added nitrous oxide). Similar decreases in left ventricular positive dP/dt50 were observed as well, reflecting decreases in contractile function. The results further suggest that the degree of functional depression produced by nitrous oxide is nearly equal when isoflurane and sufentanil groups are compared. This study demonstrates that nitrous oxide possesses direct negative inotropic actions independent of changes in autonomic nervous system tone in the chronically instrumented dog" http://www.ncbi.nlm.nih.gov/pubmed/2147368 0 12 A. L. Halberstadt and M. A. Geyer 2011 Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens "Neuropharmacology.61 (3) ()(pp 364-381), 2011.Date of Publication: September 2011." 3 364-381 "Serotonergic hallucinogens produce profound changes in perception, mood, and cognition. These drugs include phenylalkylamines such as mescaline and 2,5-dimethoxy-4-methylamphetamine (DOM), and indoleamines such as (+)-lysergic acid diethylamide (LSD) and psilocybin. Despite their differences in chemical structure, the two classes of hallucinogens produce remarkably similar subjective effects in humans, and induce cross-tolerance. The phenylalkylamine hallucinogens are selective 5-HT2 receptor agonists, whereas the indoleamines are relatively non-selective for serotonin (5-HT) receptors. There is extensive evidence, from both animal and human studies, that the characteristic effects of hallucinogens are mediated by interactions with the 5-HT2A receptor. Nevertheless, there is also evidence that interactions with other receptor sites contribute to the psychopharmacological and behavioral effects of the indoleamine hallucinogens. This article reviews the evidence demonstrating that the effects of indoleamine hallucinogens in a variety of animal behavioral paradigms are mediated by both 5-HT2 and non-5-HT2 receptors. © 2011 Elsevier Ltd" DO - http://dx.doi.org/10.1016/j.neuropharm.2011.01.017 0 13 A. Charles 2012 [Novel migraine mechanisms as targets for therapy] Rinsho Shinkeigaku 52 11 900 http://www.ncbi.nlm.nih.gov/pubmed/23196458 0 14 K. Kolandaivelu and C. S. Poon 1998 A miniature mechanical ventilator for newborn mice J.Appl.Physiol (1985.) 84 2 733-739 "Transgenic/knockout mice with pre-defined mutations have become increasingly popular in biomedical research as models of human diseases. In some instances, the resulting mutation may cause cardiorespiratory distress in the neonatal or adult animals and may necessitate resuscitation. Here we describe the design and testing of a miniature and versatile ventilator that can deliver varying ventilatory support modes, including conventional mechanical ventilation and high-frequency ventilation, to animals as small as the newborn mouse. With a double-piston body chamber design, the device circumvents the problem of air leakage and obviates the need for invasive procedures such as endotracheal intubation, which are particularly important in ventilating small animals. Preliminary tests on newborn mice as early as postnatal day O demonstrated satisfactory restoration of pulmonary ventilation and the prevention of respiratory failure in mutant mice that are prone to respiratory depression. This device may prove useful in the postnatal management of transgenic/knockout mice with genetically inflicted respiratory disorders" http://www.ncbi.nlm.nih.gov/pubmed/9475887 0 15 "H. H. Oei, A. C. Burrier and A. Y. Jeng" 1991 5-Amino-4-imidazolecarboxamide riboside raises adenosine in perfused hypoxic rat heart Eur.J.Pharmacol. 204 1 01-Jul "The effects of 5-amino-4-imidazolecarboxamide riboside (rAICA) on coronary adenosine efflux were examined in blood-free perfused working rat heart preparations subjected to mild (70% O2) and severe hypoxia (45% O2). Under these hypoxic conditions, no significant increase of coronary adenosine effluxes was observed in the presence of 300 microM rAICA alone. However, rAICA-induced augmentation of coronary adenosine efflux during hypoxia was revealed in the presence of an adenosine deaminase inhibitor, erythro-(2-hydroxy-3-nonyl)adenine hydrochloride, indicating that the failure to note the increase in coronary adenosine efflux was due to a rapid deamination of adenosine to inosine. A depression in heart rate during mild and severe hypoxia was significantly exacerbated by rAICA. These effects on heart rate were mediated by adenosine, since they were effectively blocked by 1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine, a selective adenosine A1-receptor antagonist. These results suggest that rAICA elevates adenosine efflux during hypoxia" http://www.ncbi.nlm.nih.gov/pubmed/1804658 0 16 J. P. Huston 1975 "Reinterpretation of Crow et al.'s ""Electrophysiological correlates of cortical spreading depression""" Behav.Biol. 14 3 403-404 http://www.ncbi.nlm.nih.gov/pubmed/1137554 0 17 "W. F. Fikse, A. F. Groen and P. J. Berger" 1997 Effects of data structure and selection on estimated inbreeding depression in experimental Tribolium castaneum lines J.Anim Breed.Genet. 114 01-Jun 289-297 "SUMMARY: Inbreeding depression was estimated for four experimental Tribolium castaneum lines. Each line, containing approximately 7000 animals, was selected for 16 generations either randomly (control), on pupae weight (PWT), on family size (FST) or on an index containing both PWT and FST. The inbreeding trend was 0.9, 0.5, 0.5 and 0.4 % inbreeding per generation in PWT-selected, FST-selected, index-selected, and control line, respectively. The model used to estimate the inbreeding depression included a linear regression on individual inbreeding coefficients, and random additive genetic effects. Using all the performance and pedigree data, estimated inbreeding depressions in the control line were -0.13 (SE = 0.16; #) and -8.50 (SE = 2.66; mug) per 1 % inbreeding for FST and PWT, respectively. Using only performance data of the latest generation in the control line, the estimated inbreeding depressions changed considerably: -0.17 (SE = 0.82) and -37.4 (SE= 11.9) for FST and PWT, respectively. Estimated inbreeding depression for FST in the FST-selected line was - 0.40 (SE = 0.31). Inbreeding depression for PWT in the PWT-selected line was 21.6 (SE = 25.8). This study indicates that estimating inbreeding depression might best be based on the performance data of animals with an equal and sufficiently-large number of ancestral generations known. ZUSAMMENFASSUNG: Wirkung von Datenstruktur und Selektion auf geschatzte Inzuchtdepression in experimentellen Triboleum castaneum Linien Jede der vier experimentellen Linien, aus je etwa 7000 Individuen, wurde durch 16 Generationen selektiert, zufallig die Kontrolle, auf Puppengewicht (PWT), Familiengrosse (FST), oder auf einen beide Merkmale kombinierenden Index. Inzucntzuwachse in diesen vier Linien waren 0.4, 0.9, 0.5 und 0.5% je Generation. Das Modell zur Schatzung der Inzuchtdepression beinhaltete eine lineare Regression auf individuelle Inzuchtkoeffizienten und zufallige additive-genetische Wirkungen. Aus allen Daten, Leistung und Pedigree, ergaben sich -0.13 (SE = 0.16; #) und - 8.5 (SE = 2.66; mg) je 1% Inzucht fur FST und PWT, Daten der letzten Generation ergaben deutlich andere Werte: -0.17 (SE = 0.82) und -37.4 (SE = 11.9) fur FST und PWT. Inzuchtdepressionen fur FST bzw. PWT in den jeweils hierfur selektierten Linien waren -0.40 (SE = 0.31) und 21.6 (SE = 25.8). Es wird gefolgert, dass Schatzungen auf Leistungen von hinreichend grosser Zahl von Vorfahrengenerationen beruhen sollten" http://www.ncbi.nlm.nih.gov/pubmed/21395824 0 18 C. Dixon and K. Compher 1977 "The protective action of zinc against the deleterious effects of cadmium in the regenerating forelimb of the adult newt, Notophthalmus viridescens" Growth 41 2 95-103 "Forelimbs of adult male newts (Notophthalmus viridescens) were amputated and immediately dipped in cadmium nitrate for 2 minutes; in addition, some of the newts were injected with zinc chloride 24 hours prior to, or 24 hours after amputation. Dipping the amputated forelimb of a newt in a solution of 0.4 M cadmium nitrate completely inhibited or retarded regeneration throughout the 65 days of observation. Other effects of cadmium administration included erythema of the limb, an extensive protrusion of the humerus, and in some cases atypical differentiation of regenerates. When zinc chloride was injected (0.04 mg/g of body weight) intraperitoneally into the newt 24 hours prior to limb amputation and cadmium dipping, the deleterious effects of cadmium treatment were prevented and normal regeneration occurred. When zinc chloride was administered 24 hours after amputation and cadmium dipping, it gave no protection against the cadmium. It is suggested that cadmium might inhibit regeneration through the inactivation of zinc metalloenzymes as a result of an exchange of cadmium for zinc. Zinc chloride administered to newts prior to cadmium treatment may prevent the replacement of zinc by cadmium" http://www.ncbi.nlm.nih.gov/pubmed/892583 0 19 "M. Stockert, J. Serra and R. E. De" 1988 Effect of olfactory bulbectomy and chronic amitriptyline treatment in rats. 3H-Imipramine binding and behavioral analysis by swimming and open field tests "Pharmacology Biochemistry and Behavior.29 (4) ()(pp 681-686), 1988.Date of Publication: 1988." 4 681-686 "An 'animal model' of depression, based on bulbectomy, followed by chronic treatment with amitriptyline was used in rats. In the synaptosomal membranes of the cerebral cortex pus hippocampus, the number of binding sites for 3H-imipramine increased significantly when bulbectomy was associated with the antidepressant. In the bulbectomized rats the tendency was toward a decrease in binding. The treatment with 0.2% Triton X-100 of the membranes revealed a large increase in postsynaptic sites in the bulbectomized treated rats. The behavioral parameters analyzed by the swimming with a water wheel and the open field test revealed a series of differences in the various groups of rats, with respect to handling, bulbectomy and antidepressant treatment. Handling resulted in an increase in swimming time in controls, while bulbectomy reduced this parameter. In both the swimming and open field tests, chronic bulbectomy reduces the motility of the rat. In control rats chronic amitriptyline increases locomotion and exploratory activity, a behavioral effect that is even more prominent in bulbectomized treated rats" 1 20 J. R. Hodges and S. Mitchley 1970 The effect of betamethasone on circadian and stress-induced pituitary-adrenocortical function in the rat Br.J.Pharmacol. 38 4 719-724 "1. Both the circadian and stress-induced changes in plasma corticosterone concentration were abolished by the inclusion of betamethasone in the drinking water of rats.2. Adrenal sensitivity to exogenous corticotrophin (ACTH) was unimpaired by the betamethasone treatment.3. The normal circadian rhythm in plasma corticosterone returned within 1 day of withdrawal of the steroid, but the response to stress was normal only after 3 days.4. The possible significance of these observations is discussed" http://www.ncbi.nlm.nih.gov/pubmed/4315094 0 21 V. A. Aletor 1989 "Dietary interactions of lima bean (Phaseolus lunatus) trypsin inhibitor, haemagglutinin and cyanide. Part 2. Effect on pancreatic and intestinal alpha-amylase (EC 3.21.1.1) in growing albino rats" Nahrung 33 5 457-461 "A total of 108 growing albino rats was used to evaluate the dietary interactions of the major lima bean antinutritional factors trypsin inhibitor (TI), haemagglutinin (Hgg) and cyanide (CN) with respect to their effects on pancreatic and intestinal alpha-amylase activities. The results indicate that when fed at the same level of activity as found in the raw lima bean (RLB) these factors had no significant (p greater than 0.05) influence on pancreatic alpha-amylase activity whether acting individually or in combination. However, when acting alone, CN appeared to depress pancreatic amylase level more than when interacting with TI or Hgg or both. Amylase activity was significantly (p less than 0.01) depressed by the dietary treatments in both the small and large intestine while caecal levels were not. The most severe depression in amylase activity was elicited by the RLB diet. The haemagglutinin-containing diets appeared generally associated with lower levels of intestinal amylase activity. From the present finding it is suggested that these factors alone cannot fully account for the magnitude of the depression of intestinal amylase activity which is contingent upon the ingestion of RLB by experimental rats" http://www.ncbi.nlm.nih.gov/pubmed/2788818 0 22 "M. Kobayashi, T. Hamada, M. Kogo, Y. Yanagawa, K. Obata and Y. Kang" 2008 Developmental profile of GABAA-mediated synaptic transmission in pyramidal cells of the somatosensory cortex Eur.J.Neurosci. 28 5 849-861 "Inhibitory synaptic transmission mediated by gamma-aminobutyric acid (GABA)(A) receptors is involved in regulation of experience-dependent cortical plasticity. However, little information is available on their presynaptic and postsynaptic developmental profiles. The present study aims to investigate the developmental changes of miniature and unitary inhibitory postsynaptic currents (mIPSCs and uIPSCs) in mouse barrel cortex. mIPSCs recorded from supragranular pyramidal neurons showed a gradual increase in frequency during postnatal days 6-15 (PD6-15) followed by a marked increase at PD16-20, and mIPSCs frequency reached a plateau at about PD21-30. The amplitude of mIPSCs showed a transient decrease at PD10-12 followed by an increase during PD13-30, and reached a plateau at about PD30. Their decay time constant progressively decreased during the first 30 days postnatally, and reached a steady level at about PD30. Paired recordings from interneurons and synaptically coupled target pyramidal cells revealed that uIPSC amplitude increased with age up to PD30. In contrast, failure rate and coefficient of variation decreased during PD7-15 and showed little change at a later stage. Short-term depression induced by presynaptic stimulation at 33 Hz progressively decreased during PD6-20, and was stabilized at about PD21-30. Quantal analysis revealed that the number of release sites increased with age up to PD30, while the release probability increased during PD6-12 and then reached a plateau level. These results suggest that the number of release sites and release probability of GABA and GABA(A)-mediated IPSC kinetics show distinct developmental profiles, which could play roles in regulating the onset and offset of critical periods for experience-dependent cortical plasticity" http://www.ncbi.nlm.nih.gov/pubmed/18691332 0 23 "J. Baranyi, N. Bakos and J. Haller" 2005 Social instability in female rats: the relationship between stress-related and anxiety-like consequences Physiol Behav. 84 4 511-518 "It is generally believed that anxiety and depression develop in response to stressful events that chronically increase glucocorticoid production (which in turn affects various neurotransmitter systems). In contrast to depression, however, the relationship between chronic stress and anxiety is less clear, as anxiety patients often show normal glucocorticoid levels and respond normally to dexamethasone challenge. Here we report on the interaction between symptoms of chronic stress and anxiety in female rats by making use of the social instability model of anxiety. Subjects were exposed to alternating 24 h periods of isolation and moderate crowding for 14 days. Symptoms of chronic stress and anxiety-like behaviour in the social interaction test were evaluated on the 15th day, i.e. 1 day after the last crowding phase. Social instability resulted in decreased weight gain, and chronically elevated plasma glucocorticoid levels only in rats that showed high aggressiveness during the crowding phases. In contrast, anxiety-like behaviour was increased irrespective to crowding-related aggressiveness. Thus, the development of chronic stress symptoms and anxiety-like behaviour dissociated: the former was bound to crowding-induced aggressiveness (i.e. to a higher stress load), whereas the latter occurred also when such aggressiveness was low, and symptoms of chronic stress did not develop. This finding is consistent with human data, and suggests that stressful events lead to anxiety in both cases: when stressors do or do not lead to chronic stress responses. Studying the distinctive features of anxieties associated or not with chronic endocrine stress responses would enhance our understanding of this disorder" http://www.ncbi.nlm.nih.gov/pubmed/15811385 0 24 "R. De La Garza, J. D. Jentsch, C. D. Verrico and R. H. Roth" 2002 Adaptation of monoaminergic responses to phencyclidine in nucleus accumbens and prefrontal cortex following repeated treatment with fluoxetine or imipramine Brain Res. 958 1 20-27 "The adaptive neuronal changes that follow chronic administration of antidepressant drugs are thought to underlie clinical improvement in patient populations. Recent evidence suggests that alterations specific to N-methyl-D-aspartate (NMDA) receptors may be a final common pathway to antidepressant action. To investigate this possibility, we sought to establish the effects of chronic fluoxetine or imipramine treatment on the monoamine stimulating effect of the non-competitive NMDA antagonist phencyclidine. Male, Sprague-Dawley rats (n=9/group) were treated with saline (1 ml/kg, i.p.), imipramine (10 mg/kg, i.p.) or fluoxetine (10 mg/kg, i.p.) once daily for 14 consecutive days. After a 7-day drug-free period, animals given an acute challenge of either saline or phencyclidine (5 mg/kg, i.p.). One hour later, animals were killed, brains were removed, and the prefrontal cortex, striatum, and nucleus accumbens were dissected. Samples were assayed for the monoamines and their primary metabolites by HPLC. Repeated treatment with fluoxetine or imipramine did not alter baseline dopamine or serotonin turnover. Acute phencyclidine treatment increased prefrontal cortex and nucleus accumbens dopamine turnover in saline-treated animals (P<0.01); however, the effect in the nucleus accumbens was prevented in animals pretreated with imipramine or fluoxetine. Acute phencyclidine challenge also increased serotonin turnover in prefrontal cortex of saline- or imipramine-pretreated rats (P<0.01), though this effect was attenuated in animals pretreated with fluoxetine. Overall, the data suggest that repeated antidepressant treatment alters monoamine turnover in specific brain regions in response to blockade of NMDA receptors. The data highlight the importance of adaptive responses to NMDA receptors resulting from chronic antidepressant treatment" http://www.ncbi.nlm.nih.gov/pubmed/12468026 1 25 B. M. Freeman and A. C. Manning 1971 Glycogenolysis and lipolysis in Gallus domesticus during the perinatal period Comp Gen.Pharmacol. 2 6 198-204 http://www.ncbi.nlm.nih.gov/pubmed/4353988 0 26 V. Hesse and W. Klinger 1969 [Early effect of carbon tetrachloride on the ascorbic acid concentration in liver and ascorbic acid excretion in the urine in rats] Arch.Toxikol. 24 3 306-317 http://www.ncbi.nlm.nih.gov/pubmed/5360666 0 27 P. Nijs 1968 On the nature of electron and energy transport in mitochondria. II. Multiple activation of mitochondrial respiration Biochim.Biophys.Acta 153 1 70-79 http://www.ncbi.nlm.nih.gov/pubmed/4170447 0 28 "J. Solich, M. Kolasa, M. Kusmider, A. Faron-Gorecka, P. Pabian, D. Zurawek, K. Szafran-Pilch and M. Dziedzicka-Wasylewska" 2015 Norepinephrine transporter knock-out alters expression of the genes connected with antidepressant drugs action Brain Res. 1594 284-292 "Norepinephrine transporter knock-out mice (NET-KO) exhibit depression-resistant phenotypes. They manifest significantly shorter immobility times in both the forced swim test and the tail suspension test. Moreover, biochemical studies have revealed the up-regulation of other monoamine transporters (dopamine and serotonin) in the brains of NET-KO mice, similar to the phenomenon observed after the chronic pharmacological blockade of norepinephrine transporter by desipramine in wild-type (WT) animals. NET-KO mice are also resistant to stress, as we demonstrated previously by measuring plasma corticosterone concentration. In the present study, we used a microdissection technique to separate target brain regions and the TaqMan Low Density Array approach to test the expression of a group of genes in the NET-KO mice compared with WT animals. A group of genes with altered expression were identified in four brain structures (frontal and cingulate cortices, dentate gyrus of hippocampus and basal-lateral amygdala) of NET-KO mice compared with WT mice. These genes are known to be altered by antidepressant drugs administration. The most interesting gene is Crh-bp, which modulates the activity of corticotrophin--releasing hormone (CRH) and several CRH-family members. Generally, genetic disturbances within noradrenergic neurons result in biological changes, such as in signal transduction and intercellular communication, and may be linked to changes in noradrenaline levels in the brains of NET-KO mice" http://www.ncbi.nlm.nih.gov/pubmed/25451113 1 29 K. Letnansky 1968 Strain variations in the utilization of hexoses by Ehrlich ascites tumor cells Biochim.Biophys.Acta 165 3 364-373 http://www.ncbi.nlm.nih.gov/pubmed/5737930 0 30 "T. Costa, J. Grifols and D. Perpinan" 2013 Endogenous lipid pneumonia in an African grey parrot (Psittacus erithacus erithacus) J.Comp Pathol. 149 02-Mar 381-384 "Lipid pneumonia is an unusual, non-infectious, inflammatory lung disease characterized by patchy pneumonic consolidation secondary to accumulation of lipid in macrophages. It can be classified as exogenous or endogenous, depending on whether it is associated with the aspiration of foreign material. Endogenous lipid pneumonia (EnLP) has been reported in many mammal species. In pet birds, EnLP is an incidental and uncommon lesion of unknown pathogenesis. A 35-year-old African grey parrot (Psittacus erithacus erithacus) was presented for depression lasting several months, with marked worsening over the 2 days prior to presentation. The animal died shortly after admission. Necropsy examination showed that the lungs were firm with diffuse grey discolouration. Microscopically, there was EnLP, anthracosis, severe atherosclerosis and hepatic amyloidosis. Although the pathogenesis of EnLP in birds is not clear, it has been associated with concurrent atherosclerosis, hepatic diseases and other lesions of the respiratory tract. This is the first description of EnLP in a bird associated with severe respiratory distress" http://www.ncbi.nlm.nih.gov/pubmed/23582929 0 31 H. A. Abramson 1977 Reassociation of dreams. IV. A second LSD analysis of the beetle bug dream: its relation to a shark dream and fear of lesbianism "Journal of Asthma Research.15 (1) ()(pp 23-62), 1977.Date of Publication: 1977." 1 23-62 "This summary brings together the three verbatim recorded psychoanalytic studies in this series of the fear of lesbianism in a married 40-year-old patient incapacitated by extensive eczema, asthma and severe depression. The data include dreams analyzed without and with LSD 25 (d-lysergic acid diethyl-amide). The foregoing data are also briefly discussed from the point of view that happiness in marriage is an important aspect of the life of women, contrary to many extreme views in the 'Liberation Movement'. It is suggested that happiness in marriage is not necessarily based on slogans or frequency of orgasm but is primarily dependent on this trilogy: Husband and wife give each other sexual pleasure, each endeavours to reduce old anxieties in the other, each tries to avoid developing new anxieties in the other" 0 32 "J. C. Li, W. M. Wang, H. J. Zhang and L. Dong" 2005 [Study of huchang qingfei pellets on immune function in rats infected with Mycoplasma pneumoniae] Zhongguo Zhong.Yao Za Zhi. 30 5 366-369 "OBJECTIVE: To study the effects and mechanism of Huchang Qingfei pellets on immune function in rats infected with mycoplasma pneumoniae. METHOD: A rat model of mycoplasmal pneumonia (MP) was developed in repeated intranasal infectious routes and then the humoral and cellular immunocompetences were detected by radioimmunoassay, immune-turbidimetry and flow cytometry. RESULT: The levels of serum IgG,IgM and IL-2, IL-6 were enhinced obviously, the complement C3 and TNF-alpha were decreased and the ratio of CD4+ /CD8+ was improved significantly in the Huchang groups as compared with MP model group. CONCLUSION: Huchang Qingfei pellets can reinforce immune function via preventing both cellular and humoral immunity from depression in the rats with MP" http://www.ncbi.nlm.nih.gov/pubmed/15806971 0 33 "L. Itze, S. D. Vesselinovitch, K. V. Rao, Z. Hruban and V. Itzeova" 1979 Macromolecular synthetic activity in mice regenerating liver after ethylnitrosourea injection Physiol Bohemoslov. 28 2 151-159 "The present report is a continuation of our previous studies on the biochemical mechanisms of carcinogenesis; studying the nature of interactions taking place between Ethylnitrosourea and DNA, RNA and protein of various stages of their synthetic activity. As a model system we chose partially hepatectomized mice live 36 hrs after surgery. Synthetic macromolecule activity in the remaining liver segment was determined by means of 3H-thymidine, 3H-uridine and 3H-leucine. We observed complete depression of DNA synthetic activity (immediately after Ethylnitrosourea administration it remained depressed almost through out the whole period of our observations) while protein synthetic activity was highly elevated. Qualitative changes of soluble proteins which were analyzed by isoelectric fractionation on 5% polyacrylamide after previous 3H- and 14C-leucine incorporation, could not be detected. Our biochemical data are correlated with histological studies and with the tumour incidence following the Ethylnitrosourea treatment of partially hepatectomized mice in the course of long-term experiments. The results provide guideline for further analysis, which should be modified according to the information concerning Ethylnitrosourea carcinogenesis induced 36 hours after partial hepatectmoy" http://www.ncbi.nlm.nih.gov/pubmed/156933 0 34 Q. Gu and R. L. Lin 2010 "Heavy metals zinc, cadmium, and copper stimulate pulmonary sensory neurons via direct activation of TRPA1" J.Appl.Physiol (1985.) 108 4 891-897 "Airway exposure to zinc dust and zinc-containing ambient particulates can cause symptoms of airway irritation and inflammation, but the underlying molecular and cellular mechanisms are largely unknown. Transient receptor potential A1 (TRPA1) is selectively expressed in a subpopulation of pulmonary C-fiber afferents and has been considered as a major irritant sensor in the lung and airways. Using whole cell patch-clamp recording and Ca(2+) imaging, we have demonstrated that application of ZnCl(2) concentration dependently evoked inward current and Ca(2+) transient in isolated vagal pulmonary sensory neurons; both responses were almost completely inhibited after pretreatment with AP18, a specific TRPA1 antagonist. In anesthetized spontaneously breathing animals, intratracheal instillation of ZnCl(2) (2 mM, 25 microl) induced pronounced respiratory depression in wild-type mice, and the effect was essentially absent in TRPA1-deficient mice. In addition, our study showed that two other heavy metals, cadmium and copper, also stimulated pulmonary sensory neurons via a direct activation of TRPA1. In summary, our results suggest that activation of TRPA1 in pulmonary C-fiber sensory nerves may contribute to the respiratory toxicity induced by airway exposure to these three heavy metals" http://www.ncbi.nlm.nih.gov/pubmed/20133428 0 35 "W. G. Dail, D. M. Feeney, H. M. Murray, R. T. Linn and M. G. Boyeson" 1981 Responses to cortical injury: II. Widespread depression of the activity of an enzyme in cortex remote from a focal injury Brain Res. 211 1 79-89 "As a part of a broader study of the reaction of the brain to injury, we report here an interesting loss of the activity of an enzyme in areas quite remote from the site of direct injury. At 36 h following a laceration or contusion injury to the hindpaw area of the motor cortex, a peculiar loss of staining for the enzyme alpha glycerophosphate dehydrogenase (alpha-GPDH) was noted. alpha-GPDH activity was markedly depressed in cortical layers II and III throughout the hemisphere on the side of the injury. The depression of alpha-GPDH activity extended far laterally across the rhinal fissure into the pyriform cortex. The decrease in alpha-GPDH staining was prominent 4 days after the injury: however, the staining pattern had returned to normal at 9 days. Enzyme changes in animals lesioned in the occipital cortex paralleled that seen in animals with a lesion in the motor cortex. Animals which had received an undercut lesion in the motor cortex 56 days earlier were contused in the occipital cortex. The old injury site presented the same sequelae of changes as seen in other lesioned animals. Additionally, a suction ablation injury involving only a small part of motor cortex resulted in the same widespread reduction of staining for alpha-GPDH in layers II and III. The derangement in energy metabolism suggests that cells in layers II and III of the cerebral cortex may be particularly vulnerable to perturbations induced by cortical trauma. These findings may be related to the diffuse and transient functional losses observed after head injury in man" http://www.ncbi.nlm.nih.gov/pubmed/6784887 0 36 L. B. Blanchard and G. C. McCarter 2015 Insomnia and exacerbation of anxiety associated with high-EPA fish oil supplements after successful treatment of depression Oxf Med.Case.Reports. 2015 3 244-245 "A 54-year-old male consulted his general practitioner for increasing general anxiety and mild panic attacks despite effective treatment for recurrent major depressive disorder, which included a fish oil supplement enriched in eicosapentaenoic acid (EPA). The patient would awaken suddenly at night with shortness of breath and overwhelming worry. During the daytime, he felt a general, nonspecific anxiety and frequently experienced sympathetic activation upon confronting routine challenges. He also experienced dyspnea-induced feelings of panic. He reported that he stopped taking the fish oil supplements after several more months of symptoms, and his anxiety and insomnia then largely disappeared. Several weeks later, he resumed consumption of high-EPA fish oil at the prior dosage for 2 days. On both nights, the patient reported nighttime awakening similar to the previous episodes, followed by daytime agitation. Since halting the fish oil supplements, the anxiety and insomnia have not returned and his depression remains in remission" http://www.ncbi.nlm.nih.gov/pubmed/26634135 0 37 "D. M. Boyer, E. R. Seiffert and E. L. Simons" 2010 "Astragalar morphology of Afradapis, a large adapiform primate from the earliest late Eocene of Egypt" Am.J.Phys.Anthropol. 143 3 383-402 "The approximately 37 million-year-old Birket Qarun Locality 2 (BQ-2), in the Birket Qarun Formation of Egypt's Fayum Depression, yields evidence for a diverse primate fauna, including the earliest known lorisiforms, parapithecoid anthropoids, and Afradapis longicristatus, a large folivorous adapiform. Phylogenetic analysis has placed Afradapis as a stem strepsirrhine within a clade of caenopithecine adapiforms, contradicting the recently popularized alternative hypothesis aligning adapiforms with haplorhines or anthropoids. We describe an astragalus from BQ-2 (DPC 21445C), attributable to Afradapis on the basis of size and relative abundance. The astragalus is remarkably similar to those of extant lorises, having a low body, no posterior shelf, a broad head and neck. It is like extant strepsirrhines more generally, in having a fibular facet that slopes gently away from the lateral tibial facet, and in having a groove for the tendon of flexor fibularis that is lateral to the tibial facet. Comparisons to a sample of euarchontan astragali show the new fossil to be most similar to those of adapines and lorisids. The astragali of other adapiforms are most similar to those of lemurs, but distinctly different from those of all anthropoids. Our measurements show that in extant strepsirrhines and adapiforms the fibular facet slopes away from the lateral tibial facet at a gradual angle (112-126 degrees ), in contrast to the anthropoid fibular facet, which forms a sharper angle (87-101 degrees ). Phylogenetic analyses incorporating new information from the astragalus continue to support strepsirrhine affinities for adapiforms under varying models of character evolution" http://www.ncbi.nlm.nih.gov/pubmed/20949610 0 38 "V. Uzunova, M. Ceci, C. Kohler, D. P. Uzunov and A. S. Wrynn" 2003 Region-specific dysregulation of allopregnanolone brain content in the olfactory bulbectomized rat model of depression Brain Res. 976 1 01-Aug "Allopregnanolone (ALLO) is one of the most potent positive endogenous allosteric modulators of the type A gamma-aminobutyric acid (GABA(A)) receptors. While the robust anxiolytic profile of ALLO has been extensively characterized in rodents and its antidepressant-like effect was recently demonstrated in mice, there have been only few reports on alterations of brain ALLO levels in putative animal models of depression and anxiety. Removal of the olfactory bulbs of rats produces one of the most predictive animal models with which to screen for drugs with potential antidepressant activity following repeated treatment. We therefore investigated whether the olfactory bulbectomized (OB) rat model of depression may be associated with alterations of ALLO levels in whole brain tissue and in different brain regions. We determined ALLO levels in whole brain, amygdala, frontal cortex, hippocampus, and whole cerebral cortex of OB or sham-operated rats at 7, 14, or 28 days following bulbectomy or sham surgery. We observed a significant increase of whole brain ALLO content at 7 and 28 days post-surgery in the OB rats. At days 7 and 14 following olfactory bulb removal, ALLO levels were significantly decreased in amygdala and frontal cortex and significantly increased in whole cerebral cortex. In the hippocampus we observed only a tendency for decreased ALLO levels at day 14. Our data indicates a strong region-specific dysregulation of ALLO homeostasis in brains of OB rats which may contribute to the formation of the bulbectomy syndrome via a sustained reduction in physiological GABA-ergic tone in amygdala and frontal cortex" http://www.ncbi.nlm.nih.gov/pubmed/12763616 1 39 "W. Wang, Z. Zhang, J. Shang, Z. Z. Jiang, S. Wang, Y. Liu and L. Y. Zhang" 2008 Activation of group I metabotropic glutamate receptors induces long-term depression in the hippocampal CA1 region of adult rats in vitro Neurosci.Res. 62 1 43-50 "Previous studies have implicated that long-term depression (LTD) was developmentally regulated since LTD can be readily induced by low frequency stimulation (LFS) in acute hippocampal slices prepared from juvenile but not adult animals. Here, we have examined the LTD induced by LFS (1Hz, 900 pulses) paired with a certain pattern at the Schaffer collateral-CAl synapse in adult hippocampal slices. We found that, in the 90-day-old rat hippocampus, LTD could be induced reliably by LFS paired with stronger stimulus intensity than that used during baseline recording. However, this synaptic depression could be completely abolished by application of metabotropic glutamate receptor (mGluR) antagonist (S)-amethyl-4-carboxyphenylglycine (MCPG) which had no effect on that induced by the same protocol in the 16-day-old rat hippocampus. Furthermore, preincubation with group I mGluR antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP) and (S)-2-methyl-4-carboxyphenylglycine (LY367385), also completely prevented the LFS-induced LTD. In contrast, group II mGluR antagonist (2S)-a-ethylglutamic acid (EGLU), N-methyl-d-aspartate (NMDA) receptor antagonist APV and voltage-gated calcium channel antagonist nimodipine had no effect on the LFS-induced LTD. Taken together, these observations suggest that LFS paired with strong stimulus strength can efficiently induce group I mGluR-dependent LTD in the adult hippocampal CA1 region, proving insight into the functional significance of hippocampal mGluR-mediated LTD in learning and memory" http://www.ncbi.nlm.nih.gov/pubmed/18602428 0 40 M. Verleye and F. Bernet 1987 "Behavioral effects of intrahippocampal injections of clonidine, yohimbine and salbutamol in the rat" Pharmacol.Biochem.Behav. 26 2 421-424 "Intrahippocampal injections of adrenergic drugs, clonidine (an alpha 2-agonist), yohimbine (an alpha 2-antagonist), and salbutamol (a beta 2-agonist) were performed in the awake rat. The injection of a high dose of clonidine caused a depression in locomotion in the open-field. Yohimbine partially antagonized the clonidine-induced hypomotility. The intrahippocampal injection of salbutamol had no effect on ambulatory behavior of the rat. These results suggest that the role played by the anterodorsal hippocampus in modifying behavior in novel situations is dependent on the specific sub-population of adrenoceptors that is stimulated" http://www.ncbi.nlm.nih.gov/pubmed/3575361 0 41 "J. Ullman, S. Eriksson and M. Rundgren" 2001 Losartan increases renal blood flow during isoflurane anesthesia in sheep Acta Anaesthesiol.Scand. 45 9 1168-1175 "BACKGROUND: Inhaled anesthetics cause a transient reversible depression of renal function by direct renal effects or indirectly by changes in neurohumoral systems or cardiovascular performance. When the sympathetic nervous activity is decreased during anesthesia, other vasoactive systems like vasopressin (AVP) and particularly the renin angiotensin system (RAS) are of importance for blood pressure maintenance. Little is known about how the renal circulation is affected by angiotensin receptor blockade during isoflurane anesthesia. METHODS: The study was performed on isoflurane anesthetized sheep equipped with flow probes (placed around a femoral and a renal artery) and a pulmonary artery catheter. During stable conditions the sheep were given one or more of the following substances: isotonic saline (NaCl); losartan (LOS) 10 mg x kg(-1); prazosin (PRAZ) 0.2 mg x kg(-1) and a vasopressin V1-receptor antagonist (AVP-a) 10 microg x kg(-1). RESULTS: LOS and AVP-a did not affect mean arterial pressure (MAP), whereas PRAZ lowered MAP significantly (from 98+/-12 to 65+/-7 mmHg). Renal blood flow (RBF) increased after LOS treatment (148+/-34 to 222+/-33 ml x min(-1)). The other substances were without effect on RBF. Femoral blood flow remained unchanged after all treatments. CONCLUSION: We conclude that the sympathoadrenal system is still the major determinant for blood pressure maintenance during isoflurane anesthesia in sheep. The apparently increased activity of the renin angiotensin system in this situation causes a reduction in renal blood flow, which is counteracted by angiotensin II AT1-receptor blockade" http://www.ncbi.nlm.nih.gov/pubmed/11683670 0 42 "T. C. Glenn, A. B. Patel, N. A. Martin, A. Samii, J. C. De and D. A. Hovda" 2002 Subarachnoid hemorrhage induces dynamic changes in regional cerebral metabolism in rats J.Neurotrauma 19 4 449-466 "Following a subarachnoid hemorrhage (SAH), adult rats exhibit dynamic regional changes in cerebral glucose metabolism characterized by an increase in metabolic rates and a subsequent upregulation of cytochrome oxidase (CO). We evaluated both local cerebral metabolic rates for glucose (ICMRglc: (mol/100 g/min) and CO in 23 brain regions of interest (ROI). Sham animals underwent anesthesia and superficial surgery; saline-controls received an injection of 0.9% saline into the cisterna magna; and SAH rats received an injection of autologous blood into the cisterna magna. This blood, measured by albumin labeled with radioactive carbon 14, distributed throughout the brain but predominated ventrally. After experimental animals were sacrificed at day 0 (3 h), 1, 3, and 7 days postinjection, ROI were analyzed using [14C]2-deoxy-D-glucose autoradiography and CO histochemistry. ICMRglc in SAH rats increased in many regions (ranging from 0.7% to 32.2% above sham levels). Cytochrome oxidase also increased from 1% to 9% above sham levels, peaking on day 3. Conversely, saline-controls exhibited prolonged depression of ICMRglc (ranging from 11% to 35% below sham levels) and CO (ranging from 4% to 11% below sham levels) from day 0 through day 7. All saline-control ROI for all time points showed this metabolic depression, and between 91% and 95% of saline-control ROI presented lower CO levels as compared to sham. Overall, ICMRglc and CO levels were greater in SAH than in saline-control ROI. However, when considering the influence of subarachnoid blood on metabolic changes in SAH animals, both CO and 2DG levels did not correlate well with the amount of 14C-albumin binding. While previous studies have measured both metabolic rates of glucose and CO soon after SAH, this is the first to simultaneously conduct these measurements in the same SAH rat model" http://www.ncbi.nlm.nih.gov/pubmed/11990351 0 43 "W. Shen, J. L. Plotkin, V. Francardo, W. K. Ko, Z. Xie, Q. Li, T. Fieblinger, J. Wess, R. R. Neubig, C. W. Lindsley, P. J. Conn, P. Greengard, E. Bezard, M. A. Cenci and D. J. Surmeier" 2015 M4 Muscarinic Receptor Signaling Ameliorates Striatal Plasticity Deficits in Models of L-DOPA-Induced Dyskinesia Neuron 88 4 762-773 "A balanced interaction between dopaminergic and cholinergic signaling in the striatum is critical to goal-directed behavior. But how this interaction modulates corticostriatal synaptic plasticity underlying learned actions remains unclear--particularly in direct-pathway spiny projection neurons (dSPNs). Our studies show that in dSPNs, endogenous cholinergic signaling through M4 muscarinic receptors (M4Rs) promoted long-term depression of corticostriatal glutamatergic synapses, by suppressing regulator of G protein signaling type 4 (RGS4) activity, and blocked D1 dopamine receptor dependent long-term potentiation (LTP). Furthermore, in a mouse model of L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID) in Parkinson's disease (PD), boosting M4R signaling with positive allosteric modulator (PAM) blocked aberrant LTP in dSPNs, enabled LTP reversal, and attenuated dyskinetic behaviors. An M4R PAM also was effective in a primate LID model. Taken together, these studies identify an important signaling pathway controlling striatal synaptic plasticity and point to a novel pharmacological strategy for alleviating LID in PD patients" http://www.ncbi.nlm.nih.gov/pubmed/26590347 0 44 H. Hagena and D. Manahan-Vaughan 2010 Frequency facilitation at mossy fiber-CA3 synapses of freely behaving rats contributes to the induction of persistent LTD via an adenosine-A1 receptor-regulated mechanism Cereb.Cortex 20 5 1121-1130 "Frequency facilitation (FF), comprising a rapid and multiple-fold increase in the magnitude of evoked field potentials, is elicited by low-frequency stimulation (LFS) at mossy fiber-CA3 synapses. Here, we show that in freely behaving rats, FF reliably occurs in response to 1 and 2Hz but not in response to 0.25-, 0.3-, or 0.5-Hz LFS. Strikingly, prolonged (approximately 600 s) FF was tightly correlated to the induction of long-term depression (LTD) in freely moving animals. Although LFS at 2 Hz elicited unstable FF and unstable LTD, application of LFS at 1 Hz elicited pronounced FF, as well as robust LTD that persisted for over 24 h. This correlation of prolonged FF with LTD was absent at stimulation frequencies that did not induce FF. The adenosine-A1 receptor appears to participate in these effects: Application of adenosine-A1, but not adenosine-A3, receptor antagonists enhanced mossy fiber synaptic transmission and occluded FF. Furthermore, adenosine-A1 receptor antagonism resulted in more stable FF at 1 or 2 Hz and elicited more potent LTD. These data support the fact that FF contributes to the enablement of long-term information storage at mossy fiber-CA3 synapses and that the adenosine-A1 receptor may regulate the thresholds for this process" http://www.ncbi.nlm.nih.gov/pubmed/19903765 0 45 "S. Sperti, L. Montanaro, A. Mattioli and G. Testoni" 1975 Relationship between elongation factor I- and elongation factor II- dependent guanosine triphosphatase activities of ribosomes. Inhibition of both activities by ricin Biochem.J. 148 3 447-451 "The elongation factor 1- and elongation factor 2-dependent GTPase (guanosine triphosphatase) activities of ribosomes are inhibited by ricin, a toxic protein known to inactivate the 60S ribosomal subunit. It is suggested that also in eukaryotic ribosomes a ""GTPase site', located on the larger subunit, is common to the two elongation factors" http://www.ncbi.nlm.nih.gov/pubmed/173282 0 46 "D. H. Edwards, R. A. Fricke, L. D. Barnett, S. R. Yeh and E. M. Leise" 1994 The onset of response habituation during the growth of the lateral giant neuron of crayfish J.Neurophysiol. 72 2 890-898 "1. The postembryonic development of the crayfish LG tailflip command neuron's response to mechanosensory input was studied with standard electrophysiological techniques in animals between 1 and 12 cm long. 2. LG neurons are present in each abdominal hemisegment where they receive direct and indirect excitatory input from mechanosensory afferents. In both small and large crayfish, electrical stimulation of an abdominal ganglionic nerve containing those afferents evoked a compound excitatory postsynaptic potential (EPSP) with an early, reliable alpha component and a later, depression-prone beta wave. It is known that the alpha and beta components are produced by inputs from primary mechanosensory afferents and interneurons, respectively. 3. In crayfish < 2 cm long, LG was excited by the alpha component. When superthreshold, the alpha component triggered a single spike; additional excitation provided by the later beta wave presumably was preempted by refractoriness following the alpha spike and by recurrent inhibition of LG excited by the spike. LG was excited reliably by the alpha component in response to repeated superthreshold stimulation. 4. In crayfish between 2 and 3 cm, LG was excited more readily by the beta wave than by the alpha component. LG's beta spike response habituated to repeated stimulation at 1 Hz, and the beta EPSP depressed whereas the alpha component was largely unchanged. The appearance of the cellular substrates of habituation correlates with the reported onset of behavioral habituation of the tailflip response. Higher stimulus levels brought the alpha EPSP to threshold. Repetitive stimulation at these levels reliably evoked LG spikes from the alpha EPSP.(ABSTRACT TRUNCATED AT 250 WORDS)" http://www.ncbi.nlm.nih.gov/pubmed/7983544 0 47 "U. M. Paredes, P. McGuffin and G. Breen" 2011 Finding gene expression regulators implicated in major depression using formaldehyde assisted isolation of regulatory elements (FAIRE) "European Neuropsychopharmacology.Conference: 24th Congress of the European College of Neuropsychopharmacology, ECNP 2011 Paris France.Conference Start: 20110903 Conference End: 20110907.Conference Publication: (var.pagings).21 ()(pp S190), 2011.Date" var.pagings S190 "The exact cellular mechanisms that underline major depressive disorder (MDD) remain unclear, although evidence suggests that dysregulation of neuronal gene expression plays an important role. In this study we aimed to identify novel transcriptional regulators which become active under the presence of antidepressants and hormones linked to MDD using the FAIRE technique (Formaldehyde assisted isolation of regulatory regions) [2]. The presence of Evolutionary conservation regions (ECRs) across vertebrate genomes has been suggested as indicator of transcriptional regulators [1]. We selected 42K ECRs (based on UCSC genome browser Hg18) to design a custom made Nimblegen CGH microarray (135K per sub-array, n=3 probes per ECR). DNA isolated with FAIRE was hybridised against ECR microarray. We observed 36 ECRs that became transcriptionally active in cells treated estradiol, lithium and valproate (95% confidence, set at p < 1.1x10-6, based on Bonferroni correction and FDR test) [3]. Our preliminary results indicate that some ECRs can act as regulatory domains after stimuli with 3 of 8 antidepressants and hormones related to MDD in SHSY5Y cells. Although in these cells only a 36 ECRs appear transcriptionally active, the corrected p-values threshold is very conservative. Moreover, this approach might be useful for revealing common genomic elements acting as transcriptional regulators responsive to several stimuli known to be associated to onset of MDD" DO - http://dx.doi.org/10.1016/S0924-977X%2811%2970249-8 0 48 A. Aschkenasy 1976 Graft-versus-host reaction and lymphoid organs in normally fed and protein-deprived rats Experientia 32 5 638-639 "Lymph node graft-versus-host reaction (GVHR) induced by parental splenic lymphocytes inoculated into hind foot pads of F-1 hybrid rats is correlated with the state of the thymus and the spleen of the recipients. This may explain the depression of the reaction after protracted protein deprivation. Furthermore, GVHR provokes mainly in normal rats a reduction of thymus and spleen possibly due to a T-cell transfer to the grafted area" http://www.ncbi.nlm.nih.gov/pubmed/6299 0 49 "R. D. Piper, F. Y. Li, M. L. Myers and W. J. Sibbald" 1999 Effects of isoproterenol on myocardial structure and function in septic rats J.Appl.Physiol (1985.) 86 3 993-1001 "In this study we sought to determine the effect of sepsis on two sequelae of prolonged (24-h) beta-agonist administration, myocardial hypertrophy and catecholamine-induced cardiotoxicity. Sprague-Dawley rats were randomized to cecal ligation and perforation (CLP) or sham study groups and then further randomized to receive isoproterenol (2.4 mg. kg-1. day-1 iv) or placebo treatment. At 24 h, myocardial function was assessed by using the Langendorff isolated-heart technique or the heart processed for plain light microscopy. We found that 1) sepsis reduced contractile function, indicated by a rightward shift in the Starling curve (ANOVA with repeated measures, sepsis effect, P < 0.002); 2) sepsis-induced myocardial depression was reversed by isoproterenol treatment (isoproterenol effect, P < 0.0001); 3) sepsis reduced, but did not block, isoproterenol-induced myocardial hypertrophy (isoproterenol effect, P < 0.0001); 4) sepsis did not protect the heart from catecholamine-induced tissue injury; 5) the septic heart was protected against the effects of ischemiareperfusion (decreased postreperfusion resting tension, ANOVA with repeated measures, P < 0.01), an effect attenuated by isoproterenol treatment (P < 0.005); and 6) sepsis reduced the incidence of sustained asystole or ventricular fibrillation after ischemia-reperfusion (P < 0.05), an effect also attenuated by isoproterenol treatment (P < 0.01). We conclude that, in sepsis, beta-agonists induce changes in myocardial weight and function consistent with acute myocardial hypertrophy. These changes occur at the expense of significant tissue injury and increased sensitivity to ischemia-reperfusion-induced tissue injury" http://www.ncbi.nlm.nih.gov/pubmed/10066715 0 50 A. D. Levy and L. D. Van de Kar 1992 "Endocrine and receptor pharmacology of serotonergic anxiolytics, antipsychotics and antidepressants" "Life Sciences.51 (2) ()(pp 83-94), 1992.Date of Publication: 1992." 2 83-94 "Several classes of drugs that modify serotonin (5-HT) neurotransmission are either currently used, or are being evaluated for their potential use in the treatment of anxiety, schizophrenia, and depression. 5-HT(1A) agonists are considered potential anxiolytics, while some atypical antipsychotics are potent 5-HT2 antagonists (and also have modest dopamine D2 affinity). Furthermore, there is a diverse group of serotonergic drugs that may be effective antidepressants. Secretion of ACTH, corticosterone/cortisol, prolactin, renin, oxytocin and vasopressin are stimulated by activation of different 5-HT receptor subtypes, while other neurotransmitter receptors also influence the secretion of these hormones. We compared the receptor binding profiles of 5-HT anxiolytics, antipsychotics and antidepressants with their endocrine effects. These comparisons could aid in understanding both the therapeutic and side effects of these drugs" 0 51 X. Wan and E. Puil 2002 Pentobarbital depressant effects are independent of GABA receptors in auditory thalamic neurons J.Neurophysiol. 88 6 3067-3077 "Pentobarbital, a general anesthetic, has received extensive study for its ability to potentiate inhibition at GABA(A) subtype of receptors for GABA. Using whole cell current-clamp techniques and bath applications, we determined the effects of pentobarbital and GABA receptor antagonists on the membrane properties and tonic or burst firing of medial geniculate neurons in thalamic slices. Pentobarbital (0.01-200 microM) induced depressant effects in 50 of 66 neurons (76%). Pentobarbital hyperpolarized neurons by a mean of 3 mV and decreased the number of action potentials in tonic firing, evoked by current pulse injection from near the resting potential. Pentobarbital also decreased burst firing or low threshold Ca(2+)-spikes, evoked by current pulse injection into neurons at potentials hyperpolarized from rest. The blockade of tonic and burst firing, as well as low threshold Ca(2+)-spikes, was surmountable by increasing the amplitude of input current. The GABA(A) receptor antagonists, bicuculline (100 microM) and picrotoxinin (50-100 microM), did not block the depressant effects of pentobarbital (10 microM). The GABA(B) receptor antagonist, saclofen (200 microM), and GABA(C) receptor antagonist, (1,2,3,6-tetrahydropyridine-4-yl)methylphosphinate (10-50 microM), did not significantly alter the depressant effects. Pentobarbital produced excitatory effects (0.1-50 microM) on 11 neurons (17%) but had no effects on 5 neurons (7%). The excitation consisted of approximately 3 mV depolarization, increased tonic and burst firing and the rate of rise and amplitude of low threshold Ca(2+) spikes. These effects were associated with a increase in input resistance. In contrast, the depressant effects of pentobarbital correlated to a decreased input resistance measured with hyperpolarizing current pulse injection (IC(50) = 7.8 microM). Pentobarbital reduced Na(+)-dependent rectification on depolarization and lowered the slope resistance over a wide voltage range. Tetrodotoxin eliminated both Na(+)-dependent rectification and the pentobarbital-induced decrease in membrane resistance at depolarized voltages in two-thirds of the neurons. The pentobarbital-induced decrease in membrane resistance at voltages hyperpolarized from rest was not evident during co-application with Cs(+), known to block the hyperpolarization-activated rectifiers. In summary, the pentobarbital acted at low concentrations to depress thalamocortical neurons. The depression resulted from decreased rectification on depolarization, which no longer boosted potentials over threshold, and an increased conductance that shunted spike generation. The depressant effects of pentobarbital did not involve known types of GABA receptor interactions" http://www.ncbi.nlm.nih.gov/pubmed/12466430 0 52 "M. Balazs, H. Schwarzberg and G. Telegdy" 1988 Effects of somatostatin on self-stimulation behaviour in rats pretreated with a receptor blocker Eur.J.Pharmacol. 149 01-Feb 141-144 "The effects of somatostatin on lateral hypothalamic self-stimulation were investigated in rats pretreated with haloperidol, bicuculline, phenoxybenzamine or propranolol. Somatostatin decreased the rate of self-stimulation. Halperidol, bicuculline and phenoxybenzamine potentiated the somatostatin-induced depression of self-stimulation behaviour. Propranolol had no effect. It is suggested that dopaminergic, GABAergic and noradrenergic systems are involved in the somatostatin-induced depression of self-stimulation" http://www.ncbi.nlm.nih.gov/pubmed/2899512 0 53 "S. Borges, B. Coimbra, C. Soares-Cunha, A. P. Ventura-Silva, L. Pinto, M. M. Carvalho, J. M. Pego, A. J. Rodrigues and N. Sousa" 2013 Glucocorticoid programing of the mesopontine cholinergic system Front Endocrinol.(Lausanne) 4 190 "Stress perception, response, adaptation, and coping strategies are individually distinct, and the sequel of stress and/or glucocorticoids (GCs) is also distinct between subjects. In the last years, it has become clear that early life stress is a powerful modulator of neuroendocrine stress-responsive circuits, programing intrinsic susceptibility to stress, and potentiating the appearance of stress-related disorders such as depression, anxiety, and addiction. Herein we were interested in understanding how early life experiences reset the normal processing of negative stimuli, leading to emotional dysfunction. Animals prenatally exposed to GCs (in utero glucocorticoid exposure, iuGC) present hyperanxiety, increased fear behavior, and hyper-reactivity to negative stimuli. In parallel, we found a remarkable increase in the number of aversive 22 kHz ultrasonic vocalizations in response to an aversive cue. Considering the suggested role of the mesopontine tegmentum cholinergic pathway, arising from the laterodorsal tegmental nucleus (LDT) and pedunculopontine tegmental nucleus (PPT), in the initiation of 22 kHz vocalizations and hypothetically in the control of emotional arousal and tone, we decided to evaluate the condition of this circuit in iuGC animals. Notably, in a basal situation, iuGC animals present increased choline acetyltransferase (ChAT) expression in the LDT and PPT, but not in other cholinergic nuclei, namely in the nucleus basalis of Meynert. In addition, and in accordance with the amplified response to an adverse stimulus of iuGC animals, we found marked changes in the cholinergic activation pattern of LDT and PPT regions. Altogether, our results suggest a specific cholinergic pathway programing by prenatal GC, and hint that this may be of relevance in setting individual stress vulnerability threshold" http://www.ncbi.nlm.nih.gov/pubmed/24379803 0 54 "K. Fujiwara, Y. TAKAGAKI and Y. TAJIMA" 1963 DEPRESSION OF RESPONSE IN THE CHICKS EXPOSED TO MAMMALIAN ERYTHROCYTE ANTIGEN AT HATCHING Jpn.J.Exp.Med. 33 95-106 http://www.ncbi.nlm.nih.gov/pubmed/14057140 0 55 "R. Jung, E. N. Bruce and P. G. Katona" 1989 Tonic and baroreflex effects on arterial pressure and ventilation of pentobarbital and nicotine on the rat ventral medullary surface Brain Res. 485 2 399-402 "Unilateral aortic depressor nerve stimulation caused depression of arterial pressure (baropressure reflex) and ventilation (baro-ventilatory reflex) in urethane-anesthetized, spontaneously breathing Sprague-Dawley rats. Application of sodium pentobarbital to the ventral medullary surface (VMS) depressed baseline arterial pressure and ventilation, and attenuated the baro-pressure reflex, but not the baro-ventilatory reflex. Application of nicotine on the VMS decreased baseline arterial pressure and increased ventilation, but left both baro-pressure and baro-ventilatory reflexes unaltered. The results suggest that some of the structures that affect vasomotor tone may not be involved in the baroreflex inhibition of arterial pressure. Additionally, neither the neural structures near the VMS which modulate CO2 control of ventilation, nor those that affect tonic control of vasomotor tone are likely to be significantly involved in the baro-ventilatory reflex" http://www.ncbi.nlm.nih.gov/pubmed/2720421 0 56 "D. J. de Wildt, H. Krugers, C. M. Kasbergen, L. H. De and D. H. Versteeg" 1993 The hemodynamic effects of gamma 2-melanocyte-stimulating hormone and related melanotropins depend on the arousal potential of the rat Eur.J.Pharmacol. 233 1 157-164 "In conscious rats, i.v. administered adrenocorticotropic hormone (ACTH-(4-10)) and gamma 2-melanocyte-stimulating hormone (gamma 2-MSH) induced a dose-dependent increase in blood pressure (BP), heart rate (HR) and pulse pressure (PP). No circadian influence on these effects was observed. The structurally related peptide, alpha-melanocyte-stimulating hormone (alpha-MSH), only caused an increase in HR, which was not dose-dependent, whereas the stable ACTH-(4-9) analog, Org 2766, was without effect on these hemodynamic parameters. In rats under light urethane-induced anesthesia, which is known to maintain reflexes and sufficient sympathetic tone, gamma 2-MSH caused hemodynamic responses similar to those observed in conscious rats. In contrast, gamma 2-MSH had an opposite effect in rats under deep pentobarbital-induced anesthesia: a depressor effect combined with a slight bradycardia. A comparative study with rats of a more arousable Wistar rat substrain (Riv:TOX) and of a less excitable rat substrain (U:WU) showed that the dose-pressor response curves for ACTH-(4-10) and gamma 2-MSH were shifted to the left in the more excitable rats as compared to the in the less excitable rats. We conclude that a restricted amino acid sequence in the N-terminal part of the pro-opiomelanocortin (POMC)-molecule (gamma 2-MSH/ACTH-(4-10)-like) is responsible for the stimulating effects on the cardiovascular system and that those effects are strongly dependent on the state of arousal, i.e. sympathetic tone, of the rat. These stimulatory effects override a depressor phenomenon which can only be detected during central depression" http://www.ncbi.nlm.nih.gov/pubmed/8386086 0 57 R. Hazard and A. Renier-Cornec 1972 [Power of posthypophyseal preparations partially to reestablish the hypertensive action of hordenine first suppressed by adrenolytics] C.R.Seances Soc.Biol.Fil. 166 11 1433-1435 http://www.ncbi.nlm.nih.gov/pubmed/4667356 0 58 M. Vornanen and V. Paajanen 2004 "Seasonality of dihydropyridine receptor binding in the heart of an anoxia-tolerant vertebrate, the crucian carp (Carassius carassius L.)" Am.J.Physiol Regul.Integr.Comp Physiol 287 5 R1263-R1269 "Prolonged anoxia tolerance of facultative anaerobes is based on metabolic depression and thus on controlled reduction of energy-utilizing processes. One proposed survival mechanism is the closing of ion channels to decrease energetic cost of ion pumping (Hochachka PW. Science 231: 234-241, 1986). To test this hypothesis, the involvement of L-type Ca2+ channels in seasonal anoxia tolerance of the vertebrate heart was examined by determining the number of [methyl-3H]PN200-110 (a ligand of L-type Ca2+ channel alpha-subunit) binding sites of the cardiac tissue and the density of Ca2+ current in ventricular myocytes of an anoxia-resistant fish species, the crucian carp. In their natural environment, the fish were exposed for > 3 mo of hypoxia (O2 < 2.5 mg/l) followed by almost 8 wk of anoxia that resulted in abrupt depletion of cardiac glycogen stores in late spring. Unexpectedly, however, the number of [methyl-3H]PN200-110 binding sites did not decline in hypoxia/anoxia as predicted by the channel arrest hypothesis but remained constant for most of the year. However, in early summer, the number of [methyl-3H]PN200-110 binding sites doubled for a period of approximately 2 mo, which functionally appeared as a 74% larger Ca2+ current density. Thus the anoxia tolerance of the carp heart cannot be based on downregulation of Ca2+ channel units in myocytes but is likely to depend on suppressed heart rate, i.e., regulation of the heart at the systemic level, and direct depressive effects of low temperature on Ca2+ current to achieve savings in cardiac work load and ion pumping. The summer peak in the number of functional Ca2+ channels indicates a short period of high cardiac activity possibly associated with reproduction and active perfusion of tissues after the winter stresses" http://www.ncbi.nlm.nih.gov/pubmed/15242827 0 59 E. J. Barbieri and E. I. Ciaccio 1979 Depression of drug metabolism in the mouse by a combination of Mycobacterium butyricum and anaesthetics Br.J.Pharmacol. 65 1 111-115 "1 Subcutaneous injection of Mycobacterium butyricum suspended in mineral oil into the mouse hind paw caused an oedematous local inflammation. Hind paw swelling was maximum 5 days after injection and was still apparent at day 30. 2 Drug metabolism in vivo (as monitored by ketamine- or pentobarbitone-induced sleeping times) was not affected by the inflammatory disease. However, administration of ketamine or pentobarbitone at day 1 led to significantly elevated sleeping times when the mice showing local inflammation were retested at day 5 with the anaesthetics. 3 Indomethacin inhibited hind paw oedema in the mouse but did not affect ketamine-Mycobacterium butyricum-induced depression of drug metabolism. 4 Prolongation of ketamine-induced anaesthesia by combination with Mycobacterium butyricum at day 5 correlated with the degree of hind paw inflammation at this time. 5 The data suggest that anaesthetics (i.e., ketamine and pentobarbitone) may sensitize hepatic membranes to the effect of Mycobacterium butyricum or some toxic compound elaborated during the active phase of inflammation" http://www.ncbi.nlm.nih.gov/pubmed/760885 0 60 "E. B. Burlakov, S. A. Aristarkhova, L. V. Fedorova, N. I. Sheludchenko and L. N. Shishkina" 1991 [The characteristics of the effect of dipalmitoylphosphatidylcholine and its structural fragments on the lipid peroxidation of biological membranes] Nauchnye.Doki.Vyss.Shkoly.Biol.Nauki 9 21-27 "The effect of dipalmitoyl phosphatidylcholine (DPPC) and its structural fragments--phosphatidic acid (PA) and choline chloride--on the ascorbate-dependent mice liver microsomal lipid peroxidation (LP) has been studied at the different LP rate. At DPPC, PA and choline chloride introduction into the incubation medium before the onset of peroxidation induction DPPC causes the more considerable inhibition of LP than PA each separate fragment. The inhibition effect of DPPC is lower than PA or choline chloride when DPPC, PA and choline chloride added on the background of developing process of peroxidation (e.i. after LP induction). A specific regulatory role of PC in the normal cell membrane LP process and during pathologic development is under discussion" http://www.ncbi.nlm.nih.gov/pubmed/1751614 0 61 "S. Dutta, P. S. Basu and S. Banerjee" 1977 Intestinal absorption of glucose from isolated mice jejunal loops in vivo: effect of different derivatives of tetracyclines Indian J.Exp.Biol. 15 6 452-454 http://www.ncbi.nlm.nih.gov/pubmed/598875 0 62 "V. Grimm, Z. Gottesfeld, I. Wassermann and D. Samuel" 1975 The level of GABA in the brain and locomotor behavior Pharmacol.Biochem.Behav. 3 4 573-578 "GABA content was measured in the brains of animals injected with AOAA, DPA or Saline. Significant increases in GABA were found in the motor cortex and cerebellum after treatment with both drugs as compared to saline injected controls. Increased GABA levels were associated with interference with the smooth execution of locomotor acts, especially where balancing and coordination of the hind limbs were necessary" http://www.ncbi.nlm.nih.gov/pubmed/1103159 0 63 2005 "Healthier arteries, clearer thinking. What you do for your heart pays off for your brain and memory" Heart Advis. 8 3 "1, 7" http://www.ncbi.nlm.nih.gov/pubmed/15895493 0 64 E. M. Silinsky 1978 Enhancement by an antagonist of transmitter release from frog motor nerve terminals Br.J.Pharmacol. 63 3 485-493 "1 The effect of Ba2+ on the synchronous release of acetylcholine from frog motor nerve terminals was studied by conventional electrophysiological techniques. 2 When Ca2+ and Ba2+ were the only divalent cations in the bathing fluid, Ba2+ caused a presynaptic reduction in the amplitude of the endplate potential (e.p.p.). This effect was surmountable by increasing the Ca2+ concentration. 3 The affinity constant (KA) for Ba2+, calculated on the assumption that Ba2+ is a competitive inhibitor of the agonist, Ca2+, was 1.1 +/- 0.4 mM-1 (mean +/- s.e. mean, n = 8). 4 When e.p.ps were depressed by the addition of 1 mM Mg2+, addition of Ba2+ (1 to 3 mM) caused either a further presynaptic depression of moderate magnitude or had no additional effect. 5 When e.p.p.s were depressed with [Mg2+] greater than or equal to 2 mM, addition of Ba2+ greater than or equal to 0.9 mM enhanced the e.p.p. amplitude by a presynaptic mechanism. 6 The interaction of the divalent cation antagonists Mg2+ and Ba2+ with the agonist, Ca2+ is discussed. It is demonstrated that a model which considers the nonequilibrium, kinetic properties of binding can be used to describe interactions between divalent cations at the external surface of the motor nerve ending" http://www.ncbi.nlm.nih.gov/pubmed/27281 0 65 "K. Ushijima, T. Morikawa, H. To, S. Higuchi and S. Ohdo" 2006 Chronobiological disturbances with hyperthermia and hypercortisolism induced by chronic mild stress in rats Behav.Brain Res. 173 2 326-330 "The chronic mild stress (CMS) model has been established as a realistic model of depressive disorder as it simulates anhedonia. In the present study, the consumption of sucrose solution was decreased in the rats exposed to CMS, which coincided with many published studies. Since depression is a multifaceted disorder, and a number of symptoms may be present, including circadian rhythm disturbances, we attempted to find the chronobiological abnormalities in CMS rats. After 4-week of the stress procedure, the rhythmic pattern of rectal temperature in the CMS group was extinguished. In particular, the temperature in the CMS group in the light phase was significantly higher than that in the control group. The plasma corticosterone levels in the CMS group were remarkably increased in the light phase compared to the control group, but not in the dark phase. It was concluded that the CMS procedure caused the disturbance of circadian rhythms with hyperthermia and hypercortisolism" http://www.ncbi.nlm.nih.gov/pubmed/16904763 1 66 "S. Hynie, J. Ceplik, M. Cernohorsky, V. Klenerova, J. Skrivanova and M. Wenke" 1975 7-oxa-13-prostynoic acid and polyphloretin phosphate as non-specific antagonists of the stimulatory effects of different agents on adenylate cyclase from various tissues Prostaglandins 10 6 971-981 "7-oxa-13-prostynoic acid (OPA) and polyphloretin phosphate (PPP) are believed to act as specific antagonists of prostaglandin action. In order to estimate their specificity, the inhibitory effects of these drugs were tested on the activity of adenylate cyclase from several tissues which were stimulated by prostaglandins and several other compounds. In adenylate cyclase preparation from L-fibroblasts both OPA (0.15-1.5 MM) and PPP (0.01-1.0 MG/ML) antagonized not only the stimulatory effects of PGE but also the stimulatory effects of sodium fluoride and increased enzyme activity due to the previous treatment of cell cultures by cholera toxin. Both OPA and PPP produced a dose dependent depression of adenylate cyclase activity to zero values both under basal conditions and after stimulation by sodium fluoride and various hormones in all preparations studied, including rat liver, heart, brain, epididymal adipose tissue, small intestine, renal cortex and renal medulla. The present results indicate that both prostaglandin antagonists may, in higher concentrations, act as nonspecific inhibitors of the catalytic unit of adenylate cyclase rather than specific antagonists of the prostaglandin effects on adenylate cyclase" http://www.ncbi.nlm.nih.gov/pubmed/1239793 0 67 L. Petrinovich and T. J. Crow 1977 Cortical spreading depression and memory transfer: a reply to Mayes Behav.Biol. 20 2 275-280 http://www.ncbi.nlm.nih.gov/pubmed/901360 0 68 "D. B. Goswami, B. Szewczyk, H. Fitzgibbon, C. A. Stockmeier and M. C. Austin" 2009 Gene expression of intrinsic and afferent regulators of serotonin in laser-captured dorsal raphe neurons of subjects with major depressive disorder "Biological Psychiatry.Conference: 64th Annual Scientific Convention and Meeting of the Society of Biological Psychiatry Vancouver, BC Canada.Conference Start: 20090514 Conference End: 20090516.Conference Publication: (var.pagings).65 (8 Suppl 1) ()(pp" var.pagings 238S "Background: Considerable evidence supports the hypothesis that serotonin neurotransmission is reduced in depressed patients. Candidates that regulate serotonin synthesis and neuronal activity include the intrinsic rate-limiting enzyme, tryptophan hydroxylase 2 (TPH2) and based on rodent studies, afferent factors estrogen and BDNF also modulate serotonin neuronal activity. The present study was designed to quantify mRNA concentrations of TPH2, TPH1, estrogen receptor alpha (ERalpha) and beta (ERbeta) and tyrosine kinase B receptor (TrkB) in a pure population of serotonin-containing dorsal raphe (DR) neurons of subjects with major depressive disorder (MDD) and normal control subjects. Methods: TPH2-immunostained DR neurons were harvested from midbrain sections of depressed and gender-matched control subjects using a lasercapture microdissection (LCM) system. RNA was isolated, reverse transcribed and mRNA for TPH2, TPH1, TrkB, ERalpha and ERbeta, along with two internal control genes, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and RNA polymerase II (RP-II) were quantified using real-time PCR. Results: No significant differences in the mRNA transcripts were found when analyzed by gender groups. When the data was combined across genders, ERalpha mRNA levels were significantly increased in the MDD subjects as compared to control subjects. Trends of increased expression in TPH1 and ERbeta mRNAs were observed in depressed subjects but did not reach statistical significance. TPH2 and TrkB mRNA levels did not differ between depressed and control subjects. Conclusions: These results reveal an elevation in ERalpha gene expression in DR neurons of depressed subjects that may contribute to altered intracellular signaling and serotonin neuronal activity in depression" 0 69 "D. Siuda, Z. Wu, Y. Chen, L. Guo, M. Linke, U. Zechner, N. Xia, G. Reifenberg, H. Kleinert, U. Forstermann and H. Li" 2014 Social isolation-induced epigenetic changes in midbrain of adult mice "Journal of Physiology and Pharmacology.65 (2) ()(pp 247-255), 2014.Date of Publication: APRIL 2014." 2 247-255 "Social isolation and loneliness increase the risk of death as much as well-established risk factors for mortality such as cigarette smoking and alcohol consumption. The underlying molecular mechanisms are poorly understood. In the present study, 3 months old male C57BL/6 mice were socially isolated by individual housing for another 3 months. At the age of 6 months, epigenetic changes were analyzed in midbrain. Social isolation of male adult mice led to an increased global DNAmethylation, which was associated with enhanced activity of DNAmethyltransferase. Di-and trimethylation of global histone H3 lysine 4 (H3K4) were increased in midbrain of socially isolated mice, accompanied by enhanced H3K4 histone methyltransferase activity. In addition, social isolation of adult mice led to activation of histone acetyltransferases as well as of histone deacetylases (HDAC) resulting in a net enhancement of histone H3 lysine 9 (H3K9) acetylation. Gene-specific effects were observed for Hdac1, Hdac3 and the serotonin transporter Slc6a4. Social isolation led to an up-regulation of Hdac1 and Hdac3, associated with decreased DNAmethylation in the CpG island of the respective genes. On the contrary, the Slc6a4 gene was down-regulated, which was associated with enhanced DNA methylation. Collectively, the results from the present study demonstrate for the first time that social isolation of adult mice leads to a wide range of global epigenetic changes and these effects may have profound impact on gene expression pattern and phenotype of the socially isolated animals" 0 70 "D. H. Overstreet, A. H. Rezvani and D. S. Janowsky" 1992 Genetic animal models of depression and ethanol preference provide support for cholinergic and serotonergic involvement in depression and alcoholism Biol.Psychiatry 31 9 919-936 "The present article summarizes some comparative studies of the Fawn-Hooded (FH) rat, a potential animal model of ethanol preference, and the Flinders Sensitive Line (FSL) rat, a potential animal model of depression. Both FH and FSL rats exhibit high degrees of immobility in the forced swim test and have difficulty learning a two-way active avoidance task. However, there were no differences between the FH and FSL rats in the elevated plus maze. Studies of ethanol preference indicated high rates of ethanol intake (greater than 4 g/kg) and preference (greater than 50%) in the FH rats, but low rates of ethanol intake (less than 1.1 g/kg) and preference (less than 20%) in FSL rats. It is concluded that the FSL rats exhibit behaviors consistent with their being an animal model of depression, whereas the FH rats exhibit features consistent with their being an animal model of both depression and alcoholism. Psychopharmacological challenges indicated that both FSL and FH rats were more sensitive to the hypothermic effects of oxotremorine, a muscarinic agonist. However, FSL rats were also more sensitive to serotonergic agonists, and some of the present results and other investigators have reported serotonergic subsensitivity in the FH rats. Thus, FSL rats exhibit both cholinergic and serotonergic supersensitivity, whereas FH rats exhibit cholinergic supersensitivity but normal or reduced serotonergic sensitivity. Progeny from a genetic cross between FH and FSL rats exhibit cholinergic supersensitivity and have high ethanol preference scores. These data are consistent with genetic models suggesting that ethanol preference may be influenced by dominant genes, whereas cholinergic sensitivity may be influenced by recessive genes" http://www.ncbi.nlm.nih.gov/pubmed/1386257 1 71 P. Kumar 2010 "Vishweshwaraiah Iron Steel Limited (VISL) fire disasters following steel converter blast, 30 July 2003" "Burns.36 (1) ()(pp 135-138), 2010.Date of Publication: February 2010." 1 135-138 "A fire disaster occurred in Vishweshwaraiah Iron Steel Limited (VISL), Bhadravathi, India on 30 July 2003. The steel converter containing 24,000 kg of liquid metal (pig iron) at very high temperature exploded. A total of 30 workers became victims. Seven persons died on the spot. Twenty-three victims were transferred to the VISL hospital; of these, six were transferred to the burns unit of the Kasturba Hospital, Manipal (180 km from VISL). All six treated at the burns unit suffered 3-65% total body surface area (TBSA) burn, two had external injuries and two had eye involvement. Out of the six patients admitted at the burns unit, two expired (one due to refractory shock and another due to pulmonary embolism). Out of four survivors, one underwent tangential excision; another underwent operation for removal of foreign body from both soles and the remaining two were managed conservatively. Of the four survivors, two who had eye injuries, one developed minute corneal opacities within 2 months. The total duration of hospital stay of survivors at the burns unit varied from 8 to 43 days. All the victims were counselled by VISL psychiatrists before resuming their duties. Except the one who developed mixed anxiety-depression disorder, all survivors returned to work. The article describes the mechanism of the incident, injuries sustained and suggestions in relation to future safety measures. © 2009 Elsevier Ltd and ISBI" DO - http://dx.doi.org/10.1016/j.burns.2009.04.029 0 72 V. Vulovic and I. S. Curthoys 2011 Bone conducted vibration activates the vestibulo-ocular reflex in the guinea pig Brain Res.Bull. 86 01-Feb 74-81 "The aim of the study was: (a) to test whether short duration (6 ms) 500 Hz bone-conducted vibration (BCV) of the skull in alert head free guinea pigs would elicit eye movements; (b) to test whether these eye movements were vestibular in origin; and (c) to determine whether they corresponded to human eye movements to such stimuli. In this way we sought to establish the guinea pig as an acceptable model for testing the mechanism of the effect BCV on the vestibulo-ocular reflex. Consistent short-latency stimulus-locked responses to BCV were observed. The magnitude of eye displacement was directly related to stimulus intensity as recorded by accelerometers cemented onto the animal's skull. The strongest and most consistent response component was intorsion of both eyes. In lateral-eyed animals intorsion is produced by the combined contraction of the inferior rectus and superior oblique muscles. In humans the same pair of muscles acts to cause depression of the eye. To test whether the movements were vestibular we selectively ablated the vestibular endorgans: 3 of the 8 animals underwent a bilateral intratympanic injection of gentamicin, an ototoxic aminoglycoside antibiotic, to ablate their vestibular receptors. After ablation there was an overall reduction in the magnitude of eye displacement, as well as a reduction in the effectiveness of the BCV stimulus to elicit eye movements. The animals' hearing, as measured by the threshold for auditory brainstem responses, remained unchanged after gentamicin, confirming that the cochlea was not affected. The reduced magnitude of responses after vestibular receptor ablation demonstrates that the eye-movement responses to BCV are probably caused by the stimulation of vestibular receptors, which in turn activate the vestibulo-ocular reflex" http://www.ncbi.nlm.nih.gov/pubmed/21745548 0 73 I. Jurna 1984 Depression of nociceptive sensory activity in the rat spinal cord due to the intrathecal administration of drugs: effect of diazepam Neurosurgery 15 6 917-920 "The intrathecal (i.t.) administration of morphine inhibits nociceptive motor responses and activity in ascending axons evoked by stimulation of nociceptive afferent nerve fibers (nociceptive sensory response) in the rat. The i.t. administration of cholecystokinin octapeptide and ceruletide inhibits nociceptive motor responses, but does not affect ascending nociceptive activity. This shows that drug-induced depression of nociceptive motor responses is not always associated with depression of the nociceptive sensory response of the spinal cord. The microiontophoretic application of substance P excites single dorsal horn neurons that respond to noxious stimulation, whereas the i.t. administration of substance P inhibits both nociceptive motor and sensory responses. Thus, the results obtained from the i.t. administration of a drug may differ from those obtained from its application to single spinal neurons. Diazepam inhibits spinal reflexes and may reduce pain sensation in humans. To assess whether a spinal action is involved in the pain-relieving effect of diazepam, experiments were carried out on spinalized rats in which activity evoked by the stimulation of nociceptive and nonnociceptive afferent nerve fibers of the sural nerve was recorded from single ascending axons below the site of spinal cord transection. Diazepam, 20 micrograms i.t., reduced activity evoked by afferent A delta and C fiber stimulation and by stimulation of afferent A beta fibers. The depressant effect caused by diazepam, 2 mg/kg i.v., on C fiber-evoked ascending activity was reduced by the i.t. injection of the benzodiazepine antagonist, Ro 15-1788 (40 micrograms), an imidazodiazepine. It is concluded that the depression by diazepam of C fiber-evoked ascending activity contributes to pain relief caused by the drug" http://www.ncbi.nlm.nih.gov/pubmed/6096760 0 74 B. Curran and J. J. O'Connor 2001 The pro-inflammatory cytokine interleukin-18 impairs long-term potentiation and NMDA receptor-mediated transmission in the rat hippocampus in vitro Neuroscience 108 1 83-90 "The effects of the pro-inflammatory cytokine interleukin-18 (IL-18) were investigated on both normal and isolated N-methyl-D-aspartate (NMDA) receptor-mediated field excitatory post synaptic potentials (fEPSP) and on the induction of long-term potentiation (LTP) in the rat dentate gyrus in vitro. Bath perfusion with IL-18 (100 ng/ml) for 20 min prior to high-frequency stimulation had no significant effect on baseline synaptic transmission or paired pulse depression, but did impair the induction of LTP (115.7+/-8.8% versus 150.8+/-8.1% in vehicle control slices, n=6, P<0.05 at 60 min). Further analysis demonstrated that IL-18 significantly depressed the amplitude of pharmacologically isolated NMDA receptor-mediated fEPSP (NMDA-fEPSP; 77.4+/-4.3% of baseline compared to controls at 1 h; P<0.05, n=7), an effect that may underlie the impairment of LTP by IL-18. This action of IL-18 on LTP and NMDA-fEPSPs was attenuated in full by pretreatment of slices with exogenously applied IL-1 receptor antagonist (IL-1ra, 100 ng/ml), the naturally occurring antagonist of IL-1 type 1 receptors. This ability of IL-1ra to block the inhibitory effects of IL-18 is likely to be receptor-specific as no reversal of the tumour necrosis factor-alpha-induced inhibition of LTP was seen with IL-1ra administration (110.7+/-5.4% versus tumour necrosis factor-alpha-treated slices; 107.4+/-8.7%, P=0.6, n=6). These are the first experiments providing evidence of a direct neuromodulatory role for IL-18 in synaptic plasticity" http://www.ncbi.nlm.nih.gov/pubmed/11738133 0 75 "C. Dauthier, J. H. Gaudy and J. C. Willer" 1980 [Competitive study of the effects of naloxone and of almitrine on fentanyl analgesia in the anesthetized dog: effects on the muzzle opening reflex and blood gases] Ann.Anesthesiol.Fr. 21 4 421-430 "The search for a technique making it possible to dissociate the analgesia and ventilatory depression of central analgesics led to a comparison of the effects of naloxone, a specific morphinomimetic antagonist, with almitrine, a ventilatory stimulant with a peripheral action, on muzzle opening reflex and blood gases. Five male dogs (Beagles, aged one year), anaesthetised with Alfetesine were treated separately with the two drugs used alone and after fentanyl analgesia (injection of fractionnated doses up to the threshold of apnoea). The association of the two drugs was also tested in tyhe dog after analgesia. The parameters studied were muzzle opening reflex, as an indication of analgesia, and blood gases, and were observed for 45 minutes, including 15 minutes control. RESULTS: 1 - The intravenous injection of 1,2 mg of naloxone had the effect of increasing the surface area of muscle potentials with a maximum of 7 per cent (p 0.001) at the 15 th minute. By contrast, no significant change in blood gases was seen. In the same dogs given fentanyl analgesia, naloxone not only reversed respiratory depression but had a stimulatory effect on MOR reaching 7 per cent (p 0.001) at the 30 th minute. 2 - The effects of 1 mg.kg-1 of almitrine were characterised by a fall in MOR for a period equal to that of the study and a minimum of 7.8 per cent (p 0.001) at the 20 th minute. At the same time, marked ventilatory stimulation was seen. PO2 rose by 22.7 per cent (p 0.02) at the 5 th minute. PCO2 fell during the 30 minutes studied with a minimum of 39.6 per cent (p 0.01) at the 20 th minute. Almitrine did not antagonise the depression of MOR caused by fentanyl but reversed the respiratory depression of the analgesic, increasing PO2 by 26 per cent (p 0.01) and decreasing PCO2 by 25.7 per cent (p 0.01). 3 - The combination of both drugs cancelled out the abolition of the reflex by fentanyl then facilitated it up to 24.7 per cent (p 0.001) in comparison with the animal not receiving any analgesic. By contrast, the ventilatory action of almitrine was not potentialised by naloxone. In view of these data, and in the absence of any emergency, the choice of naloxone as an antagonist of ventilatory depression of central analgesics should not be preferential in order to avoid the rebound effect" http://www.ncbi.nlm.nih.gov/pubmed/6110396 0 76 "K. Temma, T. Akera, A. Chugun, H. Kondo, K. Hagane and S. Hirano" 1993 "Comparison of cardiac actions of doxorubicin, pirarubicin and aclarubicin in isolated guinea-pig heart" Eur.J.Pharmacol. 234 02-Mar 173-181 "The cardiac actions of doxorubicin were compared with those of pirarubicin and aclarubicin to understand the mechanisms responsible for differences in cardiotoxic effects of anthracycline agents. In left atrial muscle preparations obtained from guinea-pig heart and stimulated at 2 Hz, anthracyclines produced positive inotropic effects. The magnitude of the effect was pirarubicin > doxorubicin > aclarubicin. The order for depression of potentiated postrest contraction and prolongation of the time to peak twitch tension was doxorubicin > pirarubicin > aclarubicin. Drug washout following a 2-h incubation with 100 microM doxorubicin prevented a further increase in the time to peak twitch tension, caused a marked recovery of depressed potentiated postrest contractions, and augmented the positive inotropic effect. Pirarubicin and doxorubicin, but not aclarubicin, caused a parallel rightward shift of the dose-response curve for the negative inotropic effect of acetylcholine. The potency of inhibition of [3H]quinuclidinyl benzilate binding was pirarubicin > doxorubicin > aclarubicin. These results indicate that three anthracycline anticancer agents share similar effects on cardiac muscle contractility and on muscarinic acetylcholine receptors. The actions of aclarubicin were weak compared to those of doxorubicin or pirarubicin. Increases in the time to peak twitch tension and the depression of potentiated postrest contraction are apparently mediated by mechanisms different from those responsible for the positive inotropic effects or antagonism at muscarinic acetylcholine receptors" http://www.ncbi.nlm.nih.gov/pubmed/8482324 0 77 "R. Scholz, S. Berberich, L. Rathgeber, A. Kolleker, G. Kohr and H. C. Kornau" 2010 AMPA receptor signaling through BRAG2 and Arf6 critical for long-term synaptic depression Neuron 66 5 768-780 "Central nervous system synapses undergo activity-dependent alterations to support learning and memory. Long-term depression (LTD) reflects a sustained reduction of the synaptic AMPA receptor content based on targeted clathrin-mediated endocytosis. Here we report a current-independent form of AMPA receptor signaling, fundamental for LTD. We found that AMPA receptors directly interact via the GluA2 subunit with the synaptic protein BRAG2, which functions as a guanine-nucleotide exchange factor (GEF) for the coat-recruitment GTPase Arf6. BRAG2-mediated catalysis, controlled by ligand-binding and tyrosine phosphorylation of GluA2, activates Arf6 to internalize synaptic AMPA receptors upon LTD induction. Furthermore, acute blockade of the GluA2-BRAG2 interaction and targeted deletion of BRAG2 in mature hippocampal CA1 pyramidal neurons prevents LTD in CA3-to-CA1 cell synapses, irrespective of the induction pathway. We conclude that BRAG2-mediated Arf6 activation triggered by AMPA receptors is the convergent step of different forms of LTD, thus providing an essential mechanism for the control of vesicle formation by endocytic cargo" http://www.ncbi.nlm.nih.gov/pubmed/20547133 0 78 C. A. Krause-Parello 2012 "Pet ownership and older women: the relationships among loneliness, pet attachment support, human social support, and depressed mood" Geriatr.Nurs. 33 3 194-203 "Pets can play a positive role in the both the physical and psychological health of older adults. This cross sectional study investigated the relationships among loneliness, pet attachment support, human social support, and depressed mood in a convenience sample of 159 pet-owning older women residing in the community. Participants completed loneliness, pet attachment support, human social support, and depressed mood scales. The results supported significant relationships between loneliness, pet attachment support, human social support, and depressed mood. No relationship was found between human social support and depressed mood. Pet attachment support, but not human social support, influenced the relationship between loneliness and depressed mood indicating the importance of pet attachment as a greater form of support in this sample. Clinical and social implications for nurses working with the geriatric population were identified and discussed" http://www.ncbi.nlm.nih.gov/pubmed/22321806 0 79 H. Inano and B. I. Tamaoki 1971 Regulation of testosterone biosynthesis in rat testes by 7 alpha-hydroxylated C 19 steroids Biochim.Biophys.Acta 239 3 482-493 http://www.ncbi.nlm.nih.gov/pubmed/5113505 0 80 A. J. Pappano and C. A. Skowronek 1974 Reactivity of chick embryo heart to cholinergic agonists during ontogenesis: decline in desensitization at the onset of cholinergic transmission J.Pharmacol.Exp.Ther. 191 1 109-118 http://www.ncbi.nlm.nih.gov/pubmed/4371671 0 81 P. Slater 1969 The effects of intraventricular injections of quaternary ammonium compounds on the acetylcholine content of rat brain Arch.Int.Pharmacodyn.Ther. 181 2 253-262 http://www.ncbi.nlm.nih.gov/pubmed/5403605 0 82 "E. Parise, A. Gancarz, L. Alcantara, O. Sial, D. Dietz and C. Bolanos-Guzman" 2015 Repeated ketamine exposure during adolescence produces changes in reward sensitivity and gene expression in the nucleus accumbens in adulthood "Neuropsychopharmacology.Conference: 54th Annual Meeting of the American College of Neuropsychopharmacology, ACNP 2015 Hollywood, FL United States.Conference Start: 20151206 Conference End: 20151210.Conference Publication: (var.pagings).40 ()(pp S332)," var.pagings S332 "Background: Major Depressive Disorder (MDD) is a highly debilitating mood disorder with poor treatment options and high economic burden. MDD afflicts up to 10% of adolescents. However, nearly 50% of those afflicted are considered non-responsive to available treatments. Ketamine (KET), a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist has shown potential as a rapid-acting and long-lasting treatment for MDD. Nevertheless, these effects are not permanent and it is conceivable that patients may require subsequent exposure to KET. We have recently shown that in addition to possessing antidepressant effects in adolescent rats, ketamine administered repeatedly during adolescence produces long-lasting (2 months) behavioral adaptations indicative of a stress-resilient phenotype. Given that adolescence is a critical period of brain development and KET's high abuse liability, the long-term neurobiological consequences of repeated KET treatment must be characterized. Methods: Adolescent (postnatal day [PD] 35) male rats were treated with KET (0, 20 mg/kg, twice-daily) for 15 days (PD 35-49) and then left undisturbed until adulthood (PD90). At this point, rats were divided into separate groups to assess their behavioral reactivity to the rewarding effects of KET, as measured by the place conditioning (CPP) and the drug self-administration paradigms, or behavioral reactivity to forced swimming stress. Separate groups of rats similarly treated with KET were also used for assessment of druginduced biochemical changes in the nucleus accumbens (NAc). Results: Adult rats pretreated with KET during adolescence showed increased sensitivity to the rewarding effects of KET (5, 10 mg/kg) as measured in the CPP and drug self-administration paradigms as compared to controls. Those rats exposed to forced swimming stress showed increased latency to immobility (i.e., antidepressant-like behavior), and showed a robust locomotor sensitization in response to subsequent KET exposure. RT-qPCR analysis revealed that pretreatment with KET modulates the expression of genes highly implicated in depression and drug-addiction (i.e. dopamine signaling). Conclusions: These findings indicate that repeated KET treatment during adolescence increases behavioral sensitivity to subsequent KET exposure in adulthood, and implicate the intracellular signaling pathways known to mediate responsivity to drug reward and stress" DO - http://dx.doi.org/10.1038/npp.2015.326 0 83 "N. N. Rege, H. M. Nazareth, R. D. Bapat and S. A. Dahanukar" 1989 Modulation of immunosuppression in obstructive jaundice by Tinospora cordifolia Indian J.Med.Res. 90 478-483 "A clinical study was undertaken to determine the immune status of patients with obstructive jaundice. Screening of 16 patients for phagocytic and microbicidal activity of polymorphonuclear cells (PMN) revealed a significant depression (21.2 +/- 3.7% phagocytosis and 20.85 +/- 4.5% intracellular killing) of these functions, as compared to normal values (30.37 +/- 5.1% and 26.41 +/- 4.3% respectively). An animal model of cholestasis was also established, using rats, in which a significant depression of activity of PMN and peritoneal macrophages was observed. These cellular abnormalities were found to precede and predispose to infection. The rats also showed an increased susceptibility to Escherichia coli infection (mortality rate 77.78%). A defect was detected in their serum responsible for depressing the function of phagocytic cells. An attempt was made to improve this immunosuppression by treating the rats with water extract of T. cordifolia 100 mg/kg for 7 days, following development of cholestasis. The extract improved the cellular immune functions. Mortality rate following Esch. coli infection was significantly reduced to 16.67 per cent. This study showed that cholestasis results in immunosuppression and therefore indicates the need for an immunomodulator in management of obstructive jaundice. The plant T. cordifolia seems to meet this need by consolidating host defence mechanism" http://www.ncbi.nlm.nih.gov/pubmed/2697692 0 84 B. G. Miller and R. B. Muntifering 1985 Effect of forage: concentrate on kinetics of forage fiber digestion in vivo J.Dairy Sci. 68 1 40-44 "With five rumen-fistulated Holstein steers in a Latin square design, we determined the effect of dietary concentrate (0, 20, 40, 60, or 80% cracked corn) on kinetic characteristics influencing forage fiber digestion in vivo. Rate and potential extent of neutral detergent fiber degradation were determined for fescue hay in situ by nylon bag technique. Rate of fiber passage from the rumen was measured by fecal excretion of chromium-mordanted fescue cell walls. Apparent extent of forage fiber digestion was predicted by a model in which fiber disappearance from the rumen is conceptualized as the sum of two competing first-order processes, digestion and passage, modified further by a discrete lag time during which fiber passes from the rumen before digestion commences. Stepwise multiple regression analysis revealed that potential extent of fiber degradation in situ was the primary determinant of depression of fiber digestibility as dietary concentrate increased. Rate of digestion, rate of passage, and lag effects collectively accounted for a small portion of the depression of fiber digestibility" http://www.ncbi.nlm.nih.gov/pubmed/2984271 0 85 J. L. Henry 1983 Low threshold mechanical stimulation of the vagina depresses dorsal horn unit activity in the spinal cat Neurosci.Lett. 38 3 257-262 "Low threshold (0.5-15 g) mechanical punctate stimulation of the labia and vagina depressed dorsal horn neurones in the cat with spinal transection at L1. Similar stimulation 2 mm or more from the outer margin of the labia was without effect. The depression was observable within 1-2 sec, and usually required 4-6 min for full recovery, although a smaller more prolonged depression may also have occurred. Stronger stimuli evoked greater inhibition, requiring longer times for recovery. Vaginal stimulation depressed 9 of 10 sensory dorsal horn neurones (including non-nociceptive, wide dynamic range and nociceptive specific). Depression included a decrease in spontaneous activity and a decrease of naturally elicited responses to noxious and innocuous cutaneous stimuli; therefore the effect is not modality related. One unit without sensory input was unaffected by vaginal stimulation. In the one case tested, vaginal stimulation depressed glutamate-evoked excitation, suggesting that the depression of naturally, elicited responses was via a postsynaptic mechanism" http://www.ncbi.nlm.nih.gov/pubmed/6138735 0 86 "A. R. Money-Kyrle, C. H. Davies, H. K. Ranu, P. O'Gara, N. S. Kent, P. A. Poole-Wilson and S. E. Harding" 1998 The role of cAMP in the frequency-dependent changes in contraction of guinea-pig cardiomyocytes Cardiovasc.Res. 37 2 532-540 "OBJECTIVES: beta-Receptor desensitisation, low basal cAMP, and a negative force-frequency relationship are characteristic changes in human heart failure. Isolated cardiomyocytes from noradrenaline-treated guinea pigs also show these features. We tested the hypothesis that low basal cAMP underlies the loss of contractile response to increasing stimulation frequency in this model. METHODS: Isolated cardiomyocytes were obtained from noradrenaline-treated (NA) and sham-operated (SHAM) guinea pigs. They were stimulated from 0.1-2 Hz and contraction amplitude was monitored with a video edge-detection system. RESULTS: NA cells had less positive amplitude-frequency responses (AFR) compared to SHAMs at 2 mM (P = 0.002, n = 17), or midrange Ca2+ concentrations (EC40-EC60) (P < 0.001, n = 13). When the cAMP agonist, 8-CPT-cAMP (CPT, 10 microM) or high Ca2+ (above EC75) was added to NA cells the AFR was normalised to that of SHAM myocytes (NA vs. SHAM P = ns). In control experiments the cAMP antagonists, Rp-cAMPS (Rpc) and Rp-8-CPT-cAMPS (Rp8, 100 microM), blocked the positive inotropic effects of CPT at 0.5 Hz (control pD2 = 4.36 +/- 0.06, Rp8 pD2 = 3.68 +/- 0.08, P < 0.0001), n = 6 paired). Rpc (100 microM) completely but reversibly blocked the effect of maximal isoprenaline in control experiments (P < 0.0001). Neither antagonist reduced the AFR compared to time-matched controls (P = ns, n = 6). Blockade of SERCA2a with thapsigargin resulted in a significant reduction in the AFR (ANOVA P < 0.0001). CONCLUSIONS: The results are consistent with sarcoplasmic reticulum (SR) function being a more important determinant of the amplitude-frequency relationship than tonic levels of cAMP under basal conditions. Reversal of AFR depression by CPT may result from stimulation of SR Ca2+ uptake" http://www.ncbi.nlm.nih.gov/pubmed/9614507 0 87 "A. E. Ridyard, E. A. Welsh and D. A. Gunn-Moore" 2000 Successful treatment of uterine torsion in a cat with severe metabolic and haemostatic complications J.Feline.Med.Surg. 2 2 115-119 "A peri-parturient fifteen-month-old female Maine Coon cat was presented with extreme weakness and depression, profound hypovolaemia and hypothermia. Severe hyperkalaemia, hyponatraemia and anaemia were detected. Disseminated intravascular coagulation was suspected due to marked prolongation of activated partial thromboplastin time. Uterine torsion was diagnosed at exploratory laparotomy. The cat made a full recovery following ovariohysterectomy and intensive supportive therapy" http://www.ncbi.nlm.nih.gov/pubmed/11716604 0 88 "A. N. Tchernitchin, W. Carter, J. Soto and P. Baumann" 1990 Effect of eosinophil-degranulating estrogens on spleen eosinophils and white pulp/red pulp ratio Agents Actions 31 03-Apr 249-256 "A role for eosinophils in the immune reaction has not been yet established. Considering that these leukocytes accumulate in lymphoid organs under glucocorticoid stimulation, we explored the possibility that they participate in the depression of immune reactions induced by these hormones and that they degranulate to exert this action. In this context, we investigated the dose effect of three estrogens on the number and degranulation of spleen red pulp eosinophils and on the percentage of spleen cross sectional area comprising white pulp. Estradiol-17 beta or 4 (OH) estradiol-17 beta increased red pulp eosinophils at low doses: 2 (OH) estradiol-17 beta increased them at a very high dose. The three estrogens degranulated the spleen eosinophils and decreased the lymphocyte containing spleen white pulp. We propose that the decrease in white pulp is a response mediated by agents released from degranulating eosinophils under the action of estrogen. Consequently, both estrogen-induced eosinophil degranulation and estrogen-induced increase in red pulp eosinophil numbers are conditions contributing to a decrease in white pulp volume. All above evidence supports the hypothesis that eosinophils are involved in immunoregulation by diminishing the number of lymphocytes contained in lymphoid organs" http://www.ncbi.nlm.nih.gov/pubmed/2085140 0 89 S. S. Lee and V. C. Swamy 1975 Blockade of tyramine-induced responses by short-acting 2-halogenoethylamines in the rat vas deferens Life Sci. 17 2 275-281 http://www.ncbi.nlm.nih.gov/pubmed/1160500 0 90 "S. D. Heys, A. C. Norton, C. R. Dundas, O. Eremin, K. Ferguson and P. J. Garlick" 1989 Anaesthetic agents and their effect on tissue protein synthesis in the rat Clin.Sci.(Lond) 77 6 651-655 "1. Rates of protein synthesis were measured, in vivo, in lung, liver, heart and skeletal muscle of young male rats. Groups of rats were exposed for 1 h duration to one of the following anaesthetic regimens: 1.4% halothane, 2.2% halothane, 1.4% halothane in 66% nitrous oxide, intravenous pentobarbitone (20 mg/kg) and intravenous midazolam (18 mg/kg) combined with fentanyl (2 micrograms/kg). Fractional rates of protein synthesis were determined by injecting [3H]phenylalanine (150 mumol/100 g body weight). 2. Liver protein synthesis was depressed significantly by all regimens, except midazolam/fentanyl, by up to 37.7% of control values. Lung protein synthesis was significantly reduced by all the anaesthetic agents by up to 30% of control rates. 3. The effects of the anaesthetic agents on skeletal muscle and heart were small and not statistically significant. 4. There was no evidence of ventilatory depression as manifested by changes in arterial blood gas partial pressures of CO2 and O2, except in the group treated with 2.2% halothane" http://www.ncbi.nlm.nih.gov/pubmed/2514062 0 91 "J. M. Clark, A. J. Clark, D. Warne, E. L. Rugg, S. L. Lightman and P. Winn" 1991 Neuroendocrine and behavioural responses to hyperosmolality in rats with lesions of the lateral hypothalamus made by N-methyl-D-aspartate Neuroscience 45 3 625-629 "Excitotoxic lesions of rat lateral hypothalamus produce impairments in eating and drinking, but not motor deficits. However, it has not been established what causes these eating and drinking impairments. In the present experiments, drinking, plasma osmolality and arginine-vasopressin concentration were measured in lateral hypothalamic-lesioned and control rats following systemic injection of hypertonic saline. In response to hyperosmolality, N-methyl-D-aspartate-lesioned rats drank significantly less than controls but showed normal increases in plasma osmolality and arginine-vasopressin concentration. This dissociation of neuroendocrine and behavioural responses suggests that the impairment of rats with excitotoxic lesions of the lateral hypothalamus is unrelated to physiological (as opposed to behavioural) mechanisms of homeostasis" http://www.ncbi.nlm.nih.gov/pubmed/1775237 0 92 "Y. Zhao, J. Shen, H. Su, B. Li, D. Xing and L. Du" 2008 Chronic corticosterone injections induce a decrease of ATP levels and sustained activation of AMP-activated protein kinase in hippocampal tissues of male mice Brain Res. 1191 148-156 "Chronic corticosterone injections induce hippocampus tissue damage and depression-like behavior in rodent animals, the cause of which is not known. Nevertheless, increasing evidence shows that adenylate kinase (AK) and AMP-activated protein kinase (AMPK) play a very important role in intracellular energy metabolism and are especially critical for neurons which are known to have very small energy reserves and narrow margin of safety between the energy that can be generated and the energy required for maximum activity. Abnormalities of AK or AMPK system have detrimental effects on neurons or brain function especially at times of increased activity. In this study, we investigated the effects of chronic corticosterone exposure on energy metabolism, as well as AK and AMPK in hippocampal tissues in male C57BL/6N mice. Our results show that chronic corticosterone injection induced depression-like behavior in male mice, significantly decreased the energy levels and caused a sustained increase of AMP:ATP ratio in hippocampal tissues. Interestingly, chronic corticosterone injections did not produce obvious effects on AK1 protein and mRNA levels, but caused a sustained activation of AMPK. The results indicate that sustained AMPK activation might be a mechanism by which chronic corticosterone treatment causes depression-like behavior in male mice" http://www.ncbi.nlm.nih.gov/pubmed/18164281 1 93 "B. Szewczyk, B. Pochwat, A. Rafalo, A. Palucha-Poniewiera, H. Domin and G. Nowak" 2015 Activation of mTOR dependent signaling pathway is a necessary mechanism of antidepressant-like activity of zinc Neuropharmacology 99 517-526 "The rapid antidepressant response to the N-methyl-D-aspartate (NMDA) receptor antagonists is mediated by activation of the mammalian target of the rapamycin (mTOR) signaling pathway, an increase in the synthesis of synaptic proteins and formation of new synapses in the prefrontal cortex (PFC) of rats. Zinc (Zn), which is a potent NMDA receptor antagonist, exerts antidepressant-like effects in screening tests and models of depression. We focused these studies in investigating whether activation of the mTOR signaling pathway is also a necessary mechanism of the antidepressant-like activity of Zn. We observed that a single injection of Zn (5 mg/kg) induced an increase in the phosphorylation of mTOR and p70S6K 30 min and 3 h after Zn treatment at time points when Zn produced also an antidepressant-like effect in the forced swim test (FST). Furthermore, Zn administered 3 h before the decapitation increased the level of brain derived neurotrophic factor (BDNF), GluA1 and synapsin I. An elevated level of GluA1 and synapsin I was still observed 24 h after the Zn treatment, although Zn did not produce any effects in the FST at that time point. We also observed that pretreatment with rapamycin (mTORC1 inhibitor), LY294002 (PI3K inhibitor), H-89 (PKA inhibitor) and GF109203X (PKC inhibitor) blocked the antidepressant-like effect of Zn in FST in rats and blocks Zn-induced activation of mTOR signaling proteins (analyzed 30 min after Zn administration). These studies indicated that the antidepressant-like activity of Zn depends on the activation of mTOR signaling and other signaling pathways related to neuroplasticity, which can indirectly modulate mTOR function" http://www.ncbi.nlm.nih.gov/pubmed/26297535 1 94 K. A. Kobayashi and C. M. Wood 1980 The response of the kidney of the freshwater rainbow trout to true metabolic acidosis J.Exp.Biol. 84 227-244 "Infusion of lactic acid into the bloodstream of trout produced a short-lived depression of blood pH and a long-lasting elevation of blood lactate. The lactate injected was distributed in a volume of 198 ml/kg. Renal excretion of lactate anion and total acid increased by approximately equal amounts during the period of high blood lactate levels, but total renal loss over 72 h accounted for only 2% of the lactate load and 6% of the proton load. Comparable differences in the time courses of blood lactate and pH changes occurred when lactacidosis was induced endogenously by normocapnic hypoxia. The immediate response of the kidney was similar to that with lactic acid infusion, but there was a long-lasting (12-72 + h) elevation of urinary acid efflux that was not associated with lactate excretion. Following hypoxia, renal excretion over 72 h accounted for 1% of the estimated lactate load and 12-25% of the proton load. A renal lactate threshold of 4-10 muequiv/ml prevents significant urinary lactate excretion. The response of the trout kidney to true metabolic acidosis is similar to that of the mammalian kidney" http://www.ncbi.nlm.nih.gov/pubmed/6245165 0 95 L. Z. Bito and R. A. Baroody 1975 Inhibition of pulmonary prostaglandin metabolism by inhibitors of prostaglandin biotransport (probenecid and bromcresol green) Prostaglandins 10 4 633-639 http://www.ncbi.nlm.nih.gov/pubmed/1197792 0 96 "H. Velvis, M. H. Hines, H. S. Klopfenstein, D. D. Berry and J. Vinten-Johansen" 1996 Depression of cardiac function after deep hypothermic circulatory arrest in deeply anesthetized neonatal lambs J.Thorac.Cardiovasc.Surg. 111 2 359-366 "Cardiac dysfunction is common after neonatal cardiac operations. Previous in vivo studies in neonatal animal models however, have failed to demonstrate decreased left ventricular function after ischemia and reperfusion. Cardiac dysfunction may have been masked in these studies by increased endogenous catecholamine levels associated with the use of light halothane anesthesia. Currently, neonatal cardiac operations are often performed with deep opiate anesthesia, which suppresses catecholamine surges and may affect functional recovery. We therefore examined the recovery of left ventricular function after ischemia and reperfusion in neonatal lambs anesthetized with high-dose fentanyl citrate (450 micrograms/kg administered intravenously). Seven intact neonatal lambs with open-chest preparation were instrumented with left atrial and left ventricular pressure transducers, left ventricular dimension crystals, and a flow transducer. The lambs were cooled (< 18 degrees C) on cardiopulmonary bypass (22 +/- 6 minutes), exposed to deep hypothermic circulatory arrest (46 +/- 1 minutes), and rewarmed on cardiopulmonary bypass (30 +/- 10 minutes). Catecholamine levels and indexes of left ventricular function were determined before (baseline) and 30, 60, 120, 180, and 240 minutes after termination of cardiopulmonary bypass. Levels of epinephrine, norepinephrine, and dopamine were unchanged from baseline values. Left ventricular contractility (slope of end-systolic pressure-volume relationship) was depressed from baseline value (31.7 +/- 9.3 mm Hg/ml) at 30 minutes (15.7 +/- 6.4 mm Hg/ml) and 240 minutes (22.7 +/- 6.4 mm Hg/ml) but unchanged between 60 and 180 minutes. Left ventricular relaxation (time constant of isovolumic relaxation) was prolonged from baseline value (19.0 +/- 3.0 msec) at 30 minutes (31.4 +/- 10.0 msec) and 240 minutes (22.1 +/- 2.8 msec) but unchanged between 60 and 180 minutes. Afterload (left ventricular end-systolic meridional wall stress) was decreased at 30, 60, and 240 minutes. Indexes of global cardiac function (cardiac output, stroke volume), preload (end-diastolic volume), and left ventricular compliance (elastic constant of end-diastolic pressure-volume relationship) were unchanged from baseline values. In deeply anesthetized neonatal lambs exposed to ischemia and reperfusion, left ventricular contractility, relaxation, and afterload are markedly but transiently depressed early after reperfusion and mildly depressed late after reperfusion" http://www.ncbi.nlm.nih.gov/pubmed/8583809 0 97 "M. Rodriguez-Arias, J. Minarro, M. A. Aguilar, J. Pinazo and V. M. Simon" 1998 Effects of risperidone and SCH 23390 on isolation-induced aggression in male mice Eur.Neuropsychopharmacol. 8 2 95-103 "In this study, the antiaggressive effects of risperidone and SCH 23390 have been explored. Using the paradigm of isolation-induced aggression, 150 albino male mice of the OF1 strain were allocated to control and experimental groups which received three doses of risperidone (0.01, 0.05 and 0.1 mg/kg) or two doses of SCH 23390 (0.05 and 0.1 mg/kg). Only the highest doses of risperidone decreased threat and attack behaviours but all doses significantly impaired motor behaviour. SCH 23390 decreased attack with the two doses used and also produced significant increases in immobility. Although both antipsychotics are antiaggressive, this action seems to be more specific in the case of risperidone. Finally, both drugs failed to affect animals with short attack latency, being antiaggressive only in subjects with long attack latency, which suggests that these two types of animals are different in their dopamine and serotonin neurotransmission" http://www.ncbi.nlm.nih.gov/pubmed/9619687 0 98 T. M. Panhuis and L. Nunney 2007 Insight into post-mating interactions between the sexes: relatedness suppresses productivity of singly mated female Drosophila melanogaster J.Evol.Biol. 20 5 1988-1997 "Post-mating, prefertilization inbreeding avoidance (PPIA) is well established in plants but not in animals. Support for animal PPIA comes from sperm competition studies showing success of a male's gametes declining with his relatedness to the multiply mated female; however, such studies confound female-male and male-male interaction. To avoid this problem, we investigated offspring productivity of singly mated Drosophila melanogaster females using flies from four different genetic backgrounds. Our experiments established that intrapopulation crosses using highly related parents (within-strain) were significantly less productive than intrapopulation crosses using unrelated individuals from the same population (between-strain). Furthermore, we showed that these effects were not due to inbreeding depression. The average decrease in offspring productivity of within-strain crosses relative to between-strain crosses was 18.3% [nonlaboratory populations: Zimbabwe 20.3%, Riverside 11.4%, neither of which showed inbreeding depression; and temperature-adapted laboratory populations, uncorrected (corrected) for nonsignificant inbreeding depression: 18 degrees C, 26.5% (24.2%) and 29 degrees C, 20.1% (9.5%)]. The significant reduction of within-cross productivity demonstrates PPIA in the absence of multiple mating" http://www.ncbi.nlm.nih.gov/pubmed/17714315 0 99 "S. B. Flynn, R. W. Gristwood and D. A. Owen" 1979 Differentiation of the roles of histamine H1- and H2-receptors in the mediation of the effects of histamine in the isolated working heart of the guinea-pig Br.J.Pharmacol. 65 1 127-137 "1 Differentiation of the roles of histamine H1- and H2-receptors in the mediation of the effects of histamine on the isolated working heart of the guinea-pig was achieved through the use of histamine and selective histamine receptor agonists and antagonists. 2 Histamine over the dose range 10(-9) mol to 10(-6) mol produced dose-related increases in sinus rate, left intraventricular pressure (LVP)max, LVdP/dtmax, coronary flow, aortic flow, total cardiac output and external pressure-volume work. 3 Dimaprit, a selective histamine H2-receptor agonist, produced very similar responses to histamine. 4 2-Pyridylethylamine, a selective histamine H1-receptor agonist, had little effect on cardiac function unless large doses were administered. Such doses produced increases in all measured parameters. 5 Cimetidine, a selective histamine H2-receptor antagonist, antagonized the effects of histamine and dimaprit and some but not all effects of 2-pyridylethylamine. In the presence of cimetidine a decrease in all parameters with the exception of sinus rate was observed with both histamine and 2-pyridylethylamine. 6 The selective histamine H1-receptor antagonist, mepyramine, had little effect on responses to all three agonists. However, the depressant effects observed with histamine and 2-pyridylethylamine in the presence of cimetidine were antagonized by mepyramine. 7 The results indicate the important role of the histamine H2-receptor in the mediation of the gross cardiac effects of histamine and also indicate that histamine H1-receptors can mediate cardiac depression" http://www.ncbi.nlm.nih.gov/pubmed/32943 0 100 "M. Waselus, R. J. Valentino and E. J. Van Bockstaele" 2005 Ultrastructural evidence for a role of gamma-aminobutyric acid in mediating the effects of corticotropin-releasing factor on the rat dorsal raphe serotonin system J.Comp Neurol. 482 2 155-165 "The dorsal raphe nucleus (DRN) serotonin (5-HT) system has been implicated in acute responses to stress and in stress-related psychiatric disorders such as anxiety and depression. Substantial findings suggest that the neuropeptide corticotropin-releasing factor (CRF) is instrumental in modulating the activity of this system during stress. Because the DRN is neurochemically heterogeneous, dual immunoelectron microscopy was used to examine cellular substrates for interactions between CRF and either 5-HT or gamma-aminobutyric acid (GABA) in the dorsolateral and ventromedial DRN. CRF immunoreactivity was identified primarily within axon terminals, where immunolabeling was particularly enriched in dense-core vesicles. Although CRF terminals targeted 5-HT-containing dendrites in the dorsolateral DRN (16%; n = 251 terminals), synaptic contacts with dendrites that lacked detectable 5-HT immunolabeling were more numerous (48%). In contrast, dual labeling for CRF and GABA (n = 240 terminals) in the dorsolateral DRN revealed that substantially more CRF terminals contacted GABA dendrites (42%) as opposed to unlabeled dendrites (29%). In the ventromedial DRN, contacts between CRF axon terminals and either 5-HT-labeled dendrites or GABA-containing dendrites were fewer than in the dorsolateral DRN. As in the dorsolateral DRN, CRF terminals more frequently contacted GABA dendrites than 5-HT dendrites (30% vs. 8%, respectively). The findings support physiological studies suggesting that CRF has both direct and indirect effects on DRN-5-HT neurons and further implicate GABA as a primary mediator by which CRF and stressors alter the activity of the DRN-5-HT system" http://www.ncbi.nlm.nih.gov/pubmed/15611993 0 101 "I. A. Reid, D. M. MacDonald, B. Pachnis and W. F. Ganong" 1975 Studies concerning the mechanism of suppression of renin secretion by clonidine J.Pharmacol.Exp.Ther. 192 3 713-721 "Two series of experiments were performed in anesthetized dogs to test the hypothesis that the suppression of renin secretion by clonidine results from a centrally mediated decrease in the activity in the renal sympathetic nerves. In the first series, clonidine (1 mug/kg) was administered directly into the third ventricle of a group of dogs in which renal perfusion pressure was controlled by adjusting an aortic clamp. In these animals, clonidine produced hypotension and bradycardia and suppressed plasma renin activity to 39 percent of the control value. These changes in blood pressure and plasma renin activity were closely correlated. Intraventricular clonidine produced similar alterations in blood pressure and heart rate in another group of dogs in which renal perfusion pressure was not controlled, but failed to suppress plasma renin activity. In the second series of experiments, clonidine was administered intravenously in a dose of 30 mug/kg. Intravenous clonidine produced a transient hypertension followed by hypotension, decreased heart rate and suppressed plasma renin activity to 49 percent of the control value. Renal denervation reduced renin secretion and prevented the suppression of renin secretion produced by intravenous clonidine. Thus, these data are consistent with the hypothesis that the suppression of renin secretion by clonidine results from a centrally mediated decrease in renal sympathetic neural tone. This suppression may be overcome by large falls in renal perfusion pressure" http://www.ncbi.nlm.nih.gov/pubmed/1120965 0 102 S. J. Szefler and W. J. Jusko 1973 Decreased volume of distribution of digoxin in a patient with renal failure "RES.COMMUN.CHEM.PATH.PHARMACOL.6 (3) ()(pp 1095-1098), 1973.Date of Publication: 1973." 3 1095-1098 The effect of fat rich diet and fasting on reserpine induced depression in mice has been studied. The results indicate a significant mitigating effect of fat rich diet on depression 0 103 S. H. Oh 2012 Evaluation of optimum genetic contribution theory to control inbreeding while maximizing genetic response Asian-Australas.J.Anim Sci. 25 3 299-303 "Inbreeding is the mating of relatives that produce progeny having more homozygous alleles than non-inbred animals. Inbreeding increases numbers of recessive alleles, which is often associated with decreased performance known as inbreeding depression. The magnitude of inbreeding depression depends on the level of inbreeding in the animal. Level of inbreeding is expressed by the inbreeding coefficient. One breeding goal in livestock is uniform productivity while maintaining acceptable inbreeding levels, especially keeping inbreeding less than 20%. However, in closed herds without the introduction of new genetic sources high levels of inbreeding over time are unavoidable. One method that increases selection response and minimizes inbreeding is selection of individuals by weighting estimated breeding values with average relationships among individuals. Optimum genetic contribution theory (OGC) uses relationships among individuals as weighting factors. The algorithm is as follows: i) Identify the individual having the best EBV; ii) Calculate average relationships ( [Formula: see text]) between selected and candidates; iii) Select the individual having the best EBV adjusted for average relationships using the weighting factor k, [Formula: see text]. iv) Repeat process until the number of individuals selected equals number required. The objective of this study was to compare simulated results based on OGC selection under different conditions over 30 generations. Individuals (n = 110) were generated for the base population with pseudo random numbers of N~ (0, 3), ten were assumed male, and the remainder female. Each male was mated to ten females, and every female was assumed to have 5 progeny resulting in 500 individuals in the following generation. Results showed the OGC algorithm effectively controlled inbreeding and maintained consistent increases in selection response. Difference in breeding values between selection with OGC algorithm and by EBV only was 8%, however, rate of inbreeding was controlled by 47% after 20 generation. These results indicate that the OGC algorithm can be used effectively in long-term selection programs" http://www.ncbi.nlm.nih.gov/pubmed/25049566 0 104 "S. Zhang, T. Jiao, Y. Chen, N. Gao, L. Zhang and M. Jiang" 2014 Methylglyoxal induces systemic symptoms of irritable bowel syndrome PLoS.One. 9 8 e105307 "Patients with irritable bowel syndrome (IBS) show a wide range of symptoms including diarrhea, abdominal pain, changes in bowel habits, nausea, vomiting, headache, anxiety, depression and cognitive impairment. Methylglyoxal has been proved to be a potential toxic metabolite produced by intestinal bacteria. The present study was aimed at investigating the correlation between methylglyoxal and irritable bowel syndrome. Rats were treated with an enema infusion of methylglyoxal. Fecal water content, visceral sensitivity, behavioral tests and serum 5-hydroxytryptamine (5-HT) were assessed after methylglyoxal exposure. Our data showed that fecal water content was significantly higher than controls after methylglyoxal exposure except that of 30 mM group. Threshold volumes on balloon distension decreased in the treatment groups. All exposed rats showed obvious head scratching and grooming behavior and a decrease in sucrose preference. The serum 5-HT values were increased in 30, 60, 90 mM groups and decreased in 150 mM group. Our findings suggested that methylglyoxal could induce diarrhea, visceral hypersensitivity, headache as well as depression-like behaviors in rats, and might be the key role in triggering systemic symptoms of IBS" http://www.ncbi.nlm.nih.gov/pubmed/25157984 0 105 "F. G. Revel, J. L. Moreau, B. Pouzet, R. Mory, A. Bradaia, D. Buchy, V. Metzler, S. Chaboz, Z. K. Groebke, G. Galley, R. D. Norcross, D. Tuerck, A. Bruns, S. R. Morairty, T. S. Kilduff, T. L. Wallace, C. Risterucci, J. G. Wettstein and M. C. Hoener" 2013 "A new perspective for schizophrenia: TAAR1 agonists reveal antipsychotic- and antidepressant-like activity, improve cognition and control body weight" Mol.Psychiatry 18 5 543-556 "Schizophrenia is a chronic, severe and highly complex mental illness. Current treatments manage the positive symptoms, yet have minimal effects on the negative and cognitive symptoms, two prominent features of the disease with critical impact on the long-term morbidity. In addition, antipsychotic treatments trigger serious side effects that precipitate treatment discontinuation. Here, we show that activation of the trace amine-associated receptor 1 (TAAR1), a modulator of monoaminergic neurotransmission, represents a novel therapeutic option. In rodents, activation of TAAR1 by two novel and pharmacologically distinct compounds, the full agonist RO5256390 and the partial agonist RO5263397, blocks psychostimulant-induced hyperactivity and produces a brain activation pattern reminiscent of the antipsychotic drug olanzapine, suggesting antipsychotic-like properties. TAAR1 agonists do not induce catalepsy or weight gain; RO5263397 even reduced haloperidol-induced catalepsy and prevented olanzapine from increasing body weight and fat accumulation. Finally, TAAR1 activation promotes vigilance in rats and shows pro-cognitive and antidepressant-like properties in rodent and primate models. These data suggest that TAAR1 agonists may provide a novel and differentiated treatment of schizophrenia as compared with current medication standards: TAAR1 agonists may improve not only the positive symptoms but also the negative symptoms and cognitive deficits, without causing adverse effects such as motor impairments or weight gain" http://www.ncbi.nlm.nih.gov/pubmed/22641180 0 106 D. Manahan-Vaughan and A. Kulla 2003 Regulation of depotentiation and long-term potentiation in the dentate gyrus of freely moving rats by dopamine D2-like receptors Cereb.Cortex 13 2 123-135 "Dopamine receptors are significantly involved in hippocampus-based cognitive processes. Whereas the involvement of D1-like receptors in hippocampal plasticity has been described, the role of D2-like receptors remains to be clarified. Therefore, we investigated the contribution of D2-like receptors to synaptic transmission, long-term potentiation (LTP) and depotentiation in the dentate gyrus of freely moving rats. Male Wistar rats underwent chronic implantation of a recording electrode in the granule cell layer, a stimulating electrode in the medial perforant path and a cannula in the ipsilateral cerebral ventricle (to enable drug administration). The D2-like receptor agonists quinpirole and noraporphine dose-dependently inhibited basal synaptic transmission. Agonist priming of D2-like receptors with a drug concentration which had no effect on synaptic transmission inhibited depotentiation but did not affect LTP. The agonist effects on depotentiation were prevented by the D2-like antagonist remoxipride. Remoxipride itself did not influence basal synaptic transmission or depotentiation. Interestingly, 'weak' LTP (<4 h) but not 'strong' LTP (>24 h) was inhibited by prior application of remoxipride. These results suggest a specific role for dopamine D2-like receptors in the regulation of both depotentiation and LTP in vivo and offer an important and novel insight as to the involvement of these receptors in processes related to learning and memory" http://www.ncbi.nlm.nih.gov/pubmed/12507943 0 107 S. Heinisch and L. G. Kirby 2009 Fractalkine/CX3CL1 enhances GABA synaptic activity at serotonin neurons in the rat dorsal raphe nucleus Neuroscience 164 3 1210-1223 "Serotonin (5-hydroxytryptamine; 5-HT) has an important role in mood regulation, and its dysfunction in the central nervous system (CNS) is associated with depression. Reports of mood and immune disorder co-morbidities indicate that immune-5-HT interactions may mediate depression present in immune compromised disease states including HIV/AIDS, multiple sclerosis, and Parkinson's disease. Chemokines, immune proteins that induce chemotaxis and cellular adhesion, and their G-protein coupled receptors distribute throughout the CNS, regulate neuronal patterning, and mediate neuropathology. The purpose of this study is to investigate the neuroanatomical and neurophysiological relationship between the chemokine fractalkine/CX3CL1 and its receptor CX3CR1 with 5-HT neurons in the rat midbrain raphe nuclei (RN). Immunohistochemistry was used to examine the colocalization of CX3CL1 or CX3CR1 with 5-HT in the RN, and whole-cell patch-clamp recordings in rat brain slices were used to determine the functional impact of CX3CL1 on 5-HT dorsal raphe nucleus (DRN) neurons. Greater than 70% of 5-HT neurons colocalize with CX3CL1 and CX3CR1 in the RN. CX3CL1 localizes as discrete puncta throughout the cytoplasm, whereas CX3CR1 concentrates to the perinuclear region of 5-HT neurons and exhibits microglial expression. CX3CL1 and CX3CR1 also colocalize with one another on individual RN cells. Electrophysiology studies indicate a CX3CL1-mediated enhancement of spontaneous inhibitory postsynaptic current (sIPSC) amplitude and dose-dependent increase of evoked IPSC (eIPSC) amplitude without affecting eIPSC paired-pulse ratio, a finding observed selectively in 5-HT neurons. CX3CL1's effect on eIPSC amplitude is blocked by pretreatment with an anti-CX3CL1 neutralizing antibody. Thus, CX3CL1 enhances postsynaptic GABA receptor number or sensitivity on 5-HT DRN neurons under conditions of both spontaneous and synaptically-evoked GABA release. CX3CL1 may indirectly inhibit 5-HT neurotransmission by increasing the sensitivity of 5-HT DRN neurons to GABA inputs. Therapies targeting CX3CL1 may treat serotonin related mood disorders, including depression experienced by patients with compromised immune systems" http://www.ncbi.nlm.nih.gov/pubmed/19748551 0 108 B. D. Goldman and R. A. Gorski 1971 Effects of gonadal steroids on the secretion of LH and FSH in neonatal rats Endocrinology 89 1 112-115 http://www.ncbi.nlm.nih.gov/pubmed/5089656 0 109 "E. Garcia, R. Calvo, J. M. Rodriguez-Sasiain, R. Jimenez, I. F. Troconiz and E. Suarez" 1995 Resistance to atracurium in rats with experimental inflammation: role of protein binding Acta Anaesthesiol.Scand. 39 8 1019-1023 "The influence of altered protein binding on the neuromuscular effect of atracurium has been studied in rats with experimental inflammation induced by subcutaneous injection of turpentine oil. Doses of atracurium ranging from 0.45 to 1.5 mg.kg-1 were administered to control (n = 30) and to experimental inflammation induced rats (n = 30). Neuromuscular transmission was monitored by recording the twitch tension of the tibialis-anterior muscle elicited by stimulation of the sciatic nerve. Three effect parameters were recorded: (i) intensity of the effect, measured as percentage depression of baseline twitch tension, (ii) duration of drug action (min) and (iii) recovery time (min). The dose-intensity of the effect relationship was modelled using a sigmoid Emax model. The ED50 (effective dose eliciting 50% of the maximum effect) was significantly increased (P < 0.01) in the inflammation group as compared to the control group (0.94 vs. 0.68 mg.kg-1). This change was reflected in a shift of the dose-response curve to the right in the pretreated rats. For equipotent doses ED95 (defined as the effective dose eliciting 95% of maximum effect), no differences were found in recovery time and duration of action between the two groups of rats. Mucoproteins levels (index of alpha 1-acid glycoprotein (AAG) and protein binding were significantly increased in rats with experimental inflammation as compared to control rats. Based on these results, altered serum protein binding of atracurium appears to be responsible, at least in part, for the resistance to atracurium" http://www.ncbi.nlm.nih.gov/pubmed/8607301 0 110 "F. N. Johnson, S. P. Battista and D. Reid" 1973 Lysergic acid analogs: 5-phenylnicotinamides and nipecotamides J.Pharm.Sci. 62 11 1881-1883 http://www.ncbi.nlm.nih.gov/pubmed/4271307 0 111 "H. Oshibuchi, T. Ineda, Y. Sugawara, R. So, J. Miyagi, H. Tsumura and J. Ishigooka" 2011 [Suppressive effect of valproic acid on fear conditioning induced by dopamine in the amygdala: Its verification using the microdialysis] Nihon Shinkei Seishin Yakurigaku Zasshi 31 2 77-78 http://www.ncbi.nlm.nih.gov/pubmed/21870364 0 112 "H. Yamazaki, Y. Jin, A. Tsuchiya, T. Kanno and T. Nishizaki" 2015 Adipose-derived stem cell-conditioned medium ameliorates antidepression-related behaviors in the mouse model of Alzheimer's disease "Neuroscience Letters.609 ()(pp 53-57), 2015.Date of Publication: November 16, 2015." 53-57 "The present study investigated the effect of adipose-derived stem cell-conditioned medium (ASC-CM) on behavioral disorders in 5xFAD transgenic mice, a model of Alzheimer's disease (AD). The immobility time in the tail suspension and forced swim tests for 5xFAD mice was shorter than that for wild-type mice. Intravenous injection with ASC-CM restored the shortened immobility time for 5xFAD mice to the normal levels or to an extent, being still persistent 4 weeks after injection. ASC-CM significantly suppressed phosphorylation of Akt at Ser473 and glycogen synthase kinase 3beta (GSK-3beta) at Ser9 in the hypothalamus of 5xFAD mice, without affecting Tau phosphorylation, as compared with that for control 5xFAD mice without ASC-CM injection. ASC-CM did not affect cell surface localization of the N-methyl-. d-aspartate (NMDA) receptor subunits NR1, -2A, and -2B both in the hippocampus and hypothalamus of 5xFAD mice. The results of the present study show that ASC-CM ameliorates antidepression-related behaviors in 5xFAD mice, perhaps by inhibiting Akt and activating GSK-3beta" DO - http://dx.doi.org/10.1016/j.neulet.2015.10.023 1 113 S. V. Gasteva and T. E. Raize 1975 [Intensity of respiration and the metabolism of phospholipids in isolated brain tissues of rats at various temperatures in the presence of KCN] Biull.Eksp.Biol.Med. 79 4 53-55 "The intensity of oxygen consumption, as well as phospholipid metabolism of minced rat brain tissue were studied at different temperature of the incubation media (37 degrees, 32 degrees and 27 degrees C) without cyanide and in the media containing KCN (0.5 and 1.0 mM). As shown, both parameters depended directly upon the incubation temperature within the range of 27 degrees-37 degrees. KCN inhibited both processes, but depression of phospholipid metabolism was more expressed. These data suggest that under conditions of cyanide poisoning phospholipid metabolism depends both on the toxic effect of KCN directly and on the temperature, whose reduction reinforces this effect" http://www.ncbi.nlm.nih.gov/pubmed/1191769 0 114 A. E. Dorr and G. Debonnel 2006 Effect of vagus nerve stimulation on serotonergic and noradrenergic transmission J.Pharmacol.Exp.Ther. 318 2 890-898 "Vagus nerve stimulation (VNS) is an antiepileptic treatment, which has recently shown promise as an antidepressant. Yet, its antidepressant mechanisms of action are unknown. Serotonergic [5-hydroxytryptamine (5-HT, serotonin)] and noradrenergic [norepinephrine (NE)] systems are involved in the pathophysiology of depression and in the mechanisms of action of antidepressants. The present study analyzes 5-HT and NE neuronal firing rates in their brainstem nuclei: the dorsal raphe nucleus (DRN) and locus coeruleus (LC), respectively. The basal firing rates in the DRN and LC were significantly increased after long-term treatments with VNS. After short-term VNS treatments, firing rates were significantly higher for LC (at 1 h and 3 days). As changes in their firing rate may have been due to altered autoreceptor sensitivities, the responses of autoreceptors to the acute administration of their respective agonists were assessed. However, no significant difference was seen in the DRN. No significant differences in dose response curves for 5-HT(1A) somatodendritic and alpha 2-adrenergic autoreceptors were noticed between long-term VNS and controls. VNS appears to have a novel mechanism of antidepressant action, enabling its effectiveness in treatment-resistant depression. LC firing rates significantly increase earlier than the DRN basal firing. As the LC has an excitatory influence on DRN, it is possible that the increased DRN firing rate is secondary to an initial increased LC firing rate from VNS" http://www.ncbi.nlm.nih.gov/pubmed/16690723 0 115 "A. Coulombe, A. Momtaz, P. Richer, B. Swynghedauw and E. Coraboeuf" 1994 Reduction of calcium-independent transient outward potassium current density in DOCA salt hypertrophied rat ventricular myocytes Pflugers Arch. 427 01-Feb 47-55 "Saline-drinking, left-nephrectomized rats made hypertensive by deoxycorticosterone acetate (DOCA) pellet implantation at the time of surgery develop a cardiac hypertrophy, which becomes maximal after 6-7 weeks. The hypertrophy results in a marked increase in the amplitude and duration of both the early and the late component of the ventricular action potential plateau recorded in the isolated perfused rat heart. The 4-aminopyridine(4-AP)-sensitive calcium-independent transient outward potassium current was markedly depressed in hypertrophied ventricular myocytes resulting in a highly significant decrease in current density (from 19.9 +/- 3.5 to 6.4 +/- 3.1 pA/pF at +60 mV). Activation/voltage and steady-state inactivation/voltage relationships were moderately although non-significantly shifted towards negative potentials. The steady-state outward current measured at the end of 1-s depolarizing pulses was not significantly changed in hypertrophied myocytes. 4-AP induced a smaller increase in plateau amplitude and duration in hypertrophied rather than in control hearts, a point that is well explained by the depression of the transient outward current resulting from hypertrophy. We also demonstrated that a complete recovery of both cell capacitance and transient outward current amplitude occurs in myocytes from saline-drinking rats studied 13 weeks after DOCA pellet implantation, showing that hypertrophy regresses as a result of pellet elimination. Several mechanisms can be involved in the observed phenomena, including the possibility that the expression of potassium channels responsible for the transient outward current is not enhanced by hypertrophy in contrast with what occurs in the case of calcium channels.(ABSTRACT TRUNCATED AT 250 WORDS)" http://www.ncbi.nlm.nih.gov/pubmed/8058475 0 116 "H. Einat, P. Yuan, T. D. Gould, J. Li, J. Du, L. Zhang, H. K. Manji and G. Chen" 2003 The role of the extracellular signal-regulated kinase signaling pathway in mood modulation J.Neurosci. 23 19 7311-7316 "The neurobiological underpinnings of mood modulation, molecular pathophysiology of manic-depressive illness, and therapeutic mechanism of mood stabilizers are largely unknown. The extracellular signal-regulated kinase (ERK) pathway is activated by neurotrophins and other neuroactive chemicals to produce their effects on neuronal differentiation, survival, regeneration, and structural and functional plasticity. We found that lithium and valproate, commonly used mood stabilizers for the treatment of manic-depressive illness, stimulated the ERK pathway in the rat hippocampus and frontal cortex. Both drugs increased the levels of activated phospho-ERK44/42, activated phospho-ribosomal protein S6 kinase-1 (RSK1) (a substrate of ERK), phospho-CREB (cAMP response element-binding protein) and phospho-B cell lymphoma protein-2 antagonist of cell death (substrates of RSK), and BDNF. Inhibiting the ERK pathway with the blood-brain barrier-penetrating mitogen-activated protein kinase (MAP kinase)/ERK kinase (MEK) kinase inhibitor SL327, but not with the nonblood-brain barrier-penetrating MEK inhibitor U0126, decreased immobility time and increased swimming time of rats in the forced-swim test. SL327, but not U0126, also increased locomotion time and distance traveled in a large open field. The behavioral changes in the open field were prevented with chronic lithium pretreatment. SL327-induced behavioral changes are qualitatively similar to the changes induced by amphetamine, a compound that induces relapse in remitted manic patients and mood elevation in normal subjects. These data suggest that the ERK pathway may mediate the antimanic effects of mood stabilizers" http://www.ncbi.nlm.nih.gov/pubmed/12917364 1 117 "R. Schoenborn, M. Dmowska, A. Unkiewicz and E. Modrzejewski" 1996 Effect of electrical stimulation of A and C fibres of the aortic nerves on arterial peripheral and cerebral blood pressure Folia Biol.(Krakow.) 44 03-Apr 123-129 "The effect of electrical stimulation of A and C fibres of the aortic nerves on arterial peripheral (PBP) and cerebral blood pressure (CBP) was studied in 12 rabbits (New Zealand White). The experiments have shown that selective stimulation of fibres A of the aortic nerves evokes every time depression of the arterial blood pressure in the peripheral circulation and slightly modifies pressure in the cerebral circulation. Selective stimulation of fibres C of the aortic nerves always elicits a significant decrease in arterial blood pressure in the peripheral circulation, whereas in the cerebral circulation it elicits a small decrease or a slight increase in arterial pressure. The obtained results point to a predominating role in depressor reaction of impulsation reaching the aortic arch through amyelic fibres C. The depressor reaction in the peripheral circulation is highest with simultaneous stimulation of the right and left aortic nerve during stimulation of both fibre A and C" http://www.ncbi.nlm.nih.gov/pubmed/9342937 0 118 B.-J. Cao and Y. Li 2002 Reduced anxiety- and depression-like behaviors in Emx1 homozygous mutant mice "Brain Research.937 (1-2) ()(pp 32-40), 2002.Date of Publication: 24 May 2002." 01-Feb 32-40 "Emx1 is a mammalian homolog of the Drosophila gap gene empty spiracles (ems). Although it has been implicated in the formation of the mouse forebrain, the neuronal functions of this homeobox gene remain unknown. The restricted expression of Emx1 to the cerebral cortex and hippocampus suggests that it might play a role in emotional and other behavioral processes. The present study examined the phenotypes of Emx1-deficient mice generated by gene targeting technology in a battery of behavioral tests with a fixed inter-trial interval of 7 days. Compared with their wild-type littermates, the Emx1 homozygous mutant mice displayed markedly lowered anxiety-like behaviors in the elevated plus maze and dark/light exploration tests. Moreover, they exhibited less depressive-like response as indicated by the reduced duration of immobility in the forced swimming paradigm. There was a trend toward reduction in prepulse inhibition of acoustic startle in the homozygotes. No significant alterations in locomotor activity and susceptibility to pentylenetetrazol-induced seizure were found. This behavioral profile indicates an involvement of Emx1 in the emotional responses of mice. © 2002 Elsevier Science B.V. All rights reserved" DO - http://dx.doi.org/10.1016/S0006-8993%2802%2902461-7 1 119 "P. H. Backx, W. D. Gao, M. D. Azan-Backx and E. Marban" 1994 "Mechanism of force inhibition by 2,3-butanedione monoxime in rat cardiac muscle: roles of [Ca2+]i and cross-bridge kinetics" J.Physiol 476 3 487-500 "1. We investigated the mechanism of force inhibition by 2,3-butanedione monoxime (BDM) on rat cardiac trabeculae. [Ca2+]i was measured by iontophoretic injection of fura-2 salt. Isometric force was recorded at an end-systolic sarcomere length of 2.1-2.2 microns. 2. With an external [Ca2+] of 1 mM, peak twitch force was monotonically reduced with increasing [BMD]; at 5 and 20 mM [BDM], force was 35 and 1% of the control force. In contrast, the mean peak [Ca2+]i during transients was only reduced at [BDM] > or = 10 mM. 3. The duration of the twitch was dramatically reduced by BDM in a dose-dependent fashion with no significant change in the time course of the underlying Ca2+ transients. The abbreviation of twitch force duration was much greater than expected for the observed reduction in peak force by this agent. 4. The mechanism of the inhibition of force by BDM was explored by examining the relationship between twitch force and Ca2+ transients at various values of external [Ca2+]. In the presence of BDM, the steepness of the relationship between peak force and peak [Ca2+]i was reduced compared to control conditions. As a result, significant elevation in the [Ca2+]i transient was unable to reverse the reduction in force observed in the presence of BDM. 5. The direct inhibitory effects of BDM on the contractile system were examined using ryanodine tetani in intact trabeculae to measure the steady-state force-[Ca2+]i relationship. In contrast to the effects on twitch force at 5 mM BDM, maximal force was only reduced to 71% of control. Furthermore, the [Ca2+]i required for half-maximal activation (Ca50) was increased while the Hill coefficient was reduced slightly by BDM. 6. BDM dramatically slowed the rate of rise of tetanic force. At maximal activation, the time required to reach 90% maximal force was prolonged by a factor of 3-8 in the presence of 5 mM BDM. This suggests that the observed reduction in twitch force and steady-state force may result from slowed kinetics of cross-bridge attachment, consistent with recent biochemical studies. 7. The contribution of altered cross-bridge kinetics to the effects of BDM was investigated using a co-operative cross-bridge model of the contractile system. Changing the rate constants for cross-bridge attachment in the model to mimic the reported biochemical effects of BDM reproduced the observed effects of BDM.(ABSTRACT TRUNCATED AT 400 WORDS)" http://www.ncbi.nlm.nih.gov/pubmed/8057256 0 120 "Y. Yaari, A. Konnerth and U. Heinemann" 1986 Nonsynaptic epileptogenesis in the mammalian hippocampus in vitro. II. Role of extracellular potassium J.Neurophysiol. 56 2 424-438 "The role of extracellular K+ (K+o) in nonsynaptic epileptogenesis induced in the CA1 area of rat hippocampal slices by lowering [Ca2]o was studied with K+-selective microelectrodes (KSMs). Extracellular field potentials and [K+]o were recorded simultaneously with 1-2 KSMs in the CA1 stratum pyramidale. In slices perfused with an oxygenated standard physiological solution (containing 2 mM Ca2+), base-line [K+]o was stable for several hours. The washout of Ca2+o was accompanied by a gradual tonic rise of [K+]o. Spontaneous and stimulus-evoked maximal seizurelike events (SLEs) appeared when [K+]o was approximately 0.5 mM above the initial 5 mM base line. These changes were reversible in normal medium. When K+o was pressure ejected in the CA1 stratum pyramidale of spontaneously active slices, a local rise in [K+]o of approximately 0.5 mM was necessary to trigger a SLE. A similar apparent [K+]o ""threshold"" was associated with SLEs evoked by electrical stimulation. Increasing [K+] in the perfusing solution by small increments (1 mM) markedly enhanced SLEs frequency and velocity of spread and decreased the period of absolute refractoriness that succeeded each paroxysm. Similar changes occurred during periods of transient hypoxia. Small [K+] decreases in the perfusate had the converse effects. Spontaneous SLEs were associated with phasic increases in [K+]o. In simultaneous [K+]o recordings from two layers, these transients were largest (up to 3.5 mM above base line) and rose more steeply at the stratum pyramidale. Toward the outer dendritic layers they became smaller, slower in time course, and delayed in onset. We conclude that the main source for these [K+]o transients are the hippocampal pyramidal cell bodies, which discharge intensely during a SLE, and that excess K+o is spatially dispersed around the discharge zone of the paroxysm. [K+]o continued to rise, though at a slower rate, throughout the course of a SLE. Following SLE termination, [K+]o decayed slowly to base line. The invasion of a CA1 region by a propagating SLE was preceded quite often by a slow rise in [K+]o. A sudden transition to a steeply rising [K+]o marked the explosive recruitment of this region into the discharge zone of the spreading paroxysm. The total (tonic and phasic) increase in [K+]o during SLEs did not surpass a maximal level of approximately 9 mM, which was the ceiling level of [K+]o in low [Ca2+]o. However, when spreading depression occurred, [K+]o rose up to 30-40 mM for several minutes. Spreading depression rarely appeared spontaneously despite the recurrence of SLEs, but could be provoked by repetitive electrical stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)" http://www.ncbi.nlm.nih.gov/pubmed/3760929 0 121 "C. Fernandes, C. R. McKittrick, S. E. File and B. S. McEwen" 1997 Decreased 5-HT1A and increased 5-HT2A receptor binding after chronic corticosterone associated with a behavioural indication of depression but not anxiety Psychoneuroendocrinology 22 7 477-491 "The effects of chronic corticosterone treatment (100 mg pellet implanted for 1 week) were assessed in animal tests of anxiety, exploration and motor activity, and changes in binding to 5-HT1A and 5-HT2A receptors, and the 5-HT transporter, were measured. At the end of the week's treatment, the corticosterone concentration was significantly elevated and there were significant decreases in adrenal, thymus and body weights. However, there were no changes in the measures of anxiety in the social interaction test or on trials 1 and 2 of the elevated plus-maze. Also supporting a dissociation between anxiety and elevated corticosterone concentrations are previous findings that benzodiazepine withdrawal causes increased anxiety but no change in corticosteroid concentrations. Therefore these two situations provide a double dissociation between anxiety and elevated corticosteroids. Decreased 5-HT1A receptor binding in the dentate gyrus and increased 5-HT2A receptor binding in the parietal cortex was found following chronic corticosterone treatment. This reciprocal relationship between 5-HT1A and 5-HT2A receptors has been proposed to be important in mediating depression. The significant decreases in motor activity observed in all the test situations would be compatible with this proposal. Thus the constellation of behavioural and biochemical changes detected after chronic corticosterone treatment is more pertinent to depression than anxiety. One week after removal of the pellets, the behavioural and neurochemical changes had disappeared and the only differences to remain were decreased adrenal, thymus and body weights in the animals that had been treated chronically with corticosterone" http://www.ncbi.nlm.nih.gov/pubmed/9373882 1 122 "Z. Y. Feng, X. J. Zheng, C. Tian, Y. Wang and H. Y. Xing" 2011 Changes of paired-pulse evoked responses during the development of epileptic activity in the hippocampus J.Zhejiang.Univ Sci.B 12 9 704-711 "Dysfunction of inhibitory synaptic transmission can destroy the balance between excitatory and inhibitory synaptic inputs in neurons, thereby inducing epileptic activity. The aim of the paper is to investigate the effects of successive excitatory inputs on the epileptic activity induced in the absence of inhibitions. Paired-pulse orthodromic and antidromic stimulations were used to test the changes in the evoked responses in the hippocampus. Picrotoxin (PTX), gamma-aminobutyric acid (GABA) type A (GABA(A)) receptor antagonist, was added to block the inhibitory synaptic transmission and to establish the epileptic model. Extracellular evoked population spike (PS) was recorded in the CA1 region of the hippocampus. The results showed that the application of PTX induced a biphasic change in the paired-pulse ratio of PS amplitude. A short latency increase of the second PS (PS2) was later followed by a reappearance of PS2 depression. This type of depression was observed in both orthodromic and antidromic paired-pulse responses, whereas the GABAergic PS2 depression [called paired-pulse depression (PPD)] during baseline recordings only appeared in orthodromic-evoked responses. In addition, the depression duration at approximately 100 ms was consistent with a relative silent period observed within spontaneous burst discharges induced by prolonged application of PTX. In conclusion, the neurons may ignore the excitatory inputs and intrinsically generate bursts during epileptic activity. The depolarization block could be the mechanisms underlying the PPD in the absence of GABA(A) inhibitions. The distinct neuronal responses to stimulations during different epileptic stages may implicate the different antiepileptic effects of electrical stimulation" http://www.ncbi.nlm.nih.gov/pubmed/21887845 0 123 "R. D. Whitten, A. M. Jasnow, H. E. Albers, S. Martin-Schild, J. E. Zadina and K. L. Huhman" 2001 The effects of endomorphin-1 on conditioned defeat in Syrian hamsters (Mesocricetus auratus) Brain Res. 914 01-Feb 74-80 "The present study examined the effect of endomorphin-1 (EM1), an endogenous opioid with a high affinity for the mu opiate receptor, on conditioned defeat. Conditioned defeat is a phenomenon in which hamsters that have been defeated subsequently fail to exhibit normal territorial aggression and instead display submissive/defensive behaviors even when paired with a non-aggressive intruder. In experiment 1, animals were placed in the home cage of a larger resident for 15 min and were defeated. After 24 h, animals received a 3-microl injection of EM1 (0.0, 0.3, 3.0, or 10 nmol) into the left lateral cerebral ventricle 5 min before a smaller non-aggressive intruder was placed in the home cage of the experimental animal. In experiment 2, animals were infused with EM1 immediately after the initial defeat and were paired with a non-aggressive intruder 24 h later as in experiment 1. EM1 reduced the duration of submissive/defensive behavior in experiment 1 (P<0.05) but not in experiment 2 (P>0.05). These data support the hypothesis that the highly selective mu receptor agonist endomorphin-1 modulates the expression of conditioned defeat, but provides no support for the hypothesis that endomorphin-1 modulates the consolidation of conditioned defeat" http://www.ncbi.nlm.nih.gov/pubmed/11578599 0 124 "T. C. Brown, I. C. Tran, D. S. Backos and J. A. Esteban" 2005 NMDA receptor-dependent activation of the small GTPase Rab5 drives the removal of synaptic AMPA receptors during hippocampal LTD Neuron 45 1 81-94 "The activity-dependent removal of AMPA receptors from synapses underlies long-term depression in hippocampal excitatory synapses. In this study, we have investigated the role of the small GTPase Rab5 during this process. We propose that Rab5 is a critical link between the signaling cascades triggered by LTD induction and the machinery that executes the activity-dependent removal of AMPA receptors. We have found that Rab5 activation drives the specific internalization of synaptic AMPA receptors in a clathrin-dependent manner and that this activity is required for LTD. Interestingly, Rab5 does not participate in the constitutive cycling of AMPA receptors. Rab5 is able to remove both GluR1 and GluR2 AMPA receptor subunits, leading to GluR1 dephosphorylation. Importantly, NMDA receptor-dependent LTD induction produces a rapid and transient increase of active (GTP bound) Rab5. We propose a model in which synaptic activity leads to Rab5 activation, which in turn drives the removal of AMPA receptors from synapses" http://www.ncbi.nlm.nih.gov/pubmed/15629704 0 125 "B. Mayer, S. Pfeiffer, E. Leopold, J. Muller, U. Weser and K. Schmidt" 1996 Structural and functional analogs of CuZn superoxide dismutase inhibit rat brain nitric oxide synthase by interference with the reductase (diaphorase) domain Neurosci.Lett. 209 3 169-172 "Copper complexes with superoxide dismutase (SOD) activity show a wide range of pharmacological activities. We have investigated the effect of ([N,N'-bis(2-pyridylmethylene)-1,4-butanediamine]-(N,N',N"", N""')]-Cu(II)-chloride (Cu-PuPy) and ([N,N'-bis(2-pyridyl-phenyl)methylene-1,4-butanediamine]-(N,N',N"", N""'))-Cu(II)-chloride (Cu-PuPhePy) on the multiple catalytic functions of rat brain NO synthase (NOS). Both drugs inhibited the formation of L-citrulline as well as the enzymatic reduction of cytochrome c. The uncoupled oxidation of NADPH, catalyzed by neuronal NOS in the absence of L-arginine, was inhibited by Cu-PuPy but stimulated by Cu-PuPhePy, suggesting that the phenyl-substituted compound acts as a parasitic electron acceptor. Our data identify copper complexes with SOD mimicking activity as a novel class of neuronal NOS inhibitors blocking the reductase (diaphorase) activity of the enzyme" http://www.ncbi.nlm.nih.gov/pubmed/8736637 0 126 "Y. S. Guo, J. C. Thompson and P. Singh" 1990 Role of gastrin in bombesin-stimulated somatostatin release Gastroenterology 99 5 1297-1302 "The intermediary pathways in the bombesin-induced somatostatin release were examined in isolated perfused rat stomach obtained from male rats that were fasted overnight. The stomachs were perfused by way of the celiac artery. On coinfusion of 1.0 mumol/L tetrodotoxin and 1 nmol/L bombesin, a significant depression in release of somatostatin was observed compared with that observed with bombesin alone. The 5-minute integrated somatostatin response after treatment with tetrodotoxin and bombesin was 173% +/- 14% of basal, which was significantly lower than that observed with bombesin alone (394% +/- 59% of basal, P less than 0.05) but significantly higher than that observed with medium-199 alone (95% +/- 7% of basal, P less than 0.05); this indicated that approximately 70% of the bombesin-stimulated somatostatin release was indirectly mediated through neural pathways, while a significant (approximately 30%) segment of it was mediated by nonneural mechanisms. To test if the 30% somatostatin release was secondary to gastrin release in response to bombesin, gastrin antiserum and bombesin (1 nmol/L) were coadministrated in the presence or absence of tetrodotoxin (1 mumol/L). Gastrin antiserum alone did not significantly affect basal release of somatostatin but caused a significant inhibition (approximately 23%) of bombesin-provoked somatostatin release. Coadministration of gastrin antiserum and tetrodotoxin attenuated bombesin-stimulated somatostatin release. Gastrin (1 mumol/L) alone significantly stimulated somatostatin release (150% +/- 10% of basal), which was completely attenuated in the presence of gastrin antiserum. Tetrodotoxin did not affect bombesin-elicited gastrin release, confirming that bombesin-stimulated gastrin release was directly mediated. To determine the nature of the neural pathways mediating the bombesin-induced somatostatin release, atropine (100 nmol/L) was used. Atropine inhibited bombesin-induced somatostatin release to the same extent as tetrodotoxin, indicating that cholinergic pathways mediated bombesin-induced somatostatin release. These results show that almost all the somatostatin response to bombesin is indirectly mediated, and is composed of a major neural (cholinergic) and a minor nonneural pathway. The nonneural mechanism appears to be contributed primarily by gastrin released in response to bombesin, which apparently has a short paracrine positive feedback effect on somatostatin release" http://www.ncbi.nlm.nih.gov/pubmed/1976561 0 127 "A. B. Dobkin, J. P. Su and P. H. Byles" 1966 The efficacy of managing postanaesthetic respiratory depression with analeptics Acta Anaesthesiol.Scand.Suppl 23 29-35 http://www.ncbi.nlm.nih.gov/pubmed/4388360 0 128 "T. Schnyder, H. Gross, H. Winkler, H. M. Eppenberger and T. Wallimann" 1991 Structure of the mitochondrial creatine kinase octamer: high-resolution shadowing and image averaging of single molecules and formation of linear filaments under specific staining conditions J.Cell Biol. 112 1 95-101 "The combination of high-resolution tantalum/tungsten (Ta/W) shadowing at very low specimen temperature (-250 degrees C) under ultrahigh vacuum (less than 2 x 10(-9) mbar) with circular harmonic image averaging revealed details on the surface structure of mitochondrial creatine kinase (Mi-CK) molecules with a resolution less than 2.5 nm. Mi-CK octamers exhibit a cross-like surface depression dividing the square shaped projection of 10 x 10 nm into four equally sized subdomains, which correspond to the four dimers forming the octameric Mi-CK molecule. By a combination of positive staining (with uranyl acetate) and heavy metal shadowing, internal structures as well as the surface relief of Mi-CK were visualized at the same time at high resolution. Computational image analysis revealed only a single projection class of molecules, but the ability of Mi-CK to form linear filaments, as well as geometrical considerations concerning the formation of octamers by four equal, asymmetric dimers, suggest the existence of at least two distinct faces on the molecule. By image processing of Mi-CK filaments a side view of the octamer differing from the top-bottom projections of single molecules became evident showing a funnel-like access each form the top and bottom of the octamer connected by a central channel. The general structure of the Mi-CK octamer described here is relevant to the localization of the molecule at the inner-outer mitochondrial contact sites and to the function of Mi-CK as an ""energy channeling"" molecule" http://www.ncbi.nlm.nih.gov/pubmed/1702444 0 129 "H. M. Himmel, T. Schappert and U. Ravens" 1991 Combined effects of volatile anesthetics and phosphodiesterase inhibitors on contractile performance in guinea pig hearts Anesth.Analg. 73 1 76-82 "The cardiotonic effects of the phosphodiesterase inhibitors amrinone, milrinone, and 3-isobutyl-1-methylxanthine were studied in Langendorff-perfused guinea pig hearts exposed to the cardiodepressant concentrations of halothane or isoflurane. Left ventricular pressure, rate of change of pressure (dP/dt), heart rate, and perfusion pressure were measured in the presence of increasing drug concentrations. Under control conditions, both (dP/dt)max and heart rate were increased most with 3-isobutyl-1-methylxanthine and least with amrinone. In isoflurane-pretreated hearts (1.3%, vol/vol), the phosphodiesterase inhibitors increased (dP/dt)max to a larger degree, whereas the increase in heart rate remained similar to that in the control hearts. After exposure to halothane (0.8%, vol/vol), however, amrinone and milrinone were less effective with respect to enhancement of contractile performance. There was no difference in the 3-isobutyl-1-methylxanthine-induced increase of (dP/dt)max between hearts exposed to isoflurane and those exposed to halothane. Our results suggest that contractile performance of isolated hearts is more easily stimulated by milrinone and amrinone in the presence of isoflurane than in the presence of halothane" http://www.ncbi.nlm.nih.gov/pubmed/1713427 0 130 "R. M. Post, F. Putnam, N. R. Contel and B. Goldman" 1984 Electroconvulsive seizures inhibit amygdala kindling: implications for mechanisms of action in affective illness Epilepsia 25 2 234-239 "Amygdala kindling, the progressive development of seizures following repeated electrical stimulation, has been used as a model of epileptogenesis, neural memory, and the development of behavioral alterations. In an attempt to interfere with the kindling process, electroconvulsive seizures (ECS) were administered 6 h prior to or immediately after once-daily amygdala stimulation. ECS compared with sham ECS 6 h prior to kindling profoundly inhibited the development of amygdala-kindled seizures, while ECS immediately after the afterdischarge (AD) were not effective. In a second study, seven daily ECS, but not a single ECS followed by a 6-day delay, markedly suppressed established amygdala-kindled seizures compared with sham ECS controls. The generalized seizures of ECS thus appear to be paradoxically anticonvulsant to limbic seizures. Carbamazepine, a potent anticonvulsant for temporal lobe and limbic seizures in animals and man, inhibits amygdala-kindled seizures and is effective in the treatment of manic-depressive illness. The current findings suggest the possibility that the efficacy of ECS in affective illness may be, in part, related to its limbic antikindling and anticonvulsant effects" http://www.ncbi.nlm.nih.gov/pubmed/6538480 0 131 S. C. Lee and M. L. Wang 1975 Histidinemia produced in the rat by treatment with nitromethane1 Nutr.Metab 18 2 79-88 "Metabolic effects of in vivo administration of nitromethane, a histidase inhibitor, were studied in the rat. Histidinemia produced by feeding a 5-percent histidine diet to the rat was included for comparison. Rats injected subcutaneously with nitromethane every other day appeared to be histidinemic, with a plasma histidine level of 43 mumol/100 ml (control 9.2 mumol/100 ml) after 12 days of treatment. Histidine concentrations in the brain, liver, kidney, and urine of the nitromethane-treated rats were also increased. Liver histidase activity was decreased about 78 percent after nitromethane administration, and the rate of in vivo CO2 production from histidine was also depressed. No abnormal change in liver and kidney sizes was observed in these animals. Rats fed the 5-percent histidine diet showed markedly higher plasma histidine concentrations (99 mumul/100 ml) than the nitromethane-treated rats. The magnitude of increase in plasma histidine in the histidine-fed rats was considerably greater than that observed in humans with histidinemia. Furthermore, the liver histidase activity was decreased only by about 20 percent, and a significant increase in liver and kidney sizes was noted in the histidine-fed animals. These findings indicate that histidinemia produced by nitromethane administration is a better model for studies of the genetic disorder than histidinemia induced by high levels of histidine in the diet" http://www.ncbi.nlm.nih.gov/pubmed/1178145 0 132 "R. C. Guedes, A. F. Andrade and J. E. Cabral-Filho" 1987 Propagation of cortical spreading depression in malnourished rats: facilitatory effect of dietary protein deficiency Braz.J.Med.Biol.Res. 20 5 639-642 "Adult rats, submitted from gestation to the basic regional diet (BRD) of some human populations in the northeastern region of Brazil, presented higher velocities of propagation of cortical spreading depression (SD) than well-nourished animals. This effect was also seen in rats receiving BRD during the gestation and suckling periods alone but not when this diet was administered only during adult life, suggesting that the alterations produced by BRD occur early in life. The supplementation of BRD with lipids, vitamins and minerals (but not protein) did not prevent the appearance of this facilitatory effect in the gestation + suckling group, suggesting an important effect of protein deficiency in the BRD on cortical SD" http://www.ncbi.nlm.nih.gov/pubmed/3452458 0 133 "M. V. Karpukhina, A. P. Gokin and N. E. Tikhomirov" 1991 [The neurochemical mechanisms of the inhibitory influences of stimulation of the central gray substance on the high-threshold reflex activity of the reticular formation] Neirofiziologiia. 23 4 455-463 "Influences of bulbar microinjections of some neuromodulator antagonists (methysergide, haloperidol, naloxone) on depression dynamics of spino-bulbo-spinal (SBS) reflex from the periaqueductal grey (PAG) stimulation were studied in chloralose anesthetized rats. Microinjections were made into the reticular gigantocellular nucleus which is a main supraspinal centre of SBS reflexes. It is found that methysergide administration (10(-5) mol/l) causes a considerable (two to four times as less) decrease of SBS-reflex depression evoked by PAG stimulation by a short high-frequency series of stimuli. Long-lasting depression evoked usually by a long train of PAG stimuli is less reduced: from 6-10 to 2.5-4 min. A considerable (2 to 5 times) shortening of this depression is revealed after naloxone injections (10(-5)-10(-4) mol/l). The most expressed diminution of all types of inhibitions is shown to occur after haloperidol administration. Data obtained evidence that all the studied neuromodulatory systems (5-HT, catecholamine and opioidergic ones) are involved to inhibitory action of PAG on high-threshold reflex activity of the reticular formation. Some properties of neurochemical mechanisms of the studied PAG-evoked depression are discussed" http://www.ncbi.nlm.nih.gov/pubmed/1681433 0 134 R. U. Ostrovskaia and G. M. Molodavkin 1980 [Participation of GABA-ergic structures in producing the effects of haloperidol] Biull.Eksp.Biol.Med. 89 3 313-315 "A study was made of the effect of haloperidol on convulsions induced in mice by bicuculline and thiosemicarbazide and on the recovery cycles of the primary response in the rat sensorimotor cortex. In doses of 0.3--0.5 mg/kg producing a tranquilizing effect, haloperidol exerts a protective action in convulsions induced by bicuculline blocking of the GABA receptors and enhances the depression of the testing response during recovery cycle of the rat sensorimotor cortex primary response. It means that over this dosage range haloperidol potentiates GABA-induced effects. An increase in the neuroleptic dose up to 1--2 mg/kg entails disappearance of the efficacy shown by both the tests. The authors' own and reported data suggest an important role played by the postsynaptic GABA-positive effect in realization of the tranquilizing action of haloperidol and other neurotropic agents" http://www.ncbi.nlm.nih.gov/pubmed/6248144 0 135 "F. Drago, L. Pulvirenti, F. Spadaro and G. Pennisi" 1990 Effects of TRH and prolactin in the behavioral despair (swim) model of depression in rats Psychoneuroendocrinology 15 05-Jun 349-356 "The neuropeptides thyrotropin releasing hormone (TRH) and prolactin (PRL), which affect various behaviors in animals, showed ""antidepressant"" properties in an experimental model of depression. Subcutaneous administration of TRH reduced the total immobility time of rats tested in the despair (constrained swim) test and potentiated the anti-immobility effect of intraperitoneally administered desimipramine (DMI). This effect was not mimicked by the peripheral injection of TSH, T3 or T4. Hyperprolactinemia induced by pituitary homografts under the kidney capsule and the intracerebroventricular injection of PRL also potentiated the DMI-induced reduction of total immobility time of rats in the despair test and exerted ""antidepressant"" effects in aged rats" http://www.ncbi.nlm.nih.gov/pubmed/2129310 1 136 "P. Libby, P. R. Maroko, C. M. Bloor, B. E. Sobel and E. Braunwald" 1973 Reduction of experimental myocardial infarct size by corticosteroid administration J.Clin.Invest 52 3 599-607 "The influence of the administration of pharmacologic doses of hydrocortisone on the extent and severity of acute myocardial ischemic injury and on subsequent necrosis after acute coronary occlusion was investigated in 28 dogs. In order to study acute myocardial injury, repeated epicardial electrocardiograms were recorded from 10 to 15 sites on the anterior surface of the left ventricle. Average ST segment elevation (ST) and the number of sites in which ST segment elevation exceeded 2 mV (NST), indices of the magnitude and extent of myocardial injury, respectively, were analyzed at 30 and 60 min after coronary occlusion. In the control group ST and NST did not change significantly in this time interval while in the treated group, which received 50 mg/kg hydrocortisone just after the 30 min recording, ST fell from 3.5+/-0.8 to 1.1+/-0.4 mV (P<0.01) and NST was reduced from 6.7+/-1.1 to 1.4+/-0.8 (P<0.01). In order to study the influence of hydrocortisone on necrosis, epicardial ST segment elevation 15 min after coronary occlusion was compared to myocardial creatine phosphokinase activity (CPK) and histologic appearance 24 h later in each site. In a control group (14 dogs) a relationship was established between ST segment elevation at 15 min (in millivolts) and CPK activity (in international units per milligram of protein) 24 h later: log CPK = -0.0611ST + 1.26 (N = 102 specimens, r = -0.79). In the treated groups, hydrocortisone (50 mg/kg i.v.) was given either at 30 min after occlusion (seven dogs) or at 6 h after occlusion (six dogs). Both groups received supplementary doses of hydrocortisone (25 mg/kg) 12 h after occlusion. The two treated groups exhibited less CPK depression than that expected from ST segment elevation at each site, with slopes of the regression lines which were significantly less steep: log CPK = -0.0288ST + 1.26 (N = 48, r = -0.71) and log CPK = -0.0321ST + 1.31 (N = 48, r = -0.76) in the (1/2) h and 6 h groups, respectively. Histologically, sites with ST segment elevations of less than 2 mV at 15 min after occlusion exhibited normal appearance 24 h later. Sites with ST segment elevations (> 2 mV) in the control group showed histologic changes compatible with early myocardial infarction in 96% of specimens, while this occurred only in 61% and 63% of specimens, respectively, in the treated groups, showing that over one third of the sites were protected from undergoing necrosis due to the intervening hydrocortisone treatment. Thus pharmacological doses of hydrocortisone prevent myocardial cells from progressing to ischemic necrosis even when administration is initiated 6 h after coronary occlusion" http://www.ncbi.nlm.nih.gov/pubmed/4685084 0 137 "R. K. Burt, R. M. Craig, F. Milanetti, K. Quigley, P. Gozdziak, J. Bucha, A. Testori, A. Halverson, L. Verda, W. J. S. De Villiers, B. Jovanovic and Y. Oyama" 2010 Autologous nonmyeloablative hematopoietic stem cell transplantation in patients with severe anti-TNF refractory Crohn disease: Long-term follow-up Blood 116 26 23 "We evaluated the safety and clinical outcome of autologous nonmyeloablative hematopoietic stem cell transplantation (HSCT) in patients with severe Crohn disease (CD) defined as a Crohn Disease Activity Index (CDAI) greater than 250, and/or Crohn Severity Index greater than 16 despite anti-tumor necrosis factor therapy. Stem cells were mobilized from the peripheral blood using cyclophosphamide (2.0 g/m2) and G-CSF (10 mug/kg/day), enriched ex vivo by CD34+ selection, and reinfused after immune suppressive conditioning with cyclophosphamide (200 mg/kg) and either equine antithymocyte globulin (ATG, 90 mg/kg) or rabbit ATG (6 mg/kg). Eighteen of 24 patients are 5 or more years after transplantation. All patients went into remission with a CDAI less than 150. The percentage of clinical relapse-free survival defined as the percent free of restarting CD medical therapy after transplantation is 91% at 1 year, 63% at 2 years, 57% at 3 years, 39% at 4 years, and 19% at 5 years. The percentage of patients in remission (CDAI < 150), steroid-free, or medication-free at any posttransplantation evaluation interval more than 5 years after transplantation has remained at or greater than 70%, 80%, and 60%, respectively. This trial was registered at www.clinicaltrials.gov as NCT0027853. © 2010 by The American Society of Hematology" 0 138 "C. Nicholson, R. P. Kraig, B. G. ten, H. Stockle and R. Steinberg" 1978 "Potassium, calcium, chloride and sodium changes in extracellular space during spreading depression in cerebellum [proceedings]" Arzneimittelforschung. 28 5 874-875 http://www.ncbi.nlm.nih.gov/pubmed/581976 0 139 "D. Bucci, G. Isani, E. Giaretta, M. Spinaci, C. Tamanini, E. Ferlizza and G. Galeati" 2014 Alkaline phosphatase in boar sperm function Andrology. 2 1 100-106 "Alkaline phosphatase (AP) catalyses the detachment of phosphate residues from different substrates. Its activity has been demonstrated in seminal plasma and spermatozoa from porcine and other mammalian species; anyway, the role of AP in male reproduction has not been clarified yet and the aim of this study was to determine AP function in boar sperm capacitation and in vitro fertilization (IVF). AP activity was assayed in seminal plasma and in uncapacitated and in vitro capacitated (IVC) spermatozoa; in addition, capacitation was studied in presence of different doses of AP (1.2 and 2.5 IU/mL). The effect of different doses of AP (1.2 and 2.5 IU/mL) on several sperm parameters after IVC (viability, acrosome integrity with FITC-PSA, capacitation status with CTC staining, tyrosine phosphorylation) and on fertilizing ability during IVF were also evaluated. High AP activity was detected in seminal plasma, in particular in sperm-rich fraction; a lower activity was detected in uncapacitated spermatozoa while a significant decrease was evidenced after IVC. Viability was not changed by AP supplementation of the capacitating medium, whereas acrosome integrity and capacitation status were significantly affected by 1.2 and 2.5 doses, with a dose-dependent decrease in acrosome-reacted cells as well as in CTC B pattern displaying cells. As for sperm head protein phosphorylation, a decrease in relative fluorescence was detected in AP 2.5 group, if compared with capacitated one. After IVF, a dose-dependent decrease in penetrated oocytes was recorded, with an increase in monospermic zygote rate. In conclusion, we demonstrated that AP activity decreases under capacitating condition and that addition of AP to spermatozoa during capacitation results in a depression of the capacitating process and IVF. We can infer that AP plays a role in keeping spermatozoa quiescent until they are ejaculated and in modulating the acquisition of the fertilizing ability" http://www.ncbi.nlm.nih.gov/pubmed/24249651 0 140 "D. Fekkes, A. R. Van Gool, M. Bannink, S. Sleijfer, W. H. J. Kruit, B. Van Der Holt, A. M. M. Eggermont, M. W. Hengeveld and G. Stoter" 2009 Nitric oxide production and monoamine oxidase activity in cancer patients during interferon-alpha therapy "Amino Acids.37 (4) ()(pp 703-708), 2009.Date of Publication: October 2009." 4 703-708 "Both increased and decreased nitric oxide (NO) synthesis have been reported in patients treated with interferon-alpha (IFN-alpha). Animal studies showed that IFN-alpha administration results in increased levels of biogenic amines, subsequent activation of monoamine oxidases (MAOs), and finally in a change in NO production due to the H2O2 generated by MAOs. We examined the potential relationship between NO production in plasma and MAO-B activity in platelets of 43 cancer patients during 8 weeks of treatment with IFN-alpha. NO synthesis was quantitated by measuring both the ratio of citrulline and arginine (CIT/ARG-ratio) and total nitrite/nitrate (NOx) levels. Compared to baseline, MAO activity and NOx increased, while the CIT/ARG-ratio decreased. No associations were found between NOx, MAO and CIT/ARG-ratio. Only few associations were observed between changes in the biochemical parameters and changes in psychopathology induced by IFN-alpha, of which the association between changes in CIT and lassitude was the most consistent. The results suggest that peripheral NO production and MAO activity are unrelated to each other, and that peripheral changes in these biochemical parameters induced by IFN-alpha are unlikely to contribute to definite psychiatric disturbance. © 2008 Springer-Verlag" DO - http://dx.doi.org/10.1007/s00726-008-0191-x 0 141 "C. Maudhuit, M. Hamon and J. Adrien" 1995 Electrophysiological activity of raphe dorsalis serotoninergic neurones in a possible model of endogenous depression Neuroreport 6 4 681-684 "It has been proposed that serotoninergic activity is impaired in endogenous depression. We tested this hypothesis in an experimental model, where rats which have been treated with clomipramine during the first month of life exhibit at adult age behavioural and sleep alterations which resemble the human disorder. Recording of serotoninergic neurones in the dorsal raphe nucleus revealed no modification of their spontaneous firing, but a reduced inhibitory response to the 5-HT re-uptake blocker citalopram in clomipramine-treated rats as compared to controls. This suggests that neonatal clomipramine treatment results in a long lasting desensitization of somatodendritic 5-HT1A autoreceptors, leading possibly to a dysregulation of 5-HT neurone activity in this proposed model of depression" http://www.ncbi.nlm.nih.gov/pubmed/7605927 1 142 "L. F. Ferreira, J. S. Moylan, S. Stasko, J. D. Smith, K. S. Campbell and M. B. Reid" 2012 Sphingomyelinase depresses force and calcium sensitivity of the contractile apparatus in mouse diaphragm muscle fibers J.Appl.Physiol (1985.) 112 9 1538-1545 "Diseases that result in muscle weakness, e.g., heart failure, are characterized by elevated sphingomyelinase (SMase) activity. In intact muscle, SMase increases oxidants that contribute to diminished muscle force. However, the source of oxidants, specific processes of muscle contraction that are dysfunctional, and biochemical changes underlying the weakness elicited by SMase remain unknown. We tested three hypotheses: 1) SMase-induced depression of muscle force is mediated by mitochondrial reactive oxygen species (ROS), 2) SMase depresses force and calcium sensitivity of the contractile apparatus, and 3) SMase promotes oxidation and phosphorylation of myofibrillar proteins. Our experiments included intact muscle bundles, permeabilized single fibers, and isolated myofibrillar proteins. The mitochondrial-targeted antioxidant d-Arg-2',6'-dimethyl-Tyr-Lys-Phe-NH(2), decreased cytosolic oxidants and protected intact muscle bundles from weakness stimulated by SMase. SMase depressed maximal calcium-activated force by 20% in permeabilized single fibers (in kN/m(2): control 117 +/- 6; SMase 93 +/- 8; P < 0.05). Calcium sensitivity of permeabilized single fibers decreased from 5.98 +/- 0.03 (control) to 5.91 +/- 0.02 (SMase; P < 0.05). Myofibrillar protein nitrotyrosines, carbonyls, and phosphorylation were unaltered by SMase. Our study shows that the fall in specific force of intact muscle elicited by SMase is mediated by mitochondrial ROS and can be attributed largely to dysfunction of the contractile apparatus" http://www.ncbi.nlm.nih.gov/pubmed/22362402 0 143 P. S. Schein 1969 1-methyl-1-nitrosourea depression of brain nicotinamide adenine dinucleotide in the production of neurologic toxicity Proc.Soc.Exp.Biol.Med. 131 2 517-520 http://www.ncbi.nlm.nih.gov/pubmed/4306807 0 144 S. D. Sharma and W. F. Piessens 1978 Tumor cell killing by macrophages activated in vitro with lymphocyte mediators. II. Inhibition by inhibitors of protein synthesis Cell Immunol. 38 2 264-275 http://www.ncbi.nlm.nih.gov/pubmed/209901 0 145 "G. Spennato, C. Zerbib, C. Mondadori and R. Garcia" 2008 Fluoxetine protects hippocampal plasticity during conditioned fear stress and prevents fear learning potentiation Psychopharmacology (Berl) 196 4 583-589 "RATIONALE: Contextual fear conditioning can produce both changes in hippocampal synaptic efficacy and potentiation of subsequent fear learning. OBJECTIVES: In this study, we tested whether fluoxetine reverses these effects. MATERIALS AND METHODS: In the first experiment, we examined alterations of baseline synaptic efficacy and induction of synaptic plasticity in the CA3 region of the hippocampus during re-exposure of rats, treated with fluoxetine (7 mg/kg) or vehicle, in a context where they previously received 15 eyelid shocks or no shock (controls). In the second experiment, fear learning potentiation was examined in rats that were initially submitted to conditioning (15 eyelid shocks) and extinction training and then re-exposed to a less intense stressor (three eyelid shocks). RESULTS: Conditioned fear stress decreased synaptic efficacy and blocked the induction of synaptic potentiation in the fimbria-CA3 pathway. Conditioned rats treated with fluoxetine were protected against these electrophysiological changes and did not differ from controls (i.e., no depression and normal induction of potentiation of synaptic efficacy). However, fluoxetine treatment did not suppress conditioned freezing. After fear extinction, exposure of rats to a subconditioning stressor provoked conditioning (fear learning potentiation) in rats treated with vehicle but not in those treated with fluoxetine. CONCLUSIONS: These findings indicate that fluoxetine treatment, which is ineffective on conditioned fear stress-induced freezing, may have beneficial effects on conditioned fear stress-induced disturbance of hippocampal plasticity. These data also suggest that restoration of hippocampal functioning may contribute to protection against exaggerated reactions to mild stressors reported in patients with post-traumatic stress disorder" http://www.ncbi.nlm.nih.gov/pubmed/17992518 0 146 E. Bednarski and G. Lynch 1998 Selective suppression of cathepsin L results from elevations in lysosomal pH and is followed by proteolysis of tau protein Neuroreport 9 9 2089-2094 "Incubation of cultured hippocampal slices with chloroquine, a compound that increases the pH of acidic subcellular organelles, for 10 h reduced the activity of cathepsin L by 83 +/- 0.87% (mean +/- s.e.m.) while only marginally suppressing cathepsin B. This effect was followed within 3 h by an increase in the concentration of mature, single-chain cathepsin D (up 61 +/- 28%). Selective depression of cathepsin L with N-CBZ-L-phenylalanyl-L-phenylalanine-diazomethylketone also resulted in increases in enzymatically active cathepsin D and the delayed appearance of a 29 kDa fragment of the tau protein. These findings demonstrate that the pattern of cathepsin L, B, and D changes found in the aged brain can be reproduced by reducing the acidity of the lysosomal milieu. They also indicate that such pH shifts initiate a sequence of linked disturbances (inactivation of cathepsin L > induction of cathepsin D > aberrant tau proteolysis) likely to play an important role in brain ageing" http://www.ncbi.nlm.nih.gov/pubmed/9674599 0 147 "R. C. Tasker, S. K. Sahota and S. R. Williams" 1996 Bioenergetic recovery following ischemia in brain slices studied by 31P-NMR spectroscopy: differential age effect of depolarization mediated by endogenous nitric oxide J.Cereb.Blood Flow Metab 16 1 125-133 "Proximate neurotoxic mechanisms during postischemic recovery may be influenced by stage of development and complicating factors such as cortical spreading depression or secondary brain insult. Using 31P nuclear magnetic resonance spectroscopy, we have monitored pH and cellular energy metabolites phosphocreatine (PCr) and ATP in the ex vivo rat cerebral cortex before, during, and after substrate and oxygen deprivation, which represents ""in vitro ischemia."" There were important developmental differences in resistance and response to an ischemic insult. Twenty-one-day-old (P21) rat cortical slices had no detectable beta-ATP or PCr at the end of a 20-min insult, while 7-day-old (P7) slices had 50 +/- 13.7% (mean +/- SD, n = 12) and 17 +/- 14.8% relative to preischemia levels, respectively. Postischemic depolarization resulted in age-dependent effects on PCr (p < 0.05): In the older tissue, depolarization significantly worsened the recovery of PCr, whereas in young tissue it ameliorated recovery. This amelioration could be prevented by inhibiting nitric oxide production with methylene blue (depolarization-methylene blue interaction, p < 0.05) and enhanced by administration of the nitric oxide donor glyceryl trinitrate (GTN; p < 0.01). However, in P21 tissue, GTN further exacerbated injury (age-GTN interaction, p < 0.01). Therefore, in this vascular-independent preparation, a neuronal or glial nitric oxide-dependent mechanism appears to confer improved postischemic bioenergetic recovery in the developing brain compared with the mature brain" http://www.ncbi.nlm.nih.gov/pubmed/8530545 0 148 T. Matsubara and N. S. Dhalla 1996 Effect of Oxygen Free Radicals on Cardiac Contractile Activity and Sarcolemmal Na(+)-Ca(2+) Exchange J.Cardiovasc.Pharmacol.Ther. 1 3 211-218 "BACKGROUND: Although oxygen free radicals have been shown to induce myocardial cell damage and cardiac dysfunction, the exact mechanism by which these radicals affect the heart function is not clear. Since the occurrence of intracellular Ca(2+) overload is critical in the genesis of cellular damage and cardiac dysfunction, and since the sarcolemmal Na(+)-Ca(2+) exchange is intimately involved in Ca(2+) movements in myocardium, this study was undertaken to examine the effects of oxygen free radicals on the relationship between changes in cardiac contractile force development and sarcolemmal Na(+)-Ca(2+) exchange activity. METHODS AND RESULTS: Isolated rat hearts were perfused with a medium containing xanthine plus xanthine oxidase for different times, and changes in contractile force as well as sarcolemmal Na(+)-(2+) exchange activity were monitored. Perfusion of the heart with xanthine plus xanthine oxidase resulted in a transient increase followed by a marked decrease in contractile activity; the resting tension was markedly increased. The xanthine plus xanthine oxidase-induced depression in developed tension, rate of contraction, and rate of relaxation, except the transient increase in contractile activity, was prevented by the addition of catalase, but not by superoxide dismutase, in the perfusion medium. A time-dependent depression in sarcolemmal Na(+)-Ca(2+) was also evident upon perfusing the heart with xanthine plus xanthine oxidase. This depression in Na(+)-dependent Ca(2+) uptake was associated with a decrease in the maximal velocity of reaction without any changes in the affinity of Na(+)-Ca(2+) exchanger for Ca(2+). The presence of catalase, unlike superoxide dismutase, prevented the decrease in sarcolemmal Na(+)-Ca(2+) exchange activity in hearts perfused with xanthine plus xanthine oxidase. CONCLUSIONS: The results support the view that a depression in the sarcolemmal Na(+)-Ca(2+) exchange activity may contribute to the occurrence of intracellular Ca(2+) overload and subsequent decrease in contractile activity. Furthermore, these actions of xanthine plus xanthine oxidase in the whole heart appear to be a consequence of H(2)O(2) production rather than the generation of superoxide radicals" http://www.ncbi.nlm.nih.gov/pubmed/10684419 0 149 A. Bruner 1974 Effects of 60Co on electrical self-stimulation of the brain and blood pressure in monkeys Aerosp.Med. 45 9 1058-1061 http://www.ncbi.nlm.nih.gov/pubmed/4413187 0 150 "T. M. Eriksson, P. Delagrange, M. Spedding, M. Popoli, A. A. Mathe, S. O. Ogren and P. Svenningsson" 2012 Emotional memory impairments in a genetic rat model of depression: involvement of 5-HT/MEK/Arc signaling in restoration Mol.Psychiatry 17 2 173-184 "Cognitive dysfunctions are common in major depressive disorder, but have been difficult to recapitulate in animal models. This study shows that Flinders sensitive line (FSL) rats, a genetic rat model of depression, display a pronounced impairment of emotional memory function in the passive avoidance (PA) task, accompanied by reduced transcription of Arc in prefrontal cortex and hippocampus. At the cellular level, FSL rats have selective reductions in levels of NMDA receptor subunits, serotonin 5-HT(1A) receptors and MEK activity. Treatment with chronic escitalopram, but not with an antidepressant regimen of nortriptyline, restored memory performance and increased Arc transcription in FSL rats. Multiple pharmacological manipulations demonstrated that procognitive effects could also be achieved by either disinhibition of 5-HT(1A)R/MEK/Arc or stimulation of 5-HT(4)R/MEK/Arc signaling cascades. Taken together, studies of FSL rats in the PA task revealed reversible deficits in emotional memory processing, providing a potential model with predictive and construct validity for assessments of procognitive actions of antidepressant drug therapies" http://www.ncbi.nlm.nih.gov/pubmed/21242991 1 151 "T. Furuhashi, M. Uehara, R. Kodama, R. Yoshida, A. Maruden and K. Shimamura" 1992 [Reproductive and developmental toxicity studies of FUT-187. (I)--Fertility study in rats with oral administration of FUT-187] J.Toxicol.Sci. 17 Suppl 4 201-219 "FUT-187 was given orally at 20, 120 and 720 mg/kg during the pre-pairing period (63 days prior to pairing in males and 14 days prior to pairing in females) and the pairing period to male and female rats and in the early stage of pregnancy (days 0 through 7 of gestation) to female rats, and the effects of the test compound on male and female reproductive performance and fetal development were evaluated. One male of the 720 mg/kg group died due to treatment. Temporary salivation was observed in males and females in the 20 mg/kg or more groups. In males, increases in the weight of the pancreas in the 120 mg/kg or more groups and the adrenals in the 720 mg/kg group, a depression of body weight gain and decreases in food intake and weight of the carcass in the 720 mg/kg group were statistically significant in comparison with controls. In females, an increase in the weight of the pancreas in the 120 mg/kg or more groups, a slight depression of body weight gain during the early stage of pregnancy and a decrease in the food intake, and a decrease in the weight of the carcass in the 720 mg/kg group were statistically significant in comparison with controls. No dose-related changes were found in the estrus, copulation, insemination and fertility indices. In fetuses, decreased numbers of corpora lutea, implantation and live fetuses were observed in the 720 mg/kg group. There were no treatment-related abnormalities in fetal mortality, sex ratio, weights of fetuses and placenta, and external and visceral examinations. Based on these results, it is concluded that the no-effect-dose levels of FUT-187 are less than 20 mg/kg for the parents, 720 mg/kg for reproductive performance and 120 mg/kg for fetal development" http://www.ncbi.nlm.nih.gov/pubmed/1296024 0 152 "M. Rahman, A. Khatun, M. L. Nesa, H. Hossain and I. A. Jahan" 2015 Bioactive Polyphenols from the Methanol Extract of Cnicus arvensis (L.) Roth Demonstrated Antinociceptive and Central Nervous System Depressant Activities in Mice Evid.Based.Complement Alternat.Med. 2015 794729 "Cnicus arvensis is used by many ethnic groups for inflammation, pain, and other ailments. In this study, reducing sugar, carbohydrate, alkaloid, steroid, tannin, flavonoid, and saponin groups were identified using standard chromogenic method. In high-performance liquid chromatography, vanillic acid and epicatechin were identified in the extract. Antinociceptive test by acetic acid induced writhing inhibition resulted 43.17 and 95.08% inhibition for 100 and 200 mg/kg body weight, comparing with standard diclofenac Na with 74.86% inhibition for 25 mg/kg body weight. In formalin induced paw licking test for antinociceptive activity, the extract inhibited 69.87 and 75.55% licking for 150 and 300 mg/kg body weight comparing with the inhibition (68.56%) of diclofenac Na for 10 mg/kg body weight at first phase. At late phase, the extract showed 73.12 and 87.46% licking comparing with licking inhibition (71.69%) by diclofenac Na at the same dose. In open field test for CNS depressant activity, the extract showed depression of locomotor activity for 150 and 300 mg/kg body weight comparing with diazepam for 10 mg/kg body weight. All results were statistically significant (P < 0.01). The identified polyphenols are reputed for antinociceptive and CNS depressant activity. The present findings support the use of this plant in pain" http://www.ncbi.nlm.nih.gov/pubmed/25648520 0 153 U. Persson and L. Rutberg 1974 The effect of mitomycin C on antigenic and mitogenic stimulation of mouse lymphocytes in vitro Scand.J.Immunol. 3 5 573-578 http://www.ncbi.nlm.nih.gov/pubmed/4607940 0 154 "A. L. Green, P. Gu, F. M. De, D. Dodick, M. H. Ossipov and F. Porreca" 2014 Increased susceptibility to cortical spreading depression in an animal model of medication-overuse headache Cephalalgia 34 8 594-604 "OBJECTIVE: The objective of this article is to evaluate electrically evoked thresholds for cortical spreading depression (CSD) and stress-induced activation of trigeminal afferents in a rat model of medication-overuse headache (MOH). METHODS: Sumatriptan or saline was delivered subcutaneously by osmotic minipump for six days to Sprague-Dawley rats. Two weeks after pump removal, animals were anesthetized and recording/stimulating electrodes implanted. The animals were pretreated with vehicle or topiramate followed by graded electrical stimulation within the visual cortex. CSD events were identified by decreased EEG amplitude and DC potential shift. Additional unanesthetized sumatriptan or saline-pretreated rats were exposed to bright light environmental stress and periorbital and hindpaw withdrawal thresholds were measured. Following CSD stimulation or environmental stress, immunohistochemical staining for Fos in the trigeminal nucleus caudalis (TNC) was performed. RESULTS: Sumatriptan pre-exposure significantly decreased electrical stimulation threshold to generate a CSD event. Topiramate normalized the decreased CSD threshold as well as stress-induced behavioral withdrawal thresholds in sumatriptan-treated rats compared to saline-treated animals. Moreover, CSD and environmental stress increased Fos expression in the TNC of sumatriptan-treated rats, and these effects were blocked by topiramate. Environmental stress did not elicit cutaneous allodynia or elevate TNC Fos expression in saline-treated rats. CONCLUSIONS: A previous period of sumatriptan exposure produced long-lasting increased susceptibility to evoked CSD and environmental stress-induced activation of the TNC that was prevented by topiramate. Lowered CSD threshold, and enhanced consequences of CSD events (increased activation of TNC), may represent an underlying biological mechanism of MOH related to triptans" http://www.ncbi.nlm.nih.gov/pubmed/24335852 0 155 "M. Bracke, B. Vyncke, P. Coopman and M. Mareel" 1989 Strategies for the study of tumor invasion using an assay in vitro Pathol.Biol.(Paris) 37 9 1022-1023 http://www.ncbi.nlm.nih.gov/pubmed/2608326 0 156 "G. Zhao, Y. Gai, W. J. Chu, G. W. Qin and L. H. Guo" 2009 "A novel compound N(1),N(5)-(Z)-N(10)-(E)-tri-p-coumaroylspermidine isolated from Carthamus tinctorius L. and acting by serotonin transporter inhibition" Eur.Neuropsychopharmacol. 19 10 749-758 "Safflower, the dry flower of Carthamus tinctorius L., has long been applied for empirically treating cerebral ischemia and depression in traditional Chinese medicine. Pathogenesis of major depression involves monoaminergic transmission. The present study assessed whether safflower or its isolate would be effective in functionally regulating monoamine transporter using in vitro screening cell lines. We discovered that safflower insoluble fraction significantly inhibited serotonin uptake in Chinese hamster ovary cells stably expressing serotonin transporter (i.e. S6 cells). This fraction went through an activity-guided isolation and an active ingredient was obtained, which was subsequently elucidated as a novel coumaroylspermidine analog N(1),N(5)-(Z)-N(10)-(E)-tri-p-coumaroylspermidine using NMR techniques. Pharmacologically, this compound potently and selectively inhibited serotonin uptake in S6 cells or in synaptosomes, with IC(50) of 0.74+/-0.15 microM for S6 cells or 1.07+/-0.23 microM for synaptosomes and with a reversible competitive property for the 5HT-uptake inhibition. The potency of it for 5HT uptake was weaker than that of fluoxetine whereas efficacy generally similar for both. Animals treated with this testing compound showed a significant decrease in synaptosomal 5HT uptake capacity. Thus, N(1),N(5)-(Z)-N(10)-(E)-tri-p-coumaroylspermidine is a novel serotonin transporter inhibitor, which could improve neuropsychological disorders through regulating serotoninergic transmission" http://www.ncbi.nlm.nih.gov/pubmed/19577438 0 157 "E. Pryazhnikov, A. Ostroumov, O. Druginina, F. Vyskocil and A. Skorinkin" 2012 "The mechanisms of inhibition of frog endplate currents with homologous derivatives of the 1,1-dimethyl-3-oxybutyl phosphonic acid" Physiol Res. 61 4 395-404 "The mode of inhibition of endplate currents by four esters of 1,1-dimethyl-3-oxybutyl phosphonic acid with different lipophilicities and molecule lengths were estimated by mathematical modeling based on previous electrophysiological data supplemented by several experiments with rhythmic stimulation. The aim was to discriminate between their receptor and non-receptor effects. It was shown that all esters have a two-component mechanism of depression: inhibition of the receptor open channel and allosteric modulation of the receptor-channel complex. The ratio of both functional components depends on the length and lipophilicity of the esters. Short and less lipophilic esters mostly act as open channel inhibitors and the rate of inhibition substantially depends on the rate of stimulation, i. e. probability of the receptor-channel opening. As the length of the ester radicals and their lipophilicity increased, these compounds were more active as allosteric receptor inhibitors, probably hindering the function of nAChRs from the lipid annulus" http://www.ncbi.nlm.nih.gov/pubmed/22670693 0 158 "R. R. Grady, L. Shin, M. C. Charlesworth, I. R. Cohen-Becker, M. Smith, C. Rivier, J. Rivier, W. Vale and N. B. Schwartz" 1985 Differential suppression of follicle-stimulating hormone and luteinizing hormone secretion in vivo by a gonadotropin-releasing hormone antagonist Neuroendocrinology 40 3 246-252 "Because of some indication that FSH secretion is less dependent than LH secretion on GnRH in vivo, we performed experiments to examine the effects of a GnRH antagonist (antag) on LH and FSH secretion. We first showed that pituitary cells superfused with GnRH showed a similar pattern of suppressed secretion of both LH and FSH in response to addition of antag. In contrast, antag administration to ovariectomized rats had differing effects on LH and FSH secretion. Serum LH was suppressed in a dose-dependent fashion by 2 h (20-50% of control values). Recovery from the lower doses of antag was seen by 12 h, but the two highest doses maintained serum LH levels at 10% of control values for 72 h. In contrast, the effect on serum FSH was not manifested until 12 h. FSH was maximally decreased only to 40-60% of control values. The two highest doses maintained this effect for 72 h. These results reinforce previous suggestions that FSH secretion in vivo may occur independently of acute changes in GnRH secretion, and may have an GnRH-independent component" http://www.ncbi.nlm.nih.gov/pubmed/3921860 0 159 "R. J. Campbell, L. G. Wilson, H. R. Herschman, L. V. DiCara and E. A. Stone" 1975 Paradoxical decrease in norepinephrine content of adult mouse spleen and heart after neonatal nerve growth factor treatment Biochem.Pharmacol. 24 23 2213-2216 http://www.ncbi.nlm.nih.gov/pubmed/1212268 0 160 J. W. Horton and K. R. Borman 1987 "Possible role of oxygen-derived, free radicals in cardiocirculatory shock" Surg.Gynecol.Obstet. 165 4 293-300 "The release of oxygen free radicals from ischemic myocardial tissue has been implicated as a causative factor of cell membrane damage and cardiac dysfunction in hemorrhagic shock. This study was done to determine whether or not hydrogen peroxide (H2O2) and superoxide ion (O2) are responsible for cardiac injury from hemorrhagic shock as indicated by reduced coronary perfusion and impaired contractile function. This hypothesis was tested by infusing selective O2 and H2O2 scavengers into anesthetized dogs in a state of shock, either during shock (group 3) or with fluid resuscitation (group 2) and comparing the cardiovascular response to that seen with shock and fluid resuscitation alone (group 1). We found no significant difference in shock induced derangements in myocardial oxygen metabolism or the degree of myocardial depression and regional ischemia in dogs in a state of shock given superoxide dismutase plus catalase, compared with shock alone. The results of our data suggested that, if O2 and H2O2 play a causative role in shock induced cardiac dysfunction or during reperfusion after shock, free radical scavengers must be administered early in the ischemic period. Furthermore, free radical scavengers administered with reperfusion do not enchance cardiac function nor myocardial perfusion" http://www.ncbi.nlm.nih.gov/pubmed/2821638 0 161 J. C. Mauck and H. Green 1974 Regulation of pre-transfer RNA synthesis during transition from resting to growing state Cell 3 2 171-177 http://www.ncbi.nlm.nih.gov/pubmed/4473272 0 162 "B. Winter, G. Juckel, I. Viktorov, J. Katchanov, A. Gietz, R. Sohr, M. Balkaya, H. Hortnagl and M. Endres" 2005 Anxious and hyperactive phenotype following brief ischemic episodes in mice Biol.Psychiatry 57 10 1166-1175 "BACKGROUND: Poststroke emotional and behavioral abnormalities have an impact on outcome but have scarcely been characterized in animal models. We tested whether brief ischemic episodes induce behavioral changes in mice. METHODS: 129/Sv mice were subjected to 30-min occlusion of left or right middle cerebral artery (MCAo) followed by reperfusion or sham operation (n = 9 or 10 per group). Eight to ten weeks later, mice were tested for spontaneous locomotor activity, anxiety in the elevated plus maze, and depressive behavior in the modified Porsolt forced swim test. Outcome was correlated to monoamine and amino acid levels and compared with histologic damage at 10 weeks. RESULTS: Ischemia was associated with increased activity (right MCAo) and anxiety (left MCAo), but not poststroke depression. Noradrenaline increased by 30%-45% in the ischemic striatum and correlated with locomotor activity (r = .48); dopamine and homovanillinic acid were decreased compared with sham. The lesion was confined to the striatum, and scattered neuronal death was observed in a number of remote brain regions. CONCLUSION: Brief ischemic episodes in the mouse induce an anxious, hyperactive but not depressive phenotype that may relate to left versus right hemispheric lesion location, alterations in brain monoamine levels, and selective neurodegeneration" http://www.ncbi.nlm.nih.gov/pubmed/15866557 0 163 "P. S. Miller, J. Glasner and P. W. Hedrick" 1993 Inbreeding depression and male-mating behavior in Drosophila melanogaster Genetica 88 1 29-36 "There have been relatively few studies designed to investigate the effects of inbreeding on behavioral traits. To study this phenomenon, five experimental lines of Drosophila melanogaster made isogenic for chromosome 2 were evaluated for their male-mating ability and, subsequently, male courtship behavior. All lines showed significant reductions in overall mating ability, and males from all of these lines displayed impaired mating behavior, with two lines displaying particularly aberrant courtship patterns. Line 16 displayed an inability to successfully initiate copulation following successful courtship, while line 17 displayed significant reduction in locomotor activity, resulting in virtually no successful courtship or copulatory activity. The implications of these findings for competitive mating ability in wild Drosophila populations are presented. Further, the importance of mating success as a fitness component in the management of potentially highly inbred populations of endangered species is discussed" http://www.ncbi.nlm.nih.gov/pubmed/8375666 0 164 "A. T. El-Alfy, K. Ivey, K. Robinson, S. Ahmed, M. Radwan, D. Slade, I. Khan, M. ElSohly and S. Ross" 2010 Antidepressant-like effect of DELTA9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L Pharmacology Biochemistry and Behavior 95 4 June "The antidepressant action of cannabis as well as the interaction between antidepressants and the endocannabinoid system has been reported. This study was conducted to assess the antidepressant-like activity of DELTA9-THC and other cannabinoids. Cannabinoids were initially evaluated in the mouse tetrad assay to determine doses that do not induce hypothermia or catalepsy. The automated mouse forced swim (FST) and tail suspension (TST) tests were used to determine antidepressant action. At doses lacking hypothermic and cataleptic effects (1.25, 2.5, and 5mg/kg, i.p.), both DELTA9-THC and DELTA8-THC showed a U-shaped dose response with only DELTA9-THC showing significant antidepressant-like effects at 2.5mg/kg (p<0.05) in the FST. The cannabinoids cannabigerol (CBG) and cannabinol (CBN) did not produce antidepressant-like actions up to 80mg/kg in the mouse FST, while cannabichromene (CBC) and cannabidiol (CBD) exhibited significant effect at 20 and 200mg/kg, respectively (p<0.01). The antidepressant-like action of DELTA9-THC and CBC was further confirmed in the TST. DELTA9-THC exhibited the same U-shaped dose response with significant antidepressant-like action at 2.5mg/kg (p<0.05) while CBC resulted in a significant dose-dependent decrease in immobility at 40 and 80mg/kg doses (p<0.01). Results of this study show that DELTA9-THC and other cannabinoids exert antidepressant-like actions, and thus may contribute to the overall mood-elevating properties of cannabis. © 2010" 1 165 "M. D. Opal, M. P. Seiglie and S. C. Dulawa" 2011 Selective serotonin 2C receptor antagonists exert a fast-acting antidepressant response in mouse behavioral tests "Biological Psychiatry.Conference: 66th Annual Meeting of the Society of Biological Psychiatry San Francisco, CA United States.Conference Start: 20110512 Conference End: 20110514.Conference Publication: (var.pagings).69 (9 Suppl 1) ()(pp 128S), 2011.D" var.pagings 128S "Background: The delayed onset of antidepressants is a major impediment in treating major depression. Faster-acting compounds are greatly needed. We have identified serotonin 2C (5-HT2C) antagonists that exert fast-acting antidepressant-like effects in three reliable and valid behavioral tests. Methods: Balb/cJ and C57/Bl6 mice were subjected to chronic forced swim test (cFST), olfactory bulbectomy (obx) and social defeat. Mice were treated subcutaneously with the 5-HT2C antagonists RS102221 (RS) or SB242084 (SB) according to the following parameters. Citalopram (CIT) was administered for comparison. In the cFST, balb/cJ female mice were treated either subchronic (5d) or chronic (12d) with RS, SB or CIT. In obx, balb/cJ female mice were treated subchronic with RS, SB or CIT. In social defeat, C57/ Bl6 male mice were treated subchronic with RS, SB or CIT. Results: Subchronic treatment with RS (1, 5 mg/kg) and SB (1 mg/kg) increased swimming behavior in the cFST, while RS (1 mg/kg) and SB (1 mg/kg) reduced immobility. Furthermore, RS (1 mg/kg) increased distance traveled and time spent in the center of the open field. In obx, SB (1 mg/kg) reduced obx-induced hyperactivity in the open field. In social defeat, subchronic treatment with RS (1 mg/kg) increased the number of entries into a pre-defined interaction zone, as well as distance traveled and time spent in the interaction zone compared to drug-treated non-defeated control mice. CIT (10 mg/kg) had no effect in any test when administered subchronic. Conclusions: These combined behavioral results indicate 5-HT2C antagonists exhibit fast-acting antidepressant action" DO - http://dx.doi.org/10.1016/j.biopsych.2011.03.031 0 166 "S. Hartter, M. Arand, F. Oesch and C. Hiemke" 1995 Non-competitive inhibition of clomipramine N-demethylation by fluvoxamine Psychopharmacology (Berl) 117 2 149-153 "The selective serotonin reuptake inhibitor fluvoxamine interferes with the metabolism of tricyclic antidepressants. The present investigation was set out to characterize these interactions in vitro using rat liver microsomes and in vivo by analysing levels of clomipramine and metabolites in sera of depressed patients treated concomitantly with fluvoxamine and clomipramine. Clomipramine was N-demethylated and hydroxylated in vitro by microsomes to N-desmethyl-clomipramine, 8-hydroxyclomipramine, and 10-hydroxyclomipramine. Kinetic analyses revealed Km values of 6.2 microM for N-demethylation and 1.2 microM for 8-hydroxylation. Fluvoxamine was a non-competitive inhibitor for N-demethylation with mean Ki value of 6 microM. In the sera of patients treated with daily doses of 150 mg clomipramine and varying doses of fluvoxamine, decrease in the formation of N-desmethylclomipramine and 8-hydroxyclomipramine were found in comparison to those in sera of patients receiving clomipramine as monotherapy. Taken together, the data give evidence that fluvoxamine is a potent non-competitive inhibitor of N-demethylation and to a minor extent of 8-hydroxylation of clomipramine. Because of the species differences in the metabolism of xenobiotics between rodents and humans, conclusions from animal studies on the clinical situation must be drawn cautiously. Nevertheless, the in vitro approach was helpful to understand drug interactions between clomipramine and fluvoxamine in psychiatric patients" http://www.ncbi.nlm.nih.gov/pubmed/7753960 0 167 "Z. S. Herman, A. Plech and E. Bien" 1981 "Effects of cholinomimetics, cholinolytics and atypical antidepressants in the behavioral despair test in the rat" "Polish Journal of Pharmacology and Pharmacy.31 (5) ()(pp 485-489), 1981.Date of Publication: 1981." 5 485-489 1 168 G. S. Prins and C. Lee 1983 Biphasic response of the rat lateral prostate to increasing levels of serum prolactin Biol.Reprod. 29 4 938-945 "Our previous work has shown that an increase in serum prolactin (Prl) levels produced by two pituitary grafts specifically enhances testosterone-stimulated growth of the rat lateral prostate. Since Prl has been shown in several mammalian systems to have biphasic effects, i.e., stimulatory at low doses and inhibitory or without effect at high levels, the present study was undertaken to determine whether the prostate gland would respond differentially to increasing Prl levels. Adult male rats were castrated, given s.c. testosterone implants and grafted with 0, 1, 2, 4 or 6 pituitaries under the renal capsule. Three weeks later all animals were sacrificed. The three prostate lobes were removed for analysis and blood was collected for Prl and testosterone radioimmunoassay. There were no significant differences in ventral and dorsal lobe parameters among the 5 groups whereas the lateral lobe showed a marked tropic response. As serum Prl levels increased, the weight of the lateral prostate first increased and then diminished. Mean weights (mg +/- SEM) were: 40 +/- 3, 65 +/- 3, 76 +/- 6, 70 +/- 4 and 59 +/- 3 for animals with 0, 1, 2, 4 and 6 grafts, respectively. Protein and DNA levels showed the same response pattern. To ensure that this response was a result of elevated Prl, the study was repeated with daily injections of bromoergocriptine (CB-154). The mean weights after 3 weeks in the control and CB-154-treated animals, respectively were: 0 graft, 44 +/- 3 and 43 +/- 2; 2 grafts, 81 +/- 4 and 41 +/- 3; 6 grafts, 56 +/- 3 and 44 +/- 3. Again, a biphasic response occurred in control animals.(ABSTRACT TRUNCATED AT 250 WORDS)" http://www.ncbi.nlm.nih.gov/pubmed/6640042 0 169 A. P. Ferko 1991 Cysteine sulfinic acid can enhance the central depressant effect of ethanol in mice Pharmacol.Biochem.Behav. 39 3 653-657 "The interaction between ethanol and cysteine sulfinic acid was examined in male Swiss-Webster mice. The loss of the righting reflex (LORR) was used as a measurement of central nervous system depression. In addition, the interaction between ethanol and cysteic acid, a metabolite of cysteine sulfinic acid, was studied. Immediately after the animals regained the righting reflex following ethanol injection (IP), mice were given an ICV injection of saline, cysteine sulfinic acid (1, 15 or 25 mumol/kg) or cysteic acid (1, 15, or 25 mumol/kg). There occurred a return to the LORR within 30 s after the ICV injection of drugs. The return to the LORR by the administration of the amino acids in the presence of ethanol occurred in a dose-dependent fashion. When cysteine sulfinic acid or cysteic acid (25 mumol/kg, ICV) was injected in the absence of ethanol, no loss of the righting reflex occurred. In other experiments, bicuculline methiodide was given ICV with cysteine sulfinic acid (25 mumol/kg), cysteic acid (25 mumol/kg), or GABA (25 mumol/kg) in the presence of ethanol. Bicuculline methiodide, a GABA antagonist, reduced the effects of the three amino acids to produce a return to the LORR in the presence of ethanol. These results indicate that cysteine sulfinic acid, an excitatory amino acid, and cysteic acid can enhance the central depressant properties of ethanol. Since bicuculline antagonized the effects of these two amino acids, a GABAergic mechanism may be involved in the interaction between ethanol and cysteine sulfinic acid or cysteic acid" http://www.ncbi.nlm.nih.gov/pubmed/1686102 0 170 "J. B. Munson, R. D. Johnson and L. M. Mendell" 1997 NT-3 increases amplitude of EPSPs produced by axotomized group Ia afferents J.Neurophysiol. 77 4 2209-2212 We tested the hypothesis that neurotrophin-3 (NT-3) in adult cats can rescue the central synapses made by muscle afferents from the effects of peripheral axotomy. The medial gastrocnemius (MG) muscle nerve in cats was axotomized and capped or axotomized and the distal end provided with either saline or NT-3 by mini-osmotic pump. Four to five weeks later monosynaptic excitatory postsynaptic potentials (EPSPs) elicited by electrical stimulation of the axotomized MG nerve were recorded in intact lateral gastrocnemius/soleus (LGS) motoneurons. The axotomized MG afferents without NT-3 treatment generated EPSPs averaging one-half of the amplitude of those generated by normal intact MG afferents. Axotomized MG afferents treated with NT-3 elicited EPSPs averaging 2.5 times normal amplitude and 5 times the amplitude of those from afferents axotomized but not treated. The very large EPSPs generated by NT-3-treated afferents remained as susceptible to depression during high-frequency stimulation (32 shocks at 167 Hz) as those elicited by untreated axotomized afferents. The arrival of the afferent volley of the cord dorsum potential and the onset of EPSPs were both delayed by axotomy of the group Ia afferents and were both restored by exposure to NT-3. This result suggests that the conduction velocity and thus the caliber of group Ia afferents are also controlled by NT-3. We conclude that the neurotrophin NT-3 has a continuing role in the maintenance of physiological function of muscle afferents in adult mammals http://www.ncbi.nlm.nih.gov/pubmed/9114268 0 171 "P. Asellus, P. Nordstrom and J. Jokinen" 2010 Cholesterol and CSF 5-HIAA in attempted suicide "Journal of Affective Disorders.125 (1-3) ()(pp 388-392), 2010.Date of Publication: September 2010." 01-Mar 388-392 "Background: Low serum cholesterol has been linked to suicide and violent behaviour. The same kind of associations has been reported regarding low levels of 5-hydroxyindolacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) and suicidal behaviour. The hypothesis of the link between serum cholesterol and suicide incorporate serotonin. It proposes that low cholesterol is related to altered serotonergic neurotransmission. A correlation between CSF 5-HIAA and serum cholesterol has been shown in animal studies, but has not been found in humans. Aim: To study the interrelationship between serum cholesterol and CSF 5-HIAA in suicide attempters. Since both cholesterol and CSF 5-HIAA are associated with suicide and violent suicide attempts, we also investigated the correlation with suicide, violent suicide attempt method, suicide intent, hopelessness and depression severity. Methods: Serum total cholesterol and CSF 5-HIAA were measured in 42 medication free suicide attempters. Patients were assessed with Becks's Hopelessness scale (BHS), Suicide Intent Scale (SIS) and Montgomery-Asberg depression rating scale (MADRS) and followed-up for causes of death. Results: Serum total cholesterol and CSF 5-HIAA showed a significant positive correlation adjusted for age, body mass index and substance abuse diagnosis. Cholesterol and CSF 5-HIAA levels did not differ between violent and non-violent suicide attempters or between suicide completers and survivors. Conclusions: These findings indicate that the serotonergic system may be connected to serum cholesterol in patients with a recent suicide attempt. © 2010 Elsevier B.V. All rights reserved" DO - http://dx.doi.org/10.1016/j.jad.2010.02.111 0 172 "P. Calabresi, A. Pisani, N. B. Mercuri and G. Bernardi" 1993 Heterogeneity of metabotropic glutamate receptors in the striatum: electrophysiological evidence Eur.J.Neurosci. 5 10 1370-1377 "In order to investigate the functional role of metabotropic glutamate receptors (mGluRs) in the striatum we performed extracellular and intracellular recordings from a corticostriatal brain slice preparation. The effects of L-2-amino-3-phosphopropionic acid (L-AP3), an antagonist of mGluRs, were studied both on long-term synaptic depression (LTD) and on presynaptic inhibition of excitatory postsynaptic potentials (EPSPs) induced by different agonists of mGluRs. L-AP3 produced a dose-dependent (3-30 microM) reduction of the LTD evoked in the striatum by the tetanic stimulation of the corticostriatal pathway. In contrast to this action, L-AP3 (10-100 microM) did not significantly affect the presynaptic inhibitory effect of 1-amino-cyclopentyl-trans-dicarboxylic acid (t-ACPD), an agonist of mGluRs, on corticostriatal transmission. Higher concentrations of L-AP3 (0.3-1 mM) reduced by themselves the EPSP amplitude. The inhibitory effect of t-ACPD on the cortically evoked EPSPs was mimicked either by the active stereoisomer 1S,3R-ACPD or by amino-4-phosphonobutyric acid (L-AP4), a glutamate autoreceptor agonist. In some neurons, these inhibitory actions were coupled with membrane depolarizations. The depression of synaptic transmission caused by t-ACPD, 1S,3R-ACPD and L-AP4 was not altered following the induction of LTD. Chronic lithium treatment of the animals (60-120 mg/kg i.p. for 10 days) blocked striatal LTD but not presynaptic inhibition mediated by mGluR agonists. The present findings show that the mechanisms underlying LTD and the presynaptic inhibition induced by different agonists of mGluRs exhibit functional and pharmacological differences. These data suggest heterogeneity of mGluRs in the striatum" http://www.ncbi.nlm.nih.gov/pubmed/8275236 0 173 "T. Strekalova, M. Evans, A. Chernopiatko, Y. Couch, J. Costa-Nunes, R. Cespuglio, L. Chesson, J. Vignisse, H. W. Steinbusch, D. C. Anthony, I. Pomytkin and K. P. Lesch" 2015 Deuterium content of water increases depression susceptibility: the potential role of a serotonin-related mechanism Behav.Brain Res. 277 237-244 "Environmental factors can significantly affect disease prevalence, including neuropsychiatric disorders such as depression. The ratio of deuterium to protium in water shows substantial geographical variation, which could affect disease susceptibility. Thus the link between deuterium content of water and depression was investigated, both epidemiologically, and in a mouse model of chronic mild stress. We performed a correlation analysis between deuterium content of tap water and rates of depression in regions of the USA. Next, we used a 10-day chronic stress paradigm to test whether 2-week deuterium-depleted water treatment (91 ppm) affects depressive-like behavior and hippocampal SERT. The effect of deuterium-depletion on sleep electrophysiology was also evaluated in naive mice. There was a geographic correlation between a content of deuterium and the prevalence of depression across the USA. In the chronic stress model, depressive-like features were reduced in mice fed with deuterium-depleted water, and SERT expression was decreased in mice treated with deuterium-treated water compared with regular water. Five days of predator stress also suppressed proliferation in the dentate gyrus; this effect was attenuated in mice fed with deuterium-depleted water. Finally, in naive mice, deuterium-depleted water treatment increased EEG indices of wakefulness, and decreased duration of REM sleep, phenomena that have been shown to result from the administration of selective serotonin reuptake inhibitors (SSRI). Our data suggest that the deuterium content of water may influence the incidence of affective disorder-related pathophysiology and major depression, which might be mediated by the serotoninergic mechanisms" http://www.ncbi.nlm.nih.gov/pubmed/25092571 1 174 "A. Balsamo, A. Lapucci, A. Lucacchini, M. Macchia, C. Martini, C. Nardini and S. Nencetti" 1994 3-(Methyleneaminoxy)methylpiperidine derivatives as uptake inhibitors of biogenic amines in the brain synaptosomal fraction "European Journal of Medicinal Chemistry.29 (12) ()(pp 967-973), 1994.Date of Publication: 1994." 12 967-973 "A series of 3-(methyleneaminoxy)methylpiperidines (5a-h) and their corresponding N-methyl derivatives (6a-h) with a variety of substituents on the imino carbon were synthesized arid tested for their potential antidepressant properties, their capacity to inhibit the re-uptake of biogenic amines (NA, 5-HT and DA) in rabbit brain synaptosomal fractions was also evaluated. The biological results obtained for the piperidine derivatives 5a-h and 6a-h and viloxazine 1, the reference drug, on the 3 re-uptake systems revealed that compounds 5 and 6 are generally able to inhibit biogenic amine uptake. The IC50 values for 5 and 6 were often lower than that of viloxazine 1, in particular for the serotonin- and/or dopamine-uptake systems. A higher activity was found for compounds substituted with at least one phenyl ring on the imino carbon with respect to completely aliphatic systems, and for N-unsubstituted compounds with respect to N-methyl-substituted compounds" DO - http://dx.doi.org/10.1016/0223-5234%2894%2990197-X 0 175 H. D. Nguyen and H. Libikova 1979 Selective resistance to togaviral superinfection in mice with tolerant lymphocytic choriomeningitis virus infection Acta Virol. 23 5 385-392 "Mice infected neonatally with lymphocytic choriomeningitis virus (LCMV) developed partial and complete resitance to cerebral superinfection with tick-borne encephalitis virus (TEV) in 10 and 20 days after birth, respectively. This resistance lasted at least till the age of 40 days. LCMV tolerant mice neither succumbed to TEV infection, nor circulated TEV in their blood. Moderate, gradually decreasing TEV titres were detected in the brains and TEV-induced brain interferon was lower than in control mice of the same age. TEV superinfection caused a significant depression of the blood titre of tolerated LCMV while the titres in the brains remained equal to those in tolerant but not superinfected mice. LCMV tolerant mice showed a similar resistance to another togavirus (chikungunya) but not to encephalitogenic picorna-, herpes- and rhabdoviruses" http://www.ncbi.nlm.nih.gov/pubmed/42297 0 176 "S. Sorensen, T. Dunwiddie, G. McClearn, R. Freedman and B. Hoffer" 1981 Ethanol-induced depressions in cerebellar and hippocampal neurons of mice selectively bred for differences in ethanol sensitivity: an electrophysiological study Pharmacol.Biochem.Behav. 14 2 227-234 "The recently discovered profound differential sensitivity of cerebellar Purkinje (P) cells in long-sleep (LS) verus short-sleep (SS) mice to the depressant effects of locally applied ethanol was extended in this study. First, the sensitivity of Purkinje neurons from HS mice (an outbred stock of mice from which the LS and SS lines were derived), was found to be almost exactly intermediate between the values for the long-sleep and short-sleep animals. Second, no differential sensitivity in long-sleep versus short-sleep hippocampal pyramidal neurons was observed. This was true using both spontaneous and evoked activity. Third, no differential sensitivity of P cells was seen in long- versus short-sleep mice with local application of halothane. Taken together with previous reports, these data strongly suggest that whatever genetically determined central nervous alterations result in the differential soporific effects of ethanol in the two (LS and SS) mouse lines, such alterations are brain region- and depressant drug-specific rather than generalized" http://www.ncbi.nlm.nih.gov/pubmed/7193886 0 177 "M. R. Aslani, A. R. Movassaghi, M. Mohri, M. Pedram and A. Abavisani" 2003 "Experimental Tribulus terrestris poisoning in sheep: clinical, laboratory and pathological findings" Vet.Res.Commun. 27 1 53-62 "Eleven native sheep, 1-2 years old, of both sexes were randomly divided into two groups, 6 sheep being allocated to the experimental group and 5 serving as controls. The sheep in the experimental group were fed 80% Tribulus terrestris and 20% alfalfa hay and wheat straw, while the control sheep were given a mixture of 40% alfalfa hay and 60% wheat straw. Clinical signs of hepatogenous photosensitivity were observed from day 11, including reddening and crust formation on the muzzle, nose, ears and eyelids, depression, weight loss, icterus, conjunctivitis, and yellow discoloration of the urine. Laboratory findings on weekly samples indicated significant differences (p < 0.05) in white blood cell count, total plasma protein and fibrinogen, total and direct bilirubin, blood urea nitrogen and creatinine concentrations, and aspartate aminotransferase and alkaline phosphatase activities. There were no significant differences in the packed cell volume, in the neutrophil, lymphocyte or eosinophil counts, or in the serum calcium, phosphorus, potassium, sodium or chloride concentrations. At necropsy of the experimental animals, there were various degrees of generalized icterus and the livers were swollen and discolored by bile pigment. Histopathological examination revealed varying amounts of crystalloid material in the bile ducts and renal tubules, hepatocellular degeneration, biliary fibrosis and proliferation, renal tubular necrosis and focal necrosis of cardiac muscle" http://www.ncbi.nlm.nih.gov/pubmed/12625403 0 178 D. V. Sarkisov and S. S. Wang 2008 Order-dependent coincidence detection in cerebellar Purkinje neurons at the inositol trisphosphate receptor J.Neurosci. 28 1 133-142 "Associative long-term depression (LTD) at cerebellar parallel fiber-Purkinje cell synapses is sensitive to the temporal order in which the parallel fiber is coactivated with the climbing fiber input, but how order sensitivity is achieved is unknown. Here we show that the cerebellar inositol-1,4,5-trisphosphate (IP3) receptor, whose activation is required for LTD induction, is sensitive in situ to the order of presentation of its coagonists, IP3 and cytoplasmic calcium. By focally photolyzing a novel caged IP3 compound in dendritic spines, we find that pairing IP3 with climbing fiber-mediated calcium entry leads to a large calcium release transient if the climbing fiber is activated up to 100 ms before or up to 500 ms after IP3 uncaging. This asymmetric timing window for coactivation follows the kinetics of calcium removal and IP3 unbinding from the receptor and is not limited by IP3 metabolism. IP3 receptor binding thus acts as an eligibility trace that can drive temporal order-dependent calcium release and LTD induction in Purkinje cells and event order-dependent sensory plasticity in the whole animal" http://www.ncbi.nlm.nih.gov/pubmed/18171931 0 179 J. Abramowitz and W. Chavin 1980 "Acute effects of two melanocytolytic agents, hydroquinone and beta-mercaptoethanolamine, upon tyrosinase activity and cyclic nucleotide levels in murine melanomas" Chem.Biol.Interact. 32 01-Feb 195-208 "The acute in vitro actions of two potent melanocytolytic agents, hydroquinone (HQ) and beta-mercaptoethanolamine (MEA), were determined in the B-16, Cloudman S-91 and Harding-Passey (HP) murine melanomas grown in vivo. Drug treated melanoma dice (5--480 min) were analyzed for tyrosinase activity and cyclic nucleotide levels (cAMP, cGMP). HQ and MEA effects on tyrosinase activity are complex and vary with tumor type, duration of treatment and agent tested. MEA or HQ inhibited B-16 tyrosinase activity. With combined drug therapy, low concentrations of MEA plus HQ stimulate B-16 tyrosinase activity while high concentrations of the drugs have little effect on enzymatic activity. MEA depresses tyrosinase activity while HQ elevates enzymatic activity in the S-19 melanoma. Both high and low concentrations of the combined drugs (MEA plus HQ) elicit the same response, stimulation at 10 min followed by continued depression of tyrosinase activity for the remainder of the 4 h study period. MEA initially stimulates HP tyrosinase activity followed by depression of enzymic activity. In contrast, HQ initially depresses HP tyrosinase activity followed by stimulation of enzyme activity. In combination the drugs inhibit HP tyrosinase activity. The effects of MEA and/or HQ on murine melanoma cyclic nucleotide levels are equally complex. MEA or HQ elevate cAMP and cGMP levels in all three tumors with the exception of S-91 cGMP levels which are not altered. In combination the drugs increase cyclic nucleotide levels in each of the three tumor types but at different times. No correlation is present between cyclic nucleotide levels and tyrosinase activity. Thus, the action of increased cyclic nucleotide levels in melanogenesis can not be separated from the direct actions of MEA and HQ upon melanogenesis. The divergent effects of MEA and/or HQ on tyrosinase activity and cyclic nucleotide levels in these melanomas are not correlated with the known in vivo melanocytolytic activity of these drugs. Thus, these parameters appear to be inadequate indicators of melanoma cell viability in chemotherapeutic screening of drugs effective in destroying malignant melanoma" http://www.ncbi.nlm.nih.gov/pubmed/6253089 0 180 "I. Sepil, R. Radersma, A. W. Santure, C. De, I, J. Slate and B. C. Sheldon" 2015 No evidence for MHC class I-based disassortative mating in a wild population of great tits J.Evol.Biol. 28 3 642-654 "Genes of the major histocompatibility complex (MHC) are regarded as a potentially important target of mate choice due to the fitness benefits that may be conferred to the offspring. According to the complementary genes hypothesis, females mate with MHC dissimilar males to enhance the immunocompetence of their offspring or to avoid inbreeding depression. Here, we investigate whether selection favours a preference for maximally dissimilar or optimally dissimilar MHC class I types, based on MHC genotypes, average amino acid distances and the functional properties of the antigen-binding sites (MHC supertypes); and whether MHC type dissimilarity predicts relatedness between mates in a wild great tit population. In particular, we explore the role that MHC class I plays in female mate choice decisions while controlling for relatedness and spatial population structure, and examine the reproductive fitness consequences of MHC compatibility between mates. We find no evidence for the hypotheses that females select mates on the basis of either maximal or optimal MHC class I dissimilarity. A weak correlation between MHC supertype sharing and relatedness suggests that MHC dissimilarity at functional variants may not provide an effective index of relatedness. Moreover, the reproductive success of pairs did not vary with MHC dissimilarity. Our results provide no support for the suggestion that selection favours, or that mate choice realizes, a preference for complimentary MHC types" http://www.ncbi.nlm.nih.gov/pubmed/25661713 0 181 T. L. Wimpey and C. Chavkin 1992 8-Bromo-cAMP blocks opioid activation of a voltage-gated potassium current in isolated hippocampal neurons Neurosci.Lett. 137 1 137-140 "We have previously shown that mu-selective opioid agonists activate both an inward rectifying and a voltage-gated potassium conductance in acutely dissociated non-pyramidal neurons from rat hippocampus. We now report that the opioid-activated voltage-gated potassium conductance was blocked by the membrane permeable cAMP analogue 8-bromo-cAMP. In contrast, 8-bromo-cGMP failed to inhibit opioid activation of the voltage-gated potassium current. These results suggest that the opioid-activated potassium channel is regulated by cAMP-dependent phosphorylation" http://www.ncbi.nlm.nih.gov/pubmed/1320750 0 182 P. E. Kunkler and R. P. Kraig 1998 Calcium waves precede electrophysiological changes of spreading depression in hippocampal organ cultures J.Neurosci. 18 9 3416-3425 "Although intercellular Ca2+ waves resemble spreading depression (SD) and occur in hippocampal organ cultures (HOTCs), SD has not been reported in these cultures. Accordingly, electrophysiological and Ca2+ imaging techniques were used to examine potential interrelations between Ca2+ waves and electrophysiological changes of SD. Our results show, for the first time, that HOTCs can support SD. Furthermore, two distinct Ca2+ waves were found to precede SD. The first traveled >100 micron/sec along the pyramidal cell dendritic layer. The second subsequently traveled mostly perpendicular to the pyramidal cell layer from CA3 (or CA1) but also in all directions from its area of initiation. This second, slower wave spread with the interstitial DC change of SD at millimeters per minute but always ahead of it by 6-16 sec. Heptanol, which uncouples gap junctions, blocked both of these Ca2+ waves and SD. Thus, two types of Ca2+ waves occur with the initiation and propagation of SD. The first might reflect interneuronal changes linked by gap junctions, whereas the second might stem from interastrocyte changes linked via similar connections. Because individual cells can be followed in space and time for protracted periods in HOTCs, this preparation may be ideal for studies designed to explore not only the mechanisms of SD but also the long-term consequences of SD, such as ischemic tolerance" http://www.ncbi.nlm.nih.gov/pubmed/9547248 0 183 "A. Yousefi, A. A. Dibazar and T. W. Berger" 2012 Synaptic dynamics: Linear model and adaptation algorithm Conf.Proc.IEEE Eng Med.Biol.Soc. 2012 1362-1365 "Linear model for synapse temporal dynamics and learning algorithm for synaptic adaptation in spiking neural networks are presented. The proposed linear model substantially simplifies analysis and training of spiking neural networks, meanwhile accurately models facilitation and depression dynamics in synapse. The learning rule is biologically plausible and is capable of simultaneously adjusting both of LTP and STP parameters of individual synapses in a network. To prove efficiency of the system, a small size spiking neural network is trained for generating different spike and bursting patterns of cortical neurons. The simulation results revealed that the linear model of synaptic dynamics along with the proposed STDP based learning algorithm can provide a practical tool for simulating and training very large scale spiking neural circuitry comprising of significant number of synapses and neurons" http://www.ncbi.nlm.nih.gov/pubmed/23366152 0 184 "D. Beckman, L. E. Santos, B. Stutz, F. G. de Mello and R. Linden" 2012 Prion protein modulates monoaminergic neurotransmitter systems "Journal of Neurochemistry.Conference: 5th Special Conference of the International Society for Neurochemistry, Synapses and Dendritic Spines in Health and Disease Buenos Aires Argentina.Conference Start: 20120912 Conference End: 20120915.Conference Publ" var.pagings Dec-13 "The prion protein (PrPc) functions as a dynamic cell surface scaffold protein, capable of organizing several signaling complexes, and interacts with molecules relevant to neurodegenerative disorders such as Alzheimer, Parkinson and Huntington, in addition to the prion diseases. It is also known that dysfunction of monoaminergic neurotransmission is common in many CNS diseases, including those related to the mutated, 'scrapie' form of PrPc. In particular, parallel dysfunction of serotonergic and dopaminergic systems are important in the development of clinical depression. Recent work in immortalized cells has shown that PrPc modulates the agonist-induced response of at least three serotonergic receptors (5-HT1B/De5-HT2A) (Mouillet-Richard et al, 2005, 2007). In parallel, a phage display screen done by our group indicated that both the serotonin receptor 5-HT5A and its membrane transporter (SERT) are candidate PrPc ligands (T.A. Americo et al., unpublished). In the present study, we used slices of cerebral cortex obtained from 2-3 month-old, male C57Bl10 wild type (WT) and PrPc-/- (KO) mice (Manson et al., 1994), to investigate differences in both serotonergic and dopaminergic signaling. Cerebral hemispheres were dissected and cut into 400 mum slices using a tissue chopper. Accumulation of cAMP was measured in these slices after brief stimulation with serotonin, dopamine, SKF -38393 (D1- receptor agonist), SCH- 23390 (D1-receptor antagonist) or Raclopride (D2-receptor antagonist). We detected differences between genotypes in response to both neurotransmitters. Serotonin-mediated responses were about 30% greater in KO animals, when compared with WT controls. Dopamine, on the other hand, produced a response approximately 40% greater in WT animals than in PrPc-null tissue. With the use of dopaminergic agonist and antagonists we found that the distinct dopaminergic responses can be attributed to D1-like receptors only, while D2-like receptor responses appeared to be unrelated to the differences between WT and KO mice. Using high performance liquid chromatography (HPLC), we found that serotonin levels, as well as of its metabolite (5-HIAA) were similar in both genotypes, while dopamine levels were 3-fold larger in KO than in WT animals. Dopamine metabolites (HVA and DOPAC) showed, however, no differences between the distinct genotypes. These results indicate that PrPc modulates the balance between the levels of these two neurotransmitters in the cerebral cortex, and suggest an important role for PrPc in monoaminergic synaptic transmission" DO - http://dx.doi.org/10.1111/j.1471-4159.2012.07849.x 0 185 "K. Kojima, Y. Naomoto, A. Hizuta, N. Tanaka and K. Orita" 1996 Cytokine production-suppressive effect by macrophage colony-stimulating factor (M-CSF) Res.Commun.Mol.Pathol.Pharmacol. 91 2 161-172 "Macrophage colony-stimulating factor (M-CSF) is a protein which is necessary for proliferation and differentiation of monocyte-macrophage precursor cells. We examined the effect of M-CSF on the cytokine production using BCG sensitized mice in vivo. On Day 0, BCG 1 mg/mouse was injected via the tail vein. Starting from Day 2, M-CSF 30 mu g/mouse (1 X 10(8) U/mg) was injected every 2 days for a total of six times (Day 2, 4, 6, 8, 10 and 12). On Day 14. LPS 25 mu g/mouse was injected via the tail vein, and Interferon (IFN)/Tumor necrosis factor-alpha (TNF-alpha) in serum were determined. The productions of IFN and TNF-alpha were suppressed significantly. These cytokine production-suppressive effects of M-CSF were found also in the in vitro experimental system using spleen cells collected. On Day 14, spleen cells were collected and adjusted to 5 X 10(6) cells/ml. 20 micro-grams of LPS was added to 2ml of spleen cells and they were incubated in a C02 incubator for 24 hours. IFN and TNF-alpha in the supernatant were determined. In the experiment using nude mice, the cytokine suppressive effect of M-CSF was not observed. MLR test was performed with spleen cells of C57BL/6 treated with M-CSF as the responder cells, and spleen cells of C3H were treated with mitomycin C as the stimulator cells. MLR was suppressed significantly by administration of M-CSF. These results might possibly reflect the actual effect of M-CSF in the living body, and the T-cell and cellular immunity might be concerned with the mechanism of the cytokine production-suppressive effect of M-CSF" http://www.ncbi.nlm.nih.gov/pubmed/8832908 0 186 V. Hughes 2014 Sperm RNA carries marks of trauma Nature 508 7496 296-297 http://www.ncbi.nlm.nih.gov/pubmed/24740043 0 187 "K. Obrietan, A. B. Belousov, H. C. Heller and A. N. van den Pol" 1995 Adenosine pre- and postsynaptic modulation of glutamate-dependent calcium activity in hypothalamic neurons J.Neurophysiol. 74 5 2150-2162 "1. Within the hypothalamus, adenosine has been reported to influence temperature regulation, sleep homeostasis, and endocrine secretions. The effects of adenosine on hypothalamic neurons have not been studied at the cellular level. Adenosine (5 nM-30 microM) showed no influence on intracellular Ca2+ or electrical activity in the presence of glutamate receptor antagonists D-2-amino-5-phosphonovalerate and 6-cyano-7-nitroquinoxaline-2,3-dione; consequently, we examined the role of adenosine in modulating the activity of glutamate in cultured hypothalamic neurons (n > 1,700) with fura-2 Ca2+ digital imaging and whole cell patch-clamp electrophysiology in the absence of glutamate receptor block. 2. When glutamate receptors were not blocked, adenosine (1-30 microM) and the selective adenosine A1 receptor agonist N6-cyclopentyl adenosine (CPA; 5 nM-1 microM) caused a large reduction in intracellular Ca2+ and electrical activity, suggesting that glutamate neurotransmission was critical for an effect of adenosine to be detected. Neuronal Ca2+ levels were reversibly depressed by CPA (50 nM), with a maximum depression of 90%, and these effects were blocked by coadministration of the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). 3. Ca2+ levels in immature neurons before the time of synaptogenesis were not affected by adenosine. Adenosine A1 receptor activation suppressed glutamate-mediated Ca2+ activity in neurons in vitro 8 to 73 days. 4. Adenosine (1 or 10 microM) caused a hyperpolarization of membrane potential and a reduction of large postsynaptic potentials arising from endogenously released glutamate. The administration of low concentrations of CPA (5 nM) decreased the frequency of glutamate-mediated, neuronally synchronized Ca2+ transients and the frequency of postsynaptic potentials. 5. To compare the relative effects of adenosine on hypothalamic neurons with cells from other brain regions, we assayed the effects of CPA on glutamate-mediated Ca2+ in hippocampal and cortical cultures. CPA (50 nM) reversibly depressed glutamate-mediated Ca2+ rises in hypothalamic neurons by 35%, compared with 54% in hippocampal neurons and 46% in cortical neurons. 6. If it does play a functional role, adenosine should be released by hypothalamic cells. In some neurons the adenosine A1 receptor antagonists cyclopentyltheophylline or DPCPX caused an increase in intracellular Ca2+, suggesting that adenosine was secreted by hypothalamic cells, tonically depressing glutamate-enhanced neuronal Ca2+. 7. To determine whether adenosine could exert a postsynaptic effect, we coapplied it with glutamate agonists in the presence of tetrodotoxin. Within subpopulations of hypothalamic neurons, adenosine and CPA either inhibited (18% of total neurons) or potentiated (6% of total neurons) responses to glutamate, N-methyl-D-aspartate, and kainate by > or = 20%. 8. In contrast to the modest effects found in neurons, responses of hypothalamic astrocytes to the application of glutamate or the metabotropic glutamate receptor agonist (+/-)-trans-1-amino-1,3-cyclopentanedicarboxylic acid were strongly potentiated by adenosine (mean +225%) and CPA. 9. Together, these findings suggest that adenosine exerts a major presynaptic effect and a minor postsynaptic effect in the modulation of glutamate neurotransmission in the hypothalamus, where it can play a significant role in blocking a large part of the glutamate-induced Ca2+ rise. In the absence of glutamate transmission, adenosine has relatively little effect on either neuronal intracellular Ca2+ or electrical activity" http://www.ncbi.nlm.nih.gov/pubmed/8592203 0 188 "R. A. Hensbroek, A. Kamal, A. M. Baars, M. Verhage and B. M. Spruijt" 2003 "Spatial, contextual and working memory are not affected by the absence of mossy fiber long-term potentiation and depression" Behav.Brain Res. 138 2 215-223 "The mossy fibers of the hippocampus display NMDA-receptor independent long-term plasticity. A number of studies addressed the role of mossy fiber long-term plasticity in memory, but have provided contrasting results. Here, we have exploited a genetic model, the rab3A null-mutant, which is characterized by the absence of both mossy fiber long-term potentiation and long-term depression. This mutant was backcrossed to 129S3/SvImJ and C57Bl/6J to obtain standardized genetic backgrounds. Spatial working memory, assessed in the eight-arm radial maze, was unchanged in rab3A null-mutants. Moreover, one-trial cued and contextual fear conditioning was normal. Long-term spatial memory was tested in the Morris water maze. Two different versions of this task were used, an 'easy' version and a 'difficult' one. On both versions, no differences in search time and quadrant preferences were observed. Thus, despite the elimination of mossy fiber long-term plasticity, these tests revealed no impairments in mnemonic capabilities. We conclude that spatial, contextual and working memory do not depend on mossy fiber plasticity" http://www.ncbi.nlm.nih.gov/pubmed/12527452 0 189 L. C. King and P. D. Werner 2011 "Attachment, social support, and responses following the death of a companion animal" Omega.(Westport.) 64 2 119-141 "This research tested hypotheses concerning attachment, social support, and grief responses to the loss of animal companionship. Participants whose companion cat or dog had recently died (N = 429) completed the Attachment Style Questionnaire, the Inventory of Complicated Grief, and the Multidimensional Health Profile-Psychosocial Functioning questionnaires. Both attachment anxiety and attachment avoidance were found to be positively associated with respondents' grief, depression, anxiety, and somatic symptoms. Social support was found to be negatively associated with these outcomes as well as with attachment anxiety and attachment avoidance. In multiple regression analyses, attachment anxiety incrementally predicted grief, anxiety and somatic symptoms, attachment avoidance incrementally predicted grief and depression, and social support incrementally predicted all outcomes. Interaction effects of attachment and social support in relation to outcomes were not found. The present study's implications and limitations are discussed, as are directions for future research" http://www.ncbi.nlm.nih.gov/pubmed/22375348 0 190 Z. Leish and B. A. Panaretto 1979 Effect of intravenously infused dexamethasone on collagen metabolism in skin of merino sheep Aust.J.Biol.Sci. 32 6 561-574 "The effects of an 8-day intravenous infusion of dexamethasone (7.6 mg kg-0.75 body weight) on collagen biosynthesis and wool growth in skin were examined in four Merino wethers. Plasma dexamethasone concentrations reached their peaks during the first 24 h infusion, which were followed by relatively stable levels (c. 1 X 10(-7) M) for the next 4--5 days. Minor increases in plasma dexamethasone levels were recorded during the final 2 days of treatment. Dexamethasone concentrations quickly fell below the level of detection once infusion ceased. Marked decreases in the wet weight, thickness and protein content of skin were observed at the end of infusion. DNA content was reduced to 42.4 +/- 4.9% s.e.m. during the first 2 days of treatment, but in the next 4 days of infusion gradually increased to 85.0 +/0 12.5% of controls. The level of collagen (expressed as hydroxyproline content of its acid hydrolysate) was elevated throughout the infusion and then gradually declined in 3 weeks to about 60% of controls. The biosynthesis of collagen measured by the rate of [14C]hydroxyproline formation and the activity of proline, 2-oxoglutarate dioxygenase (EC 1.14.11.2. formerly prolyl hydroxylase) was reduced during the first half of treatment to a greater extent than the rate of [14C]proline incorporation into proteins. Wool growth was reduced by 80.4 +/- 11.6% in the post-infusion period which allowed three sheep out of four to be defleeced. Inhibition of collagen biosynthesis in sheep skin was due initially to a decrease in the activity of proline, 2-oxoglutarate dioxygenase and later to the reduced rate of proline incorporation into proteins. It was also evident that changes in biosynthetic rate of collagen were not reflected in the total level of skin collagen. The extent of wool growth depression in individual animals paralleled the changes in DNA content and the extent of collagen biosynthesis inhibition" http://www.ncbi.nlm.nih.gov/pubmed/232981 0 191 "S. A. Baldwin, I. Fugaccia, D. R. Brown, L. V. Brown and S. W. Scheff" 1996 Blood-brain barrier breach following cortical contusion in the rat J.Neurosurg. 85 3 476-481 "Adult Fisher 344 rats were subjected to a unilateral impact to the dorsal cortex above the hippocampus at 3.5 m/second, resulting in a 2-mm cortical depression. This caused severe cortical damage and neuronal loss in hippocampus subfields CA1, CA3, and hilus. Breakdown of the blood-brain barrier (BBB) was assessed by injecting the protein horseradish peroxidase (HRP) 5 minutes prior to or at various times after injury (5 minutes, 1, 3, 6, and 12 hours, 1, 2, 5, and 10 days). Animals were killed 1 hour after HRP injection and brain sections were reacted with diaminobenzidine to visualize extravascular accumulation of the protein. Maximum staining occurred in animals injected with HRP 5 minutes prior to or 5 minutes after cortical contusion. Staining at these time points was observed in the ipsilateral cortex of the impact area and areas adjacent to it, as well as in the ipsilateral hippocampus. Some modest staining occurred in the dorsal contralateral cortex near the superior sagittal sinus. Cortical HRP staining gradually decreased at increasing time intervals postinjury. By 10 days, no HRP staining was observed in any area of the brain. In the ipsilateral hippocampus, HRP staining was absent by 3 hours postinjury and remained so at the 6- and 12-hour time points. Surprisingly, HRP staining was again observed in the ipsilateral hippocampus 1 and 2 days after cortical contusion, indicating a biphasic opening of the BBB following head trauma and a possible second wave of secondary brain damage days after the contusion injury. These data indicate that regions not initially destroyed by cortical impact, but evidencing BBB breach, may be accessible to neurotrophic factors administered intravenously both immediately and days after brain trauma" http://www.ncbi.nlm.nih.gov/pubmed/8751635 0 192 "T. R. Ivanov, Y. Feng, H. Wang, S. Regunathan, D. J. Reis, D. N. Chikkala, P. Gupta, J. C. Jones and J. E. Piletz" 1998 Imidazoline receptor proteins are regulated in platelet-precursor MEG-01 cells by agonists and antagonists J.Psychiatr.Res. 32 2 65-79 "The I1-imidazoline receptor is a novel brainstem modulator of sympathetic outflow that is elevated on platelets and in brains of depressed patients. A positive correlation has been reported (accompanying manuscript) between plasma norepinephrine (NE) concentrations and the densities (Bmax) of platelet I1 binding sites (I1 sites). I1-candidate proteins of 33 kDa and 85 kDa are now identified on Western blots probed with anti-imidazoline receptor antiserum (IRBP antiserum), that correlate with Bmax values for I1 sites. Furthermore, a human megakaryoblastoma cell line (MEG-01) has been used to study the regulation of these proteins on megakaryocytic cells, while bovine adrenal chromaffin cells provide a standard I1 cell type for comparison. Both the 33 kDa and 85 kDa IRBP-immunoreactive bands were enriched in plasma membrane fractions. IRBP antiserum did not cross-react with I2 imidazoline binding sites located on platelet mitochondrial membranes. The 85 kDa band was enhanced under conditions lacking fetal bovine serum (FBS) from the culture medium 6 h prior to harvesting. Conversely, 33 kDa protein was enhanced on MEG-01 cells grown in the presence of 10% FBS; suggesting that a precursor (85 kDa) and product (33 kDa) relationship might be induced by serum. The 85 kDa band was robustly up-regulated in response to imidazoline receptor-sensitive ligands; moxonidine, idazoxan and agmatine (10 microM each for 6 h). NE also up-regulated the 85 kDa IRBP-immunoreactive protein on MEG-01 membranes, but to a lesser extent. Idazoxan, an imidazoline alpha 2-antagonist, off-set its induction of 85 kDa protein by reducing the 33 kDa band. Yohimbine, a non-imidazoline alpha 2-antagonist, was ineffective alone, or in combination with moxonidine (up to 40 microM), but yohimbine blocked NE's induction of the 85 kDa band. Therefore, a rise in either plasma NE and/or endogenous I-site ligands (i.e. agmatine) could explain an elevation of imidazoline receptors observed in depression" http://www.ncbi.nlm.nih.gov/pubmed/9694002 0 193 "Y. Sadzuka, Y. Yamashita, S. Kishimoto, S. Fukushima, Y. Takeuchi and T. Sonobe" 2002 "[Glutamate transporter mediated increase of antitumor activity by theanine, an amino acid in green tea]" Yakugaku Zasshi 122 11 995-999 "We have confirmed that theanine, a major amino acid in green tea, enhances the antitumor activity of doxorubicin (DOX) without an increase in DOX-induced side effects. We believe that the action of theanine is due to decreases in glutamate uptake via inhibition of the glutamate transporter, intracellular glutathione (GSH) synthesis, GS-DOX conjugate level, and subsequent extracellular transport of GS-DOX by the MRP5/GS-X pump. To increase the clinical usefulness of theanine, we examined its effects on the antitumor activity of cisplatin and irinotecan (CPT-11), which a known to be transported by the efflux system related to MRP. Cisplatin decreased tumor volume in M5076 tumor-bearing mice. Furthermore, the combination of theanine with cisplatin increased the decrease in tumor volume as compared with the cisplatin-alone group. Tumor volume in the CPT-11-alone group did not show a decrease, but the combination of theanine with CPT-11 significantly reduced tumor volume. The concentration of cisplatin in the tumor was significantly increased by combination with theanine, and thus we assume that it correlated with the enhancement on the antitumor activity of theanine. On the other hand, changes in drug concentrations with theanine were not observed in normal tissues, but rather it is indicated that theanine tends to reduce their concentrations. Therefore theanine enhances the antitumor activity not only of DOX but also of cisplatin or CPT-11" http://www.ncbi.nlm.nih.gov/pubmed/12440157 0 194 "S. Tanaka, H. Toyoda, Y. Honda, Y. Seki, T. Sakurai, K. Honda and T. Kodama" 2015 Hypocretin/orexin prevents recovery from sickness Biomed.Rep. 3 5 648-650 "Sickness behavior is defined as states of lethargy, depression, anxiety, loss of appetite, hypersomnia, hyperalgesia, reduction of grooming and failure to concentrate that can be induced by inflammatory diseases, such as infections and cancer. Recent findings revealed that the lipopolysaccharide (LPS) injection causes lethargy as a consequence of the inhibition of hypocretin signaling. The hypocretin system maintains the vigilance state in various physiological processes. In order to investigate the sleep arousal system against sickness behavior, LPS-induced sickness behavior was examined in hypocretin-ataxin-3 transgenic mice, whose hypocretin neurons were postnatally ablated. Sleep-wake activity was determined following the administration of LPS at Zeitgeber time (ZT) 8.0 in ataxin-3 transgenic mice, and the age-, gender-matched wild-type littermates. LPS injection induced increases in non-rapid eye movement (REM) sleep in the matched wild-type littermates. In addition, a further increase in periods of sleep according to the loss of hypocretin neurons was identified in the ataxin-3 transgenic mice. A marked reduction of awakening during ZT12-ZT18 was observed as expected following LPS injection in the mouse lines. The increase in the period of non-REM sleep was not observed on the next day following LPS administration in either of the mouse lines. Complete recovery of physical activity was not observed in the matched wild-type littermates. Ataxin-3 transgenic mice recovered their physical activity to the same level as that on the first day before LPS administration. These results suggest the possibility that a faster recovery is the result of deeper resting according to the absence of hypocretin neurons, as ataxin-3 transgenic mice demonstrated more non-REM sleep" http://www.ncbi.nlm.nih.gov/pubmed/26405539 0 195 "K. N. Singh, M. Singh and V. Misra" 1977 Effect of angiotensin II on total plasma protein and albumin content in dogs Indian J.Physiol Pharmacol. 21 2 129-132 "Intravenous administration of angiotensin II caused a significant decrease in total plasma protein and albumin level in dogs. The central nervous system, the spleen and adrenal glands do not play any significant role in decreased plasma protein and albumin level. It is suggested that might be due to increased secretion of prostaglandin-like substances from the dog kidney causing increased permeability of vascularendothelium" http://www.ncbi.nlm.nih.gov/pubmed/885597 0 196 "D. Ding, W. Qi, D. Yu, H. Jiang, C. Han, M. J. Kim, K. Katsuno, Y. H. Hsieh, T. Miyakawa, R. Salvi, M. Tanokura and S. Someya" 2013 Addition of exogenous NAD+ prevents mefloquine-induced neuroaxonal and hair cell degeneration through reduction of caspase-3-mediated apoptosis in cochlear organotypic cultures PLoS.One. 8 11 e79817 "BACKGROUND: Mefloquine is widely used for the treatment of malaria. However, this drug is known to induce neurological side effects including depression, anxiety, balance disorder, and sensorineural hearing loss. Yet, there is currently no treatment for these side effects. PRINCIPAL FINDINGS: In this study, we show that the coenzyme NAD(+), known to play a critical role in maintaining the appropriate cellular redox environment, protects cochlear axons and sensory hair cells from mefloquine-induced degeneration in cultured rat cochleae. Mefloquine alone destroyed hair cells and nerve fiber axons in rat cochlear organotypics cultures in a dose-dependent manner, while treatment with NAD(+) protected axons and hair cells from mefloquine-induced degeneration. Furthermore, cochlear organs treated with mefloquine showed increased oxidative stress marker levels, including superoxide and protein carbonyl, and increased apoptosis marker levels, including TUNEL-positive nuclei and caspases-3. Treatment with NAD(+) reduced the levels of these oxidative stress and apoptosis markers. CONCLUSIONS/SIGNIFICANCE: Taken together, our findings suggest that that mefloquine disrupts the cellular redox environment and induces oxidative stress in cochlear hair cells and nerve fibers leading to caspases-3-mediated apoptosis of these structures. Exogenous NAD(+) suppresses mefloquine-induced oxidative stress and prevents the degeneration of cochlear axons and sensory hair cells caused by mefloquine treatment" http://www.ncbi.nlm.nih.gov/pubmed/24223197 0 197 "S. U.S., D. Bowers, W. K. Goodman, N. A. Shapira, K. D. Foote and M. S. Okun" 2006 Long-term habituation of the smile response with deep brain stimulation "Neurocase.12 (3) ()(pp 191-196), 2006.Date of Publication: June 2006." 3 191-196 "Human and animal research has shown that the ventral striatum, including the nucleus accumbens, may play a critical role in mediating positive emotions. Recently we described a subject with obsessive-compulsive disorder who intra-operatively exhibited the acute onset of an asymmetric smile and acute positive emotional change with contralateral deep brain stimulation (DBS) in either the right or left nucleus accumbens and anterior limb of the internal capsule region. The purpose of the present study was to examine the stability of the stimulation-induced smile(s) over a 12-month period. Custom computer software objectively quantified left and right facial movement during DBS. Although stimulation-induced smiles were elicited at one and two months post-surgery, they were no longer present from 3-12 months following chronic high frequency DBS. The smiles could not be elicited even with long washout periods. These findings imply potential long-term habituation and changes in the neural chemistry (possibly neuroplasticity) induced by chronic DBS. Copyright © Taylor & Francis Group, LLC" DO - http://dx.doi.org/10.1080/13554790600646995 0 198 "T. J. Kreeger, D. Bjornlie, D. Thompson, J. Clapp, C. Clark, C. Hansen, M. Huizenga and S. Lockwood" 2013 Immobilization of Wyoming bears using carfentanil and xylazine J.Wildl.Dis. 49 3 674-678 "Seven grizzly (Ursus arctos; four male, three female) and three black (Ursus americanus; two male, one female) bears caught in culvert traps or leg snares were immobilized in northwestern Wyoming with carfentanil and xylazine at doses, respectively, of 0.011 +/- 0.001 and 0.12 +/- 0.01 mg/kg for grizzly bears and 0.014 +/- 0.002 and 0.15 +/- 0.04 mg/kg for black bears. These drugs were antagonized with 1 mg/kg naltrexone and 2 mg/kg tolazoline. Induction and recovery times, respectively, were 4.3 +/- 0.5 and 7.1 +/- 0.8 min for grizzly bears and 5.2 +/- 0.4 and 9.1 +/- 2.2 min for black bears. Inductions were smooth and uneventful. Recoveries were characterized initially by increased respiration followed by raising of the head, which quickly led to a full recovery, with the bears recognizing and avoiding humans and moving away, maneuvering around obstacles. All bears experienced respiratory depression, which did not significantly improve with supplemental oxygen on the basis of pulse oximetry (P=0.56). Rectal temperatures were normothermic. Carfentanil-xylazine immobilization of bears provided significant advantages over other drug regimens, including small drug volumes, predictable inductions, quick and complete recoveries, and lower costs. On the basis of these data, both grizzly and black bears can be immobilized effectively with 0.01 mg/kg carfentanil and 0.1 mg/kg xylazine" http://www.ncbi.nlm.nih.gov/pubmed/23778620 0 199 "C. Caruso, A. Bellavia, E. Cillari, R. Ascoli and M. Pavone-Macaluso" 1977 Effects of high doses of peptichemio upon the humoral response to sheep erythrocytes and delayed hypersensitivity reactions to oxazolone in CBA mice Tumori 63 2 147-154 "A study has been carried out on the immunosuppressive activity of high doses of peptichemio (PTC) in CBA mice. Humoral response to sheep erythrocytes, delayed hypersensitivity to oxazolone, and cellular proliferation in lymph nodes and spleen of animals sensitized with oxazolone have been investigated. The results demonstrated that PTC had a definite immunosuppressive action, as shown by the inhibition of primary response to inoculation of sheep erythrocytes, by depression of delayed hypersensitivity to oxazolone, and by marked inhibition of 125IUdr incorporation in lymph nodes of sensitized animals. It is suggested that the inhibitory action is mediated by an effect on actively proliferating B or T lymphoid cells, although involvement of macrophages cannot be ruled out" http://www.ncbi.nlm.nih.gov/pubmed/898285 0 200 E. K. Asem and M. D. Conkright 1995 Role of progesterone in luteinizing hormone-induced fibronectin production and deposition by chicken granulosa cells in vitro Comp Biochem.Physiol C.Pharmacol.Toxicol.Endocrinol. 112 2 247-255 "The role of progesterone in luteinizing hormone- (LH) induced fibronectin production and deposition by chicken ovarian granulosa cells was examined in vitro. Granulosa cells isolated from pre-ovulatory follicles of the domestic hen ovary were incubated in serum-free Medium 199, and the total amount of fibronectin (deposited, secreted into the medium and associated with cells) produced was measured by ELISA. LH increased the amount of fibronectin deposited by granulosa cells. Similarly, it increased the quantity of fibronectin secreted into the medium or associated with cells. Cyanoketone (an inhibitor of progesterone synthesis) suppressed dose dependently basal and LH-induced fibronectin deposition. Cyanketone also attenuated the total amount of fibronectin produced by control or LH-stimulated granulosa cells. Exogenous progesterone reversed the inhibitory effects of cyanoketone on basal and LH-induced fibronectin production and deposition. The non-degradable synthetic progestin R5020 stimulated fibronectin production in a dose-dependent manner. R5020 also reversed the inhibitory effects of cyanoketone on LH-induced fibronectin production and deposition. The antiprogestin, ZK 98.299, inhibited basal and LH-stimulated fibronectin production. The data demonstrate that endogenous progesterone regulates fibronectin production and deposition perhaps in an intracrine/autocrine manner. They indicate that LH-stimulated fibronectin production and deposition by chicken granulosa cells is mediated (at least in part) by progesterone" http://www.ncbi.nlm.nih.gov/pubmed/8788593 0 201 "C. Marchesi, P. C. De, M. Tonna and P. Ossola" 2013 Is placebo useful in the treatment of major depression in clinical practice? "Neuropsychiatric Disease and Treatment.9 ()(pp 915-920), 2013.Date of Publication: 24 Jun 2013." 915-920 "Background: For many years, placebo has been defined by its inert content and use in clinical trials. In recent years, several studies have demonstrated its effect in the treatment of major depression. The aim of this paper is to present the conclusions of recent meta-analyses of the placebo effect in major depression, to explain the mechanism by which placebo exerts its effect, and to discuss whether placebo can be used in the treatment of patients with major depression in clinical practice. Recent meta-analyses have demonstrated that the placebo effect is estimated to account for 67% of the treatment effect in patients receiving antidepressants, and furthermore that placebo is as effective as antidepressants in patients with mild to moderate major depression (reporting a Hamilton Depression Rating Scale score lower than 25), whereas placebo is less effective than antidepressants in severely depressed patients. However, several limitations make the translation of these conclusions into clinical practice impracticable. Clinicians should learn from the ""placebo lesson"" to maximize the nonspecific effects of treatment when they prescribe an antidepressant, particularly in less severely depressed patients, who show a higher placebo response in randomized controlled trials. This strategy can increase the antidepressant effect and may reduce nonadherence with treatment. © 2013 Marchesi et al, publisher and licensee Dove Medical Press Ltd" DO - http://dx.doi.org/10.2147/NDT.S44519 0 202 "W. Ahmad, S. Ahad and D. Sturhan" 2013 "A new species of the rare nematode genus Margollus Pena-Santiago, Peralta & Siddiqi, 1993 (Nematoda: Tylencholaimoidea) from Turkey" Zootaxa. 3646 575-580 "Margollus turcicus sp. n., is described and illustrated from vineyard soil in Turkey. The new species is characterized by having a medium sized body (L=1.0-1.2 mm); cuticle with distinct striations; radial refractive elements abundant; lip region distinctly narrower than the adjoining body and slightly offset from the body contour by a depression; cephalic and labial papillae not discernible; strong labial and post-labial sclerotization present; amphids well developed with sclerotized walls; stylet 27-28.5 microm long, odontophore distinctly flanged, 0.3 times the odontostyle length; pharyngeal bulb offset by constriction, 33-37 microm long; mono-opisthodelphic female genital system with anterior branch 22-41 microm long; spicules 49 microm long; single weak ventromedian supplement and short hemispheroid tail in both sexes" http://www.ncbi.nlm.nih.gov/pubmed/26213781 0 203 "C. R. Steinhart, S. Permutt, G. H. Gurtner and R. J. Traystman" 1983 beta-Adrenergic activity and cardiovascular response to severe respiratory acidosis Am.J.Physiol 244 1 H46-H54 "The mechanism responsible for the depressive myocardial effects of severe respiratory acidosis is unclear; however, sympathetic stimulation and catecholamines are known to be involved. The influence of beta-adrenergic receptor activity on the myocardial response to severe respiratory acidosis was studied in 18 anesthetized, mechanically ventilated dogs. Arterial CO2 tension (PaCO2) was raised by increasing the inspired CO2 fraction in O2. In control animals, as PaCO2 increased, heart rate (HR) decreased (PaCO2 approximately 110 mmHg), then returned to control (PaCO2 approximately 220 mmHg), whereas arterial blood pressure (Pa) and cardiac output (Q) remained unchanged from prehypercapnia levels. At PaCO2 greater than 350 mmHg, Pa, HR, and Q decreased and left ventricular function (LVF) curves were depressed. Death occurred at a PaCO2 of 404 +/- 25 mmHg (pH 6.48 +/- 0.02). In a second group of animals, administration of isoproterenol during the increase in PaCO2 did not result in depression of myocardial function, and death did not occur even at a significantly higher PaCO2 (PaCO2 496 +/- 12 mmHg; pH 6.39 +/- 0.02) than in the control group. Administration of propranolol to a third group of animals as PaCO2 increased did not change Pa, HR, and Q; however, LVF curves indicated a more rapid and severe depression of myocardial performance than in control, and death occurred at a significantly lower PaCO2 (PaCO2 220 +/- 25 mmHg; pH 6.65 +/- 0.02). We conclude that beta-adrenergic receptor stimulation can prevent hypercapnic heart failure and that beta-adrenergic receptor activity is involved in the mechanism responsible for this failure" http://www.ncbi.nlm.nih.gov/pubmed/6295189 0 204 "D. A. Edwards, L. Zhang and B. E. Alger" 2008 Metaplastic control of the endocannabinoid system at inhibitory synapses in hippocampus Proc.Natl.Acad.Sci.U.S.A 105 23 8142-8147 "The modifiability of neuronal response plasticity is called ""metaplasticity."" In suppressing synaptic inhibition and facilitating induction of long-term excitatory synaptic plasticity, endocannabinoids (eCBs) act as agents of metaplasticity. We now report the discovery of a calcium-dependent mechanism that regulates eCB mobilization by metabotropic glutamate receptor (mGluR) activation. The switch-like mechanism primes cells to release eCBs and requires a transient rise in intracellular Ca2+ concentration ([Ca2+]i) but not concurrent activation of mGluRs. Conversely, short-term, [Ca2+]i-dependent eCB release can be persistently enhanced by mGluR activation. Hence, eCBs are also objects of metaplasticity, subject to higher levels of physiological control" http://www.ncbi.nlm.nih.gov/pubmed/18523004 0 205 "J. J. Doherty, S. Alagarsamy, K. J. Bough, P. J. Conn, R. Dingledine and D. D. Mott" 2004 Metabotropic glutamate receptors modulate feedback inhibition in a developmentally regulated manner in rat dentate gyrus J.Physiol 561 Pt 2 395-401 "We investigated group II metabotropic glutamate receptor (mGluR) modulation of glutamatergic input onto hilar-border interneurones and its regulation of feedback inhibition in the dentate gyrus. Selective activation of group II mGluRs with (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV) depressed mossy fibre (MF)-evoked excitatory drive to these interneurones with significantly greater depression in juvenile than adult rats. During 20 Hz MF stimulus trains, EPSCs became depressed. Depression during the early, but not later part of the train was significantly greater in juvenile than adult rats and was blocked by the mGluR antagonist (2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid (LY341495). In dentate granule cells from juvenile rats polysynaptic feedback IPSCs, but not monosynaptic IPSCs, were strongly suppressed by DCG-IV. DCG-IV also suppressed feedback inhibition of perforant path-evoked population spikes. In contrast, in adult animals DCG-IV did not significantly depress feedback inhibition. During 20 Hz stimulus trains in juvenile animals the summation of polysynaptic, but not monosynaptic IPSCs was suppressed by synaptically activated group II mGluRs. Blockade of these mGluRs with LY341495 significantly increased the area and duration of the summated IPSC, causing greater feedback inhibition of granule cell firing. In contrast, in adult animals LY341495 did not alter feedback inhibition following the stimulus train. These findings indicate that group II mGluRs modulate excitatory drive to interneurones in a developmentally regulated manner and thereby modulate feedback inhibition in the dentate gyrus" http://www.ncbi.nlm.nih.gov/pubmed/15513941 0 206 "R. N. Russell, W. J. McBride, L. Lumeng, T. K. Li and J. M. Murphy" 1996 Apomorphine and 7-OH DPAT reduce ethanol intake of P and HAD rats Alcohol 13 5 515-519 "Adult male rats of the alcohol-preferring (P) line (N = 10) and high alcohol drinking (HAD) line (N = 12) were used to study the effects of IP administration of 0.125-0.50 mg/kg 7-OH DPAT (a putative D agonist) and 0.25-1.0 mg/kg apomorphine (a dopamine agonist with 50-fold higher affinities for the D1 and D2 receptors than for the D3 receptor) on the concurrent intakes of 10% (v/v) ethanol and 0.0125% (g/v) saccharin during a daily 4-h scheduled access period. Control intakes by the P rats for the 4-h period were 17.9 +/- 0.5 and 7.2 +/- 0.4 ml for the ethanol and saccharin solutions, respectively. For the HAD line, ethanol consumption was 18.7 +/- 0.2 ml and saccharin intake was 8.7 +/- 1.6 ml for the 4-h period. In terms of grams ethanol/kg body wt, the 4-h intakes were 2.2 +/- 0.2 for the P line and 3.0 +/- 0.3 for the HAD rats. Both P and HAD rats consumed approximately 40% of their total ethanol intake in the first 15 min of access while consuming only about 15% of their total saccharin intake during this 15-min period. The putative D3 agonist 7-OH DPAT produced a decrease in ethanol intake in the first h to 45-55% of control levels for the P rat (p < 0.01) and to 25-70% of control values in the HAD line (p < 0.001). Apomorphine caused a dose-dependent decrease in ethanol intake in the first hour to 15-70% of control values in the P rat (p < 0.001) and to 25-60% of control levels in the HAD line (p < 0.001). Saccharin and 4-h food intakes for both lines were not altered by either 7-OH DPAT or apomorphine. Overall, these results suggest that D2 and D3 dopamine receptors may play a role in mediating alcohol drinking behavior of the selectively bred HAD and P lines of rats" http://www.ncbi.nlm.nih.gov/pubmed/8888949 0 207 "M. O. Fisher, R. G. Nager and P. Monaghan" 2006 Compensatory growth impairs adult cognitive performance PLoS.Biol. 4 8 e251 "Several studies have demonstrated that poor early nutrition, followed by growth compensation, can have negative consequences later in life. However, it remains unclear whether this is attributable to the nutritional deficit itself or a cost of compensatory growth. This distinction is important to our understanding both of the proximate and ultimate factors that shape growth trajectories and of how best to manage growth in our own and other species following low birth weight. We reared sibling pairs of zebra finches on different quality nutrition for the first 20 d of life only and examined their learning performance in adulthood. Final body size was not affected. However, the speed of learning a simple task in adulthood, which involved associating a screen colour with the presence of a food reward, was negatively related to the amount of growth compensation that had occurred. Learning speed was not related to the early diet itself or the amount of early growth depression. These results show that the level of compensatory growth that occurs following a period of poor nutrition is associated with long-term negative consequences for cognitive function and suggest that a growth-performance trade-off may determine optimal growth trajectories" http://www.ncbi.nlm.nih.gov/pubmed/16834460 0 208 "R. Duraisami, D. Srinivasan and S. Ramasamy" 2008 Antidepressant and anxiolytic activities of bio flavonoid-gossypin "Pharmacologyonline.2 ()(pp 683-693), 2008.Date of Publication: 2008." 683-693 "Gossypin is a bioflavonoid compound and is found in various herbs, especially in Malvaceae family. The pharmacological properties of Gossypin have been rarely reported with the exception of its antioxidant and anti-inflammatory activity. The purpose of this study was to characterize the putative anxiolytic-like properties and antidepressant activity using an elevated plus maze (EPM), Light -Dark test forced swim test, chronic mild stress (CMS) and sedative property by pentobarbitone induced sleeping time. Control mice were treated with an equal volume of vehicle (Saline 0.9% w/v), and positive control mice were treated with diazepam. (1 mg/kg). All the test drugs were administered orally. Gossypin (20mg/kg) significantly increase the time spent in open arms of EPM test (p< 0.01). In the light-dark test, Gossypin significantly increased the time spent in light space at 20mg/kg (p<0.01). The Antidepressant effect was supported by the forced swim test, Gossypin (20mg/kg) significantly shortened the immobility time and the effect was comparable to Imipramine (20mg/kg) (p<0.01). In the CMS test, mice were subjected to CMS exhibited as reduction in sucrose intake, the reversal of the intake has been shown by Gossypin (20mg/kg) in 21 days treatment, which was comparable to Amytriptaline (20mg/kg) (p<0.01). At higher doses, a sedative effect produced by acute administration of Gossypin (20mg/kg) was indicated by the potentiation of pentobarbital induced sleep. The present results shows the anxiolytic profile and antidepressant effect of Gossypin" 1 209 "S. Kurashige, Y. Akuzawa and F. Endo" 1999 "Effects of astragali radix extract on carcinogenesis, cytokine production, and cytotoxicity in mice treated with a carcinogen, N-butyl-N'-butanolnitrosoamine" Cancer Invest 17 1 30-35 "We studied the effects of astragali radix extract, a Chinese herb and one of eight components in Shikaron, on carcinogenesis, natural killer (NK) cell activity, and the cytokine production of lymphocytes in mice treated with a carcinogen, N-butyl-N'-butanolnitrosoamine (BBN). We found a significantly lower incidence of urinary bladder carcinoma in mice treated with BBN plus 10 mg/kg/day or more of Astragalus extract (7, 2, and 3 mice among 15 mice in 10, 20, and 40 mg/kg/day group, respectively, vs. 14 of 15 mice treated with BBN alone). Astragalus extract prevented the cytotoxic activity of lymphocytes against YAC-1 cells from the depression by BBN. It also protected the production of interleukin-2 and gamma-interferon of lymphocytes from the depression by BBN. These results, including our previous findings, suggest that the Astragalus extract exerts an anticarcinogenic effect in carcinogen-treated mice through activation of cytotoxic activity and the production of cytokines" http://www.ncbi.nlm.nih.gov/pubmed/10999046 0 210 "J.-J. Li, Y.-G. Yuan, G. Hou and X.-R. Zhang" 2011 Dose-related effects of venlafaxine on pCREB and brain-derived neurotrophic factor (BDNF) in the hippocampus of the rat by chronic unpredictable stress "Acta Neuropsychiatrica.23 (1) ()(pp 20-30), 2011.Date of Publication: February 2011." 1 20-30 "Background: The molecular pathogenesis of depression and psychopharmacology of antidepressants remain elusive. Recent hypotheses suggest that changes in neurogenesis and plasticity may underlie the aetiology of depression. The hippocampus is affected by depression and shows neuronal remodelling during adulthood. Objective: The present study on the adult rat hippocampus, was to evaluate the dose-related effects of chronic venlafaxine on the expression of brain-derived neurotrophic factor (BDNF) and phosphorylated cyclic-AMP response element binding protein (pCREB). Methods: Sprague-Dawley rats were exposed to a variety of chronic unpredictable stressors (CUSs) to establish a depression model. Rats were treated for either 14 or 28 days with venlafaxine (5 and 10 mg/kg, respectively). The hippocampal expression of pCREB and BDNF mRNA and protein was assessed by using immunohistochemistry, western blotting and reverse transcription polymerase chain reaction (RT-PCR). Results: Rats subjected to CUS procedure consumed less sucrose solution compared with non-stressed rats. The CUS influenced exploratory activity resulting in a reduction of the motility counts. Chronic low dose (5 mg/kg, 14 and 28 days), but not high dose (10 mg/kg, 14 and 28 days) of venlafaxine treatment increased the expression of pCREB and BDNF mRNA and protein in the CUS rat hippocampus. Conclusion: Neuronal plasticity-associated proteins such as pCREB and BDNF play an important role both in stress-related depression and in antidepressant effect. © 2011 John Wiley & Sons A/S" DO - http://dx.doi.org/10.1111/j.1601-5215.2010.00512.x 1 211 "K. I. Welsh, H. Burgos and J. R. Batchelor" 1977 The immune response to allogeneic rat platelets; Ag-B antigens in matrix form lacking Ia Eur.J.Immunol. 7 5 267-272 "Allogeneic rat platelets fail to induce either primary antibody or cell-mediated immune responses despite repeated injections. Platelets bear Ag-B epitopes which are capable of being recognized by antigen-reactive T and B cells since primed rats develop secondary responses after challenge with allogeneic platelets. The secondary responses induced decrease rather than increase on repeated injection of platelets. Repeated injection of allogeneic platelets into nonprimed rats leads to a state of specific, partial non-reactivity; recipients given such treatment show marked depression of cytotoxic antibody responses, but normal cellular immunity after challenge with viable lymphoid cells taken from the platelet-donor strain. Injection of normal rats with allogeneic platelets mixed with 3rd party, viable lymphoid cells, does not provoke an anti-platelet Ag-B antibody response" http://www.ncbi.nlm.nih.gov/pubmed/872867 0 212 "A. M. Walker, J. Fleming, J. Smolich, R. Stunden, R. Horne and J. Maloney" 1984 "Fetal oxygen consumption, umbilical circulation and electrocortical activity transitions in fetal lambs" J.Dev.Physiol 6 3 267-274 "Chronically instrumented fetal lambs were employed to test the hypothesis that the high voltage electrocortical activity phase is a state of low fetal oxygen consumption compared with the low voltage electrocortical activity phase. Measurements of umbilical flow (electromagnetic flowmeter) together with oxygen saturations and haemoglobin concentration of umbilical venous and arterial blood were used to calculate oxygen consumption. Significant depression of umbilical flow occurred at the transition from low voltage electrocortical activity to high voltage electrocortical activity; the maximum change averaged 14% 2 min after the onset of the high voltage phase. Significant depressions of oxygen saturation in umbilical venous and arterial blood were found within 5 min of the onset of high voltage electrocortical activity, averaging 2.2% and 5.2% respectively. No depression of oxygen consumption was found during these transient changes in early high voltage electrocortical activity, as the venous-arterial oxygen content difference widened significantly as a consequence of a greater fall in umbilical arterial oxygen content (0.7 ml/dl) than in umbilical venous oxygen content (0.3 ml/dl). Overall, we detected no significant depression of oxygen consumption in high voltage electrocortical activity. However a small but significant depression of oxygen consumption (6%) was found late in the high voltage electrocortical activity phase when the level of oxygen consumption in low voltage electrocortical activity was greater than 7 ml/min per kg. We conclude that the high voltage electrocortical activity in fetal lambs is not associated with a marked depression of oxygen consumption, despite significant transient depressions of umbilical flow and oxygen levels in umbilical venous and arterial blood.(ABSTRACT TRUNCATED AT 250 WORDS)" http://www.ncbi.nlm.nih.gov/pubmed/6747228 0 213 "S. C. Bhatia, S. Bhatia and S. Rous" 1975 Gluconeogenesis from L-serine in rat liver Life Sci. 17 2 267-273 http://www.ncbi.nlm.nih.gov/pubmed/1160499 0 214 "W. R. Marrs, J. L. Blankman, E. A. Horne, A. Thomazeau, Y. H. Lin, J. Coy, A. L. Bodor, G. G. Muccioli, S. S. Hu, G. Woodruff, S. Fung, M. Lafourcade, J. P. Alexander, J. Z. Long, W. Li, C. Xu, T. Moller, K. Mackie, O. J. Manzoni, B. F. Cravatt and N. Stella" 2010 The serine hydrolase ABHD6 controls the accumulation and efficacy of 2-AG at cannabinoid receptors Nat.Neurosci. 13 8 951-957 "The endocannabinoid 2-arachidonoylglycerol (2-AG) regulates neurotransmission and neuroinflammation by activating CB1 cannabinoid receptors on neurons and CB2 cannabinoid receptors on microglia. Enzymes that hydrolyze 2-AG, such as monoacylglycerol lipase, regulate the accumulation and efficacy of 2-AG at cannabinoid receptors. We found that the recently described serine hydrolase alpha-beta-hydrolase domain 6 (ABHD6) also controls the accumulation and efficacy of 2-AG at cannabinoid receptors. In cells from the BV-2 microglia cell line, ABHD6 knockdown reduced hydrolysis of 2-AG and increased the efficacy with which 2-AG can stimulate CB2-mediated cell migration. ABHD6 was expressed by neurons in primary culture and its inhibition led to activity-dependent accumulation of 2-AG. In adult mouse cortex, ABHD6 was located postsynaptically and its selective inhibition allowed the induction of CB1-dependent long-term depression by otherwise subthreshold stimulation. Our results indicate that ABHD6 is a rate-limiting step of 2-AG signaling and is therefore a bona fide member of the endocannabinoid signaling system" http://www.ncbi.nlm.nih.gov/pubmed/20657592 0 215 "B. Alessandri, J. S. Tretzel, A. Heimann and O. Kempski" 2012 Spontaneous cortical spreading depression and intracranial pressure following acute subdural hematoma in a rat Acta Neurochir.Suppl 114 373-376 "Acute subdural hemorrhage (ASDH) is a frequent and devastating consequence of traumatic brain injury. Tissue damage develops rapidly and makes treatment even more difficult. Management of increased intracranial pressure (ICP) due to extravasated blood volume and brain swelling is often insufficient to control all adverse effects of ASDH. In addition to sheer volume, spontaneously triggered cortical spreading depression (CSD) that leads to cell death following ischemia or trauma may contribute to injury development after ASDH. Therefore, we explored the occurrence of CSD by tissue impedance (IMP) measurement in a rat model subjected to ASDH. IMP and intraventricular and mean arterial pressure were monitored before (baseline), during (blood infusion), and after ASDH for 3 h.Tissue impedance increased by around 203% of baseline during subdural infusion of 300 mul of autologous, venous blood and dropped back to baseline within 22 min. Fifty-six minutes after the start of ASDH a cluster of four short-lasting (3-3.5 min; 140-160% of baseline) IMP increases started that reflected spontaneous CSDs. This pattern presumes that CSD occurs early after ASDH and therefore may contribute to the rapid lesion development in this disease" http://www.ncbi.nlm.nih.gov/pubmed/22327726 0 216 "R. K. Jaiswal, K. P. Gupta and A. Kumar" 1979 Monoamine oxidase inhibition by substituted benzylideneamino guanidines and their CNS activities "Pharmacology.19 (3) ()(pp 132-137), 1979.Date of Publication: 1979." 3 132-137 "The present study reports the synthesis and characterization of 8 new substituted benzylideneamino guanidines. All compounds inhibited the monoamine oxidase (MAO) activity of rat brain mitochondria in vitro. The I50 values were determined and were found to be in the range of 10-4 to 10-5 mol/l. Preincubation, dialysis and kinetic studies carried out with isolated brain mitochondria by conventional Dixon plot revealed reversible and noncompetitive type of MAO inhibition. These compounds were also screened for anticonvulsant and antidepressant activities. In the present series of compounds only 1 compound - 1-amino-3-(4-chloromethylbenzylidene-amino)guanidine hydroiodide - was found to afford 20% protection against pentetrazol-induced seizures in mice. 1-Amino-3-(3,4-dichlorobenzylideneamino)guanidine hydroiodide which produced maximum inhibition of MAO activity, also produced reversal of reserpine-induced sedation and miosis into excitation and mydriasis in mice" 0 217 "C. E. Schiller, M. W. O'Hara, D. R. Rubinow and A. K. Johnson" 2013 Estradiol modulates anhedonia and behavioral despair in rats and negative affect in a subgroup of women at high risk for postpartum depression Physiol Behav. 119 137-144 "In an effort to address inconsistencies in the literature, we tested a cross-species estrogen withdrawal model of postpartum depression (PPD) with a series of rodent experiments and a prospective, naturalistic human study. All rats were ovariectomized prior to experimentation. The first rat experiment examined the effects of low- and high-dose estradiol administration and withdrawal on lateral-hypothalamic self-stimulation, a behavioral index of anhedonia, in experimental (n=7) and vehicle-only control animals (n=7). The second rat experiment examined the effects of high-dose estradiol withdrawal on activity and immobility during the forced swim test, an index of behavioral despair, in a separate group of experimental (n=8) and vehicle-only control animals (n=8). In the human study, women with (n=8) and without (n=12) a history of PPD completed mood ratings and collected saliva samples (to assess estradiol levels) daily during the third trimester of pregnancy through 10 days postpartum. The presence of PPD was assessed at one month postpartum. In the animal studies, rats in the estradiol withdrawal group demonstrated significantly greater immobility and less swimming than controls. Estradiol withdrawal resulted in reduced responding for electrical stimulation (multiple intensities) relative to estradiol administration. In the human study, there was no significant association between estradiol and negative affect among women with or without a history of PPD. However, there was a correlation between daily estradiol levels and negative affect in the women with incident PPD at one month postpartum. Despite important cross-species differences, both the rat and human studies provided evidence of the effects of estradiol on perinatal depressive symptoms" http://www.ncbi.nlm.nih.gov/pubmed/23770328 1 218 "J. J. de, P. R. Schoofs, A. M. Snabilie, A. Bast and W. J. van der Vijgh" 1993 The role of biotransformation in anthracycline-induced cardiotoxicity in mice J.Pharmacol.Exp.Ther. 266 3 1312-1320 "Anthracyclines are highly efficacious antineoplastic agents but they become cardiotoxic after repeated dosing. For the major anthracycline, doxorubicin (Dox), this toxicity is thought to be associated with the formation of the 13-dihydro metabolite. Paced mouse left atria were used to assess the cardiotoxicity of Dox, 4'-epidoxorubicin (Epi), daunorubicin (Dauno) and their major metabolites. Apart from the aglycons, all compounds (1-500 microM) reduced the contractile force. To correct for differences in cellular uptake, anthracycline concentrations were determined in the atria after 1 h of incubation. IC50 values ranged from 0.33 mumol/g for 13-dihydro-Dox to 3.5 mumol/g for Dauno. The toxicities relative to Dox, i.e., the ratio of IC50,Dox/IC50,anthracycline, ranged from 0.19 for Dauno to 2.1 for 13-dihydro-Dox (the most toxic). For Dox, Epi and Dauno, the 13-dihydro metabolite had greater toxicity than the corresponding parent compound. The pharmacokinetics of Dox and Epi in the murine heart are comparable and, thus, cannot explain the reduced cardiotoxicity of Epi. However, when pharmacokinetic data of Dox and Epi in murine heart tissue were interpreted using the relative toxicity factors, Epi would be expected to be threefold less cardiotoxic than Dox, thus providing a better correlation with in vivo data. This simple pharmacological model in combination with preclinical pharmacokinetics may contribute to the prediction of the cardiotoxic potency of new anthracyclines relative to Dox" http://www.ncbi.nlm.nih.gov/pubmed/8371139 0 219 "M. L. Hess, S. Krause and H. A. Kontos" 1983 Mediation of sarcoplasmic reticulum disruption in the ischemic myocardium: proposed mechanism by the interaction of hydrogen ions and oxygen free radicals Adv.Exp.Med.Biol. 161 377-389 "Acute myocardial ischemia results in a decrease in developed tension and an increase in resting tension. A breakdown of the excitation-contraction coupling system can explain the behavior of the ischemic muscle at a subcellular level. We have identified a specific defect in the sarcoplasmic reticulum (SR) from the ischemic myocardium; i.e., the uncoupling of calcium transport from ATP hydrolysis. The mediators of this excitation-contraction uncoupling process have not been identified. It is now established that the intracellular pH of the ischemic myocardium is in the range of 6.4 but the role of protons and potential role of free radicals have not been identified. We have hypothesized that protons and free radicals may interact to produce the excitation-contraction uncoupling of the ischemic myocardium. Cardiac SR was isolated from the wall of canine left ventricle and calcium uptake velocity and Ca2+ stimulated-Mg2+ dependent ATPase activity determined. Increasing proton concentration between pH 7.0 and 6.4 significantly reduced calcium uptake rates (pH 7.0 = 0.95 +/- 0.02; 6.4 = 0.50 +/- 0.02 mumoles Ca2+/mg-min; p less than 0.01) with no effect on ATPase activity. Calculated coupling ratios (mumoles Ca2+/mumoles Pi) decreased from 0.87 +/- 0.06 at pH 7.0 to 0.51 +/- 0.05 at pH 6.4. At pH 7.0, the generation of exogenous free radicals from the xanthine-xanthine oxidase system significantly depressed both calcium uptake rates (Control = 0.95 +/- 0.02; X+XO = 0.15 +/- 0.02) and ATPase activity (Control = 1.05 +/- 0.02; X+XO + 0.30 +/- 0.01 mumoles Pi/mg-min; p less than 0.01). The decreases in calcium uptake and in ATPase activity were completely reversible with superoxide dismutase (SOD). At pH 6.4 in the presence of xanthine and xanthine oxidase, there is a further depression of calcium uptake rates (Control = 0.50 +/- 0.02; X+XO = 0.11 +/- 0.01; p less than 0.05) but there is no SOD reversible component. The addition of SOD + 20mM mannitol normalized calcium transport at pH 6.4. The calculated coupling ratio at pH 6.4 in the presence of free radicals was 0.13. In contrast sarcoplasmic reticulum isolated from ischemic myocardium demonstrated a significant depression of calcium uptake rates at pH 7.1 which was further accentuated at pH 6.4. Ca2+-ATPase was significantly depressed at pH 7.1 but there was no accentuation at pH 6.4. It is concluded that no single species of free radical can explain the intracellular excitation-contraction uncoupling of the ischemic myocardium. The system can be explained by the interaction of hydrogen ions and superoxide anions producing both injury to the sarcoplasmic reticulum and the formation of lipid free radicals with hydroxyl-like activity" http://www.ncbi.nlm.nih.gov/pubmed/6307008 0 220 "C. W. Purdy, D. C. Straus, C. W. Livingston, Jr. and G. S. Foster" 1990 Immune response to pulmonary injection of Pasteurella haemolytica-impregnated agar beads followed by transthoracic challenge exposure in goats Am.J.Vet.Res. 51 10 1629-1634 "A method of inducing Pasteurella haemolytica serotype 1 (Ph1) lung infection in goats, using low numbers of bacteria and without impairing host immunity, was developed. Two trials were conducted. Results of trial 1, using 10 principals (Ph1 agar beads) and 6 controls (agar beads alone), indicated that Ph1 organisms imbedded in agar beads could survive host lung defenses for 32 days. Results of trial 2 indicated that lung immunity in the inoculated goats (principals) was high and they were more protected than controls against a transthoracic challenge of Ph1 (1.18 x 10(7) colony-forming units) injected into a lung of each goat on posttreatment day 35. When comparing challenge-exposed principals with controls, the controls developed rectal temperatures above normal for a longer time, duration of anorexia was longer, and signs of depression were seen. The controls developed large areas of consolidated lung tissue, more Ph1 isolates were recovered from nasal turbinates and lung tissue, and higher Ph1 concentrations were found in the lungs. The serum Ph1 indirect hemagglutination antibody titers in the principals of both trials increased, compared with titers in controls. Principal goats in trial 2 had higher Ph1 indirect hemagglutination antibody titers after injection of Ph1-impregnated agar beads and less severe lung lesions after challenge exposure than did controls. The small pneumonic consolidated lesions in the principals, compared with extensive lesions in controls after Ph1 challenge exposure, indicated a high degree of immunity after exposure to Ph1 organisms imbedded in agar beads" http://www.ncbi.nlm.nih.gov/pubmed/2240785 0 221 "A. K. Nag, K. Saha, A. N. Mehrotra and D. Ray" 1976 Succinic dehydrogenase and glucose-6-phosphate dehydrogenase activities in brain of mice after administration of Salmonella typhi endotoxin Indian J.Med.Res. 64 1 Sep-16 http://www.ncbi.nlm.nih.gov/pubmed/1270104 0 222 "S. L. Rodis, P. H. D'Amato, E. Koch and G. V. Vahouny" 1970 "Effect of carnitine on uptake, oxidation and esterification of palmitate by the perfused rat heart" Proc.Soc.Exp.Biol.Med. 133 3 973-977 http://www.ncbi.nlm.nih.gov/pubmed/5435592 0 223 "S. S. Saravi, S. E. Mousavi, S. S. Saravi and A. R. Dehpour" 2016 Minocycline Attenuates Depressive-Like Behaviour Induced by Rat Model of Testicular Torsion: Involvement of Nitric Oxide Pathway Basic Clin.Pharmacol.Toxicol. 118 4 249-258 "Testicular torsion/detorsion (T/D) can induce depression in pre- and post-pubertal patients. This study was conducted to investigate the psychological impact of testicular torsion and mechanism underlying its depressive-like behaviour, as well as antidepressant-like activity of minocycline and possible involvement of nitric oxide (NO)/cyclic GMP pathway in this paradigm in male rats undergoing testicular T/D. Unilateral T/D was performed in 36 male adult Wistar rats, and different doses of minocycline were injected alone or combined with N(omega) -nitro-l-arginine methyl ester (l-NAME), non-specific NO synthase (NOS) inhibitor; aminoguanidine (AG), specific inducible NOS inhibitor; l-arginine, an NO precursor; and selective PDE5I, sildenafil. After assessment of locomotor activity in open-field test, immobility times were recorded in the forced swimming test (FST). Moreover, 30 days after testicular T/D, testicular venous testosterone and serum nitrite concentrations were measured. A correlation was observed between either a decrease in plasma testosterone or an increase in serum nitrite concentrations with prolongation in immobility time in the testicular T/D-operated rats FST. Minocycline (160 mg/kg) exerted the highest significant antidepressant-like effect in the operated rats in the FST (p < 0.001). Furthermore, combination of subeffective doses of minocycline (80 mg/kg) and either l-NAME (10 mg/kg) or AG (50 mg/kg) demonstrated a significant robust antidepressant-like activity in T/D group (p < 0.01). Consequently, NO/cGMP pathway was involved in testicular T/D-induced depressive-like behaviour and antidepressant-like activity of minocycline in the animal model. Moreover, a contribution was observed between either decreased testosterone or elevated serum nitrite levels and depressive-like behaviour following testicular T/D" http://www.ncbi.nlm.nih.gov/pubmed/26381433 1 224 J. H. Coats and J. Roeser 1977 In vivo inhibition of R-factor transfer by clindamycin and its analogues J.Antimicrob.Chemother. 3 Suppl C 53-58 http://www.ncbi.nlm.nih.gov/pubmed/340446 0 225 "D. BARGETON, C. KRUMM-HELLER and M. EON" 1955 [Comparative activity of different analeptics against morphine-induced respiratory depression in rabbits] Arch.Int.Pharmacodyn.Ther. 103 02-Mar 146-159 http://www.ncbi.nlm.nih.gov/pubmed/13259727 0 226 E. A. Gubarev and T. A. Buttseva 1970 [Analysis of bathmotropic effect of diprazin and dimedrol] Farmakol.Toksikol. 33 1 35-37 http://www.ncbi.nlm.nih.gov/pubmed/5425612 0 227 "L. L. Liao, S. M. Kupchan and S. B. Horwitz" 1976 "Mode of action of the antitumor compound bruceantin, an inhibitor of protein synthesis" Mol.Pharmacol. 12 1 167-176 http://www.ncbi.nlm.nih.gov/pubmed/1256442 0 228 V. J. Galani and B. G. Patel 2010 "Effect of hydroalcoholic extract of Sphaeranthus indicus against experimentally induced anxiety, depression and convulsions in rodents" Int.J.Ayurveda.Res. 1 2 87-92 "To investigate the effects of a hydroalcoholic extract of the Sphaeranthus indicus (SIE) against experimentally induced anxiety, depression and convulsions in rodents. The SIE (100, 200, 500 mg/kg, p.o.) was used in elevated plus maze, open field, forced swimming, and tail suspension tests in mice. The same doses were also used to evaluate its anticonvulsant effect on pentylenetetrazole (PTZ)-induced convulsions in mice and maximal electroshock (MES)-induced convulsions in rats. SIE was found to increase the number of entries and the time spent in the open arms of the maze at a dose of 100 mg/kg, p.o., indicating its anxiolytic activity. On the other hand, higher doses of SIE (200 and 500 mg/kg, p.o.) decreased open arm entries and time spent in the open arms of the maze in the elevated plus maze test indicating an absence of anxiolytic activity. However, this effect could have been related to a decrease in the locomotor activity of the mice and not to an anxiogenic effect, as indicated by the reduction in the total number of entries in the elevated plus maze. SIE also (at doses of 200 and 500 mg/kg, p.o.) decreased locomotor activity but did not affect emotional activity parameters in the open field test, suggesting a possible central nervous depressant activity. SIE also increased the immobility time in the forced swimming test at an oral dose of 500 mg/kg but did not significantly modify the activity in the tail suspension test. SIE protected rats against MES-induced convulsions and mice against PTZ-induced convulsions. Sphaeranthus indicus demonstrated anxiolytic, central nervous depressant, and anticonvulsant activities in rodents, thus supporting the folk medicinal use of this plant in nervous disorders" http://www.ncbi.nlm.nih.gov/pubmed/20814521 1 229 "T. Suzuki, H. Uchiyama, Y. Koike, M. Ono, K. Shirakawa, M. Nagata and R. Konishi" 1996 [Reproductive and developmental toxicity studies of calcipotriol (MC903): (1)--A fertility study in rats by subcutaneous administration] J.Toxicol.Sci. 21 Suppl 2 389-401 "Calcipotriol (MC903), an anti-psoriasic agent, was given subcutaneously at dose levels of 1, 5 and 25 micrograms/kg/day during the pre-pairing period (9 weeks prior to pairing in males and 2 weeks prior to pairing in females) and the pairing period to male and female rats and in the early stage of pregnancy (day 0 through 7 of gestation) to female rats, and the effects of the test compound on male and female reproductive performance and fetal development were evaluated. 1. In the male 25 micrograms/kg group, opacity of the eyeball surface was observed, and depression of body weight gain, and decreases of body weight and food consumption, and increases in the weight of the kidney were statistically significant in comparison with vehicle controls. 2. In the female 25 micrograms/kg group, depression of body weight gain and food consumption were statistically significant in comparison with vehicle controls. 3. No changes in parameters of reproductive performance were seen in any dosed groups. 4. No changes in parameters of implantation performance were seen. There were no treated-related abnormalities in fetal mortality, weights of fetuses, and external, visceral and skeletal examinations. Based on there results, it is considered that in the present study the no-toxic dose levels of MC903 were 5 micrograms/kg/day for parents, 25 micrograms/kg/day for reproductive performance and fetal development" http://www.ncbi.nlm.nih.gov/pubmed/8741421 0 230 M. Burrows 2014 "Jumping mechanisms in dictyopharid planthoppers (Hemiptera, Dicytyopharidae)" J.Exp.Biol. 217 Pt 3 402-413 "The jumping performance of four species of hemipterans belonging to the family Dictyopharidae, from Europe, South Africa and Australia, were analysed from high-speed images. The body shape in all was characterised by an elongated and tapering head that gave a streamlined appearance. The body size ranged from 6 to 9 mm in length and from 6 to 23 mg in mass. The hind legs were 80-90% of body length and 30-50% longer than the front legs, except in one species in which the front legs were particularly large so that all legs were of similar length. Jumping was propelled by rapid and simultaneous depression of the trochantera of both hind legs, powered by large muscles in the thorax, and was accompanied by extension of the tibiae. In the best jumps, defined as those with the fastest take-off velocity, Engela minuta accelerated in 1.2 ms to a take-off velocity of 5.8 m s(-1), which is the fastest achieved by any insect described to date. During such a jump, E. minuta experienced an acceleration of 4830 m s(-2) or 490 g, while other species in the same family experienced 225-375 g. The best jumps in all species required an energy expenditure of 76-225 muJ, a power output of 12-80 mW and exerted a force of 12-29 mN. The required power output per mass of jumping muscle ranged from 28,000 to 140,200 W kg(-1) muscle and thus greatly exceeded the maximum active contractile limit of normal muscle. To achieve such a jumping performance, these insects must be using a power amplification mechanism in a catapult-like action. It is suggested that their streamlined body shape improves jumping performance by reducing drag, which, for a small insect, can substantially affect forward momentum" http://www.ncbi.nlm.nih.gov/pubmed/24198256 0 231 R. Khanam and K. K. Pillai 2007 Effect of chronic chromium picolinate in animal models of anxiety and memory Fundam.Clin.Pharmacol. 21 5 531-534 "Diabetes mellitus is associated with certain neurological problems such as depression, anxiety, memory impairment, etc. As chromium picolinate (CrP), a widely used trace element is shown to have beneficial effects in diabetes and depression, we investigated its effects on elevated plus maze and spontaneous alternation behavior paradigm as a measure of anxiety and memory, respectively. CrP (8 microg/mL in drinking water) significantly increased percentage preference to open arm in elevated plus maze in diabetic and normal rats. However, no significant changes were observed in percentage alternation after CrP chronic treatment. The possible anxiolytic effect of CrP might be related to its effect on serotonergic transmission" http://www.ncbi.nlm.nih.gov/pubmed/17868206 0 232 "M. R. Malinow, J. O. Gardner, J. T. Nelson, P. McLaughlin, B. Upson and R. Aigner-Held" 1986 Effects of alpha- and beta-tigogenin cellobiosides on cholesterol absorption Steroids 48 03-Apr 197-211 "We have synthesized alpha- and beta-anomers of tigogenin cellobioside and have determined their effects on intestinal absorption of [1,2-3H]cholesterol in rats. We demonstrated that the loss of tritium label likely to occur in the conversion of cholesterol to coprostanone was minimal. Dose response studies showed that both anomers depressed intestinal absorption of cholesterol but the depression was greater with the beta-anomer" http://www.ncbi.nlm.nih.gov/pubmed/3445279 0 233 "M. Enriquez-Denton, E. Manjarrez and P. Rudomin" 2004 Persistence of PAD and presynaptic inhibition of muscle spindle afferents after peripheral nerve crush Brain Res. 1027 01-Feb 179-187 "Two to twelve weeks after crushing a muscle nerve, still before the damaged afferents reinnervate the muscle receptors, conditioning stimulation of group I fibers from flexor muscles depolarizes the damaged afferents [M. Enriquez, I. Jimenez, P. Rudomin, Changes in PAD patterns of group I muscle afferents after a peripheral nerve crush. Exp. Brain Res., 107 (1996), 405-420]. It is not known, however, if this primary afferent depolarization (PAD) is indeed related to presynaptic inhibition. We now show in the cat that 2-12 weeks after crushing the medial gastrocnemius nerve (MG), conditioning stimulation of group I fibers from flexors increases the excitability of the intraspinal terminals of both the intact lateral gastrocnemius plus soleus (LGS) and of the previously damaged MG fibers ending in the motor pool, because of PAD. The PAD is associated with the depression of the pre- and postsynaptic components of the extracellular field potentials (EFPs) evoked in the motor pool by stimulation of either the intact LGS or of the previously damaged MG nerves. These observations indicate, in contrast to what has been reported for crushed cutaneous afferents [K.W. Horch, J.W. Lisney, Changes in primary afferent depolarization of sensory neurones during peripheral nerve regeneration in the cat, J. Physiol., 313 (1981), 287-299], that shortly after damaging their peripheral axons, the synaptic efficacy of group I spindle afferents remains under central control. Presynaptic inhibitory mechanisms could be utilized to adjust the central actions of muscle afferents not fully recovered from peripheral lesions" http://www.ncbi.nlm.nih.gov/pubmed/15494169 0 234 S. L. Asa 2010 Ikaros: A mediator of neural-endocrine-immune interactions "Endocrine Pathology.Conference: 11th Meeting of the International Pituitary Pathology Society Awaji Island Japan.Conference Start: 20091016 Conference End: 20091020.Conference Publication: (var.pagings).21 (1) ()(pp 49-50), 2010.Date of Publication:" var.pagings 49-50 "Ikaros was originally identified as a transcription factor that binds regulatory sequences of genes expressed in lymphoid cells (1). The single copy gene contains seven exons that can, by alternative splicing, give rise to eight isoforms. The Nterminal region includes a zinc finger domain critical for DNA-binding. Dominant-negative (dn) forms of Ikaros lack the DNA-binding domain. The various isoforms can act either as transcriptional activators or repressors as part of an integral component of a functionally diverse chromatin remodeling network. Recent evidence implicates Ikaros as a key factor whose transcriptional actions and chromatin remodeling properties determine the fate of hypothalamic neuroendocrine and pituitary cell populations during development. Ikaros regulates expansion of corticomelanotrophs and is implicated in binding and activation of the POMC promoter (2). Ikaros also plays a key role in the development of hypothalamic GHRH neurons and thereby indirectly in pituitary somatotroph population expansion (3). Interestingly, this same factor is expressed in pituitary cells of the Pit-1 lineage where it mediates histone acetylation and chromatin remodeling in the selective regulation of pituitary GH and PRL hormone gene expression (4). Ikaros is expressed in pituitary tumors, with the dn-Ik6 identified in nearly 50% of human pituitary adenomas (5). Forced expression of this dn form of Ikaros results in histone 3 acetylation with activation of the Bcl-XL promoter (6). Parallel induction of the endogenous gene results in enhanced pituitary cell survival and evasion from apoptotic signals. Ikaros has also provided a novel link between metabolism and cancer: cDNA microarray analysis uncovered mediators of cholesterol uptake including the lowdensity lipoprotein receptor (LDL-R) and sterol-regulatory element binding protein 2 (SREBP2) as targets of Ik action (7). Ikaros regulates the low-density lipoprotein receptor (LDL-R) to alter lipid metabolism in pituitary corticotroph cells, expanding the repertoire of Ikaros actions to include regulation of the cholesterol uptake metabolic pathway (7). Transient spatio-temporal expression of Ikaros was also identified in striatal medium spiny neurons of the developing murine CNS. Ikaros deficient mice exhibit significant differences in several behavioral tests (8). Pinch-induced catalepsy was markedly extended. In the Porsolt forced swim test, Iknull mice showed reduced immobility, consistent with an anti-depressive effect. The acoustic startle response of Ik-null mice was also markedly diminished. These findings extend the role of Ikaros to the maturation and differentiation of striatal medium spiny neurons and indicate important actions for Ik in the development of neurocognitive functions and affecting depressive behaviors" DO - http://dx.doi.org/10.1007/s12022-010-9109-8 0 235 "C. Babiuk, F. Marceau, S. St-Pierre and D. Regoli" 1982 Kininases and vascular responses to kinins Eur.J.Pharmacol. 78 2 167-174 "We have utilized several inhibitors to assess the effects of kininases on the contractile activity of bradykinin (BK), kallidin (KD), des-Arg9-BK and des-Arg10-KD on two isolated blood vessels, the rabbit aorta and mesenteric vein. The response of the two vessels to kinins are mediated by B1-receptors, implying that fragments of kinins without the C-terminal arginine are much more active on these tissues than the whole kinin sequences. Blockers of carboxypeptidase B-like enzymes, such as SQ24798 and pivalyl-L-arginine decrease the apparent affinity of BK and KD on the two vessels, while not changing those of des-Arg9-BK and des-Arg10-KD; this suggests that a major part of the contractile activities of BK and KD are mediated by des-Arg metabolites formed in situ at the tissue level by a kininase I. The block of kininase II by captopril or desacetylated MK-421 bring about a complex pattern of activity changes that include the potentiation of BK and KD and the depression of des-Arg10-KD. These results, in conjunction with those obtained with the non-specific inhibitors of metallopeptidases, thioglycolic acid and EDTA, suggest that the relative contribution of kininase I and kininase II to the degradation of kinins in arterial and venous vessels may be different. The implications of these findings on the pharmacology of B1-receptors are discussed" http://www.ncbi.nlm.nih.gov/pubmed/6122586 0 236 "L. Lambas-Senas, O. Mnie-Filali, V. Certin, C. Faure, L. Lemoine, L. Zimmer and N. Haddjeri" 2009 Functional correlates for 5-HT(1A) receptors in maternally deprived rats displaying anxiety and depression-like behaviors Prog.Neuropsychopharmacol.Biol.Psychiatry 33 2 262-268 "Maternal separation is known to induce long-term changes in neuroendocrine and emotional responsiveness to stress in a large variety of models. We examined an animal model of early deprivation in Sprague-Dawley rats consisting of separating litters from their mothers and littermates 3 h daily during postnatal days 2 to 15. In adulthood, maternally deprived rats in comparison with non-deprived controls exhibited an increase in anxiety and depression-related behaviors in the open-field and forced swim tests. Because serotonin (5-HT) 5-HT(1A) receptors seem to play an important role in the pathophysiology of major depression and in the mechanism of action of antidepressants, we investigated if 5-HT(1A) receptor function is altered in deprived rats. Although the hypothermic response to the 5-HT(1A) receptor agonist 8-OH-DPAT was increased in adult deprived rats compared to non-deprived control group, no differences between groups were found in the effect of the systemic 8-OH-DPAT administration on serotoninergic cell firing in dorsal raphe nucleus and in the 5-HT release at the ventral hippocampus levels. These results suggest that 5-HT(1A) receptors are not substantially affected in adult Sprague-Dawley rats that were subjected to a maternal deprivation 3 h daily during the neonatal period" http://www.ncbi.nlm.nih.gov/pubmed/19111592 1 237 L. Wolpert 2004 Lewis Wolpert discusses development and depression. Interview by Joanne Clough Drug Discov.Today 9 11 471-472 "Lewis Wolpert is Professor of Biology as Applied to Medicine in the Department of Anatomy and Developmental Biology at University College, London, UK. His research interests focus on the mechanisms that are involved in embryonic development. Lewis originally trained as a civil engineer in South Africa but in 1955 made the move to research in cellular biology at King's College, London. He was made a Fellow of the Royal Society in 1980 and awarded the CBE in 1990. Lewis was also made a Fellow of the Royal Society of Literature in 1999 and has presented science on both radio and TV for several years. He was awarded The Royal Society Michael Faraday Prize in 2000 for his contribution to the public understanding of science, most notably through his Chairmanship of the Committee for the Public Understanding of Science (COPUS; 1993-1998). He is the author of numerous books, including Malignant Sadness: The Anatomy of Depression, Principles of Development, The Unnatural Nature of Science and The Triumph of the Embryo. He also writes a regular column for The Independent" http://www.ncbi.nlm.nih.gov/pubmed/15149619 0 238 "L. Dubuisson, P. Bioulac-Sage, C. Bedin and C. Balabaud" 1982 Sinusoidal cells in rats with portacaval shunt: a morphometric study J.Submicrosc.Cytol. 14 3 453-460 "Sinusoidal cells were studied in rats 2 weeks after portacaval shunt. Livers were perfused with glutaraldehyde via the aorta. Morphometric analysis was performed in periportal and centrolobular zones of the liver acinus. Liver atrophy was the main consequence of portal blood derivation. Per unit of hepatic parenchyma the number of hepatocytes and Kuppfer cells counted on 1 micron section was comparable in portacaval shunt and sham operated rats. 2 weeks after the shunt, sinusoidal cell ultrastructure was nearly normal. Morphometric analysis showed sinusoids slightly enlarged and Kupffer cell volume density increased in both zones. Kupffer cell lysosomal-like structures such as electron-lucent vacuoles and phagolysosomes had larger volume density. Ito cells number and volume density slightly increased after portacaval shunt. These findings suggest that endotoxemia which could occur after portal blood shunting might be better related to shunting than to depression of the reticuloendothelial system" http://www.ncbi.nlm.nih.gov/pubmed/7175982 0 239 "E. Erdmann, V. Rupprecht, E. Matthews, M. Kukley, S. Schoch and D. Dietrich" 2012 Depression of release by mGluR8 alters Ca2+ dependence of release machinery Cereb.Cortex 22 7 1498-1509 "The ubiquitous presynaptic metabotropic glutamate receptors (mGluRs) are generally believed to primarily inhibit synaptic transmission through blockade of Ca(2+) entry. Here, we analyzed how mGluR8 achieves a nearly complete inhibition of glutamate release at hippocampal synapses. Surprisingly, presynaptic Ca(2+) imaging and miniature excitatory postsynaptic current recordings showed that mGluR8 acts without affecting Ca(2+) entry, diffusion, and buffering. We quantitatively compared the Ca(2+) dependence of the inhibition of release by mGluR8 with the inhibition by omega-conotoxin GVIA. These calculations suggest that the inhibition produced by mGluR8 may be explained by a decrease in the apparent Ca(2+) affinity of the release sensor and, to a smaller extent, by a reduction of the maximal release rate. Upon activation of mGluR8, phasic transmitter release toward the end of a train of action potentials is greater as compared with presynaptic inhibition induced by blocking Ca(2+) entry, which is consistent with the important role of Ca(2+) in accelerating the replenishment of released vesicles. The action of mGluR8 was resistant to blockers of classical G-protein transduction pathways including inhibition of adenylate cyclase and may represent a direct effect on the release machinery. In conclusion, our data identify a mode of presynaptic inhibition which allows mGluR8 to profoundly inhibit vesicle fusion while not diminishing vesicle replenishment and which thereby differentially changes the temporal transmission properties of the inhibited synapse" http://www.ncbi.nlm.nih.gov/pubmed/21903594 0 240 "V. I. Koroleva, V. I. Davydov, R. I. Roshchina and A. V. Sulimov" 2003 [Lengthy unilateral EEG changes in alert rabbits after a spreading single depressed wave] Zh.Vyssh.Nerv.Deiat.Im I.P.Pavlova 53 4 437-445 "Effects of a single wave of the cortical spreading depression (SD) on the ECoG of a waking rabbit was studied with chronically implanted intracortical calomel and silverball epidural electrodes. DC potential shifts and integral electrical activity were recorded monopolary in reference to a nasal-bone electrode. ECoG spectral analysis (FFT) showed that an SD wave was accompanied by a suppression of the neocortical activity in a broad frequency range (0.25-80 Hz). However, the SD-related ECoG depression was a rather short phenomenon (5-7 min) as compared to a following rebound effect, i.e., persistent (1.5-2 h) unilateral exaltation of bioelectrical activity. The spectral power in the delta (6-14 fold) and beta bands (2-6-fold) increased, whereas the high-frequency activity (40-80 Hz) remained suppressed. Similar changes in the contralateral neocortex were poorly pronounced or absent; this resulted in a strong interhemispheric asymmetry. It is suggested that (1) exaltation of the delta activity after SD wave is related not only to a dendrite swelling and changes in the extracellular space structure but to increase in synaptic transmission efficiency, probably, by the type of anoxic potentiation, (2) activation of some subcortical structures by the mechanism of their release from the inhibitory neocortical control is an additional factor of the augmentation of the delta and spindle-like beta activity after an SD wave, and (3) the long-term attenuation of the high-frequency gamma activity is a result of its strong suppression during the SD and its reciprocal relations with the exalted delta activity" http://www.ncbi.nlm.nih.gov/pubmed/14598551 0 241 "L. L. Carpenter, A. R. Tyrka, C. J. McDougle, R. T. Malison, M. J. Owens, C. B. Nemeroff and L. H. Price" 2004 Cerebrospinal fluid corticotropin-releasing factor and perceived early-life stress in depressed patients and healthy control subjects "Neuropsychopharmacology.29 (4) ()(pp 777-784), 2004.Date of Publication: April 2004." 4 777-784 "Previous studies have reported elevated concentrations of cerebrospinal fluid (CSF) corticotropin-releasing factor (CRF) in patients with major depression. Elevations of CSF CRF have also been reported in adult laboratory animals exposed to the stress of brief maternal deprivation or maternal neglect in the neonatal or preweaning period. The present study was designed to determine whether major depression and a history of perceived early adversity in childhood are independently associated with elevated CSF CRF concentrations in adults. In this case-control study, 27 medication-free adults with major depression and 25 matched controls underwent standardized lumbar puncture for collection of a single CSF sample at 1200. Subjects provided data about significant adverse early-life experiences and rated their global perceived level of stress during pre-school and preteen years on a six-point Likert scale. The mean difference in CSF CRF between depressed patients and controls did not reach statistical significance. In a regression model, perceived early-life stress was a significant predictor of CSF CRF, but depression was not Perinatal adversity and perceived adversity in the preteen adversity years (ages 6-13 years) were both independently associated with decreasing CSF CRF concentrations. The relationship observed between perceived early-life stress and adult CSF CRF concentrations in this study closely parallels recent preclinical findings. More work is needed to elucidate the critical nature and timing of early events that may be associated with enduring neuroendocrine changes in humans" DO - http://dx.doi.org/10.1038/sj.npp.1300375 0 242 "K. E. Baerlocher, C. R. Scriver and F. Mohyuddin" 1971 The ontogeny of amino acid transport in rat kidney. II. Kinetics of uptake and effect of anoxia Biochim.Biophys.Acta 249 2 364-372 http://www.ncbi.nlm.nih.gov/pubmed/5134189 0 243 "R. Takahashi, K. H. Tachiki and K. Nishiwaki" 1976 Biochemical basis of an animal model of depressive illness. A preliminary report "Folia Psychiatrica et Neurologica Japonica.30 (2) ()(pp 207-218), 1976.Date of Publication: 1976." 2 207-218 Biochemical analyses of brain samples of an Animal Model of Depression indicate that the state of motionlessness observed in response to a conditioned stimulus was due to an excess in functional activity of serotonin. An excess functional activity of serotonin may be directly responsible for human depressive illness. This conflicting conclusion to the currently popular theories of serotonin deficiency was discussed with reference to the animal and clinical data in the literature which are consistent with the conclusion 1 244 J. M. Ahluwalia 1979 Abolition of a viscerosomatic reflex during oxygen deprivation J.Appl.Physiol Respir.Environ.Exerc.Physiol 46 6 1143-1148 "Effect of hypoxia was studied on the J reflex, a term used for the reflex inhibition of muscular exercise by activation of type J pulmonary endings. Hypoxia was induced by ventilating the animal with gas mixtures varying from 18 to 9% oxygen in nitrogen. The blood gas tensions of the arterial blood (PaO2) were measured before, during, and after hypoxia. It was found that the J reflex is sensitive to a reduction in oxygen. A fall in PaO2 between 67 and 47 Torr abolished this reflex. Studies were also undertaken to exclude the possibility that the effect of hypoxia was predominantly exerted on monosynaptic reflex itself. A similar fall in PaO2 also depressed the monosynaptic reflex. Minimum time required for the significant depression was 32 s. On the contrary the J reflex was abolished within this period suggesting that the abolition of J reflex is independent of the changes in monosynaptic reflex during hypoxia" http://www.ncbi.nlm.nih.gov/pubmed/468639 0 245 "M. Ansorge, C. Tanneberger, B. Davies, F. Theuring and H. Kusserow" 2004 Analysis of the murine 5-HT receptor gene promoter in vitro and in vivo Eur.J.Neurosci. 20 2 363-374 "The expression level of the 5-HT(1A) receptor gene (htr1a) in the central nervous system (CNS) is implicated in the aetiology and treatment of anxiety disorders and depression. Previous studies of the murine htr1a have revealed that its proximal promoter is GC rich and TATA-less. Several functional transcription factor binding sites, including MAZ and SP1 recognition sequences, have been identified. To further analyse the promoter of this receptor gene, additional upstream sequence information extending to -5.5 kb of the murine htr1a was generated and promoter fragments extending to -20 kb were analysed for activity in cell culture and transgenic animals. Promoter fragments greater than 4.5 kb in length were active in 5-HT(1A) receptor mRNA positive cells and inactive in 5-HT(1A) receptor mRNA negative cells. Smaller fragments were not able to confer this specificity. In agreement, using additive transgenesis to drive LacZ expression in vivo, CNS specific reporter gene expression was found with these longer constructs. Transgene expression in the 4.5- and 20-kb mouse lines resembled the endogenous htr1a expression pattern, whereas the 5.5-kb mouse lines surprisingly revealed strongly reduced expression. None of the three constructs was prone to confer ectopic expression, however, variation of expression between the transgenic lines was observed. Using colocalization studies we analysed the degree of concurrence of transgenic and endogenous htr1a expression brought about by these three different constructs. The highest degrees of colocalization were observed in mice harbouring the 20-kb construct, suggesting a large promoter fragment is required to faithfully direct transgene expression in a 5-HT(1A) receptor like pattern" http://www.ncbi.nlm.nih.gov/pubmed/15233746 0 246 "S. C. Azad, J. Kurz, G. Marsicano, B. Lutz, W. Zieglgansberger and G. Rammes" 2008 Activation of CB1 specifically located on GABAergic interneurons inhibits LTD in the lateral amygdala Learn.Mem. 15 3 143-152 "Previously, we found that in the lateral amygdala (LA) of the mouse, WIN55,212-2 decreases both glutamatergic and GABAergic synaptic transmission via activation of the cannabinoid receptor type 1 (CB1), yet produces an overall reduction of neuronal excitability. This suggests that the effects on excitatory transmission override those on inhibitory transmission. Here we show that CB1 activation by WIN55,212-2 and Delta(9)-THC inhibits long-term depression (LTD) of basal synaptic transmission in the LA, induced by low-frequency stimulation (LFS; 900 pulses/1 Hz). The CB1 agonist WIN55,212-2 blocked LTD via G(i/o) proteins, activation of inwardly rectifying K+ channels (K(ir)s), inhibition of the adenylate cyclase-protein kinase A (PKA) pathway, and PKA-dependent inhibition of voltage-gated N-type Ca2+ channels (N-type VGCCs). Interestingly, WIN55,212-2 effects on LTD were abolished in CB1 knock-out mice (CB1-KO), and in conditional mutants lacking CB1 expression only in GABAergic interneurons, but were still present in mutants lacking CB1 in principal forebrain neurons. LTD induction per se was unaffected by the CB1 antagonist SR141716A and was normally expressed in CB1-KO as well as in both conditional CB1 mutants. Our data demonstrate that activation of CB1 specifically located on GABAergic interneurons inhibits LTD in the LA. These findings suggest that CB1 expressed on either glutamatergic or GABAergic neurons play a differential role in the control of synaptic transmission and plasticity" http://www.ncbi.nlm.nih.gov/pubmed/18323569 0 247 "R. B. Schlesinger, K. E. Driscoll, A. F. Gunnison and J. T. Zelikoff" 1990 Pulmonary arachidonic acid metabolism following acute exposures to ozone and nitrogen dioxide J.Toxicol.Environ.Health 31 4 275-290 "Ozone (O3) and nitrogen dioxide (NO2) are common air pollutants, and exposure to these gases has been shown to affect pulmonary physiology, biochemistry, and structure. This study examined their ability to modulate arachidonic acid metabolites (eicosanoids) in the lungs. Rabbits were exposed for 2 h to O3 at 0.1, 0.3, or 1 ppm; NO2 at 1, 3, or 10 ppm; or to a mixture of 0.3 ppm O3 and 3 ppm NO2. Groups of animals sacrificed either immediately or 24 h after each exposure underwent broncho-pulmonary lavage. Selected eicosanoids were assessed in lavage fluid by radioimmunoassay. Increases in prostaglandins E2 (PGE2) and F2 alpha (PGF2 alpha) were found immediately after exposure to 1 ppm O3. Exposure to 10 ppm NO2 resulted in a depression of 6-keto-PGF1 alpha, while thromboxane B2 (TxB2) was elevated after exposure to 1 ppm NO2 and depressed following 3 and 10 ppm. The O3/NO2 mixture resulted in synergistic increases in PGE2 and PGF2 alpha, with the response appearing to be driven by O3. This study has demonstrated that acute exposure to either O3 or NO2 can alter pulmonary arachidonic acid metabolism and that the responses to these oxidants differ, both quantitatively and qualitatively" http://www.ncbi.nlm.nih.gov/pubmed/2147723 0 248 "K. G. Lalitha, R. Sathish, R. Gayathri, S. Karthikeyan, P. Kalaiselvi, G. Muthuboopathi and T. Venkatachalam" 2010 Pharmacological evaluation of Clerodendrum philippinum schauer flowers for antianxiety and central nervous system depressant activity International Journal of Pharmaceutical Research 2 2 April-June "The research work deals with the ethanolic extract of Clerodendrum philippinum schauer flowers for anti anxiety and central nervous system depressant activity. The C.philippinum flowers are known to contain sterols, flavonoid, glycosides and phenyl propanoid derivatives as chemical components and are reported to have antifungal activity. It is used as folk medicine in the treatment of colic pain. In the present study the elevated plusmaze test models were used to evaluate anti-anxiety activity and locomotor activity was evaluated on actophotometer with 125 and 250 mg/kg p.o. doses of C.philippinum. The ethanolic extract of the C.philippinum flowers (125 and 250 mg/kg p.o) significantly (P > 0.01) decreased loco motor activity (45.20%, 53.47%) and significantly (P > 0.01) increased the number of entries, time spent and rears in open arm of the elevated plus maze model" 0 249 R. N. de and H. Stephan 1974 [Inhibition of heat denaturation of albumin by a combination of coumarin and rutin derivative] Arzneimittelforschung. 24 1 126-127 http://www.ncbi.nlm.nih.gov/pubmed/4406100 0 250 R. J. Bernacki and H. B. Bosmann 1970 Warfarin and vitamin K accelerate protein and glycoprotein synthesis in isolated rat liver mitochondria in vitro Biochem.Biophys.Res.Commun. 41 2 498-505 http://www.ncbi.nlm.nih.gov/pubmed/5518179 0 251 "M. T. Littleton-Kearney, J. M. Gaines, K. P. Callahan, S. J. Murphy and P. D. Hurn" 2005 Effects of estrogen on platelet reactivity after transient forebrain ischemia in rats Biol.Res.Nurs. 7 2 135-145 "Estrogen's prothrombotic effects are of increasing concern, particularly in stroke risk and recovery. Using an ischemic rodent model, the authors sought to determine (a) if estrogen replacement increases postischemic platelet reactivity, (b) if changes in estrogen status alter intraplatelet endothelial nitric oxide synthase (eNOS) synthesis, and (c) if estrogen-mediated effects on platelets alter cerebral blood flow during reperfusion. Intact (I), ovariectomized (OVX), and OVX + 17 beta-estradiol (E50) rats were subjected to 30 min of forebrain ischemia and 60 min of reperfusion. Using the platelet activation marker P-selectin, postischemic platelet reactivity was quantified by flow cytometry. In a separate cohort (I, OVX, E50), the authors quantified platelet eNOS by Western blot. Another cohort (OVX, E50) was subjected to ischemia/reperfusion, and cerebral blood flow was determined using the iodoantipyrine technique. Collagen-stimulated platelet P-selectin expression was increased in the OVX rats at 60 min of reperfusion, and this effect was reversed by estrogen treatment. No differences in platelet eNOS expression were detected among groups. Cerebral blood flow at 60 min reperfusion was comparable between the OVX and the E50 rats. The authors conclude that during reper-fusion, estrogen deficiency increases postischemic platelet sensitivity to stimuli in estrogen-deficient rats. Estrogen treatment mitigates effects of estrogen loss on platelets, but this early effect is apparently not caused by intraplatelet eNOS depression. Neither estrogen deficiency nor estrogen treatment changes early postischemic regional brain blood flow. In this rodent global cerebral ischemic model, physiologic doses of estrogen are not deleterious to platelet reactivity and may initially reduce postischemic platelet reactivity" http://www.ncbi.nlm.nih.gov/pubmed/16267375 0 252 "S. W. Park, l. H. Nhu, H. Y. Cho, M. K. Seo, C. H. Lee, N. N. Ly, C. M. Choi, B. J. Lee, G. M. Kim, W. Seol, J. G. Lee and Y. H. Kim" 2016 p11 mediates the BDNF-protective effects in dendritic outgrowth and spine formation in B27-deprived primary hippocampal cells J.Affect.Disord. 196 01-Oct "BACKGROUND: p11 (S100A10) is a key regulator of depression-like behaviors and antidepressant drug response in rodent models. Recent studies suggest that p11 mediates the behavioral antidepressant action of brain-derived neurotrophic factor (BDNF) in rodents. BDNF improves neural plasticity, which is linked to the cellular actions of antidepressant drugs. In the present study, we investigated whether p11 regulated BDNF action on neural plasticity in vitro. METHODS: We generated primary hippocampal cultures. p11 expression, total dendritic length, and spine density were investigated under toxic conditions induced by B27 deprivation, which causes hippocampal cell death. RESULTS: B27 deprivation significantly decreased p11 expression. Treatment with BDNF significantly prevented the B27 deprivation-induced decrease in p11 levels in a concentration-dependent manner, whereas these concentrations had no effect on control cultures. B27 deprivation significantly reduced the total length of hippocampal dendrites and spine density. BDNF increased the total dendritic length and spine density in conditions with or without B27. Furthermore, p11 knockdown through small interfering RNA (siRNA) transfection blocked these effects. The overexpression of p11 in B27-deprived cells increased the total dendritic length and spine density, and treatment with BDNF potentiated these effects. LIMITATION: This study should be confirmed in animal models of depression. CONCLUSION: Taken together, our data suggest that BDNF-induced improvement in neural plasticity may depend on the regulation of p11 in hippocampal cells with B27 deprivation. These results provide evidence to strengthen the theoretical basis of a role for p11 in BDNF-induced antidepressant action" http://www.ncbi.nlm.nih.gov/pubmed/26896741 0 253 "H. Nagayama, J. N. Hingtgen and M. H. Aprison" 1982 The role of serotonin in depression studied through the action of antidepressants on an animal model "Folia Psychiatrica et Neurologica Japonica.36 (2) ()(pp 209-210), 1982.Date of Publication: 1982." 2 209-210 1 254 "G. Kochan, D. Gonzalez and J. F. Rodriguez" 2003 "Characterization of the RNA-binding activity of VP3, a major structural protein of Infectious bursal disease virus" Arch.Virol. 148 4 723-744 "Infectious bursal disease virus (IBDV) is the agent of an immune-depressive disease affecting the poultry industry worldwide. Infection of IBDV leads to expression of five mature virus-encoded proteins. Proteolytic processing of the virus-encoded polyprotein generates VP3 which coats the inner surface of the IBDV capsid. In this report, we describe the characterization of the RNA-binding activity of VP3. For these studies, the VP3 coding region was fused to a histidine tag and expressed in insect cells using a recombinant baculovirus. The histidine-tagged VP3 was affinity-purified and used to study its ability to bind RNA molecules using three complementary methods: (i) Northwestern blotting; (ii) binding of VP3 protein-RNA complexes to nitrocellulose membranes; and (iii) electrophoretic mobility shift assays. The results demonstrated that VP3 efficiently bound ssRNA and dsRNA. Under the experimental conditions used in this study, the formation of VP3-RNA complexes did not depend upon the presence of specific RNA sequences. A series of histidine-tagged VP3 deletion mutants spanning the whole VP3 coding region were generated. The use of these mutants revealed that the VP3 RNA-binding domain layed in a highly conserved 69 aa stretch close to the N-terminus of the protein" http://www.ncbi.nlm.nih.gov/pubmed/12664296 0 255 "B. H. Vickery, G. I. McRae, W. Briones, A. Worden, R. Seidenberg, B. D. Schanbacher and R. Falvo" 1984 "Effects of an LHRH agonist analog upon sexual function in male dogs. Suppression, reversibility, and effect of testosterone replacement" J.Androl 5 1 28-42 "Male beagle dogs were injected once daily with 10 micrograms/kg of [6-D-(2-naphthyl)alanine]-LHRH (D-Nal(2)6-LHRH), a potent LHRH agonist, for periods up to 42 days, with recovery periods up to 172 days. Blood samples collected at regular intervals were assayed for LH, FSH, and testosterone; total ejaculates were collected and analyzed weekly, and animals were sacrificed at various intervals for sex organ weights and histology. The first injection of D-Nal(2)6-LHRH caused an acute elevation in plasma levels of LH, FSH, and testosterone, measured at 2 and 4 hours after the injection. This acute response to injection was attenuated with each successive injection and by two weeks no elevation was seen, suggesting a down-regulation of pituitary response. Basal levels of LH and testosterone were maximally depressed by four days of treatment. Testis volume, duration of erection, ejaculate volume, sperm count, sperm motility and testis volume all declined during treatment, with sperm count significantly lowered by two weeks and ejaculation volume becoming zero by five weeks of treatment. Spermatogenesis, assessed histologically, was partially suppressed at ten days and completely suppressed by 38 days of treatment. All parameters returned to normal following cessation of treatment. Recovery time was longer for the dogs treated for 42 days than for those treated for ten days. When testosterone was supplemented during 42 days of agonist treatment, basal plasma testosterone levels were maintained at the low end of the normal range. Testosterone supplementation did not prevent pituitary down-regulation, suppression of spermatogenesis, or the decrease in testis and epididymis weights, but prevented the decline in duration of erection. Ejaculate volume and sperm count declined more slowly with combination treatment than with agonist alone. During the decline in sperm count sperm motility was maintained with combination treatment. Injection of hCG into control and agonist treated dogs resulted in similar percentage increases in plasma levels of testosterone, although peak levels were greater in control than in treated animals. The data suggest a pituitary desensitization with this LHRH agonist in the dog but only a minor role for testicular desensitization" http://www.ncbi.nlm.nih.gov/pubmed/6231277 0 256 "N. Vashist, S. Drabu, P. Nand and P. Arora" 2011 Treatment strategies for monkey malaria: An overview "Research Journal of Pharmaceutical, Biological and Chemical Sciences.2 (4) ()(pp 478-487), 2011.Date of Publication: October-December 2011." 4 478-487 "After Swine Flu, another disease that is making news these days is Monkey Malaria.. Several questions on public health impact have arisen from the discovery of a large focus of the simian malaria parasite, Plasmodium knowlesi, in the human population. It is not newly emergent but was overlooked until molecular tools to distinguish between P. knowlesi and the morphologically similar Plasmodium malariae became available. Information on knowlesi malaria should be included in medical and public health guidelines to encourage the accurate diagnosis and treatment of patients, and monitor the incidence and distribution of cases. Since the parasites reproduce every 24 hours, even a short delay in accurate diagnosis and treatment could lead to the rapid onset of complications, including liver and kidney failure, and death.. Malaria case management remains a vital component of the malaria control strategies. Malaria control requires an integrate approach, including prevention (primarily vector control) and prompt treatment with effective antimalarials. A complete emergence of P. knowlesi into the human population could be overwhelming and, although exigent, the prevention of this situation deserves serious concern" 0 257 R. Bass and D. Oerter 1977 Embryonic development and mitochondrial function. 2. Thiamphenicol induced embryotoxicity Naunyn Schmiedebergs Arch.Pharmacol. 296 3 191-197 "Inhibition of mitochondrial protein synthesis in rat embryos during late organogenesis leads to impaired embryonic development. 1. Thiamphenicol (TAP), similar to chloramphenicol, inhibits in vivo the synthesis of cytochrome oxidase (cytox), which is partially synthesized by the mitochondrion. Subsequently, DNA synthesis and embryonic growth are affected. 2. Embryos on day 10 and 11, in contrast to embryos on day 9 of gestation, show a high sensitivity of mitochondrial protein synthesis, measured as cytox activity. From day 10 onwards, such an inhibition leads to pronounced impairment of DNA synthesis. The rat hemochorial placenta starts functioning on day 12 of gestation. Larger doses of TAP are required to inhibit cytox and DNA synthesis for treatment after placentation rather than before placentation. 3. Dose-response relationships differ depending on the date and duration of treatment. Application of TAP for 1 day requires 10-30 mg/kg TAP to inhibit cytox synthesis and 60-100 mg/kg to impair embryonic growth. Prolongation of treatment to 4 days (day 10-13) lowers the dose required for inhibition of DNA synthesis to 10 mg TAP/kg/day. This is lower than the human therapeutic dose. Larger doses lead to embryolethality. 4. The extent of inhibition of DNA synthesis provoked by inhibition of mitochondrial protein synthesis depends on a number of factors which include: different growth rates during organogenesis, the number of mitochondria present prior to treatment, availability of extramitochondrial ATP sources and placental permeability barrier" http://www.ncbi.nlm.nih.gov/pubmed/190546 0 258 Z. P. Sof'ina 1969 "[Comparative study of the side effects of embikhin, sarcolysin and asalin]" Farmakol.Toksikol. 32 3 312-316 http://www.ncbi.nlm.nih.gov/pubmed/5810949 0 259 "J. H. Lee, E. Ko, Y. E. Kim, J. Y. Min, J. Liu, Y. Kim, M. Shin, M. Hong and H. Bae" 2010 Gene expression profile analysis of genes in rat hippocampus from antidepressant treated rats using DNA microarray BMC.Neurosci. 11 152 "BACKGROUND: The molecular and biological mechanisms by which many antidepressants function are based on the monoamine depletion hypothesis. However, the entire cascade of mechanisms responsible for the therapeutic effect of antidepressants has not yet been elucidated. RESULTS: We used a genome-wide microarray system containing 30,000 clones to evaluate total RNA that had been isolated from the brains of treated rats to identify the genes involved in the therapeutic mechanisms of various antidepressants, a tricyclic antidepressant (imipramine). a selective serotonin reuptake inhibitor (fluoxetine), a monoamine oxidase inhibitor (phenelzine) and psychoactive herbal extracts of Nelumbinis Semen (NS). To confirm the differential expression of the identified genes, we analyzed the amount of mRNA that was isolated from the hippocampus of rats that had been treated with antidepressants by real-time RT-PCR using primers specific for selected genes of interest. These data demonstrate that antidepressants interfere with the expression of a large array of genes involved in signaling, survival and protein metabolism, suggesting that the therapeutic effect of these antidepressants is very complex. Surprisingly, unlike other antidepressants, we found that the standardized herbal medicine, Nelumbinis Semen, is free of factors that can induce neurodegenerative diseases such as caspase 8, alpha-synuclein, and amyloid precursor protein. In addition, the production of the inflammatory cytokine, IFNgamma, was significantly decreased in rat hippocampus in response to treatment with antidepressants, while the inhibitory cytokine, TGFbeta, was significantly enhanced. CONCLUSIONS: These results suggest that antidepressants function by regulating neurotransmission as well as suppressing immunoreactivity in the central nervous system" http://www.ncbi.nlm.nih.gov/pubmed/21118505 0 260 R. A. Slaastad 1974 Prevention of thromboplastin-induced intravascular coagulation in rabbits by warfarin as monitored by thrombotest Scand.J.Haematol. 13 2 140-145 http://www.ncbi.nlm.nih.gov/pubmed/4547438 0 261 S. Otani and J. A. Connor 1995 Long-term depression of naive synapses in adult hippocampus induced by asynchronous synaptic activity J.Neurophysiol. 73 6 2596-2601 "1. Two independent Schaffer collateral pathways converging to the same pyramidal cell were alternately stimulated by 2-Hz trains (900 pulses) offset by a 150-ms interval in adult rat hippocampal slices. The second input underwent an immediate and persistent long-term depression (LTD). Depression in the first input was smaller than the second input. A narrower interpulse interval (20 ms) failed to induce LTD in either input. 2. Neither the N-methyl-D-aspartate receptor antagonist DL-2-amino-5-phosphonovaleric acid nor the metabotropic glutamate receptor antagonist (+)-alpha-methyl-4-carboxylphenyl-glycine blocked this associative LTD. However, coapplication of these two antagonists blocked LTD. 3. Associative LTD was blocked by prior injection of the Ca2+ chelator bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid into the postsynaptic cell and by bath-applied L-NG-nitroarginine, a nitric oxide synthesis inhibitor. 4. We propose that temporally confined, asynchronous synaptic activity weakens the efficacy of naive synapses in slices from the adult hippocampus" http://www.ncbi.nlm.nih.gov/pubmed/7666167 0 262 "H. T. Baalsrud, B. E. Saether, I. J. Hagen, A. M. Myhre, T. H. Ringsby, H. Parn and H. Jensen" 2014 Effects of population characteristics and structure on estimates of effective population size in a house sparrow metapopulation Mol.Ecol. 23 11 2653-2668 "Effective population size (N(e)) is a key parameter to understand evolutionary processes and the viability of endangered populations as it determines the rate of genetic drift and inbreeding. Low Ne can lead to inbreeding depression and reduced population adaptability. In this study, we estimated contemporary N(e) using genetic estimators (LDNE, ONeSAMP, MLNE and CoNe) as well as a demographic estimator in a natural insular house sparrow metapopulation. We investigated whether population characteristics (population size, sex ratio, immigration rate, variance in population size and population growth rate) explained variation within and among populations in the ratio of effective to census population size (N(e)/N(c)). In general, N(e)/N(c) ratios increased with immigration rates. Genetic N(e) was much larger than demographic N(e), probably due to a greater effect of immigration on genetic than demographic processes in local populations. Moreover, although estimates of genetic N(e) seemed to track N(c) quite well, the genetic N(e) -estimates were often larger than Nc within populations. Estimates of genetic N(e) for the metapopulation were however within the expected range (7 receptor agents: Structure-activity relationships and potential therapeutic applications in central nervous system disorders "Pharmacology and Therapeutics.129 (2) ()(pp 120-148), 2011.Date of Publication: February 2011." 2 120-148 "Since its discovery in the 1940s in serum, the mammalian intestinal mucosa, and in the central nervous system, serotonin (5-HT) has been shown to be involved in virtually all cognitive and behavioral human functions, and alterations in its neurochemistry have been implicated in the etiology of a plethora of neuropsychiatric disorders. The cloning of 5-HT receptor subtypes has been of importance in enabling them to be classified as specific protein molecules encoded by specific genes. The 5-HT7 receptor is the most recently classified member of the serotonin receptor family. Since its identification, it has been the subject of intense research efforts driven by its presence in functionally relevant regions of the brain. The availability of some selective antagonists and agonists, in combination with genetically modified mice lacking the 5-HT7 receptor, has allowed for a better understanding of the pathophysiological role of this receptor. This paper reviews data on localization and pharmacological properties of the 5-HT 7 receptor, and summarizes the results of structure-activity relationship studies aimed at the discovery of selective 5-HT7 receptor ligands. Additionally, an overview of the potential therapeutic applications of 5-HT7 receptor agonists and antagonists in central nervous system disorders is presented. © 2010 Elsevier Inc. All rights reserved" DO - http://dx.doi.org/10.1016/j.pharmthera.2010.08.013 0 267 H. Kroger and D. Papanastasiu 1968 [Influence of endoxan (cyclophosphamide) and 6-mercaptopurine on nucleic acid metabolism of rat spleen during synthesis of antibodies against Brucella abortus] Z.Naturforsch.B 23 1 73-77 http://www.ncbi.nlm.nih.gov/pubmed/4387858 0 268 "M. L. Woodruff, R. C. Kearley and R. L. Isaacson" 1974 Deficient brightness discrimination acquisition produced by daily intracranial injections of penicillin in rats Behav.Biol. 12 4 445-460 http://www.ncbi.nlm.nih.gov/pubmed/4451538 0 269 "C. Y. Hung, S. S. Lefkowitz and W. F. Geber" 1973 Interferon inhibition by narcotic analgesics Proc.Soc.Exp.Biol.Med. 142 1 106-111 http://www.ncbi.nlm.nih.gov/pubmed/4345713 0 270 K. Ross 2008 Mapping pathways from stress to cancer progression J.Natl.Cancer Inst. 100 13 "914-5, 917" http://www.ncbi.nlm.nih.gov/pubmed/18577741 0 271 "R. Wasserkort, E. Hoppe, M. Reddington and P. Schubert" 1991 "Modulation of A1 adenosine receptor function in rat brain by the polyamine, spermine" Neurosci.Lett. 124 2 183-186 "Studies on factors modulating the binding of agonist ligands to A1 adenosine receptors in rat forebrain membranes revealed that the reduction of [3H]cyclohexyladenosine [( 3H]CHA) binding, observed after removing Mg2+ by pretreatment with ethylene-dinitrilo-tetraacetic acid (EDTA), was restored by the polyamine, spermine (1mM). Parallel electrophysiological experiments performed on rat hippocampal slices in Mg(2+)-free medium indicated that spermine also led to a recovery of the depressive effect of 1 microM adenosine on stimulus train-evoked neuronal Ca2+ influx. These observations suggest that the polyamine, spermine is, like Mg2+, able to control the physiological adenosine-mediated modulation of synaptic transmission by changing the affinity state of A1 receptors" http://www.ncbi.nlm.nih.gov/pubmed/1648689 0 272 E. Nowakowska and A. Chodera 1997 Inhibitory monoamine oxidases of the new generation "Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego.3 (13) ()(pp 1-4), 1997.Date of Publication: Jul 1997." 13 01-Apr "This review deals with the new generation of selective and partly reversible monoamine oxidase (MAO) inhibitors. In contrast to the non selective inhibitors, used in the year 1957-1970, the selective inhibitors bind to and block only one of the two isoenzymes, MAO-A or MAO-B. The MAO-A inhibitors and part of the MAO-B inhibitors differ also from the classic drugs by their reversibility. The inhibition of MAO-A cause the rise of norepinephrine, dopamine and serotonin in the synaptic cleft, of MAO-B only of dopamine. The new inhibitors diminish also to some extent the reuptake of monoamines. The molecular action mechanism of the new drug generation is the same as in the non-selective drugs: increase of monoamines, near to the receptor, leads, after a number of intermediate steps, to activation of functional proteins in the cell. The selective block of one of the isoenzymes does not stop the metabolism of tyramine (from cheese, red wine), because this toxic compound is metabolised by both isoenzymes. The control of therapy with MAO-A inhibitors is easier, because of their reversibility. Selective inhibitors of MAO have found a secure place in therapy of depression (inh. of MAO-A, esp. Moclobemide) and Parkinson's disease (inh. of MAO-B, at this time mainly selegiline). Discussed is possible use of selective MAO-inhibitors for achieving an increase in cognitive function and protections of neurone cells from biochemical lesions" 0 273 Y. Watanabe and L. S. Dreifus 1968 "Electrophysiologic effects of 3-(p-chlorophenyl)-(2-imadazolin-2-yl-methyl)-1,2,3,4-tetrahydro-1-benzepine hydrochloride (SU-13197), a new antiarrhythmic agent" J.Pharmacol.Exp.Ther. 159 1 146-152 http://www.ncbi.nlm.nih.gov/pubmed/5643942 0 274 E. D. Bulochnik and M. G. Kurbatov 1977 [Dynamics of transcallosal potentials following local exposure of the cerebral cortex to high temperature] Biull.Eksp.Biol.Med. 84 10 408-411 "Experiments were conducted on cats, anesthetized with nembutal. The influence of local heating of the sensomotor cortex on the transcallosum response was examined. It was revealed that heating for short and long periods of limited regions of the cortex of both hemispheres induced a primary depression of the negative component of the transcallosum response at 44 degrees C and above it. The depression was replaced by an irreversible block of both response phases at 47--49 degrees C. It was concluded that the direct inhibitory influence of high temperatures on the cortical neurons was expressed only within the range of extreme temperature incompatible with vital activity of the whole organism. Experiments with the thermal block of the hemisphere region could testify to the fact that the transcallosum responses occurred mainly as a result of the direct irritation of the callosum fibers by stimulating electrodes and entirely reflected the post-synaptic potentials" http://www.ncbi.nlm.nih.gov/pubmed/912052 0 275 T. Hayashi and T. P. Su 2003 Sigma-1 receptors (sigma(1) binding sites) form raft-like microdomains and target lipid droplets on the endoplasmic reticulum: roles in endoplasmic reticulum lipid compartmentalization and export J.Pharmacol.Exp.Ther. 306 2 718-725 "The brain sigma-1 receptors can bind neurosteroids and psychotropic drugs, including neuroleptics and cocaine and are implicated in schizophrenia, depression, and drug dependence. In this study, we found that sigma-1 receptors specifically target lipid storage sites (lipid droplets) on the endoplasmic reticulum by forming a distinct class of lipid microdomains. Both endogenously expressing sigma-1 receptors and transfected C-terminally enhanced yellow fluorescent protein (EYFP)-tagged sigma-1 receptors (Sig-1R-EYFP) target unique ""ring-like"" structures associated with endoplasmic reticulum reticular networks in NG108-15 cells. The ring-like structures contain neutral lipids and are enlarged by the oleate treatment, indicating that they are endoplasmic reticulum-associated lipid droplets (ER-LDs). sigma-1 receptors colocalize with caveolin-2, a cholesterol-binding protein in lipid rafts on the ER-LDs, but not with adipocyte differentiation-related protein (ADRP), a cytosolic lipid droplet (c-LD)-specific protein. When the double-arginine ER retention signal on the N terminus of sigma-1 receptors is truncated, sigma-1 receptors no longer exist on ER-LDs, but predominantly target c-LDs, which contain ADRP. sigma-1 receptors on ER-LDs form detergent-resistant raft-like lipid microdomains, the buoyancy of which is different from that of plasma membrane lipid rafts. (+)-Pentazocine causes sigma-1 receptors to disappear from the microdomains. N-Terminally EYFP-tagged sigma-1 receptors (EYFP-Sig-1R) failed to target ER-LDs. EYFP-Sig-1R-transfected cells showed an unrestricted distribution of neutral lipids all over the endoplasmic reticulum network, decreases in c-LDs and cholesterol in plasma membranes, and the bulbous aggregation of endoplasmic reticulum. Thus, sigma-1 receptors are unique endoplasmic reticulum proteins that regulate the compartmentalization of lipids on the endoplasmic reticulum and their export from the endoplasmic reticulum to plasma membrane and c-LDs" http://www.ncbi.nlm.nih.gov/pubmed/12730355 0 276 S. Arrenbrecht and G. F. Mitchell 1975 T cell-dependent helper and suppressive influences in an adoptive IgG antibody response Immunology 28 3 485-495 "When immune spleen cells of mice immunized to a hapten carrier preparation 4 days previously were transferred to normal syngeneic hosts, they began to produce 7S antibody (presumably of the IgG class), provided that relatively small numbers of cells (about 1/10 spleen equivalent) were transferred. Increasing the number of transferred cells resulted in less IgG antibody formed. Depletion of the immune spleen cells of T cells by treatment with anti-theta serum and complement prevented IgG antibody formation. IgG antibody production by untreated and anti-therta serum-treated immune spleen cells could be enhanced (reinduced) by addition of small numbers of cells enriched for carrier-activated T cells. These suggest that T cells are necessary to stimulate antigen-activated B cells into IgG antibody production. Larger numbers of 'carrier-activated T cells' depressed IgG antibody production. Both enhancement and depression could be demonstrated to be antigen-specific. IgG antibody production high numbers of transferred immune spleen cells could be induced by treating the cells prior to transfer with suboptimal amounts of anti-theta serum and complement. It is argued that this results from the elimination of a T cell-dependent suppressor influence arising during a normal immune response" http://www.ncbi.nlm.nih.gov/pubmed/1092611 0 277 K. H. Berecek and D. N. Shier 1986 Alterations in renal vascular reactivity induced by chronic central administration of captopril in the spontaneously hypertensive rat Clin.Exp.Hypertens.A 8 7 1081-1106 "We have previously demonstrated that chronic intracerebroventricular (ICV) administration of captopril attenuates the development of hypertension in young SHR in association with a depression in whole animal reactivity to vasoactive agents and an increased baroreflex sensitivity. In the present study we analyzed vascular reactivity in perfused kidneys from SHR treated with captopril or vehicle to determine whether the depression in reactivity was due to changes in baroreflex activity or an effect on the vasculature. Captopril (1.25 micrograms/hr) was infused (osmotic mini pumps) for 4 weeks. Vascular reactivity to norepinephrine, angiotensin and vasopressin was assessed in isolated kidneys perfused with an artificial medium at constant flow. SHR treated with ICV captopril showed a significantly lower arterial pressure and basal renal vascular resistance than SHR treated with ICV vehicle or IV captopril. In addition, these rats showed decreased vascular reactivity to all vasoactive agents tested as signified by a shift in the dose-response curves to the right with an increase in threshold (ED16) and ED50. Kidneys from WKY treated with ICV captopril also showed a decrease in vascular reactivity in comparison to WKY treated with ICV vehicle. Our data suggest that captopril, through a central action, attenuates the development of hypertension by decreasing vascular reactivity to vasoconstrictors" http://www.ncbi.nlm.nih.gov/pubmed/3533326 0 278 H. Tjalve 2009 Adverse reactions to veterinary medicinal products: An overview based on the Swedish experience "Journal of Veterinary Pharmacology and Therapeutics.32 (Suppl 1) ()(pp 41-44), 2009.Date of Publication: August 2009." Suppl 1 41-44 DO - http://dx.doi.org/10.1111/j.1365-2885.2008.01035.x 0 279 F. Mira-Moser 1969 "[Action of goitrogens on tadpoles of the toad, Bufo bufo L]" Arch.Anat.Histol.Embryol. 52 5 313 http://www.ncbi.nlm.nih.gov/pubmed/4100800 0 280 "J. S. Rennie, H. A. McCormack, C. Farquharson, J. L. Berry, E. B. Mawer and C. C. Whitehead" 1995 "Interaction between dietary 1,25-dihydroxycholecalciferol and calcium and effects of management on the occurrence of tibial dyschondroplasia, leg abnormalities and performance in broiler chickens" Br.Poult.Sci. 36 3 465-477 "1. Two experiments were performed to compare the relative effectiveness of feeding 1,25-dihydroxycholecalciferol (1,25-DHCC) in minimising leg abnormalities in broilers with other methods and to investigate interactions between dietary 1,25-DHCC and calcium. 2. Adding 5 micrograms 1,25-DHCC/kg to a diet containing 12 g calcium/kg was more effective than early food restriction or meal feeding in preventing leg abnormalities but was found to cause a growth depression. 3. The second experiment, which had a factorial design, with diets containing 7.5, 10.0 and 12.5 g calcium and 0, 2.0, 3.5 and 5.0 micrograms 1,25-DHCC/kg, showed linear and quadratic interactions between these dietary factors. Diets with higher concentrations of both 1,25-DHCC and calcium resulted in growth depression associated with hypercalcaemia. 4. The incidence of tibial dyschondroplasia (TD) at 3 weeks of age was highest with the basal diet containing 7.5 g calcium/kg and was markedly reduced by addition of 1,25-DHCC and/or calcium. The incidence was very low or non-existent when 1,25-DHCC was fed at 3.5 micrograms/kg or greater. 5. Feeding 5 micrograms/kg 1,25-DHCC had no effect on plasma 1,25-DHCC concentrations, although at the higher dietary calcium contents plasma concentrations of 25-hydroxy- and 24,25-dihydroxy-cholecalciferol were lower in those birds fed 1,25-DHCC. 6. It is concluded that 1,25-DHCC is most effective in preventing TD without accompanying growth depression when it is fed in conjunction with diets containing less than 10 g calcium/kg" http://www.ncbi.nlm.nih.gov/pubmed/7583377 0 281 "N. Li, Q. Liu, X. J. Li, X. H. Bai, Y. Y. Liu, H. B. Zhao, Z. Y. Jin, Y. X. Jing, Z. Y. Yan and J. X. Chen" 2015 TCM Formula Xiaoyaosan Decoction Improves Depressive-Like Behaviors in Rats with Type 2 Diabetes Evid.Based.Complement Alternat.Med. 2015 415243 "The mechanism of depression with type 2 diabetes remains elusive, requiring further study. Objective. To evaluate the effect of TCM formula Xiaoyaosan on depressive-like behaviors in rats with type 2 diabetes. Methods. Rats were divided into 5 groups and drugs were administered during the model period of 21 days. The model of depressive-like behaviors in rats with type 2 diabetes was induced by a high fat diet, low doses of STZ injection, and chronic restraint stress for 21 days. The body weight, fasting blood glucose, ITT, OGTT, 5-HT, DA, depression behaviors, and morphological changes of formation were measured and observed. Results. After modeling, marked changes were found in model rats; behavioral analyses of rats indicated that this modeling method negatively impacts locomotor function. In the H&E staining, changes were found predominately in the CA1 and DG subregions of the hippocampus. After 21 days of treatment by fluoxetine and Xiaoyaosan, rats' body weights, behaviors and fasting blood glucose, and hippocampal formation were modified. Conclusions. A new model of depressive-like behaviors in rats with type 2 diabetes was successfully created. Xiaoyaosan and fluoxetine in this study independently contribute to exacerbate the disease progression" http://www.ncbi.nlm.nih.gov/pubmed/26508978 1 282 "K. Kuhl, W. Schurmann and W. Rief" 2008 Mental disorders and quality of life in COPD patients and their spouses "International Journal of COPD.3 (4) ()(pp 727-736), 2008.Date of Publication: 2008." 4 727-736 "In the current study, the prevalence of the most common psychological disorders in COPD patients and their spouses was assessed cross-sectionally. The influence of COPD patients' and their spouses' psychopathology on patient health-related quality of life was also examined. The following measurements were employed: Forced expiratory volume in 1 second expressed in percentage predicted (FEV1%), Shuttle-Walking-Test (SWT), International Diagnostic Checklists for ICD-10 (IDCL), questionnaires on generic and disease-specific health-related quality of life (St. George's Respiratory Questionnaire (SGRQ), European Quality of Life Questionnaire (EuroQol), a modified version of a Disability-Index (CDI)), and a screening questionnaire for a broad range of psychological problems and symptoms of psychopathology (Symptom-Checklist-90-R (SCL-90-R)). One hundred and forty-three stable COPD outpatients with a severity grade between 2 and 4 (according to the GOLD criteria) as well as 105 spouses took part in the study. The prevalence of anxiety and depression diagnoses was increased both in COPD patients and their spouses. In contrast, substance-related disorders were explicitly more frequent in COPD patients. Multiple linear regression analyses indicated that depression (SCL-90-R), walking distance (SWT), somatization (SCL-90-R), male gender, FEV1%, and heart disease were independent predictors of COPD patients' health-related quality of life. After including anxiousness of the spouses in the regression, medical variables (FEV1% and heart disease) no longer explained disability, thus highlighting the relevance of spouses' well-being. The results underline the importance of depression and anxiousness for health-related quality of life in COPD patients and their spouses. Of special interest is the fact that the relation between emotional distress and quality of life is interactive within a couple. © 2008 Kuhl et al, publisher and licensee Dove Medical Press Ltd" 0 283 J. Karbowski 2000 Fisher information and temporal correlations for spiking neurons with stochastic dynamics Phys.Rev.E.Stat.Phys.Plasmas.Fluids Relat Interdiscip.Topics. 61 4 Pt B 4235-4252 "Population coding accuracy can be studied using Fisher information. Here the Fisher information and correlation functions are determined analytically for a network of coupled spiking neurons with a more general than Poisson stochastic dynamics. It is shown that stimulus-driven temporal correlations between neurons always increase the Fisher information, whereas stimulus-independent correlations need not do so. Additionally, we find that for subthreshold stimuli there is some nonzero level of noise for which network coding is optimal. We also find that the Fisher information is larger for purely excitatory than for purely inhibitory networks, but only in a limited range of values of synaptic coupling strengths. In most cases the dependence of the Fisher information on time is linear, except for excitatory networks with strong synaptic couplings and for strong stimuli. In the latter case this dependence shows two distinct regimes: fast and slow. For excitatory networks short-term synaptic depression can improve the coding accuracy significantly, whereas short-term facilitation can lower the coding accuracy. For inhibitory networks, coding accuracy is insensitive to short-term synaptic dynamics" http://www.ncbi.nlm.nih.gov/pubmed/11088220 0 284 S. J. Haleen and D. B. Evans 1985 Selective effects of adenosine receptor agonists upon coronary resistance and heart rate in isolated working rabbit hearts Life Sci. 36 2 127-137 "Dose dependent changes in heart rate (HR) and coronary resistance (CR) were determined for adenosine, 5'-N-ethylcarboxamide adenosine (NECA) and l-N6-phenylisopropyladenosine (l-PIA) over a dose range of 1 X 10(-9) to 1 x 10(-5) M. Changes in CR were determined under controlled metabolic demand conditions (constant mean aortic pressure, constant mean left atrial pressure, and constant HR). Decreases in HR were determined by allowing the paced hearts to beat spontaneously between doses for 15 seconds. Adenosine significantly decreased CR and HR at greater than or equal to 1 X 10(-5) M. NECA significantly decreased both CR and HR at greater than or equal to 3 X 10(-8) M. l-PIA significantly decreased HR at greater than or equal to 3 X 10(-8) M; however a dose at greater than or equal to 3 X 10(-6) M was required to significantly decrease CR. These results provide evidence that the coronary vasodilator action of adenosine may primarily be mediated by A2 receptors. Furthermore, the data are in support of previous observations that the bradycardic action of adenosine is principally mediated via A1 receptors" http://www.ncbi.nlm.nih.gov/pubmed/3965846 0 285 "J. Zhong, H. R. Adams and L. J. Rubin" 1997 Cytosolic Ca2+ concentration and contraction-relaxation properties of ventricular myocytes from Escherichia coli endotoxemic guinea pigs: effect of fluid resuscitation Shock 7 5 383-388 "Hearts isolated from a guinea pig model of Escherichia coli endotoxemia exhibit decreased systolic contractile function and reduced diastolic compliance of the left ventricle within 4 h after injection of endotoxin. Fluid resuscitation prevented the endotoxin-induced decrease in diastolic compliance without affecting systolic contractile depression. Because intrinsic myocardial dysfunction after endotoxemia may result from alterations in intracellular Ca2+ handling, we tested the hypothesis that in vivo fluid resuscitation improved diastolic function by altering Ca2+ handling of the myocardium. We tested this hypothesis by measuring cell shortening and intracellular Ca2+ of ventricular myocytes isolated from endotoxemic guinea pigs. E. coli endotoxin (LPS, 1 mg/kg)-injected guinea pigs were divided into resuscitated and nonresuscitated groups. Fluid resuscitated animals received a Ringer's infusion (8 mL.kg-1.h-1) intravenously (i.v.) beginning immediately after endotoxin injection. Four hours later, ventricular myocytes were isolated enzymatically and loaded with fura-2/AM. When myocytes were field stimulated at .8 Hz, peak systolic Ca2+ transients of LPS-resuscitated (619 +/- 75 nM) and LPS-nonresuscitated (599 +/- 60 nM) myocytes were not significantly different from each other, but both were significantly less than values from control myocytes (1187 +/- 118 nM, p < .05). The percentage of cell shortening of LPS-resuscitated (6.2 +/- .9%) and LPS-nonresuscitated (6.2 +/- .3%) myocytes were also less than control (11.8 +/- .5%, p < .05). In contrast to improved diastolic compliance of fluid-resuscitated hearts, diastolic [Ca2+]i of myocytes (at .8 Hz) from LPS-resuscitated animals (138 +/- 47 nM) was not statistically different from LPS-nonresuscitated animals (129 +/- 19 nM). Diastolic values of both LPS groups were consistently lower than control value (251 +/- 38 nM, p < .05). These data suggest that improved diastolic compliance of LPS hearts following fluid resuscitation is not associated with improved myocyte contractility or myoplasmic Ca2+ handling" http://www.ncbi.nlm.nih.gov/pubmed/9165675 0 286 "J. S. Serrano, F. Pelayo, J. L. Tamargo and P. D. Garcia de Jalon" 1975 Influence of preexperimental blood pressure level on hypotensive responses to vasodilator drugs Arch.Farmacol.Toxicol. 1 2 91-98 http://www.ncbi.nlm.nih.gov/pubmed/1230033 0 287 "L. L. Ferrari, L. J. Agostinelli, M. J. Krashes, B. B. Lowell, T. E. Scammell and E. Arrigoni" 2016 Dynorphin inhibits basal forebrain cholinergic neurons by pre- and postsynaptic mechanisms J.Physiol 594 4 1069-1085 "KEY POINTS: The basal forebrain is an important component of the ascending arousal system and may be a key site through which the orexin neurons promote arousal. It has long been known that orexin-A and -B excite basal forebrain cholinergic neurons, but orexin-producing neurons also make the inhibitory peptide dynorphin. Using whole-cell recordings in brain slices, we found that dynorphin-A directly inhibits basal forebrain cholinergic neurons via kappa-opioid receptors, and decreases afferent excitatory synaptic input to these neurons. While the effects of dynorphin-A and orexin-A desensitize over multiple applications, co-application of dynorphin-A and orexin-A produces a sustained response that reverses depending on the membrane potential of basal forebrain cholinergic neurons. At -40 mV the net effect of the co-application is inhibition by dynorphin-A, whereas at -70 mV the excitatory response to orexin-A prevails. ABSTRACT: The basal forebrain (BF) is an essential component of the ascending arousal systems and may be a key site through which the orexin (also known as hypocretin) neurons drive arousal and promote the maintenance of normal wakefulness. All orexin neurons also make dynorphin, and nearly all brain regions innervated by the orexin neurons express kappa opiate receptors, the main receptor for dynorphin. This is remarkable because orexin excites target neurons including BF neurons, but dynorphin has inhibitory effects. We identified the sources of dynorphin input to the magnocellular preoptic nucleus and substantia innominata (MCPO/SI) in mice and determined the effects of dynorphin-A on MCPO/SI cholinergic neurons using patch-clamp recordings in brain slices. We found that the orexin neurons are the main source of dynorphin input to the MCPO/SI region, and dynorphin-A inhibits MCPO/SI cholinergic neurons through kappa-opioid receptors by (1) activation of a G protein-coupled inwardly rectifying potassium current, (2) inhibition of a voltage-gated Ca(2+) current and (3) presynaptic depression of the glutamatergic input to these neurons. The responses both to dynorphin-A and to orexin-A desensitize, but co-application of dynorphin-A and orexin-A produces a sustained response. In addition, the polarity of the response to the co-application depends on the membrane potential of BF neurons; at -40 mV the net effect of the co-application is inhibition by dynorphin-A, whereas at -70 mV the excitatory response to orexin-A prevails. This suggests that depending on their state of activation, BF cholinergic neurons can be excited or inhibited by signals from the orexin neurons" http://www.ncbi.nlm.nih.gov/pubmed/26613645 0 288 "A. A. Gomaa, L. H. Mohammed, H. N. Ahmed and A. M. A. Farghaly" 1991 "Interaction of butorphanol, with monoamine oxidase inhibitor, tranylcypromine" "Forensic Science International.49 (2) ()(pp 185-192), 1991.Date of Publication: 1991." 2 185-192 "This investigation examines the possibility of interaction between tranylcypromine and butorphanol in comparison to pethidine. The LD50 of pethidine and butorphanol were determined in mice pretreated with the non-selective monoamine oxidase (MAO) inhibitor, tranylcypromine orally for 8 days or with oral saline solution. Tranylcypromine decreased the LD50 of both pethidine and butorphanol by 78% and 41%, respectively. Anesthetized rabbits with halothane pretreated with tranylcypromine or saline were given pethidine (5 mg/kg i.v.) or butorphanol (0.5, 1 and 2 mg/kg i.v.). Pethidine produced a marked increase in blood pressure in rabbits pretreated with tranylcypromine and did not affect significantly the heart rate. Butorphanol did not affect either blood pressure or heart rate at doses of 0.5 or 1 mg/kg. However, the largest dose of butorphanol (2 mg/kg) produced hypotension and tachycardia in rabbits pretreated with tranylcypromine. Neither pethidine nor butorphanol affected the temperature of anesthetized rabbits pretreated with tranylcypromine or saline" DO - http://dx.doi.org/10.1016/0379-0738%2891%2990078-W 0 289 "G. A. Blondin, W. J. Vail and D. E. Green" 1969 The mechanism of mitochondrial swelling. II. Pseudoenergized swelling in the presence of alkali metal salts Arch.Biochem.Biophys. 129 1 158-172 http://www.ncbi.nlm.nih.gov/pubmed/5762961 0 290 D. Malamud and R. Baserga 1968 Uridylate kinase activity: effect of isoproterenol Science 162 3851 373-374 "Isoproterenol stimulates cell proliferation in mouse salivary glands. Prior to the stimulation of DNA synthesis, (3)H-uridine incorporation into RNA is decreased. This decreased incorporation results from a depression of uridylate kinase activity" http://www.ncbi.nlm.nih.gov/pubmed/5677533 0 291 "M. Pawlikowski, J. Kunnert-Radek and H. Stepien" 1978 Somatostatin inhibits the mitogenic effect of thyroliberin Experientia 34 2 271-272 "The effect of somatostatin and of thyroliberin on the mitotic incidence in the organ-cultured anterior pituitary lobe of the rat was investigated, using the colchicine metaphase-arrest technique. It was found that somatostatin added to the culture medium, together with thyroliberin, blocked the mitogenic effect of the latter" http://www.ncbi.nlm.nih.gov/pubmed/414934 0 292 M. Nelson and D. S. Nelson 1981 II. Tumor growth at sites of inflammation induced by mitogens in mice Am.J.Pathol. 104 2 125-131 "Experiments were carried out to determine whether the growth of tumors could be influenced by local inflammatory reactions induced by mitogens; Gram-negative bacterial lipopolysaccharide (LPS), concanavalin A (Con A) and phytohemagglutinin (PHA). Mice received injections, beneath the footpad or subcutaneously in the flank, of cells of syngeneic chemically induced fibrosarcomas with or without varying doses of mitogen. In the footpad (a) LPS caused a dose-dependent increase in the size; (b) Con A caused a decrease in the size of one of the three tumors, the decrease being inversely related to the dose of Con A; (c) PHA caused a dose-dependent decrease in the size of all three tumors: (d) PHA caused much smaller macroscopic inflammatory reactions than LPS or Con A. Subcutaneously injected tumor growth was inhibited by all three agents. Subcutaneous tumors contained a higher proportion of host inflammatory cells when mitogens had been mixed with the tumor inoculum. It is concluded that mitogens that can induce inflammatory reactions in mice can also bring about some suppression of tumor growth but that the depression is site-dependent and not clearly related to the apparent intensity of inflammation" http://www.ncbi.nlm.nih.gov/pubmed/7258299 0 293 "L. B. Esberg, G. J. Wang, Y. L. Lin and J. Ren" 2003 "Iso-S-petasin, a hypotensive sesquiterpene from Petasites formosanus, depresses cardiac contraction and intracellular Ca2+ transients in adult rat ventricular myocytes" J.Pharm.Pharmacol. 55 1 103-107 "Petasites formosanus is an indigenous species of the medicinal plant Petasites which has been used to treat hypertension. Both S-petasin and its isoform iso-S-petasin have been shown to be the effective ingredients in P. formosanus. However, their effect on heart function has not been revealed. This study was to examine the effect of iso-S-petasin on cardiac contractile function at the myocyte level. Ventricular myocytes were isolated from adult rat hearts and were stimulated to contract at 0.5 Hz under 1.0 mM extracellular Ca(2+). Contractile properties were evaluated using an IonOptix MyoCam system including peak shortening (PS), time to PS (TPS), time to 90% re-lengthening (TR(90)) and maximal velocity of shortening/re-lengthening (+/-dL/dt). Intracellular Ca(2+) properties were assessed by fura-2 and presented as Ca(2+)-induced Ca(2+) release (CICR) and intracellular Ca(2+) decay. Acute application of iso-S-petasin (10(-7) to 10(-4) M) elicited a concentration-dependent inhibition in PS and CICR, with maximal inhibitions of 51.0% and 31.0%, respectively. Iso-S-petasin also induced a concentration-dependent inhibition of+/-dL/dt without affecting TPS, TR(90), baseline intracellular Ca(2+) level or intracellular Ca(2+) decay. Elevation of extracellular Ca(2+) from 1.0 mM to 2.7 mM significantly antagonized the iso-S-petasin-induced depression in PS and CICR. These results demonstrated a direct depressant action of iso-S-petasin on ventricular contraction, which may work in concert with its antihypertensive action to reduce the cardiac load. The iso-S-petasin-induced decrease in CICR may play a role in its cardiac depressant effect" http://www.ncbi.nlm.nih.gov/pubmed/12625873 0 294 "E. E. Redei, L. C. Solberg, J. M. Kluczynski and W. P. Pare" 2001 Paradoxical hormonal and behavioral responses to hypothyroid and hyperthyroid states in the Wistar-Kyoto rat Neuropsychopharmacology 24 6 632-639 "Wistar-Kyoto (WKY) rats show endogenous depressive behavior that can be reversed by antidepressants. Given that WKYs exhibit decreased sensitivity to some antidepressants and treatment-resistant depressed patients often show hypothalamic-pituitary-thyroid (HPT) dysregulation, we examined the behavioral and HPT hormonal responses of WKYs to altered thyroid status. ""Euthyroid"" WKYs had elevated basal plasma TSH and T(3) levels as compared to Wistars. Hypothyroidism increased TSH levels more in WKYs than in Wistars and increased response latency in the open field test (OFT) of WKYs only. Administration of T(4) and T(3) suppressed plasma TSH equally in both strains. Wistars responded to increased T(3) levels with decreased response latency and increased activity in the OFT, but increased immobility in the forced swim test. In contrast, WKYs responded only to the high T(3) levels with decreased response latency in the OFT. These results suggest the existence of a decreased central nervous system sensitivity to thyroid hormones in WKYs that could be related to their depressive behavior" http://www.ncbi.nlm.nih.gov/pubmed/11331143 1 295 "M. Sansone, P. Renzi and J. Vetulani" 1987 Tolerance to diazepam-induced avoidance depression in mice Pol.J.Pharmacol.Pharm. 39 1 75-79 "The disrupting action on avoidance responses, exerted by diazepam given during shuttle-box training (5 mg/kg before each session), was abolished by a pretreatment with the drug (5 mg/kg) for five days. Similarly, avoidance depression, produced by diazepam in trained mice, was prevented by a pretreatment with five daily doses and was attenuated by previous administration of three daily injections or even of a single dose of the drug. The results demonstrate that tolerance rapidly develops to diazepam-induced avoidance depression, as to other behavioral actions of benzodiazepines" http://www.ncbi.nlm.nih.gov/pubmed/3671188 1 296 G. F. Dvortsin and V. N. Shatalov 1991 [Anti-stress effect of dalargin in immobilization stress in rats] Biull.Eksp.Biol.Med. 111 6 617-619 "The function of the isolated perfused rat hearts was studied in four groups of experiments. Group 1--included the hearts of intact animals (""absolute control""), group 2--the hearts of rats subjected to 24 hour immobilization in supine position against the background of triple intramuscular injections of placebo (control), group 3 included the hearts of rats, which during 24 hour immobilization stress were thrice injected a synthetic analogue of endogenous opioids Dalargin in a dose of 3 g/kg, and group 4 included the hearts of animals, which during immobilization were administered Dalargin in a dose of 10 g/kg of body mass. Ulcer index as indicator of stress injury of gastric mucosa was also determined. In the control group of experiments (group 2) 24 hour immobilization stress resulted in complete depression of cardiac performance as compared with group 1, and ulcer index approximated 1. In group 3 the indices of cardiac performance even exceeded those in group 1 (intact animals). As compared with group 2, ulcer index in group 3 decreased by 9 times. In application of Dalargin in a dose of 10 g/kg complete preservation of heart function indices and complete prevention of stress injury of gastric mucosa were also observed. Thus, Dalargin possesses cardioprotective and anti-ulcerogenic effect in immobilization stress in rats. Most probably, this phenomenon can be attributed to its ability to inhibit the activity of sympathoadrenal system, which gets enhanced during stress" http://www.ncbi.nlm.nih.gov/pubmed/1893187 0 297 "C. J. Hewson, P. D. Conlon, U. A. Luescher and R. O. Ball" 1998 The pharmacokinetics of clomipramine and desmethylclomipramine in dogs: Parameter estimates following a single oral dose and 28 consecutive daily oral doses of clomipramine "Journal of Veterinary Pharmacology and Therapeutics.21 (3) ()(pp 214-222), 1998.Date of Publication: 1998." 3 214-222 "Clomipramine is a tricyclic antidepressant that has been recommended for the treatment of canine compulsive disorder. The pharmacokinetics of clomipramine in dogs have not been reported. This study describes the pharmacokinetics of clomipramine and its active metabolite, desmethylclomipramine, in six male dogs. Serial blood samples were collected following both a single oral dose of clomipramine (3 mg/kg) and 28 consecutive daily oral doses (3 mg/kg q 24 h). In addition, 'peak' and 'trough' samples were taken throughout the 28-day dosing period. Plasma was assayed for total (free and protein-bound) clomipramine and desmethylclomipramine, using gas-chromatography with mass spectrometric detection. Various pharmacokinetic parameters were then determined. Following a single dose of clomipramine, time of maximum plasma concentration (t(max)) of clomipramine was 0.75-3.1 h, maximum plasma concentration (C(max)) was 16- 310 ng/mL and elimination half-life (t( 1/4 el)) was 1.2-16 h; t(max) of desmethylclomipramine was 1.4-8.8 h, C(max) was 21-134 ng/mL and t( 1/4 el) was 1.2-2.3 h. Following multiple dosing, there was a numeric increase in these parameters; t(max) of clomipramine was 3-8 h, C(max) was 43222 ng/mL and t( 1/4 el) was 1.2-16 h; t(max) of desmethylclomipramine was 1.48.8 h, C(max) was 21-134 ng/mL and t( 1/4 e1) was 1.2-2.3 h. Clinically significant differences between dogs and humans in the pharmacokinetics of oral clomipramine are discussed" DO - http://dx.doi.org/10.1046/j.1365-2885.1998.00138.x 0 298 M. Korth 1975 Influence of glyceryl trinitrate on force of contraction and action potential of guinea-pig myocardium Naunyn Schmiedebergs Arch.Pharmacol. 287 4 329-347 "1. The inotropic effect of glyceryl trinitrate (GTN) was studied in guinea-pig papillary muscles and atrial strips by analysing the isometric contraction curve and the monophasic action potential (AP). 2. GTN, 7X10(-5)M in papillary muscles and at 1.4x10(-4)M in atrial strips. The maximum of the contractile force was reached in both preparations at 2x10(-4)M GTN. Positive inotropic effects were transitory (3--5 min) and were followed by marked negative inotropic effects. 3. In the presence of GTN, only 15 of 26 papillary muscles showed a positive inotropic response and there was a great variance in its intensity. Prior exposure of papillary muscles to a low GTN concentration, which by itself reduced force of contraction (like every single GTN application), was the prereqch by itself reduced force of contraction (like every single GTN application), was the prerequisite for the positive inotropic effect of a subsequent higher GTN concentration. In atrial strips the positive inotropic action was consistent and uniform. The maximum force of contraction in response to single applications of GTN was only about 50% of that in response to cumulatively increased GTN concentrations. 4. In the presence of 5x10(-4)M GTN, the tyramine concentration-effect curve was shifted to the left (by one log unit at the ED50 level). 5. Beta-Adrenoceptor blockade by(+/-)-propranolol (5x10(-6)M) or noradrenaline depletion by pretreatment of the animals with reserpine (5 mg/kg, 18--22 hrs prior to the experiment)prevented the positive inotropic effects of GTN in both preparations. Hence, the GTN-induced increase in contractile force is induced by the liberation of noradrenaline and an inhibitory effect on the monoamine oxidase (MAO) of sympathetic nerve endings might be involved. 6. In atrial preparations exposed to 5x10(-4)M GTN, time to peak force (tu) and relaxation time(t2) were shortened by 12% and 33%, respectively. Pretreatment of the animals with reserpine prevented the shortening og t1 and changed the shortening of t2 from 33% to 19%. 7. In papillary muscles, 5x10(-4) M GTN shortened t1 by 10%, while t2 was prolonged by 17% in noradrenaline-depleted, and by 36% in control muscles. Prolongation of t2 at 5x10(-4)M GTN was accompanied by an increase in the duration of the monophasic action patential (AP) in reserpine-pretreated as well as in control muscles by 12% and 26%, respectively (measured at 90% repolarization). The same GTN concentration slowed the maximum rate of depolarisiation by 32%. After 35 min the AP returned to approximately the control value. In the presence of 5x10(-4) M GTN, noradrenalin (1x10(-5)M) lengthened the AP by 38% in both, control muscles and noradrenaline-depleted preparations" http://www.ncbi.nlm.nih.gov/pubmed/806816 0 299 "K. A. Krobert, R. L. Sutton and D. M. Feeney" 1994 Spontaneous and amphetamine-evoked release of cerebellar noradrenaline after sensorimotor cortex contusion: an in vivo microdialysis study in the awake rat J.Neurochem. 62 6 2233-2240 "Microdialysis sampling combined with HPLC was used to assess spontaneous and d-amphetamine (AMPH)-evoked release of noradrenaline (NA) in the cerebellum 1 day after probe implantation and 1 day after contusion of the right sensorimotor cortex (SMCX) in rats. In normal controls the mean +/- SEM basal NA release was 10.08 +/- 0.97 pg in the left cerebellar hemisphere and 8.21 +/- 1.17 pg in the right hemisphere 22-24 h after probe implantation. The average +/- SEM NA release in a 3-h period after administration of AMPH (2 mg/kg, i.p.) increased to 453 +/- 47.35 pg in the left and to 402 +/- 49.95 pg in the right cerebellar hemisphere. NA release (range of 413-951% increase over baseline) was maximal 20-40 min postdrug, returned to basal levels within 5 h, and remained unchanged for the 22-24-h postdrug measurement period. Animals with a focal SMCX contusion had a marked depression of both spontaneous and AMPH-evoked NA release. Mean +/- SEM basal NA release was 4.84 +/- 1.09 pg in the left and 4.95 +/- 0.43 pg in the right cerebellar hemisphere from 22 to 24 h postinjury, with NA levels increasing to 259 +/- 75.44 and 219 +/- 23.45 pg in the respective hemispheres over a 3-h period after AMPH. The maximal AMPH-induced increase in NA release ranged from 522 to 1,088% of basal levels in contused rats, with NA release returning to predrug levels within 5 h and remaining depressed for at least 48 h postinjury.(ABSTRACT TRUNCATED AT 250 WORDS)" http://www.ncbi.nlm.nih.gov/pubmed/8189231 0 300 "N. J. Peak, J. C. Overholser, J. Ridley, A. Braden, L. Fisher, J. Bixler and M. Chandler" 2016 Too Much to Bear Crisis 37 1 59-67 "BACKGROUND: People who feel they have become a burden on others may become susceptible to suicidal ideation. When people no longer feel capable or productive, they may assume that friends and family members would be better off without them. AIM: The present study was designed to assess preliminary psychometric properties of a new measure, the Perceived Burdensomeness (PBS) Scale. METHOD: Depressed psychiatric patients (N = 173) were recruited from a veterans affairs medical center. Patients were assessed with a structured diagnostic interview and self-report measures assessing perceived burdensomeness, depression severity, hopelessness, and suicidal ideation. RESULTS: The present study supported preliminary evidence of reliability and concurrent validity of the PBS. Additionally, perceived burdensomeness was significantly associated with higher levels of hopelessness and suicidal ideation. CONCLUSION: It is hoped that with the aid of the PBS clinicians may be able to intervene more specifically in the treatment of suicidality" http://www.ncbi.nlm.nih.gov/pubmed/26620916 0 301 "S. N. Kharchenko, V. P. Litvin and G. T. Pis'ko" 1978 [Antimicrobial properties of hexamethylene diamine and piperidine derivatives] Mikrobiol.Zh. 40 1 76-79 http://www.ncbi.nlm.nih.gov/pubmed/634174 0 302 "S. Holzapfel, J. Riecke, W. Rief, J. Schneider and J. A. Glombiewski" 2016 Development and Validation of the Behavioral Avoidance Test - Back pain (BAT-Back) for Patients with Chronic Low Back Pain Clin.J.Pain "OBJECTIVES: Pain-related fear and avoidance of physical activities are central elements of the fear-avoidance model of musculoskeletal pain. Pain-related fear has typically been measured via self-report instruments. In this study, we developed and validated a Behavioral Avoidance Test (BAT) for chronic low back pain (CLBP) patients with the aim of assessing pain-related avoidance behavior via direct observation. METHODS: The BAT-Back was administered to a group of CLBP patients (N=97) as well as healthy controls (N=31). Furthermore, pain, pain-related fear, disability, catastrophizing, and avoidance behavior were measured using self-report instruments. Reliability was assessed with intraclass correlation coefficient (ICC) and Cronbach's Alpha. Validity was assessed by examining correlation and regression analysis. RESULTS: The ICC for the BAT-Back avoidance score was r=0.76. Internal consistency was alpha=0.95. CLBP patients and healthy controls differed significantly on BAT-Back avoidance scores as well as self-report measures. BAT-Back avoidance scores were significantly correlated with scores on each of the self-report measures (r's=0.27-0.54). They were not significantly correlated with general anxiety and depression, age, body mass index, and pain duration. The BAT-Back avoidance score was able to capture unique variance in disability after controlling for other variables (e.g. pain intensity and pain-related fear). DISCUSSION: Results indicate that the BAT-Back is a reliable and valid measure of pain-related avoidance behavior. It may be useful for clinicians in tailoring treatments for chronic pain as well as an outcome measure for exposure treatments" http://www.ncbi.nlm.nih.gov/pubmed/26736023 0 303 "C. R. Percaccio, N. D. Engineer, A. L. Pruette, P. K. Pandya, R. Moucha, D. L. Rathbun and M. P. Kilgard" 2005 Environmental enrichment increases paired-pulse depression in rat auditory cortex J.Neurophysiol. 94 5 3590-3600 "Temporal features are important for the identification of natural sounds. Earlier studies have shown that cortical processing of temporal information can be altered by long-term experience with modulated sounds. In a previous study, we observed that environmental enrichment dramatically increased the response of cortical neurons to single tone and noise burst stimuli in both awake and anesthetized rats. Here, we evaluate how enrichment influences temporal information processing in the auditory cortex. We recorded responses to repeated tones and noise bursts in awake rats using epidural evoked potentials and in anesthetized rats using microelectrodes. Enrichment increased the response of cortical neurons to stimuli presented at slow rates and decreased the response to stimuli presented at fast rates relative to controls. Our observation that enrichment substantially increased response strength and forward masking is consistent with earlier reports that long-term potentiation of cortical synapses is associated with increased paired-pulse depression. Enrichment also increased response synchronization at slow rates and decreased synchronization at fast rates. Paired-pulse depression increased within days of environmental enrichment and was restored to normal levels after return to standard housing conditions. These results are relevant to several clinical disorders characterized by abnormal gating of sensory information, including autism, schizophrenia, and dyslexia" http://www.ncbi.nlm.nih.gov/pubmed/16093336 0 304 "Q. Z. Bahlool, A. Skovgaard, P. W. Kania and K. Buchmann" 2013 Effects of excretory/secretory products from Anisakis simplex (Nematoda) on immune gene expression in rainbow trout (Oncorhynchus mykiss) Fish.Shellfish.Immunol. 35 3 734-739 "Excretory/secretory (ES) products are molecules produced by parasitic nematodes, including larval Anisakis simplex, a parasite occurring in numerous marine fish hosts. The effects of these substances on host physiology have not been fully described. The present work elucidates the influence of ES substances on the fish immune system by measuring immune gene expression in spleen and liver of rainbow trout (Oncorhynchus mykiss) injected intraperitoneally with ES products isolated from A. simplex third stage larvae. The overall gene expression profile of exposed fish showed a generalized down-regulation of the immune genes tested, suggesting a role of ES proteins in immunomodulation. We also tested the enzymatic activity of the ES proteins and found that lipase, esterase/lipase, valine and cysteine arylamidases, naphthol-AS-BI-phosphohydrolase and alpha-galactosidase activities were present in the ES solution. This type of hydrolytic enzyme activity may play a role in nematode penetration of host tissue. In addition, based on the notion that A. simplex ES products may have an immune-depressive effect (by minimizing immune gene expression) it could also be suggested that worm enzymes directly target host immune molecules which would add to a decreased host immune response and increased worm survival" http://www.ncbi.nlm.nih.gov/pubmed/23769875 0 305 "P. Tadoori, R. Ravella, J. H. Silverstein, J. Gintautas and A. R. Abadir" 1990 Sufentanil-induced respiratory depression in dogs Prog.Clin.Biol.Res. 328 393-396 http://www.ncbi.nlm.nih.gov/pubmed/1968269 0 306 "C. Tian, C. J. Moore, P. Dodmane, C. H. Shao, D. J. Romberger, M. L. Toews and K. R. Bidasee" 2013 Dust from hog confinement facilities impairs Ca2+ mobilization from sarco(endo)plasmic reticulum by inhibiting ryanodine receptors J.Appl.Physiol (1985.) 114 5 665-674 "Individuals working in commercial hog confinement facilities have elevated incidences of headaches, depression, nausea, skeletal muscle weakness, fatigue, gastrointestinal disorders, and cardiovascular diseases, and the molecular mechanisms for these nonrespiratory ailments remain incompletely undefined. A common element underlying these diverse pathophysiologies is perturbation of intracellular Ca(2+) homeostasis. This study assessed whether the dust generated inside hog confinement facilities contains compounds that alter Ca(2+) mobilization via ryanodine receptors (RyRs), key intracellular channels responsible for mobilizing Ca(2+) from internal stores to elicit an array of physiologic functions. Hog barn dust (HBD) was extracted with phosphate-buffered saline, sterile-filtered (0.22 mum), and size-separated using Sephadex G-100 resin. Fractions (F) 1 through 9 (Mw >10,000 Da) had no measurable effects on RyR isoforms. However, F10 through F17, which contained compounds of Mw 0.05). Dietary supplementation of both organic and inorganic chromium significantly increased primary and secondary antibody responses (P < 0.01), and also improved H/L ratio (P < 0.05), CBH response (P < 0.01) as well as relative weights of thymus (P < 0.05) and spleen (P < 0.01). Both dietary organic and inorganic chromium caused an increase in serum concentrations of Cr and Zn (P < 0.01), but decreased the serum concentration of Cu (P < 0.01). These results suggest that supplemental chromium especially in organic form offers a good management practice to reduce heat stress-related depression in immunocompetence of broiler chicks" http://www.ncbi.nlm.nih.gov/pubmed/22127829 0 326 "E. J. Perez-Stable, J. Miranda, R. F. Munoz and Y. W. Ying" 1990 Depression in medical outpatients. Underrecognition and misdiagnosis Arch.Intern.Med. 150 5 1083-1088 "Depression is a common problem in medical outpatients, yet primary care physicians recognize the disorder in only about half of their depressed patients. We compared physician recognition of depression (defined by chart notation or prescription of antidepressants) with diagnoses generated by the Diagnostic Interview Schedule (DIS) in 265 medical outpatients. Using DIS criteria, diagnoses of major depression in the past year or dysthymia (chronic minor depression) were made in 70 patients. Physicians recognized as depressed only 25 (35.7%) of the 70 DIS-depressed patients. However, 36 patients who were not depressed according to DIS were ""recognized"" as depressed by physicians. Patients misdiagnosed as depressed by physicians were older, less educated, had more outpatient visits, and were prescribed more medications. Receiver operating characteristic curves of two self-report depression scales suggest that these scales may assist physicians in recognizing depressed outpatients. We conclude that physicians underrecognize and misdiagnose depression in medical outpatients" http://www.ncbi.nlm.nih.gov/pubmed/2184790 0 327 "N. C. de Fiebre, R. Dawson, Jr. and C. M. de Fiebre" 2002 The selectively bred high alcohol sensitivity (HAS) and low alcohol sensitivity (LAS) rats differ in sensitivity to nicotine Alcohol Clin.Exp.Res. 26 6 765-772 "BACKGROUND: Studies in rodents selectively bred to differ in alcohol sensitivity have suggested that nicotine and ethanol sensitivities may cosegregate during selective breeding. This suggests that ethanol and nicotine sensitivities may in part be genetically correlated. METHODS: Male and female high alcohol sensitivity (HAS), control alcohol sensitivity, and low alcohol sensitivity (LAS) rats were tested for nicotine-induced alterations in locomotor activity, body temperature, and seizure activity. Plasma and brain levels of nicotine and its primary metabolite, cotinine, were measured in these animals, as was the binding of [3H]cytisine, [3H]epibatidine, and [125I]alpha-bungarotoxin in eight brain regions. RESULTS: Both replicate HAS lines were more sensitive to nicotine-induced locomotor activity depression than the replicate LAS lines. No consistent HAS/LAS differences were seen on other measures of nicotine sensitivity; however, females were more susceptible to nicotine-induced seizures than males. No HAS/LAS differences in nicotine or cotinine levels were seen, nor were differences seen in the binding of nicotinic ligands. Females had higher levels of plasma cotinine and brain nicotine than males but had lower brain cotinine levels than males. CONCLUSIONS: Sensitivity to a specific action of nicotine cosegregates during selective breeding for differential sensitivity to a specific action of ethanol. The differential sensitivity of the HAS/LAS rats is due to differences in central nervous system sensitivity and not to pharmacokinetic differences. The differential central nervous system sensitivity cannot be explained by differences in the numbers of nicotinic receptors labeled in ligand-binding experiments. The apparent genetic correlation between ethanol and nicotine sensitivities suggests that common genes modulate, in part, the actions of both ethanol and nicotine and may explain the frequent coabuse of these agents" http://www.ncbi.nlm.nih.gov/pubmed/12068243 0 328 T. Szklarzewicz and A. Moskal 2001 "Ultrastructure, distribution, and transmission of endosymbionts in the whitefly Aleurochiton aceris Modeer (Insecta, Hemiptera, Aleyrodinea)" Protoplasma 218 01-Feb 45-53 "The body of the whitefly Aleurochiton aceris contains specialized cells, termed mycetocytes, that enclose endosymbiotic microorganisms. The endosymbionts are transmitted from one generation to the next transovarially. In contrast to other insects, in whiteflies whole intact mycetocytes migrate into the ovaries, traverse the follicular epithelium, and reach the oocyte surface (i.e., perivitellin space). The migration of mycetocytes begins in the last instar, called puparium, from which imagines emerge. During this stage the cytoplasm of mycetocytes is tightly packed with pleomorphic bacteria and less numerous coccoid microorganisms. In adult females the mycetocytes gather extracellularly in the depression of the vitellarial oocyte. Till the end of oogenesis neither pleomorphic nor coccoid microorganisms are released from mycetocytes into the oocyte" http://www.ncbi.nlm.nih.gov/pubmed/11732319 0 329 S. Gralewicz and R. Socko 1990 "Effects of a single exposure to chlorphenvinphos, an organophosphate insecticide, on hot-plate behaviour in rats" Pol.J.Occup.Med. 3 2 215-220 "Effect of a single i.p. exposure to an organophosphate insecticide, chlorphenvinphos (CVP), in doses of 1.0 and 3.0 mg/kg (one third and one tenth LD50, respectively), on the latency of the paw-lick response (hot plate test) was investigated in rats before and after a short inescapable footshock. The test was repeated twice on the 18th and 19th days after the exposure, i.e. after a time sufficient for a full recovery of cholinesterase activity in the blood and brain. On the first day of testing the groups did not differ with respect to the paw-lick latency before footshock. However, the paw-lick latency after footshock (the index of stress-induced analgesia) was significantly longer in rats exposed to the higher dose of CVP (3.0 mg/kg) than in the control animals. Twenty four hours later, in the control animals, the paw-lick latencies before footshock were shortened in comparison with those recorded on the day before. An opposite effect was observed in the rats exposed to 3.0 mg/kg of CVP. The data suggest that some alterations in the brain functional state may outlast the CVP induced depression of cholinesterase activity" http://www.ncbi.nlm.nih.gov/pubmed/2130875 0 330 "J. Cassuto, P. Nellgard, L. Stage and A. Jonsson" 1990 Amide local anesthetics reduce albumin extravasation in burn injuries Anesthesiology 72 2 302-307 "Burn injury was induced in anesthetized rats by exposing the abdominal skin to a temperature of 55 degrees C by means of a hot aluminum rod. Temperature was registered on a Grass polygraph. Skin exposure was interrupted when hot rod temperature had decreased to 45 degrees C. A full-thickness burn trauma of the skin was induced as judged from histologic sections. The burned skin was dissected and extravasation of Evans blue (EB) bound plasma albumin was quantified by a spectrophotometric technique and visualized by fluorescence microscopy. In the first set of experiments, one group of rats (n = 15) was topically treated with a lidocaine-prilocaine cream 5% (25 mg of each in 1 g; EMLA) for 1.5 h starting 15 min after inducing the burn injury. In one control group (n = 14) the thermal injury was treated with placebo cream. A second control group (n = 15) was topically treated with placebo cream without being exposed to thermal trauma. Results showed a significant inhibition of EB-albumin extravasation in the skin of burned rats treated with lidocaine-prilocaine cream compared with placebo-treated burned skin (P less than 0.001). EB-albumin contents in the skin of burned rats treated with lidocaine-prilocaine cream did not differ significantly from unburned skin (P greater than 0.05). In the second set of experiments continuous iv lidocaine infusions at a rate of 5 (n = 10), 10 (n = 12), 20 (n = 10), or 30 (n = 10) micrograms.kg-1.min-1 was given.(ABSTRACT TRUNCATED AT 250 WORDS)" http://www.ncbi.nlm.nih.gov/pubmed/2301761 0 331 T. Tervo and A. Palkama 1974 Histochemical findings on sodium-potassium activated adenosine triphosphatase (NaK-ATPase) activity in the cornea Acta Ophthalmol.Suppl 123 88-93 http://www.ncbi.nlm.nih.gov/pubmed/4368773 0 332 "B. Balaji, E. P. Kumar and A. Kumar" 2015 "Evaluation of standardized Bacopa monniera extract in sodium fluoride-induced behavioural, biochemical, and histopathological alterations in mice" Toxicol.Ind.Health 31 1 18-30 "Effect of standardized Bacopa monniera (BM; family: Scrophulariaceae) extract (100 and 300 mg/kg) against sodium fluoride (NaF; 100 and 200 ppm)-induced behavioural, biochemical, and neuropathological alterations in mice was evaluated. Akinesia, rotarod (motor coordination), forced swim test (depression), open field test (anxiety), transfer latency (memory), cholinesterase (ChE), and oxidative stress (superoxide dismutase, catalase, glutathione peroxidase, and lipid peroxidation) were determined in mice treated with NaF for 30 days alone and in combination with BM. NaF induced motor incoordination, depression, and memory impairment, and these were prevented by coadministration of BM in mice. However, NaF did not alter the weight gain, feed/water consumption, and anxiety profile. Suppression of ChE levels and increased oxidative stress were observed in mice treated with NaF. Coadministration of BM significantly improved the memory, ChE levels, and antioxidant enzymes but failed to alter the fluoride levels in NaF-treated mice. Histopathological studies revealed that BM protected the neuropathological alterations induced by NaF" http://www.ncbi.nlm.nih.gov/pubmed/23222693 1 333 "E. C. Padilla, P. Brevis, R. Zemelman and E. Vivaldi" 1988 [Effect of subinhibitory concentrations of antibacterial agents on the adherence of fimbriated Escherichia coli to uroepithelial cells] Rev.Latinoam.Microbiol. 30 1 05-Sep http://www.ncbi.nlm.nih.gov/pubmed/2902677 0 334 "M. K. Fouladi, M. J. Moseley, H. S. Jones and M. J. Tobin" 1998 Sleep disturbances among persons who are visually impaired: Survey of dog guide users "Journal of Visual Impairment and Blindness.92 (7) ()(pp 522-530), 1998.Date of Publication: July 1998." 7 522-530 "It is claimed that blindness may predispose individuals to disturbed sleep because light is an important mechanism for entraining circadian rhythms. One in five respondents in a survey described the quality of their sleep as either poor or very poor. Exercise was associated with better sleep, and depression with poorer sleep. That visual acuity did not predict the quality of sleep casts doubt on the notion that restricted visual (photic) input is a widespread cause of sleep disturbance among persons who are visually impaired. As with sighted persons, depression appears to be a highly significant risk factor for disturbed sleep in persons who are visually impaired" 0 335 S. J. Birren and E. Marder 2013 Neuroscience. Plasticity in the neurotransmitter repertoire Science 340 6131 436-437 http://www.ncbi.nlm.nih.gov/pubmed/23620040 0 336 "J. Kupper, A. Bidaut, A. Waldvogel, B. Emmenegger and H. Naegeli" 2005 Treatment of chronic copper poisoning with oral application of ammonium molybdate and natrium sulphate in milk sheep "Schweizer Archiv fur Tierheilkunde.147 (5) ()(pp 219-224), 2005.Date of Publication: May 2005." 5 219-224 "Four weeks after the introduction of a new ration, a herd of sheep in the Swiss midland area was affected by depression, anorexia, decreased milk production, anemia, hemoglobinuria and frequent recumbency. Seventeen ewes died within a few days. A diagnosis of chronic copper poisoning was based on the results of feed analysis, histopathological findings and the toxicological examination of liver tissue. The remaining sheep were treated with oral ammonium molybdate and sodium sulfate, which together provide an inexpensive alternative to the chelator D-penicillamine. This combination not only prevents further copper intake, but also supports its elimination from the hepatocellular storage compartments. Serum copper levels have been determined to monitor the mobilization of copper following this antidote therapy. © 2005 by Verlag Hans Huber, Hogrefe AG" DO - http://dx.doi.org/10.1024/0036-7281.147.05.219 0 337 K. J. Rose and F. L. Strand 1988 Mammalian neuromuscular development accelerated with early but slowed with late gestational administration of ACTH peptide Synapse 2 3 200-204 "The neuropeptide ACTH 4-10, a nonsteroidogenic fragment of adrenocorticotropic hormone, has two distinct and opposite effects on developing nerve and muscle. Muscle is positively influenced by ACTH during the first part of gestation (G days 3-12) before innervation occurs. Subsequent effects on innervation are largely depressive and exerted only during G13-21. Treatment during G3-12 increases twitch amplitude, rise time and speed of contraction of directly and indirectly stimulated extensor digitorum longus (EDL) muscle of two wk old rats. Treatment during G13-21 slows contractions of indirectly stimulated EDL, whereas treatment throughout gestation (G3-G21) shows little effect. Thus, ACTH first accelerates muscle development then modulates this development through neuronal depression" http://www.ncbi.nlm.nih.gov/pubmed/2850627 0 338 "C. L. Chang, J. C. Lee, C. C. Tseng, Y. H. Chang and J. T. Cheng" 1995 Decrease of anesthetics activity by electroacupuncture on Jen-Chung point in rabbits Neurosci.Lett. 202 01-Feb 93-96 "The effect of acupuncture at life-saving point on the central nervous depressive action of anesthetics was investigated in rabbits. Stimulation with electroacupuncture (EA) inserted in Jen-Chung point, which is located at the mid-point on the upper lip, decreased the sleeping time induced by pentobarbital or propofol. However, this action of acupuncture was not modified by naloxone at the doses sufficient to block opiate receptors. Plasma beta-endorphin detected by radioimmunoassay was also not markedly changed in rabbits which received similar electrostimulation. Moreover, pretreatment with para-chlorophenylalanine at a dose sufficient to deplete endogenous 5-hydroxytryptamine (5-HT) failed to influence the action of EA. Mediation of endogenous opioids and/or 5-HT in this action of EA was then ruled out. Prazosin reversed the sleeping time decreasing action of acupuncture in a dose-dependent manner. Also, the action of acupuncture was eliminated in rabbits which received intracerebroventricular injection of guanethidine at a dose which could block noradrenergic nerve terminals. It is suggested that stimulation of Jen-Chung point through EA can activate noradrenergic neurotransmission in the brain, which in turn reduces the central nervous depressive activity of anesthetics" http://www.ncbi.nlm.nih.gov/pubmed/8787839 0 339 "R. E. Carlson, R. J. Schott and A. J. Buda" 1989 Neutrophil depletion fails to modify myocardial no reflow and functional recovery after coronary reperfusion J.Am.Coll.Cardiol. 14 7 1803-1813 "Recent studies suggest that neutrophil accumulation and activation in postischemic myocardium may be responsible for myocardial no reflow, which is characterized by an incomplete restoration of blood flow after reperfusion. To examine this further, 11 open chest, anesthetized dogs received bolus injections of a bovine neutrophil antiserum that produced an average 81 +/- 5% depletion of circulating neutrophils, and 10 control dogs received nonimmune serum. Each animal underwent 2 h of left circumflex artery occlusion followed by 4 h of reperfusion. Simultaneous two-dimensional echocardiography and radioactive microsphere blood flow studies were performed at baseline, 2 h of occlusion and early (approximately 5 min) and 4 h of reperfusion. During occlusion, both groups developed similar reductions in myocardial blood flow and levels of ischemic zone myocardial wall thinning. At early reperfusion, similar levels of hyperemia and regional hypokinesia were observed for both groups. By late reperfusion, both groups experienced significant no reflow in the subendocardium (p less than 0.05) and reduced reflow in the mid-myocardium. Regional depression in ischemic zone function persisted throughout the reperfusion period in both groups. However, infarct size expressed as a percent of left ventricular weight, assessed by triphenyltetrazolium chloride staining, was smaller for the neutrophil depletion group compared with the control group (8.7 +/- 1.3% versus 13.1 +/- 1.8%, p less than 0.05). It is concluded that an 81% neutrophil depletion fails to modify the no reflow phenomenon or improve functional recovery after 2 h of coronary artery occlusion and 4 h of coronary reperfusion despite modification of the ultimate size of necrosis" http://www.ncbi.nlm.nih.gov/pubmed/2584572 0 340 E. Hayashi and S. Yamada 1975 "Pharmacological studies on surugatoxin, the toxic principle from Japanese ivory mollusc (Babylonia japonica)" Br.J.Pharmacol. 53 2 207-215 "1 Some pharmacological properties of surugatoxin (SGTX), a purified toxic substance from the Japanese ivory mollusc (Babylonia japonica), have been investigated. SGTX (50 nmol/kg i.v.) produced a prolonged fall of blood pressure in anaesthetized cats. This hypotensive effect was neither blocked by atropine and propranolol nor by spinal cord transection. 2 SGTX (37-50 nmol/kg i.v.) inhibited the hypertensive and hypotensive response to 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) and to electrical stimulation of the splanchnic and vagal nerve, whereas it usually augmented the hypertensive response to adrenaline and to 4-(m-chlorophenylcarbamoyloxy)-2-butynyltrimethylammonium chloride (McN-A-343) in anaesthetized cats. 3 Close intra-arterial injection of SGTX (6.2-12.3 nmol/kg) to the superior cervical ganglion blocked the contractile response of the nictitating membrane to preganglionic stimulation of cervical sympathetic nerve or injected DMPP, but not to postganglionic stimulation or to injected adrenaline and McN-A-343. 4 SGTX affected neither the indirectly nor the directly stimulated response of the rat isolated phrenic nerve-diaphragm at concentrations less than 12.3 mum. 5 The effect of SGTX on the contractile response to some agonists and on the twitch response to transmural stimulation in the guinea-pig isolated ileum was investigated. At less than 12.3 mumSGTX did not depress responses to acetylcholine or histamine. The curves for nicotine- and DMPP-induced contractions were shifted to the right and depressed gradually as the concentration of SGTX was increased (12.3 nm-1.23 mum). SGTX partially inhibited the contraction induced by 5-hyroxytryptamine and the transmurally-stimulated twitch response. 6 These results suggest that SGTX has a ganglion-blocking action. The mode of anti-nicotinic action of SGTX in the guinea-pig isolated ileum seems to differ from that of hexamethonium and tetraethylammonium and to resemble more closely that of mecamylamine" http://www.ncbi.nlm.nih.gov/pubmed/238699 0 341 "M. Kemp, P. Roberts, P. Pook, D. Jane, A. Jones, P. Jones, D. Sunter, P. Udvarhelyi and J. Watkins" 1994 Antagonism of presynaptically mediated depressant responses and cyclic AMP-coupled metabotropic glutamate receptors Eur.J.Pharmacol. 266 2 187-192 "The depression of monosynaptic excitation of neonatal rat motoneurones by (1S,3S)- and (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate (ACPD) and by L-2-amino-4-phosphonobutyrate (L-AP4), which is probably presynaptically mediated, is antagonized by (+/-)- and (+)-alpha-methyl-4-carboxyphenylglycine (MCPG). The same phenylglycine derivatives also antagonize the depression of forskolin-stimulated cyclic AMP synthesis effected by the two ACPD stereoisomers and by L-AP4. These results support previous suggestions that presynaptic depression is mediated by metabotropic glutamate receptors negatively coupled to adenylyl cyclase activity. MCPG is the first antagonist to be reported for these receptors" http://www.ncbi.nlm.nih.gov/pubmed/8157072 0 342 "P. B. Timmermans, P. H. Fluitman, J. C. Mackaay and P. A. van Zwieten" 1978 Hypotensive and bradycardic effects of classical alpha-sympathomimetic drugs upon intravenous administration to pentobarbitone-anaesthetized rats Arch.Int.Pharmacodyn.Ther. 231 1 98-103 "The effects of the classical alpha-sympathomimetic drugs naphazoline, tramazoline, xylometazoline, tetryzoline and oxymetazoline on blood pressure and heart rate of pentobarbitone-anaesthetized (75 mg/kg; i.p.) normotensive rats were studied following intravenous injections. With the aid of this experimental animal model a dose dependent decrease in mean arterial pressure and heart rate could be established for these agents, oxymetazoline excepted, for which only the bradycardia could be quantified. It is suggested that central alpha-adrenoceptors are involved in the mechanism of this cardiovascular inhibition in view of the most specific alpha-adrenoceptor-stimulating properties of these ddrugs. Additionally, the results indicate that the use of pentobarbitone as the anaesthetic enhances the hypotensive action of these agents, so that their pronounced peripheral vasopressive response can be overcome" http://www.ncbi.nlm.nih.gov/pubmed/25053 0 343 L. G. Garland 1973 Effect of cromoglycate on anaphylactic histamine release from rat peritoneal mast cells Br.J.Pharmacol. 49 1 128-130 Cromoglycate (1-30 muM) produced a concentration-dependent inhibition of anaphylactic histamine release from actively sensitized rat peritoneal mast cells but at lower concentrations (0.01-0.1 muM) occasionally produced a concentration-dependent enhancement of histamine release http://www.ncbi.nlm.nih.gov/pubmed/4132518 0 344 "R. E. Catalan, M. P. Castillon and J. G. Priego" 1978 Effect of clofibrate treatment on the protein kinase and cyclic AMP-binding activities in rat liver Horm.Metab Res. 10 5 450-451 http://www.ncbi.nlm.nih.gov/pubmed/213360 0 345 "N. Ghisovan, A. Nemri, S. Shumikhina and S. Molotchnikoff" 2009 Long adaptation reveals mostly attractive shifts of orientation tuning in cat primary visual cortex Neuroscience 164 3 1274-1283 "In the adult brain, sensory cortical neurons undergo transient changes of their response properties following prolonged exposure to an appropriate stimulus (adaptation). In cat V1, orientation-selective cells shift their preferred orientation after being adapted to a non-preferred orientation. There are conflicting reports as to the direction of those shifts, towards (attractive) or away (repulsive) from the adapter. Moreover, the mechanisms underlying attractive shifts remain unexplained. In the present investigation we show that attractive shifts are the most frequent outcome of a 12 min adaptation. Overall, cells displaying selectivity for oblique orientations exhibit significantly larger shifts than cells tuned to cardinal orientations. In addition, cells selective to cardinal orientations had larger shift amplitudes when the absolute difference between the original preferred orientation and the adapting orientation increased. Conversely, cells tuned to oblique orientations exhibited larger shift amplitudes when this absolute orientation difference was narrower. Hence, neurons tuned to oblique contours appear to show more plasticity in response to small perturbations. Two different mechanisms appear to produce attractive and repulsive orientation shifts. Attractive shifts result from concurrent response depression on the non-adapted flank and selective response facilitation on the adapted flank of the orientation tuning curve. In contrast, repulsive shifts are caused solely by response depression on the adapted flank. We suggest that an early mechanism leads to repulsive shifts while attractive shifts engage a subsequent late facilitation. A potential role for attractive shifts may be improved stimulus discrimination around the adapting orientation" http://www.ncbi.nlm.nih.gov/pubmed/19747528 0 346 "R. M. Quock, G. A. Beal and E. L. Chan" 1976 Quipazine: a serotoninergic hyperthermic agent in the rabbit J.Pharm.Pharmacol. 28 2 170-172 http://www.ncbi.nlm.nih.gov/pubmed/6684 1 347 "C. F. Simpson, R. C. Robbins and R. H. Harms" 1971 Microscopic and biochemical observations of aortae of turkeys fed copper-deficient diets with and without ascorbic acid J.Nutr. 101 10 1359-1366 http://www.ncbi.nlm.nih.gov/pubmed/5098876 0 348 "N. H. Zawia, C. J. Mattia and S. C. Bondy" 1991 Differential effects of difluoromethylornithine on basal and induced activity of cerebral ornithine decarboxylase and mRNA Neuropharmacology 30 4 337-343 "The induction of the activity of cerebral ornithine decarboxylase (EC 4.1.1.17) and mRNA by electrical stimulation exhibits regional differences. The effects of the enzyme inhibitor difluoromethylornithine on these regional variations was examined. Administration of this inhibitor resulted in pronounced depression of both basal and induced activity of ornithine decarboxylase in the hippocampus. Basal activity of the enzyme in the neocortex and the cerebellum appeared to be resistant to difluoromethylornithine but the induced enzyme activity was sensitive to the effects of this inhibitor. Susceptibility to difluoromethylornithine may be directly correlated with a slower turnover rate for ornithine decarboxylase. These results suggest that ornithine decarboxylase in the hippocampus may possess a longer half-life than its counterparts in other regions of the brain. Pretreatment with difluoromethylornithine had no effect on the induced ornithine decarboxylase mRNA in the neocortex. Thus, elevated activity of ornithine decarboxylase enzyme, due to electrical stimulation, appears to not have any effect on either the transcription or the decay rate of the induced ornithine decarboxylase mRNA. These findings support the concept of region-specific regulation of cerebral ornithine decarboxylase" http://www.ncbi.nlm.nih.gov/pubmed/1852267 0 349 "F. M. Schmidt, S. Schindler, M. Adamidis, M. Strauss, A. Trankner, R. Trampel, M. Walter, U. Hegerl, R. Turner, S. Geyer and P. Schonknecht" 2016 Habenula volume increases with disease severity in unmedicated major depressive disorder as revealed by 7T MRI Eur.Arch.Psychiatry Clin.Neurosci. "The habenula is a paired epithalamic structure involved in the pathogenesis of major depressive disorder (MDD). Evidence comes from its impact on the regulation of serotonergic and dopaminergic neurons, the role in emotional processing and studies on animal models of depression. The present study investigated habenula volumes in 20 unmedicated and 20 medicated MDD patients and 20 healthy controls for the first time by applying a triplanar segmentation algorithm on 7 Tesla magnetic resonance (MR) whole-brain T1 maps. The hypothesis of a right-side decrease of habenula volumes in the MDD patients was tested, and the relationship between volumetric abnormalities and disease severity was exploratively investigated. Absolute and relative total and hemispheric habenula volumes did not differ significantly between the three groups. In the patients with short duration of disease for which medication effects could be ruled out, significant correlations were found between bilateral habenula volumes and HAMD-17- and BDI-II-related severities. In the medicated patients, this positive relationship disappeared. Our findings suggest an involvement of habenula pathology in the beginning of MDD, while general effects independent of severity or stage of disease did not occur. Our findings warrant future combined tractographic and functional investigation using ultra-high-resolution in vivo MR imaging" http://www.ncbi.nlm.nih.gov/pubmed/26873703 0 350 "I. Bottger, H. Kriegel and O. Wieland" 1970 Fluctuation of hepatic enzymes important in glucose metabolism in relation to thyroid function Eur.J.Biochem. 13 2 253-257 http://www.ncbi.nlm.nih.gov/pubmed/4191594 0 351 "X. Zhu, P. Li, X. Hao, K. Wei, S. Min, J. Luo, F. Xie and J. Jin" 2015 Ketamine-mediated alleviation of electroconvulsive shock-induced memory impairment is associated with the regulation of neuroinflammation and soluble amyloid-beta peptide in depressive-like rats Neurosci.Lett. 599 32-37 "Electroconvulsive therapy (ECT) is an effective treatment for depression, but can result in memory deficits. This study aimed to determine whether ketamine could alleviate electroconvulsive shock (ECS, an analog of ECT in animals)-induced memory impairment and the potential molecular mechanism. Chronic unpredictable mild stress was used to generate animal models of depressive-like symptoms. Sixty adult male Sprague-Dawley rats were randomly divided into the following five groups: control group (group C); depressive-like model group (group D); ECS group (group DE); ketamine+ECS group (group DKE); and ketamine group (group DK). The sucrose preference test and Morris water maze were used to assess behavioral changes. The expression levels of Iba-1, IL-1beta and TNF-alpha were measured by immunohistochemistry and real-time PCR. Enzyme-linked immunosorbent assays were used to detect the levels of soluble Abeta. We found that ECS up-regulated the expression of Iba-1, promoted the release of IL-1beta and TNF-alpha, increased the levels of Abeta1-40 and Abeta1-42 in the hippocampus, and aggravated memory impairment of the depressive-like rats. However, ketamine reversed these ECS-induced molecular changes and effectively attenuated ECS-induced memory impairment. This cognitive protective effect of ketamine may be attributed to its suppression of ECS-induced neuroinflammation and reduction of the levels of soluble Abeta" http://www.ncbi.nlm.nih.gov/pubmed/25980993 1 352 "J. C. Romero, C. E. Ott, J. J. Aguilo, V. E. Torres and C. G. Strong" 1975 Role of prostaglandins in the reversal of one-kidney hypertension in the rabbit Circ.Res. 37 5 683-689 "Hypertensive rabbits with a clip on the renal artery of their solitary remaining kidney show an abrupt decrease in blood pressure after the arterial constriction is released. Although the mechanism underlying this phenomenon remains controversial, some experimental evidence suggests that it could be humorally mediated. The involvement of prostaglandins was investigated by examining the effect of the release of the arterial constriction on blood pressure, renal blood flow, glomerular filtration rate, and urinary output in five conscious single-kidney hypertensive rabbits in which prostaglandin synthesis was blocked with indomethacin (priming intravenous injection of 9 mg/kg followed by a constant infusion of 1 mg/kg hour-1). The results were compared with those obtained in another group of five single-kidney hypertensive rabbits submitted to the same protocol but not treated with indomethacin. The blockade of prostaglandin synthesis with indomethacin prevented the increments in renal blood flow and glomerular filtration rate seen in the control rabbits after unclipping a significantly retarded the appearance of diuresis and the fall in blood pressure. Despite these observations, the results do not indicate a major participation of prostaglandins in the reversal of single-kidney hypertension, because the decrease in blood pressure 9 hours after the removal of the arterial constriction was similar in both groups" http://www.ncbi.nlm.nih.gov/pubmed/1192565 0 353 "M. Wallisch, N. M. El Rody, B. Huang, D. R. Koop, J. R. Baker, Jr. and G. D. Olsen" 2012 Naloxone pro-drug rescues morphine induced respiratory depression in Sprague-Dawley rats Respir.Physiol Neurobiol. 180 1 52-60 "Respiratory depression is the main obstacle for the safe administration of morphine for acute pain after injury. Due to this complication, new delivery methods are needed to insure that safe and effective doses of opioid analgesics are administered during emergencies. A depot formulation containing a naloxone pro-drug was designed to release the antidote when morphine causes dangerous hypoxic conditions in the blood. The aim of this work was to test the naloxone release in vivo in response to a severe overdose of morphine in the Sprague-Dawley rat model. Non-invasive two-chamber plethysmography was used to monitor and record respiration and to test the capability of the naloxone pro-drug to respond to and rescue morphine-induced respiratory depression in the animal. We show that the pro-drug formulation can both prevent and reverse severe morphine induced respiratory depression. The animal model demonstrates that co-administration of the naloxone pro-drug reliably antagonizes profound respiratory depressive effects of morphine" http://www.ncbi.nlm.nih.gov/pubmed/22027217 0 354 "D. Andrzejczak, K. Kocon and R. Zieba" 2008 Influence of mirtazapine on the hypotensive activity of enalapril and propranolol in spontaneously hypertensive rats Basic Clin.Pharmacol.Toxicol. 103 5 450-454 "Mirtazapine is a noradrenergic and specific serotonergic antidepressant. The influence of the drug on the cardiovascular system has not been definitely determined. Therefore, we made an attempt to evaluate the influence of chronic administration of mirtazapine on the hypotensive action of a single administered dose of propranolol and enalapril in spontaneously hypertensive rats. The animals were divided into eight experimental groups. Mirtazapine (5 and 10 mg/kg) was administered intraperitoneally for 14 days. Twenty-four hours after the last administration of the drug, the rats received a single intraperitoneal dose of hypotensive drugs (propranolol 5 mg/kg or enalapril 10 mg/kg) or 1% solution of methylcellulose. Mirtazapine administered chronically did not affect the hypotensive effect of a single dose of propranolol or enalapril in spontaneously hypertensive rats. It seems that mirtazapine could be a useful drug in patients with depression accompanied by hypertension" http://www.ncbi.nlm.nih.gov/pubmed/18699796 0 355 G. D. Frye and G. R. Breese 1982 GABAergic modulation of ethanol-induced motor impairment J.Pharmacol.Exp.Ther. 223 3 750-756 "Direct or indirect pharmacological manipulation of gamma-aminobutyric acid (GABA) receptor activity was examined in relation to the motor incoordinating actions of ethanol in the rat. Ethanol (1.13-3.0 g/kg i.p.) caused a dose-dependent increase in the height of aerial righting. This motor impairment was increased selectively by intracisternal injection of the GABA agonists muscimol (0.10 microgram), 4,5,6,7-tetrahydroisoxazole(5,4-c) pyridin(3-ol) (1.0 microgram) and GABA (1000 micrograms). The GABA antagonist, bicuculline (1.0 and 5.0 micrograms intracisternally), reduced impairment. Thus, direct manipulation of GABA receptor activity modulated motor incoordination caused by ethanol. In addition, indirect-acting GABA-mimetics, such as gamma-acetylenic GABA (100 mg/kg i.p.), aminooxyacetic acid (50 mg/kg i.p.), ethanolamine-O-sulfate (250 mg/kg i.p.) and L-2,4-diaminobutyric acid (600 mg/kg i.p.) all potentiated the increase in the height of aerial righting caused by ethanol treatment. Failure of ethanol to modify the binding of [3H]muscimol to cerebral cortical membranes in vitro suggested there was no direct competition for GABA binding sites or facilitation of the binding of GABA to these sites by ethanol. Also, no simple relationship was observed between the degree of motor impairment caused by either ethanol or gamma-acetylenic GABA and changes in GABA concentration in three brain areas. Although GABAergic neurons may be involved in the mechanism underlying ethanol-induced depression of motor coordination, the interaction does not involve a direct activation of GABA receptors by ethanol" http://www.ncbi.nlm.nih.gov/pubmed/6292399 0 356 "M. Mancini, V. Ghiglieri, V. Bagetta, V. Pendolino, A. Vannelli, F. Cacace, D. Mineo, P. Calabresi and B. Picconi" 2016 Memantine alters striatal plasticity inducing a shift of synaptic responses toward long-term depression Neuropharmacology 101 341-350 "Memantine is an open channel blocker that antagonizes NMDA receptors reducing the inappropriate calcium (Ca(2+)) influx occurring in presence of moderately increased glutamate levels. At the same time, memantine has the ability to preserve the transient physiological activation of NMDA receptor, essential for learning and memory formation at synaptic level. In the present study we investigated the effects exerted by memantine on striatal synaptic plasticity in rat striatal spiny projection neurons (SPNs). In vitro application of memantine in striatal slices elicited a disruption of long-term potentiation (LTP) induction and maintenance, and revealed, in the majority of the recorded neurons, a long-term depression (LTD), whose amplitude was concentration-dependent (0.3-10 muM). Interestingly, preincubation with the dopamine (DA) D2 receptor antagonist sulpiride (10 muM) prevented memantine-induced LTD and restored LTP. Moreover, the DA D2 agonist quinpirole (10 muM), similarly to memantine, induced LTD in a subgroup of SPNs. In addition, memantine-induced LTD was also prevented by the CB1 endocannabinoid receptor antagonist AM 251 (1 muM). These results suggest that the actions exerted by memantine on striatal synaptic plasticity, and in particular the induction of LTD observed in SPNs, could be attributed to its ability to activate DA D2 receptors. By contrast, blockade of NMDA receptor is not involved in memantine-induced LTD since APV (30 muM) and MK801 (10 muM), two NMDA receptor antagonists, failed to induce this form of synaptic plasticity. Our data indicate that memantine could be used as treatment of neurological disorders in which DA D2 receptor represents a possible therapeutic target" http://www.ncbi.nlm.nih.gov/pubmed/26471421 0 357 "E. M. Jutkiewicz, K. C. Rice, J. R. Traynor and J. H. Woods" 2005 Separation of the convulsions and antidepressant-like effects produced by the delta-opioid agonist SNC80 in rats Psychopharmacology (Berl) 182 4 588-596 "RATIONALE: Delta-opioid agonists produce a number of behavioral effects, including convulsions, antinociception, locomotor stimulation, and antidepressant-like effects. The development of these compounds as treatments for depression is limited by their convulsive effects. Therefore, determining how to separate the convulsive and antidepressant-like characteristics of these compounds is essential for their potential clinical use. OBJECTIVE: The present study tests the hypothesis that the rate of delta-opioid agonist administration greatly contributes to the convulsive properties, but not the antidepressant-like effects, of delta-opioid agonists. MATERIALS AND METHODS: The delta-opioid agonist SNC80 (1, 3.2, and 10 mg kg-1 or vehicle) was administered to Sprague-Dawley rats by intravenous infusion over different durations of time (20 s, 20, or 60 min). Convulsions were measured by observation prior to determining antidepressant-like effects in the forced swim test. RESULTS: Slowing the rate of SNC80 administration minimized delta agonist-induced convulsions without altering the effects of SNC80 in the forced swim test. CONCLUSIONS: These data suggest that delta agonist-induced antidepressant properties are independent of convulsive effects, and that it may be possible to eliminate the convulsions produced by delta agonists, further promoting their potential clinical utility" http://www.ncbi.nlm.nih.gov/pubmed/16163520 1 358 "S. M. Albarenque, J. Shinozuka, K. Suzuki, H. Nakayama and K. Doi" 2000 Kinetics and distribution of transforming growth factor (TGF)-beta 1 mRNA in the dorsal skin of hypotrichotic WBN/ILA-Ht rats following topical application of T-2 toxin Exp.Toxicol.Pathol. 52 4 297-301 "Depression of basal cell proliferating activity and subsequent induction of basal cell apoptosis in the epidermis and infiltration of inflammatory cells including mast cells in the dermis were observed in the dorsal skin of hypotrichotic WBN/ILA-Ht rats following the topical application of T-2 toxin in our previous study (ALBARENQUE et al. 1999). In the present study, kinetics of TGF-beta 1 mRNA was investigated using the same experimental system. The level of TGF-beta 1 mRNA of the whole skin tissue measured by competitive RT-PCR method showed a slight elevation from 6 to 12 hours after treatment (HAT) and reached the significantly higher level at 24HAT compared with the control skin. The increase in signals of TGF-beta 1 mRNA detected by in situ hybridization method started at 3HAT in the epidermis and progressed thereafter both in the epidermis and in the dermis. These results suggest that the elevated level of TGF-beta 1 mRNA may have a close relation to the induction of epidermal basal cell apoptosis as well as to the intradermal infiltration of mast cells and fibroblasts following the topical application of T-2 toxin" http://www.ncbi.nlm.nih.gov/pubmed/10987180 0 359 A. S. Rice and S. B. McMahon 1994 Pre-emptive intrathecal administration of an NMDA receptor antagonist (AP-5) prevents hyper-reflexia in a model of persistent visceral pain Pain 57 3 335-340 "Dorsal horn sensitization following somatic noxious stimuli is partly mediated by the N-methyl-D-aspartate (NMDA) sub-type of glutamate receptor. This phenomenon has been comparatively sparsely investigated in the area of visceral pain. We have therefore investigated the role of spinal NMDA receptors in central sensitization in an animal model of persistent visceral pain. In anaesthetized rats the lumbosacral spinal cord was exposed by laminectomy and the pre-emptive effect of intrathecal AP-5 upon the hyper-reflexia associated with chemical inflammation of the bladder was investigated. The effect of intrathecal AP-5 (an NMDA receptor antagonist) upon the normal cystometrogram (CMG) was also measured. AP-5 (125-1000 micrograms) prevented the hyper-flexia associated with bladder inflammation in a dose-dependant fashion. In general, within the dose range 62.5-1000 micrograms, AP-5 had no significant effect upon the normal micturition reflex. However, at the top of this dose range a minor non-significant depression of this reflex was noted. NMDA receptors do not appear to mediate the micturition reflex at a spinal cord level. However, they are involved in the induction of hyper-reflexia following urinary bladder inflammation, this hyper-reflexia can be prevented by pre-emptive intrathecal administration of AP-5" http://www.ncbi.nlm.nih.gov/pubmed/7936711 0 360 "U. Knief, G. Hemmrich-Stanisak, M. Wittig, A. Franke, S. C. Griffith, B. Kempenaers and W. Forstmeier" 2015 Quantifying realized inbreeding in wild and captive animal populations Heredity (Edinb.) 114 4 397-403 "Most molecular measures of inbreeding do not measure inbreeding at the scale that is most relevant for understanding inbreeding depression-namely the proportion of the genome that is identical-by-descent (IBD). The inbreeding coefficient FPed obtained from pedigrees is a valuable estimator of IBD, but pedigrees are not always available, and cannot capture inbreeding loops that reach back in time further than the pedigree. We here propose a molecular approach to quantify the realized proportion of the genome that is IBD (propIBD), and we apply this method to a wild and a captive population of zebra finches (Taeniopygia guttata). In each of 948 wild and 1057 captive individuals we analyzed available single-nucleotide polymorphism (SNP) data (260 SNPs) spread over four different genomic regions in each population. This allowed us to determine whether any of these four regions was completely homozygous within an individual, which indicates IBD with high confidence. In the highly nomadic wild population, we did not find a single case of IBD, implying that inbreeding must be extremely rare (propIBD=0-0.00094, 95% CI). In the captive population, a five-generation pedigree strongly underestimated the average amount of realized inbreeding (FPed=0.0131A receptor agonist" British Journal of Pharmacology 156 2 January "Background and purpose: Activation of post-synaptic 5-HT1A receptors may provide enhanced therapy against depression. We describe the signal transduction profile of F15599, a novel 5-HT1A receptor agonist. Experimental approach: F15599 was compared with a chemical congener, F13714, and with (+)8-OH-DPAT in models of signal transduction in vitro and ex vivo. Key results: F15599 was highly selective for 5-HT1A receptors in binding experiments and in [35S]-GTPgammaS autoradiography of rat brain, where F15599 increased labelling in regions expressing 5-HT 1A receptors. In cell lines expressing h5-HT1A receptors, F15599 more potently stimulated extracellular signal-regulated kinase (ERK1/2) phosphorylation, compared with G-protein activation, internalization of h5-HT1A receptors or inhibition of cAMP accumulation. F13714, (+)8-OH-DPAT and 5-HT displayed a different rank order of potency for these responses. F15599 stimulated [35S]-GTPgammaS binding more potently in frontal cortex than raphe. F15599, unlike 5-HT, more potently and efficaciously stimulated Galphai than Galphao activation. In rat prefrontal cortex (a region expressing post-synaptic 5-HT1A receptors), F15599 potently activated ERK1/2 phosphorylation and strongly induced c-fos mRNA expression. In contrast, in raphe regions (expressing pre-synaptic 5-HT1A receptors) F15599 only weakly or did not induce c-fos mRNA expression. Finally, despite its more modest affinity in vitro, F15599 bound to 5-HT1A receptors in vivo almost as potently as F13714. Conclusions and implications: F15599 showed a distinctive activation profiles for 5-HT1A receptor-mediated signalling pathways, unlike those of reference agonists and consistent with functional selectivity at 5-HT1A receptors. In rat, F15599 potently activated signalling in prefrontal cortex, a feature likely to underlie its beneficial effects in models of depression and cognition. Mandarin translation of abstract. © 2009 The British Pharmacological Society" 0 394 J. N. Wiig 1974 Effect of neuraminidase on lymphoid cells. Differences in structure of B and T cells and thymocytes of the mouse shown by cell electrophoresis and sialic acid determination Scand.J.Immunol. 3 3 357-363 http://www.ncbi.nlm.nih.gov/pubmed/4604390 0 395 R. Dargel and E. Strack 1967 [Proton transport by mitochondrial membranes under the influence of L-palmitoylcarnitine] Naturwissenschaften 54 6 143 http://www.ncbi.nlm.nih.gov/pubmed/5584636 0 396 "K. Ohara, Y. Kobayashi, N. Tsuchiya, H. Furuoka and T. Matsui" 2001 Renal dysplasia in a Shih Tzu dog in Japan J.Vet.Med.Sci. 63 10 1127-1130 "A 5-month-old, male, Shih Tzu dog manifesting polyuria and polydipsia since 2-month-old was presented to our hospital with additional clinical complaints of vomiting and depression during recent a few days. Despite the symptomatic therapy for chronic renal failure, he died on the day after medication. Macroscopically, both kidneys were small in size with rough surface. Microscopical examination revealed bilateral renal fibrosis with dysplastic changes consisting of immature glomeruli and tubules, and foci of adenomatoid proliferation of tubular epithelium. In addition, incomplete lobulation of medulla with pelvic structures was also noticed in the right kidney. From these findings, the present case was diagnosed as renal dysplasia in Shih Tzu dog which was documented in the literatures" http://www.ncbi.nlm.nih.gov/pubmed/11714030 0 397 "L. Liu, J. Riese, K. Resch and V. Kaever" 1994 Impairment of macrophage eicosanoid and nitric oxide production by an alkaloid from Sinomenium acutum Arzneimittelforschung. 44 11 1223-1226 "The effects of sinomenine (7,8-didehydro-4-hydroxy-3,7-dimethoxy-17-methyl- 9 alpha,13 alpha,14 alpha-morphinan-6-one), a pure alkaloid extracted from the Chinese medical plant Sinomenium acutum, on different macrophage capacities were investigated in vitro using resident mouse peritoneal macrophages and the macrophage-like cell line RAW 264.7. Sinomenine markedly decreased prostaglandin E2 and leukotriene C4 synthesis of macrophages stimulated by zymosan or calcium ionophore and also significantly inhibited the nitric oxide production of RAW 264.7 cells activated by interferon-gamma/lipopolysaccharide. It can be considered that these effects are part of the analgesic, anti-inflammatory, and antirheumatic mechanisms of sinomenine" http://www.ncbi.nlm.nih.gov/pubmed/7848335 0 398 C. T. Hanks and E. O. Smith 1978 Inhibition of connective tissue proliferation by dermal extract J.Invest Dermatol. 71 3 172-176 "Following the subcutaneous injection of a water soluble dermal extract (DE) of neonatal rat skin into young adult male rats, depression of nuclear labeling (DNA synthesis) was observed in proliferating connective tissue in several wound sites. At 16--20 hr following DE injection, DNA synthesis was depressed most in back wounds (57--87%) and maxillary palatal wounds (45--68%), and least in ear wounds (24--29%). Epithelium in the wound margins of back, ear and palate did not show a similar depression in DE-injected animals. This study suggests that a chalone-like negative feedback mechanism may be partially responsible for in vivo control of fibroblastic proliferation in wound healing" http://www.ncbi.nlm.nih.gov/pubmed/690479 0 399 G. D'Mello and I. P. Stolerman 1977 Interaction of cocaine with chlordiazepoxide assessed by motor activity in mice Br.J.Pharmacol. 59 1 141-145 1 Effects of a range of doses of cocaine and chlordiazepoxide given separately and as mixtures were determined on the spontaneous locomotor activity of mice. 2 Cocaine increased locomotor activity (walking) during 3 or 5 min trials in a dose-related manner. 3 Chlordiazepoxide had little effect on the total amount of locomotor activity except for depression at very high doses. A lower dose of chlordiazepoxide increased activity at the beginning of the trials only. 4 Mixtures containing certain doses of cocaine and chlordiazepoxide increased locomotor activity ot a much greater extent than cocaine alone. This high level of activity was manifested throughout 5 min trials. 5 This action of cocaine is similar to that of amphetamine http://www.ncbi.nlm.nih.gov/pubmed/836994 0 400 "T. Tsunetoshi, A. Otsuka, H. Mikami, K. Katahira, A. Moriguchi and T. Ogihara" 1991 Effect of cromakalim (BRL 34915) on hemodynamic and electrocardiographic changes induced by endothelin in dogs Basic Res.Cardiol. 86 1 49-55 "We evaluated whether cromakalim (BRL 34915), a vasorelaxant agent which acts by opening potassium channels, could affect the systemic effects of endothelin, a newly discovered vasoconstrictive peptide. Intravenous administration of endothelin alone (400 pmol/kg) to anesthetized dogs produced blood pressure elevation, which was associated with an increase in cardiac output in the early phase, and was associated with an increase in total peripheral resistance in the late phase. Electrocardiogram showed significant ST-elevation in II, III, and aVF, and ST-depression in aVR and aVL. The same dose of endothelin given to dogs pretreated with cromakalim did not induce these hemodynamic and electrocardiographic changes. Thus, cromakalim, a potassium activator, inhibited the hemodynamic and electrocardiographic actions of endothelin, suggesting that hyperpolarization due to potassium channel activation inhibited the voltage-dependent calcium channel, which is thought to be a major mechanism for the pressor action of endothelin" http://www.ncbi.nlm.nih.gov/pubmed/1850597 0 401 T. A. Pugsley and W. Lippmann 1979 "Effect of acute and chronic treatment of tandamine, a new heterocyclic antidepressant, on biogenic amine metabolism and related activities" Naunyn Schmiedebergs Arch.Pharmacol. 308 3 239-247 "The effects of tandamine, a clinically effective heterocyclic antidepressant, administered either acutely (10 mg/kg i.p.) or chronically (10 mg/kg i.p. daily for 21 days) on biogenic amine uptake and metabolism in the rat were determined and a comparison with desipramine was made. Tandamine, similarly to desipramine, blocked norepinephrine (NE) uptake in rat brain and heart following both acute and chronic administration. No effect of tandamine on dopamine (DA) or serotonin (5-HT) uptake was observed. Both drugs lowered endogenous brain NE when given chronically but not acutely. In contrast, no such effect on brain DA and 5-HT or heart NE was observed. Tandamine, like desipramine, administered chronically prior to an intraventricular injection of 3H-NE, produced increases in the decline of 3H-NE as indicated by decreased 3H-NE with increased levels of 3H-normetanephrine in brain stem of rats, suggesting an increased turnover of NE. No such effect was observed following acute treatment. Both drugs increased the behavioural effects of L-Dopa following and acute oral administration, with tandamine appearing superior to desipramine at the lower dose examined (10 mg/kg). Tandamine was 57--833 times less effective in binding to rat brain muscarinic receptors than desipramine, imipramine, butriptyline and amitriptyline, respectively. Thus, tandamine affects biogenic amine mechanism following either acute or chronic administration in a fashion similar to desipramine, but unlike desipramine, it exhibits relatively little anticholinergic properties, a further indication of the potential use of tandamine in the treatment of human depression, particularly where an increase in drive is desired" http://www.ncbi.nlm.nih.gov/pubmed/503251 1 402 I. P. Ashmarin and E. L. Abenirova 1969 "[Effect of histones, protamine and actinomycin D and synthesis of brain RNA]" Vopr.Med.Khim. 15 5 532-535 http://www.ncbi.nlm.nih.gov/pubmed/5368091 0 403 "M. M. van Borren, J. G. Zegers, A. Baartscheer and J. H. Ravesloot" 2006 Contribution of NHE-1 to cell length shortening of normal and failing rabbit cardiac myocytes J.Mol.Cell Cardiol. 41 4 706-715 "At the same intracellular pH (pHi) Na+/H+ exchange (NHE-1) fluxes of ventricular myocytes of hypertrophied failing hearts (HFH) are increased. We assessed how NHE-1 affected cell length shortening. pHi was measured fluorimetrically in resting and twitching (1-3 Hz) normal and HFH rabbit myocytes. In HEPES-buffered solutions, increased NHE-1 fluxes (P=0.001, n=14) made HFH resting pHi 0.2+/-0.03 units more alkaline than control (n=27). In CO2/HCO3--buffered solutions, HFH resting pHi was not different (7.05+/-0.02, n=30). Twitching myocytes of both groups shortened 15-16% less per 0.1 pH unit acidification. In HEPES-buffered solutions, cariporide depressed cell length shortening of normal myocytes (1-3 Hz) by 16+/-5.4% (n=9, P=0.005). In HFH myocytes cariporide restored the positive force-frequency relationship (n=7, P=0.009), by depressing twitch amplitudes at 1 Hz (16+/-11%, P=0.047) but not at 2 and 3 Hz. The depressions were all caused by pHi acidification. In CO2/" http://www.ncbi.nlm.nih.gov/pubmed/16916522 0 404 W. R. Swindell and J. L. Bouzat 2006 Inbreeding depression and male survivorship in Drosophila: implications for senescence theory Genetics 172 1 317-327 "The extent to which inbreeding depression affects longevity and patterns of survivorship is an important issue from several research perspectives, including evolutionary biology, conservation biology, and the genetic analysis of quantitative traits. However, few previous inbreeding depression studies have considered longevity as a focal life-history trait. We maintained laboratory populations of Drosophila melanogaster at census population sizes of 2 and 10 male-female pairs for up to 66 generations and performed repeated assays of male survivorship throughout this time period. On average, significant levels of inbreeding depression were observed for median life span and age-specific mortality. For age-specific mortality, the severity of inbreeding depression increased over the life span. We found that a baseline inbreeding load of 0.307 lethal equivalents per gamete affected age-specific mortality, and that this value increased at a rate of 0.046 per day of the life span. With respect to some survivorship parameters, the differentiation of lineages was nonlinear with respect to the inbreeding coefficient, which suggested that nonadditive genetic variation contributed to variation among lineages. These findings provide insights into the genetic basis of longevity as a quantitative trait and have implications regarding the mutation-accumulation evolutionary explanation of senescence" http://www.ncbi.nlm.nih.gov/pubmed/16204222 0 405 G. D. Kuznetsov 1976 [Conditions for development of spreading cortical depression during application of direct current] Zh.Vyssh.Nerv.Deiat.Im I.P.Pavlova 26 3 647-650 http://www.ncbi.nlm.nih.gov/pubmed/941516 0 406 R. Chakraborty 1989 Can molecular imprinting explain heterozygote deficiency and hybrid vigor? Genetics 122 3 713-717 "Molecular imprinting, the phenomenon of differential expressions of a gene based on whether it is paternally or maternally derived, has been noted in mice, humans, and other nonmammalian organisms. Effects of differential imprinting are important not only in the study of the manifestation of deleterious genes; they have important evolutionary implications as well. It is shown here that molecular imprinting may mimic observations that are often construed to be due to hybrid vigor and/or inbreeding depression. Furthermore, if a locus undergoes differential imprinting, it also yields observed genotypic proportions which mimic heterozygote deficiency in the population without the aid of natural selection" http://www.ncbi.nlm.nih.gov/pubmed/2759426 0 407 T. J. Campbell 1983 "Kinetics of onset of rate-dependent effects of Class I antiarrhythmic drugs are important in determining their effects on refractoriness in guinea-pig ventricle, and provide a theoretical basis for their subclassification" Cardiovasc.Res. 17 6 344-352 "The kinetics of onset of rate-dependent depression of maximum rate of depolarisation (Vmax) of guinea-pig ventricular action potentials were studied for nine Class I anti-arrhythmic drugs using standard microelectrode techniques. The drugs were found to fall into three well-demarcated subgroups with ""fast"" (lignocaine, tocainide and mexiletine), ""intermediate"" (quinidine, disopyramide and procainamide) and ""slow"" (flecainide, encainide and lorcainide) kinetics. The ""fast"" drugs were found to share the ability to markedly prolong the effective refractory period (ERP) relative to the action potential duration (APD). The ""slow"" drugs had only minor effects on this parameter. The ""intermediate"" drugs produced small to moderate increases in ERP relative to APD but in addition significantly prolonged APD, which was shortened by the ""fast"" drugs. Thus, using the parameters of speed of onset of rate-dependent depression of Vmax and APD it was possible to subdivide the nine Class I drugs into three distinct subclasses" http://www.ncbi.nlm.nih.gov/pubmed/6883410 0 408 "D. W. Lorimer, N. E. Hakanson, P. D. Pion and R. E. Merideth" 1989 The effect of intravenous mannitol or oral glycerol on intraocular pressure in dogs Cornell Vet. 79 3 249-258 The effect of IV mannitol (1.5 gm/kg) or oral glycerol (1.4 and 2.0 gm/kg) on intraocular pressure (IOP) and serum osmolality (SOSM) was investigated in 24 normal dogs. Mean IOPs were significantly decreased from baseline values from 0.5 through 5.5 hours following mannitol administration with a mean maximum depression of 8.7 +/- 1.8 mm Hg whereas mean SOSM was significantly increased from baseline values. Mean IOPs were significantly decreased from baseline values from 1.0 through 10 hours following oral administration of 1.4 gm/kg glycerol with a mean maximal depression of 5.4 +/- 2.7 mm Hg. Mean SOSM increased initially followed by a significant decrease. The change in IOP following mannitol administration showed less variation (smaller standard deviations) than glycerol (1.4 gm/kg). Five of the 6 dogs that received the 2.0 gm/kg glycerol vomited; the mean IOP and SOSM values were not significantly altered from baseline values in these dogs. Four of 5 dogs given cooled (10C) 2.0 gm/kg glycerol vomited. The incidence of vomiting appeared to be dose related. Both mannitol and glycerol (1.4 gm/kg) are effective for decreasing IOP in normal dogs http://www.ncbi.nlm.nih.gov/pubmed/2502361 0 409 "K. Kabaya, M. Kusaka and M. Seki" 1994 Effect of recombinant human granulocyte colony-stimulating factor on variations of morphologically identifiable bone marrow cells in myelosuppressed mice In Vivo 8 6 1033-1039 "To examine the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on neutrophilic recovery after cytotoxic agents, the variations of marrow colony-forming units of granulocytes and macrophages (CFU-GM) and morphologically identifiable bone marrow cells were investigated in cyclophosphamide (CPA)-treated mice. In mice treated with CPA at 200mg/kg intraperitoneally (day 0), marked decreases in peripheral neutrophils and nucleated cells in the femur were observed. In the femur of mice treated with CPA, the greatest depression in number occurred firstly with CFU-GM and the most immature granulocytes, such as myeloblasts and promyelocytes, followed in turn by myelocytes, metamyelocytes and mature neutrophils. Administration of rhG-CSF for four successive days (days 1-4) after CPA treatment completely prevented the neutropenia. In the femur, rhG-CSF enhanced the recovery of progenitors and immature granulocytes from their depression in the order of their differentiation, and recovery of marrow neutrophils was also promoted. From these studies, we confirmed that rhG-CSF effects an increase in peripheral neutrophils by enhancing the proliferation and differentiation of CFU-GM and immature marrow granulocytes" http://www.ncbi.nlm.nih.gov/pubmed/7539636 0 410 Y. Takei and T. Tsuchida 2000 Role of the renin-angiotensin system in drinking of seawater-adapted eels Anguilla japonica: a reevaluation Am.J.Physiol Regul.Integr.Comp Physiol 279 3 R1105-R1111 "The role of ANG II, a potent dipsogenic hormone, in copious drinking of seawater eels was examined. SQ-14225 (SQ), an angiotensin-converting enzyme inhibitor, infused intra-arterially at 0.01-1 microgram. kg(-1). min(-1), depressed drinking and arterial blood pressure in a dose-dependent manner. The inhibition was accompanied by a small decrease in plasma ANG II concentration, which became significant at 1 microgram. kg(-1). min(-1). After the infusate was changed back to the vehicle, the depression of drinking and arterial pressure continued for >2 h, although plasma ANG II concentration rebounded above the level before SQ infusion. By contrast, infusion of anti-ANG II serum (0.01-1 microgram. kg(-1). min(-1)) did not suppress drinking and arterial pressure, although plasma ANG II concentration decreased to undetectable levels. Plasma atrial natriuretic peptide and plasma osmolality, which influence drinking rate in eels, did not change during SQ or antiserum infusions. These results suggest that the renin-angiotensin system plays only a minor role in the vigorous drinking observed in seawater eels. The results also suggest that the antidipsogenic and vasodepressor effects of SQ in seawater eels are not due solely to the inhibition of ANG II formation in plasma" http://www.ncbi.nlm.nih.gov/pubmed/10956272 0 411 M. D. Jones and I. Lucki 2005 Sex differences in the regulation of serotonergic transmission and behavior in 5-HT receptor knockout mice Neuropsychopharmacology 30 6 1039-1047 "Few studies have examined the relationship between genetics, stress, and sex-linked differences in neurotransmitter systems. Examining serotonin (5-HT) receptor knockout mice on stress-induced behavioral depression, female 5-HT1B receptor knockout mice demonstrated significantly reduced immobility than either male 5-HT1B receptor knockout mice or male and female wild-type mice on the tail suspension test (TST) and forced swimming test. The behavioral phenotype was identified as likely due to a disinhibition of 5-HT release, because depletion of 5-HT with parachlorophenylalanine selectively reduced immobility of female 5-HT1B receptor knockout mice in the TST. In contrast, male and female 5-HT1A receptor knockout mice demonstrated reduced immobility compared with control mice, but the depletion of 5-HT with PCPA did not reverse the antidepressant-like phenotype. Microdialysis studies confirmed significantly higher baseline levels of hippocampal 5-HT in female, but not male, 5-HT1B receptor knockout mice. Both male and female 5-HT1B receptor knockout mice demonstrated augmented dialysate responses to fluoxetine. Also, both male and female 5-HT1B receptor knockout mice demonstrated reductions of immobility in the TST after treatment with fluoxetine. Therefore, female 5-HT1B receptor knockout mice demonstrate a sex-linked disinhibition of 5-HT release that sustained higher baseline levels of hippocampal 5-HT and behavioral vulnerability to 5-HT depletion" http://www.ncbi.nlm.nih.gov/pubmed/15688089 1 412 "N. A. Curtin, J. V. Howarth, J. A. Rall, M. G. Wilson and R. C. Woledge" 1984 Simultaneous heat and tension measurements from single muscle cells Adv.Exp.Med.Biol. 170 887-899 "Simultaneous force and heat measurements were made in single cells from skeletal muscle of the frog during isometric twitches and tetani at 10 and 0 degree C. A Hill- Downing type thermopile of low heat capacity was used. In twitches, peak force development was found to be well correlated with heat production at both temperatures, during posttetanic twitch potentiation (at 10 degrees C) and during posttetanic twitch depression (at 0 degree C). In a twitch at 0 degree C, heat production started less than 14 msec after the stimulus had begun, before force development. As in whole muscle, the heat during a tetanus could be separated into two components: an early component produced at an exponentially decreasing rate, labile heat, and a steady rate, stable maintenance heat rate. Increasing temperature from 0 to 10 degrees C doubled the stable maintenance heat rate. At the higher temperature the time constant of labile heat production was halved and the quantity of labile heat decreased. When two tetani were given at 10 degrees C, a 5 min rest interval was required before the second tetanus produced the same force and heat as the first. At 0 degree C this interval was at least 10 min. With shorter intervals, both heat and force were depressed. At 10 degrees C both were depressed equally but at 0 degree C the effect on heat was greater than on force. At both temperatures labile heat was depressed to a greater extent than the stable maintenance heat rate. Results are interpreted in terms of possible calcium-parvalbumin interaction during a tetanus" http://www.ncbi.nlm.nih.gov/pubmed/6611044 0 413 "R. Cespuglio, C. Rousset, G. Debilly, C. Rochat and M. J. Millan" 2005 "Acute administration of the novel serotonin and noradrenaline reuptake inhibitor, S33005, markedly modifies sleep-wake cycle architecture in the rat" Psychopharmacology (Berl) 181 4 639-652 "RATIONALE: The interrelationship between depressive states and sleep-wake cycle architecture is characterised by a decreased latency to the first paradoxical sleep (PS) episode, together with an enhancement of PS during the first part of the night. Conversely, slow-wave sleep (SWS) is decreased and intermittent awakenings increased. Notably, antidepressant treatment is generally associated with a diminution of PS. OBJECTIVES: In light of these observations, we examined the influence of acute administration of the novel mixed serotonin-noradrenaline reuptake blocker, (-)1-(1-dimethylaminomethyl 5-methoxybenzocyclobutan-1-yl)-cyclohexanol HCl (S33005), upon sleep-wake architecture in rats. METHODS: Animals were injected with vehicle or incremental doses of S33005 at the onset of either the dark or light periods. Digitised polygraphic recordings were performed, and changes evoked by S33005 were determined over 24-h recording periods, i.e., number and duration of sleep-wake episodes, latencies to PS and SWS, power band spectra of the electroencephalogram (EEG) and circadian changes. RESULTS: At 0.04 mg/kg, S33005 was inactive, whereas at 0.63 mg/kg, it modestly increased PS latencies and diminished PS duration during the light period. At 10 mg/kg, S33005 reduced markedly PS duration for about 4-h when injected prior to both light and dark periods. Latency to PS was prolonged, and the circadian acrophase was delayed. These effects are in keeping with previous studies of monoamine reuptake inhibitors, but, notably, SWS duration was increased when S33005 was injected at the onset of the light phase (+4%). These changes occurred without marked modifications in circadian rhythmicity or EEG spectral band power. Finally, even at the highest dose of S33005, only a limited rebound of SWS (+5%) and PS (+10%) was apparent. Amongst antidepressant to date examined, this is an original profile of influence upon sleep patterns. CONCLUSIONS: These results demonstrate a pattern of influence of S33005 upon sleep-wake architecture in rats which is globally consistent with antidepressant properties, but with a distinctive enhancement of restorative slow-wave sleep" http://www.ncbi.nlm.nih.gov/pubmed/15983796 0 414 "A. Goldberg, P. A. Meredith, S. Miller, M. R. Moore and G. G. Thompson" 1978 Hepatic drug metabolism and haem biosynthesis in lead-poisoned rats Br.J.Pharmacol. 62 4 529-536 "1 Pretreatment of rats with intraperitoneal injections of lead was shown to result in a depression of the microsomal mixed function oxidase system, as assessed by a decrease in hepatic microsomal P-450 and b5 content and by a decrease in the activity of the enzymes aniline hydroxylase and aminopyrine demethylase. Lead had a more marked effect on cytochrome P-450 than b5. 2 The activity of the rate-limiting enzyme of haem biosynthesis, delta-aminolaevulinic acid synthase, was inversely correlated with the microsomal cytochrome P-450 content. 3 The activity of the haem biosynthetic enzymes delta-aminolaevulinic acid dehydratase, coproporphyrinogen oxidase and ferrochelatase were decreased by increasing lead pretreatment. 4 The activity of the haem catabolic enzyme, haem oxygenase, was increased by lead pretreatment" http://www.ncbi.nlm.nih.gov/pubmed/656697 0 415 "Y. Wang, M. Sunamori and T. Yoshida" 1996 Effect of the potassium-channel opener nicorandil as an adjunct to cardioplegia on myocardial preservation in isolated rabbit hearts Surg.Today 26 10 782-792 "We studied the effect of nicorandil on the hemodynamic, biochemical, and ultrastructural changes in rabbit hearts (n = 50) rendered cardioplegic with a single injection of Bretschneider's HTK solution over 30 min or 60 min at 37 degrees C or 15 degrees C, followed by reperfusion at 37 degrees C for 60 min. Particular attention was focused on the aspects of dose-response relationship, temperature sensitivity, and ischemic tolerance. Isolated hearts were prepared for modified Langendorff circulation using modified Krebs-Henseleit bicarbonate solution bubbled with a 95% O2(-5)% CO2 gas mixture, to which nicorandil (0, 0.1, 1, and 5 mM) was added. The optimal concentration of nicorandil was 1mM, which increased the recovery of left ventricular (LV) function, affecting coronary flow and the myocardial cyclic adenosine monophosphate, but not the myocardial concentrations of adenine nucleotide compounds or total calcium. These effects were abolished by the addition of glibenclamide to the HTK, but they were not diminished by a high potassium (K+) concentration of 20mM. The addition of nicorandil 1mM to the HTK at 15 degrees C did not improve the recovery of LV function. Our result suggested that nicorandil used adjunctly prevents LV functional depression after 30min, and possibly 60min of cardioplegia at 37 degrees C, and that this effect is not disturbed by a high K+ concentration up to 20 mM. However, nicorandil has temperature sensitivity whereby it loses its efficacy at 15 degrees C" http://www.ncbi.nlm.nih.gov/pubmed/8897676 0 416 "U. Trendelenburg, P. R. Draskoczy and K. H. Graefe" 1972 The influence of intraneuronal monoamine oxidase on neuronal net uptake of noradrenaline and on sensitivity to noradrenaline Adv.Biochem.Psychopharmacol. 5 371-377 http://www.ncbi.nlm.nih.gov/pubmed/5054208 0 417 "S. V. Rendig, E. A. Amsterdam, G. L. Henderson and D. T. Mason" 1980 "Comparative cardiac contractile actions of six narcotic analgesics: morphine, meperidine, pentazocine, fentanyl, methadone and l-alpha-acetylmethadol (LAAM)" J.Pharmacol.Exp.Ther. 215 1 259-265 "Cardiac muscle contractile responses to six narcotic analgesics (morphine, meperidine, pentazocine, fentanyl, methadone and l-alpha-acetylmethadol), at concentrations from 10(-8) to 10(-4) M, both in the presence and absence of the narcotic antagonist, naloxone, were studied in the isolated, isometric cat right ventricular papillary muscle preparation. Measurements of maximum developed tension (T), maximum rate of tension development (dT/dt) and time to peak tension indicated that no major changes in contractile function occurred with any narcotic at concentrations of 10(-8) to 10(-6) M except for small but significant (P < .05) increases in all three parameters at 10(-6) M fentanyl, and small but significant increases in dT/dt at 10(-8) to 10(-6) M meperidine. At 10(-5) M narcotic, dT/dt was significantly elevated in meperidine-treated muscles (+7%), but significantly reduced in muscles exposed to pentazocine (-8%) or l-alpha-acetylmethadol (-11%). For all six narcotics, the 10(-4) M drug concentration resulted in depression of contractile function that was often associated with nonresponsiveness to electrical stimulation. Pretreatment of muscles with naloxone (10(-4) M) did not prevent this reduction of contractile performance except at the highest concentration (10(-4) M) of meperidine. Following removal of drug, contractile performance improved to varying degrees (recovery to 72-97% of control T), except in l-alpha-acetylmethadol-treated muscles, in which there was no recovery of T. Isoproterenol (0.8 X 10(-7) M) elicited a positive inotropic response whether administered in the presence of 10(-4) M narcotic or following narcotic removal. We conclude that narcotic analgesics in high concentrations exert a direct myocardial depressant effect which is not prevented by naloxone and therefore is not mediated by interaction with opiate receptors. Rather, several effects, including myocardial depression, its reversibility by both drug removal and isoproterenol and decreased muscle excitability are consistent with the hypothesis that narcotic analgesics in high concentrations exert nonspecific, local anesthetic effect on the myocardium" http://www.ncbi.nlm.nih.gov/pubmed/6109016 0 418 "P. Ganguly, F. H. Holland and H. C. Brenhouse" 2015 Functional Uncoupling NMDAR NR2A Subunit from PSD-95 in the Prefrontal Cortex: Effects on Behavioral Dysfunction and Parvalbumin Loss after Early-Life Stress Neuropsychopharmacology 40 12 2666-2675 "Exposure to early-life stress increases vulnerability to psychiatric disorders, including depression, schizophrenia, and anxiety. Growing evidence implicates aberrant development of the prefrontal cortex (PFC) in the effects of early-life stress, which often emerge in adolescence or young adulthood. Specifically, early-life stress in the form of maternal separation (MS) in rodents has been shown to decrease parvalbumin (PVB)-positive interneurons in the adolescent PFC; however, the mechanism underpinning behavioral dysfunction and PVB loss is not yet known. We recently reported that MS causes overexpression of the NMDA subunit NR2A in the PFC of adolescent rats. Elevated PFC NR2A is also found in developmental models of schizophrenia and is correlated with behavioral deficits, acting largely through its association with the postsynaptic protein PSD-95. In addition, adolescent maturation of PVB-positive interneurons relies on NR2A-driven NMDA activity. Therefore, it is possible that the NR2A/PSD-95 signaling complex has a role in adolescent MS effects. Here, we aimed to determine whether a discrete manipulation of PFC NR2A could prevent MS effects on PFC-controlled behaviors, including cognition, anxiety, and novelty-induced hyperlocomotion, as well as PVB loss in adolescence. We intracranially infused the NR2A-specific blocking peptide TAT2A in order to uncouple NR2A from PSD-95 in the early-adolescent PFC, without antagonizing the NMDA receptor. We demonstrated that MS rats treated with TAT2A during early adolescence were protected from MS-induced PVB loss and exhibited less anxious behavior than those infused with control peptide. These data implicate NR2A-related N-methyl-D-aspartate receptor development in adolescent behavioral and neural consequences of early-life stress" http://www.ncbi.nlm.nih.gov/pubmed/25953359 1 419 M. I. Steinberg and K. Greenspan 1976 Intracellular electrophysiological alterations in canine cardiac conducting tissue induced by aprindine and lignocaine Cardiovasc.Res. 10 2 236-244 "The effects of aprindine and lignocaine (lidocaine USP) were compared on intracellularly recorded potentials from normal canine conducting tisues. Only aprindine produced marked depression of the maximum rate of rise (Vmax) of action potentials elicited at normal cycle lengths (1000 ms). Both compounds, however, produced enhanced depression of Vmax at short cycle lengths or at short S1-S2 coupling intervals at normal membrane resting potential. Both lignocaine and aprindine shorten the action potential duration (APD) and effective refractory period (ERP) but increase the EPR/APD ratio. These effects are easily reversible upon perfusion with drug-free solution only in the case of lignocaine" http://www.ncbi.nlm.nih.gov/pubmed/938991 0 420 "E. Cataldo, M. Brunelli, J. H. Byrne, E. Av-Ron, Y. Cai and D. A. Baxter" 2005 Computational model of touch sensory cells (T Cells) of the leech: role of the afterhyperpolarization (AHP) in activity-dependent conduction failure J.Comput.Neurosci. 18 1 May-24 "Bursts of spikes in T cells produce an AHP, which results from activation of a Na+/K+ pump and a Ca2+-dependent K+ current. Activity-dependent increases in the AHP are believed to induce conduction block of spikes in several regions of the neuron, which in turn, may decrease presynaptic invasion of spikes and thereby decrease transmitter release. To explore this possibility, we used the neurosimulator SNNAP to develop a multi-compartmental model of the T cell. The model incorporated empirical data that describe the geometry of the cell and activity-dependent changes of the AHP. Simulations indicated that at some branching points, activity-dependent increases of the AHP reduced the number of spikes transmitted from the minor receptive fields to the soma and beyond. More importantly, simulations also suggest that the AHP could modulate, under some circumstances, transmission from the soma to the synaptic terminals, suggesting that the AHP can regulate spike conduction within the presynaptic arborizations of the cell and could in principle contribute to the synaptic depression that is correlated with increases in the AHP" http://www.ncbi.nlm.nih.gov/pubmed/15789166 0 421 "M. Kubera, K. Curzytek, W. Duda, M. Leskiewicz, A. Basta-Kaim, B. Budziszewska, A. Roman, A. Zajicova, V. Holan, E. Szczesny, W. Lason and M. Maes" 2013 A new animal model of (chronic) depression induced by repeated and intermittent lipopolysaccharide administration for 4 months Brain Behav.Immun. 31 96-104 "Chronic activation of immune-inflammatory and oxidative and nitrosative stress (O&NS) pathways plays an important role in the pathophysiology of clinical depression. Increased IgA responses directed against LPS of gram-negative bacteria, indicating increased bacterial translocation, may be one of the drivers underpinning these pathways. There is a strong association between signs of bacterial translocation and chronicity of depression and O&NS, but not pro-inflammatory cytokines. The aims of the present study were to: (1) develop a new neurobehavioral model of (chronic) depression (anhedonic behavior) that may reflect chronic LPS stimulation and is associated with increased oxidative stress, and (2) to delineate the effects of fluoxetine on this new depression model. We established that in female mice repeated LPS injections once daily for 5 days (from 750 mug/kg to a maximal dose 1250 mug/kg; increasing doses for the first three days which were then gradually decreased on day 4 and 5) at a one-month interval and this repeated for 4 consecutive months induced chronic anhedonia (estimated by the preference to drink a 1% sucrose) lasting for at least 7 weeks. Chronic LPS administration significantly decreased thymus weight, proliferative activity of splenocytes, production of interferon (IFN)gamma and interleukin-(IL)10, and increased superoxide and corticosterone production. Treatment with fluoxetine for 3 weeks abolished the neurobehavioral effects of LPS. The antidepressant effect of fluoxetine was accompanied by increased production of IL-10 and reduced superoxide and corticosterone production. Our results suggest that repeated intermittent LPS injections to female mice may be a useful model of chronic depression and in particular for the depressogenic effects of long standing activation of the toll-like receptor IV complex" http://www.ncbi.nlm.nih.gov/pubmed/23313516 1 422 "G. Balsamo, V. M. De, F. Marmo and G. Parisi" 1969 "The effect of 4,5-dichlor-1,3-benzendisulfonamide and of 4,5-dichlor-1,3-benzendisulfonylaniline on the morphogenesis of the otoliths in the chick embryo" Experientia 25 3 292-293 http://www.ncbi.nlm.nih.gov/pubmed/5781545 0 423 I. Pushkarev 1984 [Adrenergic mechanisms of the cystic plexus in the cat] Fiziol.Zh.SSSR Im I.M.Sechenova 70 4 464-467 "Hypogastric and pelvic nerves were stimulated in experiments carried out on isolated vesical plexuses of the cat as well as intra-or extracellular recording of the activity of vesical ganglion neurons was conducted. Characteristics of evoked responses, ganglionic lability, rhythmic and posttetanic potentiation were studied. Homosynaptic presynaptic origin of posttetanic potentiation was noted. Suppression of ganglionic recording in stimulation of sympathetic fibres and in intraarterial injections of catecholamines is suggested to be connected with presynaptic adrenergic inhibition. This suggestion was confirmed in experiments with administration of reserpine and phenoxybenzidine" http://www.ncbi.nlm.nih.gov/pubmed/6734841 0 424 "M. L. Van Etten, J. A. Tate, S. H. Anderson, D. Kelly, J. J. Ladley, M. F. Merrett, P. G. Peterson and A. W. Robertson" 2015 "The compounding effects of high pollen limitation, selfing rates and inbreeding depression leave a New Zealand tree with few viable offspring" Ann.Bot. 116 5 833-843 "BACKGROUND AND AIMS: Interactions between species are especially sensitive to environmental changes. The interaction between plants and pollinators is of particular interest given the potential current global decline in pollinators. Reduced pollinator services can be compensated for in some plant species by self-pollination. However, if inbreeding depression is high, selfed progeny could die prior to reaching adulthood, leading to cryptic recruitment failure. METHODS: To examine this scenario, pollinator abundance, pollen limitation, selfing rates and inbreeding depression were examined in 12 populations of varying disturbance levels in Sophora microphylla (Fabaceae), an endemic New Zealand tree species. KEY RESULTS: High pollen limitation was found in all populations (average of 58 % reduction in seed production, nine populations), together with high selfing rates (61 % of offspring selfed, six populations) and high inbreeding depression (selfed offspring 86 % less fit, six populations). Pollen limitation was associated with lower visitation rates by the two endemic bird pollinators. CONCLUSIONS: The results suggest that for these populations, over half of the seeds produced are genetically doomed. This reduction in the fitness of progeny due to reduced pollinator service is probably important to population dynamics of other New Zealand species. More broadly, the results suggest that measures of seed production or seedling densities may be a gross overestimate of the effective offspring production. This could lead to cryptic recruitment failure, i.e. a decline in successful reproduction despite high progeny production. Given the global extent of pollinator declines, cryptic recruitment failure may be widespread" http://www.ncbi.nlm.nih.gov/pubmed/26229065 0 425 "G. Benzi, E. Arrigoni, A. Ferrara and P. Mascherpa" 1969 Action of adenosine triphosphate on the depressed spontaneous electrical activity of the dog cerebral cortex J.Pharm.Sci. 58 9 1161-1163 http://www.ncbi.nlm.nih.gov/pubmed/5346088 0 426 H. H. Barahona and L. V. Melendez 1971 Herpesvirus saimiri: in vitro sensitivity to virus-induced interferon and to polyriboinosinic acid: polyribocytidylic acid Proc.Soc.Exp.Biol.Med. 136 4 1163-1167 http://www.ncbi.nlm.nih.gov/pubmed/4324740 0 427 S. D. Turner and R. L. Hazelwood 1973 "Does histamine play a role in the secretogogic effect of avian pancreatic ""gastrin""?" Proc.Soc.Exp.Biol.Med. 144 3 852-856 http://www.ncbi.nlm.nih.gov/pubmed/4765963 0 428 J. Moniuszko-Jakoniuk 1974 An influence of insulin on the effect of prostigmin in healthy mice and in mice with alloxan-induced diabetes mellitus Acta Physiol Pol. 25 5 497-508 http://www.ncbi.nlm.nih.gov/pubmed/4428994 0 429 K. Mlyniec and G. Nowak 2012 Zinc deficiency induces behavioral alterations in the tail suspension test in mice. Effect of antidepressants Pharmacol.Rep. 64 2 249-255 "BACKGROUND: Recently, experimental zinc deficiency has been correlated with depression-like alterations in rodents. METHODS: In the first part of present study, the time course of zinc deficient diet induced alterations in the tail suspension test (TST) in mice was investigated. In the second part, the effect of imipramine and escitalopram in control and zinc-deprived for 3 weeks mice was examined in the TST. RESULTS: A4- and 10-week administration of a Zn-deficient diet enhanced the immobility time in the TST (by 20% and 57%, respectively). By contrast, a 2-week period of a zinc deficient diet effected the reduction (by 24%) of the immobility time. Moreover, a 2- and 4-week (but not 10-week) of a Zn-deficient diet resulted in the reduction of the body weight (by 37% and 18%, respectively). These results indicate the developing response to zinc deficiency induced by a zinc-deficient diet. The antidepressant-like effect (reduction in the immobility time) of both drugs was significantly reduced in zinc-deprived mice, which suggests treatment-resistance induced by zinc deprivation. CONCLUSION: Zinc deprivation induces ""pro-depressive"" behavior and alters antidepressant efficacy" http://www.ncbi.nlm.nih.gov/pubmed/22661173 1 430 M. Degre and K. Elgjo 1974 Influence of synthetic polynucleotides and interferon on in vitro growth of cells derived from a mouse sarcoma Acta Pathol.Microbiol.Scand.Suppl Suppl 248 61-68 http://www.ncbi.nlm.nih.gov/pubmed/4217556 0 431 E. N. Serdiuk and L. A. Koval'chuk 1971 [Comparative evaluation of the antiarrhythmic effect of derivatives of diphenylacetic acid and novocaine amide] Farmakol.Toksikol. 34 2 168-170 http://www.ncbi.nlm.nih.gov/pubmed/5563386 0 432 M. I. Maizelis and A. L. Zabludovskii 1976 [Changes in the incorporation of labelled amino acids into proteins and homogenates of the brains of rats that have suffered acute hypoxia in the antenatal period] Biull.Eksp.Biol.Med. 82 9 1061-1064 "The authors studied C14-leucine and S35-methionine incorporation into the brain tissue homogenates and protein from different parts of the brain of rats subjected to intrauterine hypoxia. Depression of protein synthesis in certain brain structures, particularly in the hyppocampus was observed alongside with the stimulation of the amino acid incorporation into proteins of the other parts of the brain. Changes of the amino acid penetration into tissue homogenates fialed to correlate with the rate of their incorporation into proteins in separate structures of the brain. Experimental results pointed to disfunction in the protein metabolism intensity and in the blood-brain barrier system occurring during the late ontogenesis in rats surviving the intrauterine hypoxia" http://www.ncbi.nlm.nih.gov/pubmed/1033001 0 433 "C. J. Winrow, K. Q. Tanis, D. R. Reiss, A. M. Rigby, J. M. Uslaner, V. N. Uebele, S. M. Doran, S. V. Fox, S. L. Garson, A. L. Gotter, D. M. Levine, A. J. Roecker, P. J. Coleman, K. S. Koblan and J. J. Renger" 2010 Orexin receptor antagonism prevents transcriptional and behavioral plasticity resulting from stimulant exposure Neuropharmacology 58 1 185-194 "Orexin is a key neurotransmitter of central arousal and reward circuits in the CNS. Two receptors respond to orexin signaling, Orexin 1 Receptor (OX1R) and Orexin 2 Receptor (OX2R) with partially overlapping brain distributions. Genetic and pharmacological studies suggest orexin receptor antagonists could provide therapeutic benefit for insomnia and other disorders in which sleep/wake cycles are disrupted. Preclinical data has also emerged showing that the orexin system is involved in the behavioral and neurological effects of drugs of abuse (Aston-Jones et al., 2009; Harris et al., 2005). Here we report sleep promoting effects of a recently described small molecule dual orexin receptor OX1R and OX2R antagonist. This dual orexin receptor antagonist (DORA) also inhibits the ability of subchronic amphetamine to produce behavioral sensitization measured 10 days following pre-treatment. Transcriptional profiling of isolated reward and arousal circuits from brains of behaviorally sensitized animals showed that the DORA blocked the significant alteration of gene expression levels in response to amphetamine exposure, particularly those associated with synaptic plasticity in the VTA. Further, DORA attenuates the ability of nicotine to induce reinstatement of extinguished responding for a reinforcer, demonstrating selectivity of the effect to reward pathways and not to food intake. In summary, these data demonstrate efficacy of a dual orexin receptor antagonist for promotion of sleep and suggest that pharmacological inhibition of the orexin system may play a role in both prevention of drug-induced plasticity and drug-relapse" http://www.ncbi.nlm.nih.gov/pubmed/19596018 0 434 K. Watanabe and Y. Goto 1975 Dibenamine blockade on gastric acid secretion in vitro and its protection by histamine antagonists Eur.J.Pharmacol. 30 2 133-139 "Experiments to protect the histamine receptor against dibenamine blockade were carried out to elucidate the pharmacological characteristics of the H2-histamine receptor system for gastric acid secretion in isolated bullfrog gastric mucosa. Dibenamine alone (5 times 10-minus 5 g/ml) irreversibly blocked both basal and histamine-stimulated acid secretion. However, when the preparation was treated with dibenamine in combination with histamine (1 times 10-minus 5 g/ml) irreversibly blocked both basal and histamine-stimulated acid secretion. However, when the preparation was treated with dibenamine in combination with histamine (1 times 10-minus 5 g/ml), the acid secretory response to histamine was restored after washing out dibenamine. Burimamide, an H2-receptor antagonist, also protected the histamine sensitivity against dibenamine blockade in the concentration of 1 times 10-minus 4 g/ml. Diphenhydramine and pyribenzamine were also protected with histamine receptor against dibenamine blockade. The acid secretion induced by the action of histamine on the diphenhydramine-protected receptor was antagonized by diphenhydramine as well as burimamide" http://www.ncbi.nlm.nih.gov/pubmed/236188 0 435 "G. Conductier, N. Dusticier, G. Lucas, F. Cote, G. Debonnel, A. Daszuta, A. Dumuis, A. Nieoullon, R. Hen, J. Bockaert and V. Compan" 2006 Adaptive changes in serotonin neurons of the raphe nuclei in 5-HT(4) receptor knock-out mouse Eur.J.Neurosci. 24 4 1053-1062 "Decreased serotonin (5-HT) transmission is thought to underlie several mental diseases, including depression and feeding disorders. However, whether deficits in genes encoding G protein-coupled receptors may down-regulate the activity of 5-HT neurons is unknown currently. Based on recent evidence that stress-induced anorexia may involve 5-HT(4)receptors (5-HT(4)R), we measured various aspects of 5-HT function in 5-HT(4)R knock-out (KO) mice. When compared to dorsal raphe nucleus (DRN) 5-HT neurons from wild-type mice, those from 5-HT(4)R KO mice exhibited reduced spontaneous electrical activity. This reduced activity was associated with diminished tissue levels of 5-HT and its main metabolite, 5-hydroxyindole acetic acid (5-HIAA). Cumulative, systemic doses of the 5-HT uptake blocker citalopram, that reduced 5-HT cell firing by 30% in wild-type animals, completely inhibited 5-HT neuron firing in the KO mice. This effect was reversed by administration of the 5-HT(1A) receptor (5-HT(1A)R) antagonist, WAY100635, in mice of both genotypes. Other changes in DRN of the KO mice included increases in the levels of 5-HT plasma membrane transporter sites and mRNA, as well as a decrease in the density of 5-HT(1A)R sites without any change in 5-HT(1A) mRNA content. With the exception of increased 5-HT turnover index in the hypothalamus and nucleus accumbens and a decreased density of 5-HT(1A)R sites in the dorsal hippocampus (CA1) and septum, no major changes were detected in 5-HT territories of projection, suggesting region-specific adaptive changes. The mechanisms whereby 5-HT(4)R mediate a tonic positive influence on the firing activity of DRN 5-HT neurons and 5-HT content remain to be determined" http://www.ncbi.nlm.nih.gov/pubmed/16930432 1 436 "C. C. Huang, P. C. Yang, H. J. Lin and K. S. Hsu" 2007 Repeated cocaine administration impairs group II metabotropic glutamate receptor-mediated long-term depression in rat medial prefrontal cortex J.Neurosci. 27 11 2958-2968 "Drug-induced neuroadaptations within the medial prefrontal cortex (mPFC) are thought to underlie the development of cocaine sensitization. Here, we report that repeated cocaine administration in vivo impaired the long-term depression (LTD) induced by bath application of group II metabotropic glutamate receptor (mGluR) agonists DCG-IV [2S, 2'R, 3'R)-2-(2', 3'-dicarboxycyclopropyl)glycine] or LY379268 [(1R,4R,5S,6R)-4-amino-2-oxabicyclo[3.1.0]hexane-4,6-dicarboxylic acid] at excitatory synapses onto layer V pyramidal neurons of rat mPFC. In contrast, this impairment was not found in slices from rats treated with saline or a single dose of cocaine. Such effect of cocaine was selectively prevented when cocaine was coadministered with the selective D1-like receptor antagonist SCH23390 [(R)-(+)-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine]. In slices from control rats, a brief application of either protein kinase C (PKC) activator phorbol-12,13-dibutyrate or adenosine A3 receptor agonist 2-chloro-N6-(3-iodobenzyl)-adenosine-5-N-methyluronamide mimicked the effect of repeated cocaine treatment to impair the induction of LTD. Bilateral intra-mPFC infusion of PKC inhibitor bisindolylmaleimide I or adenosine A3 receptor antagonist MRS1220 (N-[9-chloro-2-(2-furanyl)[1,2,4]-triazolo[1,5-c]quinazolin-5-benzeneacetamide) before cocaine injection prevented cocaine-induced impairment of LTD induction. Furthermore, endogenous adenosine tone is greater in slices from cocaine-treated rats than from the saline-treated controls. When the metabolism of cAMP to adenosine was blocked, the extent of LTD in slices from saline and cocaine-treated rats was similar. These results suggest that cocaine-induced impairment of group II mGluR-mediated LTD is caused, at least in part, by an increase in adenosine subsequent to the rise in cAMP after D1-like receptor activation, which leads to an adenosine A3 receptor-mediated upregulation of PKC activity and thereby triggers an inhibition of group II metabotropic glutamate receptor function" http://www.ncbi.nlm.nih.gov/pubmed/17360919 0 437 "J. Sandegard, O. Jonsson and B. E. Zachrisson" 1974 Ionic distribution in arterial smooth muscle and persistent vasodilation after soft-tissue trauma Eur.Surg.Res. 6 6 321-329 http://www.ncbi.nlm.nih.gov/pubmed/4448207 0 438 "M. Kanter, H. Uysal, T. Karaca and H. O. Sagmanligil" 2006 Depression of glucose levels and partial restoration of pancreatic beta-cell damage by melatonin in streptozotocin-induced diabetic rats Arch.Toxicol. 80 6 362-369 "Diabetes mellitus is a common but serious metabolic disorder associated with many functional and structural complications. Glucose metabolism is disturbed due to an absolute or relative insulin deficiency. The experiment was carried out to determine the effect of melatonin on blood glucose and insulin concentrations, and histopathology of pancreatic beta-cells in streptozotocin (STZ)-induced diabetic rats. The rats were randomly allocated into one of the four experimental groups: group A (control), group B (diabetic untreated), group C (diabetic treated with melatonin for 6 weeks) and group D (diabetic treated with melatonin for 8 weeks); each group contained ten animals. Diabetes was induced in B, C and D groups by a single intraperitoneal (i.p.) injection of STZ (50 mg/kg, freshly dissolved in 5 mmol/l citrate buffer, pH 4.5). The rats in melatonin-treated groups were subjected to the daily i.p injection of 10 mg kg(-1) of melatonin for 6 or 8 weeks starting the day after STZ injection. Control and diabetic untreated rats were injected with the same volume of isotonic NaCl as the melatonin treated groups. Almost all insulin-positive beta-cells were degranulated, degenerated or necrotic in the STZ-treated rats leading to decrease in insulin secretion and an increase in blood glucose concentration. Melatonin treatment caused a sharp decrease in the elevated serum glucose, a slight increase in the lowered serum insulin concentrations and small partial regeneration/proliferation of beta-cells of islets. It is concluded that the hypoglycemic action of melatonin could be partly due to small amelioration in the beta-cells of pancreatic islets causing a slight increase in insulin secretion, it is mostly due to the extrapancreatic actions of the melatonin" http://www.ncbi.nlm.nih.gov/pubmed/16341692 0 439 "C. Hoyo-Becerra, A. Huebener, M. Trippler, M. Lutterbeck, Z. J. Liu, K. Truebner, T. Bajanowski, G. Gerken, D. M. Hermann and J. F. Schlaak" 2013 Concomitant interferon alpha stimulation and TLR3 activation induces neuronal expression of depression-related genes that are elevated in the brain of suicidal persons PLoS.One. 8 12 e83149 "We have previously identified 15 genes that are associated with the development of severe depressive side effects during the standard therapy with interferon alpha and ribavirin in the peripheral blood of hepatitis C virus infected patients. An enhanced expression of these genes was also found in the blood of psychiatric patients suffering severe depressive episode. Herein, we demonstrate that the same depression-related interferon-inducible genes (DRIIs) are also upregulated in post-mortem brains of suicidal individuals. Using cultured mouse hippocampal and prefrontal neurons we show that costimulation with murine IFN (mIFN) and the TLR3 agonist poly(I:C) promotes the expression of the described DRIIs, at the same time inducing pro-inflammatory cytokine expression through Stat1 and Stat3 activation, promoting neuronal apoptosis. Consequently, the upregulation of selective DRIIs, production of inflammatory cytokines and inhibition of neuronal plasticity may be involved in the pathogenesis of IFN-associated depression" http://www.ncbi.nlm.nih.gov/pubmed/24391741 0 440 "U. Meyer, K. M. van, E. Isovich, G. Flugge and E. Fuchs" 2001 Chronic psychosocial stress regulates the expression of both GR and MR mRNA in the hippocampal formation of tree shrews Hippocampus 11 3 329-336 "A persistent hyperactivity of the hypothalamic-pituitary-adrenal axis and thus elevated glucocorticoid levels are main neuroendocrine features of depressive symptomatology in humans. The broad range of effects that are set off by glucocorticoids is mediated by glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs), which themselves are subject to autoregulation. In order to investigate the impact of long-lasting psychological stress on corticosteroid receptor mRNA expression in the hippocampal formation, we employed the psychosocial stress paradigm in male tree shrews (Tupaia belangeri). By in situ hybridization studies and semiquantitative evaluation of stress-induced changes of GR and MR mRNA expression at the single-cell level, brain tissue from subordinate animals which were exposed to 27 days (1 h/day) of social confrontation was compared to that of nonstressed animals. Four weeks of stress exposure resulted in a downregulation of GR mRNA in the dentate gyrus and hippocampal subfields CA1 and CA3 of subordinate male tree shrews compared to controls. The MR mRNA content in these subfields of the anterior hippocampus was also clearly reduced. On the contrary, in a more posterior location on the longitudinal axis of the tree shrew hippocampus, the MR message was increased in subfields CA1 and CA3 and in the dentate gyrus. These results suggest a relevance of the stress-induced regulation of both corticosteroid receptor subtype mRNAs in a naturalistic challenging situation. Moreover, the differential regulation of MR mRNA along the rostrocaudal axis of the hippocampus adds another feature to the heterogenous composition of this structure" http://www.ncbi.nlm.nih.gov/pubmed/11769314 1 441 "K. A. Rahn, Y. J. Cao, C. W. Hendrix and A. I. Kaplin" 2015 The role of 5-HT1A receptors in mediating acute negative effects of antidepressants: implications in pediatric depression Transl.Psychiatry 5 e563 "Acute antidepressant exposure elevates the frequency of impulsive behavior and suicidal thoughts in children and adolescents with major depressive disorder (MDD). Long-term antidepressant treatment, however, is beneficial for pediatric MDD, so it is necessary to explore novel treatments that prevent the potentially dangerous consequences of acute antidepressant initiation. In the present study, a treatment strategy designed to reverse the acute negative behavioral effects of antidepressants was tested in rodents. Co-administration of the 5-HT1A receptor (5-HT1AR) antagonist WAY-100635 reversed the negative effects of acute fluoxetine, a serotonin reuptake inhibitor, but not reboxetine, a norepinephrine reuptake inhibitor, supporting the involvement of 5-HT1AR in mediating the negative consequences of acute selective serotonin reuptake inhibitor (SSRI) treatment. No 5-HT1AR antagonists are currently approved for use in pediatric populations, so alternative strategies should be explored. One such strategy was suggested based on the hypothesis that the rate of 5-HT1AR activation and the subsequent inhibition of serotonergic neuron activity caused by acute SSRI administration is proportional to the loading rate of an antidepressant. Existing pharmacological data were examined, and significant correlations were observed between the half-life of antidepressants and the rate of suicide-related events (SREs). Specifically, antidepressants with longer half-lives have lower rates of SREs. On the basis of these data, novel dosing strategies were developed for five antidepressants to mimic the pharmacological profile of the antidepressant with the longest half-life, fluoxetine. These dosing strategies could be used to decrease the rate of SREs associated with acute antidepressant treatment in pediatric MDD until an improved pharmacological treatment is developed" http://www.ncbi.nlm.nih.gov/pubmed/25942044 0 442 "P. Ghezzi, B. Saccardo and M. Bianchi" 1986 Induction of xanthine oxidase and heme oxygenase and depression of liver drug metabolism by interferon: a study with different recombinant interferons J.Interferon Res. 6 3 251-256 "Induction of xanthine oxidase in mouse liver by interferon (IFN) was studied with three different recombinant human leukocyte IFN molecules: IFLrA, IFLrD and the hybrid IFLrA/D(Bgl II). The ability of different IFN species to induce xanthine oxidase correlated with their ability to depress liver cytochrome P-450-dependent drug metabolism, supporting the hypothesis that reactive oxygen metabolites generated by xanthine oxidase might be responsible for this impairment of liver function by IFN. The antioxidant N-acetylcysteine protected in vivo against the depression of liver drug metabolism by IFLrA/D. IFLrA/D was also found to induce liver microsomal heme oxygenase, an effect that was probably secondary to the observed depression of cytochrome P-450" http://www.ncbi.nlm.nih.gov/pubmed/3018103 0 443 "E. Komatsu, I. Yamaguchi, H. Fukuyama, K. Takahashi and K. Miyazawa" 1993 Response of post-ischemic myocardium to sympathetic stimulation--relation to local norepinephrine release Jpn.Circ.J. 57 10 969-978 "Myocardial ischemia interrupts neurotransmission and causes the depression of norepinephrine release. However, the effects of sympathetic nerve stimulation on neurotransmission and norepinephrine release in post-ischemic myocardium are not well defined. We measured regional myocardial length and norepinephrine (NE) release during sympathetic nerve stimulation in anesthetized dogs. Dogs were divided into 2 groups: Group 1 (n = 14); sympathetic nerve stimulation, Group 2 (n = 9); pre-treatment with alpha-blockade yohimbine hydrochloride (0.2 mg/kg) followed by sympathetic nerve stimulation. The left anterior descending artery was occluded for 15 min. Sympathetic nerve stimulation was performed before coronary occlusion and after reperfusion. In group 1, the decrease in systolic shortening in the ischemic region persisted for more than 60 min. Although sympathetic nerve stimulation caused an increase in systolic shortening, it was lower than the pre-ischemic value. NE release from the post-ischemic myocardium remained decreased for 60 min. The decrease in the post-ischemic myocardial response to sympathetic nerve stimulation was associated with diminished NE release. When the cardiac sympathetic nerve was denervated with an epicardial phenol application, NE release decreased even further. In group 2, NE release did not decrease following reperfusion. These results suggest that sympathetic nerve conduction is not completely impaired in post-ischemic myocardium and that pre-synaptic alpha -2 receptors might play an important role in diminished NE release" http://www.ncbi.nlm.nih.gov/pubmed/8230678 0 444 "G. Bondesson, C. Hedbom, O. Magnusson and N. E. Stjernstrom" 1975 Potential hypolipidemic agents. XII. Synthesis and plasma lipid-lowering properties of some 3-pyridylmethyl ethers Acta Pharm.Suec. 12 05-Jun 445-454 http://www.ncbi.nlm.nih.gov/pubmed/1217497 0 445 "M. Chiavarini, E. Barocelli, V. Ballabeni, R. Razzetti and M. Impicciatore" 1992 Omeprazole-like compounds on histamine-stimulated acid and peptic secretions in conscious dog and cat Boll.Soc.Ital.Biol.Sper. 68 7 429-436 "A newly synthetized aniline derivative series has been tested on histamine-stimulated gastric acid secretion in conscious cats and dogs and compared to the proton pump inhibitors omeprazole and NC 1300. The compounds markedly and long-lastingly inhibited acid output with a potency lower than omeprazole but very close to the reference compound NC 1300. The results show that the introduction of a nitrogen atom, irrespective of the position in the benzimidazole ring does not seem to influence the gastric antisecretory activity" http://www.ncbi.nlm.nih.gov/pubmed/1482561 0 446 "P. A. Kelly, F. H. Gage, M. Ingvar, O. Lindvall, U. Stenevi and A. Bjorklund" 1985 Functional reactivation of the deafferented hippocampus by embryonic septal grafts as assessed by measurements of local glucose utilization Exp.Brain Res. 58 3 570-579 "Transection of the septo-hippocampal connections through fimbria-fornix damage in the rat results in profound hippocampal cholinergic deafferentation, and, when applied bilaterally, leads to severe and long-lasting impairments in learning and memory. Previous studies have shown that intrahippocampal septal grafts can reestablish a new cholinergic in the initially denervated hippocampal formation and at least partly compensate for the lesion-induced learning impairments in fimbria-fornix lesioned rats. The purpose of the present study was to determine the magnitude of lesion-induced alterations in cerebral function as reflected in local glucose use measured by (14C)-2-deoxyglucose (2-DG) autoradiography, and the degree to which this index of functional activity could be normalized following reinnervation from transplants of fetal cerebral tissue from the primordial septal region. Six months after unilateral fimbria-fornix transection the rate of glucose utilization was reduced markedly throughout the ipsilateral hippocampus when compared to the intact contralateral side, while in the neocortex only the cingulate cortex showed long-lasting reductions in glucose use. Rats that received a transplant of fetal septal-diagonal band tissue at the time of fimbria-fornix transection, and were sacrificed 6 months later, displayed significantly greater glucose utilization in the ipsilateral hippocampus and cingulate cortex than was measured in these areas in rats with lesion alone. The recovery in glucose use was paralleled by a significant increase in acetylcholinesterase (AChE) staining in several areas of the ipsilateral hippocampal formation and cingulate cortex. This index of graft-induced cholinergic reinnervation was, moreover, significantly correlated with the rate of glucose use. Thus, in the fimbria-fornix transected animals the magnitude of glucose depression correlated with the extent of reduction in AChE staining, and in the grafted animals the degree of normalization of glucose use was correlated with the graft-induced increase in AChE-staining density. These results thus indicate that the 2-DG autoradiographic technique can provide a unique opportunity to map both altered functional activity in localized areas of the brain following specific lesions and the extent to which transplant-derived reinnervation of the host may induce a return to normal functional levels in the target site" http://www.ncbi.nlm.nih.gov/pubmed/4007095 0 447 "C. R. A. F. Diniz, P. C. Casarotto and S. R. L. Joca" 2014 Antidepressant like effect of losartan infused into the ventral hippocampus "European Neuropsychopharmacology.Conference: 27th European College of Neuropsychopharmacology, ECNP Congress Berlin Germany.Conference Start: 20141018 Conference End: 20141021.Conference Publication: (var.pagings).24 ()(pp S368-S369), 2014.Date of Pu" var.pagings S368-S369 "Purpose: With the discovery of renin angiotensin system in the mammalian brain (limbic structures) arose the need to study its role on the behavior responses related to the stress exposure, including depression. In the population there is a high prevalence of both depression and hypertensive disorders and a high comorbidity between them. In this way, pieces of evidence suggest that drugs imparing the angiotensin system could relieve depressive symptoms [1]. In animals, several models related to the depression studies showed antidepressant effect by blocking this same system systemically [2]. But, until the moment little is known about the effect of this drugs on animal model of depression when brain infused in specific limbic structures related to depressive behavior. Our results introduce the influencing effect of losartan (angiotensin II, ANG II, antagonist AT1 receptor), administered systemically or infused into the dorsal (DH) or ventral hippocampus (VH) or in the ventral medial prefrontal cortex - prelimbic (PL), in rats submitted to the forced swimming test (FST). Methods: Male wistar rats were used. Losartan was intraperitoneally administered at 3, 10 and 30 mg/kg dose 1 before the test session. Independent groups were submitted to stereotactic surgery to bilateral guide cannula placement in the DH, VH or in the PL. Losartan was infused (500 nl/site) at the 0.1 or 1 or 10 nmol doses 10 min before the test session. If some treatment was successful in the FST open field (OF) test was performed to evaluate animal locomotor activity to avoid false positive antidepressant effect. Results: Losartan 30 mg/kg descreased the immobility time in the FST [F3,27 = 3.635; p<0.05]. Losartan at 0.1 or 1 or 10 nmol doses was also able to decrease immobility time when infused in the VH [F3,11 = 10.66; p<0.05], but not in the DH [F3,24 = 0.505; p>0.05] or in the PL [F2,24 = 0.604; p>0.05]. The treatment effect of systemic losartan or VH losartan in the FST wasn't due to any change in the animal locomotor activity, since both situations of treatment did not alter the number of animal crossing in the OF (systemic: t12 = 0.3492; VH: F3,11 = 0.1606; p>0.05). Conclusion: According to the results, losartan putatively acting in the VH AT1 receptors might be the responsible by systemic antidepressant effect of losartan. AT1 block in the PL and DH don't seem important for the effect of systemic losartan. It might also be speculated that ANG II acting on the AT1 receptor in the VH can be related to the depressive disorder. This last state finds support in evidence susggesting AT1 receptor gene polymorphism is associated with increased responsiveness to ANGII in depressive patients. According to our results revealing angiotensin system block influencing behavior responses related to the stress exposure, studies have shown systemic AT1 antagonistsprevents the hormonal, sympathoadrenal and anxiogenic response to isolation stress and prevents the formation of stress induced gastric ulcers [3]" 0 448 "F. Miglior, E. B. Burnside and J. C. Dekkers" 1995 Nonadditive genetic effects and inbreeding depression for somatic cell counts of Holstein cattle J.Dairy Sci. 78 5 1168-1173 "A total of 65,491 lactation means of log2-transformed SCC measures were analyzed from first lactation Holstein cows in Ontario. Effects of inbreeding on SCC were estimated by a nonadditive sire and dam model that included additive, dominance, and additive by additive genetic effects and regression of lactation somatic cell score on inbreeding coefficients of the cows. Variance components were estimated using the tildehat approximation to REML. Solutions were by iteration on data. Estimates of heritability for lactation somatic cell score in the narrow sense were .165 and in the broad sense were .203. The additive by additive component (2.5% of the total phenotypic variance) was almost twice as large as the dominance component (1.3%). The regression coefficient of lactation somatic cell score per 1% increase of inbreeding was .012. The average increase of the population mean of lactation somatic cell score caused by a 10% increase of inbreeding coefficient was estimated to be 10.5% of the original phenotypic standard deviation of 1.153. The inbreeding depression was thus relatively low, but, on average, inbred animals tended to have higher lactation somatic cell score. This study provides preliminary evidence that inbreeding is related to disease prevalence in large purebred dairy populations" http://www.ncbi.nlm.nih.gov/pubmed/7622727 0 449 J. H. Liles and P. A. Flecknell 1993 The effects of surgical stimulus on the rat and the influence of analgesic treatment Br.Vet.J. 149 6 515-525 "The effects of three graded mid-line abdominal operations were investigated in rats. All of the surgical procedures caused a significant reduction in food and water consumption, body weight and locomotor activity. Animals which had the skin incision alone showed significantly less depression of food and water consumption and body weight than groups which underwent laparotomy. The detrimental effects on water consumption and body weight could be significantly reduced by the administration of the opioid analgesic buprenorphine (TEMGESIC, Reckitt & Colman) (0.05 mg kg-1, s.c.). The stepped response to graded surgery, and the reduction of the depressant effects of surgery on food and water consumption by buprenorphine, suggest that some of these changes may be related to the presence of pain after an operation" http://www.ncbi.nlm.nih.gov/pubmed/8111612 0 450 "K. C. Kregel, D. G. Reynolds, N. J. Gurll and C. V. Gisolfi" 1985 Effects of opiate receptor drugs injected intracerebrally into the normovolemic and hypovolemic monkey Peptides 6 6 1161-1166 "Systemic injection of naloxone (NAL), an opioid-receptor antagonist, significantly elevates systolic blood pressure (SBP) in anesthetized hypovolemic monkeys, providing indirect evidence that endogenous opioids contribute to cardiovascular depression during shock. The purpose of this study was to identify specific centrally located opioid receptor sites that participate in SBP regulation under normovolemic and hypovolemic conditions. In 6 monkeys, bilateral guide cannulae were stereotaxically implanted above areas ranging from the diencephalon to the lower medulla. Microinjections (1 microliter) of D- Ala2-Met-enkephalinamide (DAME) (3.4-27.2 nM) into normovolemic unanesthetized monkeys reduced SBP by 10-65 mm Hg in a dose-related fashion. Subsequent injection of NAL (12.2 nM) attenuated this hypotensive response. Heart rate fell 20-40 bpm with DAME, but not in response to dose. In the anesthetized animal rendered hypotensive (SBP = 45 mm Hg) by hemorrhage. NAL injected into predetermined DAME-sensitive sites failed to increase SBP more than 5 mm Hg. Even consecutive injections into multiple sites elevated SBP only 20 mm Hg. We conclude that the centrally located opioid-sensitive sites tested exert only a mild influence in mediating hemorrhagic hypotension" http://www.ncbi.nlm.nih.gov/pubmed/3010258 0 451 "P. J. Allen, K. E. D'Anci, R. B. Kanarek and P. F. Renshaw" 2012 Sex-specific antidepressant effects of dietary creatine with and without sub-acute fluoxetine in rats Pharmacol.Biochem.Behav. 101 4 588-601 "The potential role of metabolic impairments in the pathophysiology of depression is motivating researchers to evaluate the treatment efficacy of creatine, a naturally occurring energetic and neuroprotective compound found in brain and muscle tissues. Growing evidence is demonstrating the benefit of oral creatine supplements for reducing depressive symptoms in humans and animals. A novel question is whether dietary creatine, when combined with antidepressant drug therapy, would be more effective than either compound alone. To answer this question, four studies were conducted to investigate the behavioral effects of combined creatine and low-dose fluoxetine treatment using the forced swim test in male and female rats. Sprague-Dawley rats were fed powdered rodent chow supplemented with 0%, 2% or 4% w/w creatine monohydrate for 5 weeks. Rats were injected with fluoxetine (5.0 or 10.0 mg/kg) or saline according to a sub-acute dosing schedule. Female rats maintained on a 4% creatine diet displayed antidepressant-like effects compared to non-supplemented females prior to fluoxetine treatment. In contrast, creatine did not alter behavior reliably in males. Following drug treatment and a second forced swim trial, the antidepressant-like profile of creatine remained significant only in females co-administered 5.0 mg/kg fluoxetine. Moreover, in females only, supplementation with 4% creatine produced a more robust antidepressant-like behavioral profile compared to either dose of fluoxetine alone. Estrous cycle data indicated that ovarian hormones influenced the antidepressant-like effects of creatine. Addressing the issue of sex differences in response to treatment may affect our understanding of creatine, its relationship with depressive behavior, and may lead to sex-specific therapeutic strategies" http://www.ncbi.nlm.nih.gov/pubmed/22429992 1 452 "P. A. Raymond, S. S. Easter, Jr., J. A. Burnham and M. K. Powers" 1983 Postembryonic growth of the optic tectum in goldfish. II. Modulation of cell proliferation by retinal fiber input J.Neurosci. 3 5 1092-1099 "The proliferation of cells in the germinal zone of the optic tectum of adult goldfish was studied following unilateral optic nerve crush or removal of one eye. Dividing germinal cells were labeled with [3H]thymidine, which was injected at various times (0 to 30 days) following surgery; fish were sacrificed after short (48 hr) survival times. The numbers of labeled nuclei in the tectal germinal zones were compared on the two sides (intact and denervated). We show that permanent removal of optic input (by enucleation) resulted in a sustained depression of [3H]thymidine incorporation in the tectal germinal zone on the denervated compared to the intact side. Temporary denervation (by optic nerve crush) initially had a similar effect; however, upon reinnervation of the tectum by regenerating optic fibers, proliferation was enhanced on the experimental side compared to the intact side. Because cells in the germinal zone are known to produce new tectal cells, neurons as well as glia, in the normal growing adult brain (Raymond, P. A. and S. S. Easter, Jr. (1983) J. Neurosci. 3: 1077-1091), some of the proliferating cells may have been generating neurons. This inference is supported by the observation that in two fish whose right eye had been removed more than 2 years earlier, there were fewer neurons in the denervated tectum than in the intact tectum. Thus, it is likely that the observed decrease in incorporation of [3H]thymidine by cells in the germinal zone of the denervated optic tectum resulted in a slower rate of addition of new tectal cells on the affected side. We conclude that cytogenesis in the germinal zone of the growing optic tectum of adult goldfish is regulated by optic fiber input. This mechanism may be important in matching the rates of growth of retina and tectum in the normal brain of the growing adult fish" http://www.ncbi.nlm.nih.gov/pubmed/6842283 0 453 "A. Matsubara, T. Miyashita, R. Inamoto and N. Mori" 2013 Presence of adrenergic receptors in rat endolymphatic sac epithelial cells J.Membr.Biol. 246 2 109-114 "Intravenous application of catecholamines produces a depression in the endolymphatic sac direct current potential (ESP) and increases endolymphatic pressure via the beta-adrenergic receptor (AR) in guinea pigs, suggesting that catecholamines play a role in the endolymphatic system. However, the localization of ARs in the endolymphatic sac (ES) is still undetermined. The presence of ARs in the rat ES was investigated by reverse transcriptase-polymerase chain reaction using laser capture microdissection (LCM) and immunohistochemical analysis. Expression of alpha(1A)-, alpha(1B)-, alpha(2A)-, alpha(2B)-, beta(1)-, beta(2)- and beta(3)-ARs was observed in LCM samples of ES epithelia. Immunohistochemical analysis using specific antibodies showed immunofluorescence of beta(2)- and beta(3)-ARs in epithelial cells of the ES intermediate portion, and no specific staining results were obtained for alpha(1)-, alpha(2A)-, alpha(2B)- and beta(1)-ARs. The presence of beta(2)-AR with no clear immunostaining of beta(1)-AR in ES epithelial cells is in accordance with previous electrophysiological and pharmacological results, which suggests that beta(2)-AR mediates the action of catecholamines on the ESP. The presence of beta(3)-AR in the ES epithelial cells and its absence in the stria vascularis implies that beta(3)-AR plays a specific role in the ES" http://www.ncbi.nlm.nih.gov/pubmed/23124944 0 454 I. Beltcheva and T. Stoytchev 1983 Central depressive action of two N-aminomethyl derivatives of diethylpyridinedione Acta Physiol Pharmacol.Bulg. 9 1 35-43 "The central depressive action of N-aminomethylmorpholine-3,3-diethyl-2,4-pyridinedione (DKMM) and N-aminomethylpiperazine-3,3-diethyl-2,4-pyridinedione (DKMP), compounds having a marked anticonvulsive effect, has been studied applying a set of methods characterizing this action. DKMM and DKMP are found to prolong hexobarbital, chlorhydrate and alcohol sleeping time. Investigated by the modified jumping test, the two substances inhibit the central nervous system to the same degree. They show at the same time properties of hypnosedatives and neuroleptics as well. DKMM and DKMP manifest motor-incoordination activity in doses nearly 3.5 times higher than the doses inhibiting corazol convulsions. The compounds have a marked antiaggressive effect in the case of isolation syndrome, particularly pronounced for DKMP in a dose of 1/12 of LD50. The results obtained show that DKMM and DKMP are central depressants with marked sedative-tranquillizing action" http://www.ncbi.nlm.nih.gov/pubmed/6684873 0 455 "S. Spinelli, T. Muller, M. Friedel, H. Sigrist, K. P. Lesch, M. Henkelman, M. Rudin, E. Seifritz and C. R. Pryce" 2013 Effects of repeated adolescent stress and serotonin transporter gene partial knockout in mice on behaviors and brain structures relevant to major depression Front Behav.Neurosci. 7 215 "In humans, exposure to stress during development is associated with structural and functional alterations of the prefrontal cortex (PFC), amygdala (AMY), and hippocampus (HC) and their circuits of connectivity, and with an increased risk for developing major depressive disorder particularly in carriers of the short (s) variant of the serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR). Although changes in these regions are found in carriers of the s allele and/or in depressed patients, evidence for a specific genotype x developmental stress effect on brain structure and function is limited. Here, we investigated the effect of repeated stress exposure during adolescence in mice with partial knockout of the 5-HTT gene (HET) vs. wildtype (WT) on early-adulthood behavioral measures and brain structure [using magnetic resonance imaging (MRI)] relevant to human major depression. Behaviorally, adolescent stress (AS) increased anxiety and decreased activity and did so to a similar degree in HET and WT. In a probabilistic reversal learning task, HET-AS mice achieved fewer reversals than did HET-No-AS mice. 5-HTT genotype and AS were without effect on corticosterone stress response. In terms of structural brain differences, AS reduced the volume of two long-range white matter tracts, the optic tract (OT) and the cerebral peduncle (CP), in WT mice specifically. In a region-of-interest analysis, AS was associated with increased HC volume and HET genotype with a decreased frontal lobe volume. In conclusion, we found that 5-HTT and AS genotype exerted long-term effects on behavior and development of brain regions relevant to human depression" http://www.ncbi.nlm.nih.gov/pubmed/24427124 1 456 A. J. Azzaro and K. T. Demarest 1982 Inhibitory effects of type A and type B monoamine oxidase inhibitors on synaptosomal accumulation ofdopamine: A reflection of antidepressant potency "Biochemical Pharmacology.31 (12) ()(pp 2195-2197), 1982.Date of Publication: 1982." 12 2195-2197 "The authors have shown that the newer selective MAO-inhibitor drugs, which demonstrate clinical efficacy as antidepressants, also inhibit the accumulation of [3H]catecholamines by brain tissue. These results are consistent with the previous suggestion that clinical efficacy of antidepressant MAO inhibitors is reflected in the inhibitory potency of these drugs on catecholamine neuronal uptake" DO - http://dx.doi.org/10.1016/0006-2952%2882%2990515-9 0 457 "A. Higgins, S. Yuan, Y. Wang and B. D. Burrell" 2013 Differential modulation of nociceptive versus non-nociceptive synapses by endocannabinoids Mol.Pain 9 26 "BACKGROUND: Although a number of clinical and preclinical studies have demonstrated analgesic effects of cannabinoid treatments, there are also instances when cannabinoids have had no effect or even exacerbated pain. The observed pro-nociceptive effects appear to be due to cannabinoid-induced disinhibition of afferent synaptic input to nociceptive circuits. To better understand how cannabinoid-mediated plasticity can have both pro- and anti-nociceptive effects, we examined the possibility that cannabinoids differentially modulate nociceptive vs. non-nociceptive synapses onto a shared postsynaptic target. These experiments were carried out in the central nervous system (CNS) of the medicinal leech, in which it is possible to intracellularly record from presynaptic nociceptive (N-cell) or pressure-sensitive (P-cell) neurons and their shared postsynaptic targets. RESULTS: The endocannabinoid 2-arachidonoyl glycerol (2AG) elicited significant long-lasting depression in nociceptive (N-cell) synapses. However, non-nociceptive (P-cell) synapses were potentiated following 2AG treatment. 2AG-induced potentiation of non-nociceptive synapses was blocked by the TRPV antagonist SB366791, suggesting involvement of the same TRPV-like receptor that has already been shown to mediate endocannabinoid-dependent depression in nociceptive inputs. Treatment with the GABA receptor antagonist bicuculline also blocked 2AG-induced potentiation, consistent with the idea that increased synaptic signaling was the result of endocannabinoid-mediated disinhibition. Interestingly, while bicuculline by itself increased non-nociceptive synaptic transmission, nociceptive synapses were depressed by this GABA receptor antagonist indicating that nociceptive synapses were actually excited by GABAergic input. Consistent with these observations, GABA application depolarized the nociceptive afferent and hyperpolarized the non-nociceptive afferent. CONCLUSIONS: These findings show that endocannabinoids can differentially modulate nociceptive vs. non-nociceptive synapses and that GABAergic regulation of these synapses plays an important role in determining whether endocannabinoids have a potentiating or depressing effect" http://www.ncbi.nlm.nih.gov/pubmed/23725095 0 458 "K. I. Pasternak, C. Timo-Iaria, C. J. Rodrigues, D. A. Maria, A. J. Duarte, L. Paiva, D. H. Pozzi, B. B. de Mendonca, M. L. Wong and J. Licinio" 1998 Circumscribed lesion of the medial forebrain bundle area causes structural impairment of lymphoid organs and severe depression of immune function in rats Mol.Psychiatry 3 5 397-404 "Interactions between the immune system and the brain are a key element in the pathophysiology of diseases such as multiple sclerosis, neuroAIDS, and Alzheimer's, which affect large numbers of individuals and are associated with a high social cost. However, the neuroanatomical basis of brain-immune interactions has not been elucidated. We report that in Wistar rats of either sex bilateral electrolytic lesion of the medial forebrain bundle reduces body weight by 28% 7 days after lesioning, and causes widespread infections, aphagia, adypsia, structural damage to the lymphoid organs and heavy depression of T lymphocytes cytotoxicity. The following alterations occur in the immune system after those lesions: the weight of the thymus, spleen and lymphonodes is reduced by 77.9%, 49.1% and 48.4%, respectively. The thymus is atrophied and contains fewer lymphoid cells in the cortex than in the medulla. In the spleen the white pulp is reduced and lymphoid cells from periarteriolar zones and at the chords are almost absent. In lymph nodes cortical small lymphocytes are depleted and primary and secondary nodules and germinal centers all but disappear. Cytotoxicity of lymphocytes is reduced by 86.2% in the thymus, 77.6% in the spleen and 70.2% in lymph nodes. The critical area of lesion is at the medialmost portion of the medial forebrain bundle, at the preoptic area and rostral part of the anterior hypothalamus. We suggest that this area contains neural circuits that are crucial for keeping the structure of lymphoid organs and the functional integrity of the immune system" http://www.ncbi.nlm.nih.gov/pubmed/9774772 0 459 "M. Robson, C. Zhu, K. Lindler, N. Baganz, J. Wright, W. Hewlett and R. Blakely" 2014 "Conditional elimination of the interleukin-1 receptor: Connecting CNS immune signaling, serotonin transporter modulation and depressive behavior" "Basic and Clinical Pharmacology and Toxicology.Conference: 17th World Congress of Basic and Clinical Pharmacology Cape Town South Africa.Conference Start: 20140713 Conference End: 20140718.Conference Publication: (var.pagings).115 ()(pp 288-289), 2014" var.pagings 288-289 "Background: Presynaptic 5-HT transporters (SERT) remove synaptic 5-HT in the brain and periphery and are targets for common antidepressant medications. Recently, studies have linked depression and disruptions in immune system function, including increases in proinflammatory cytokines such as interleukin-1beta (IL-1beta). We have shown that interleukin-1 receptor (IL-1R) signaling regulates SERT function within the CNS through a p38 MAPK-dependent mechanism (Zhu et al. 2006, Zhu et al. 2010) and is required for the enduring effects of early life stress (Baganz et al, preliminary findings). Since IL-1Rs are widely expressed, constitutive IL-1R KO mice are insufficient to determine the site(s) and timing of IL-1R expression that supports these actions. Here we report the generation of mice suitable for the conditional elimination of IL-1Rs (IL-1Rflox/flox). Methods: Conventional homologous recombination was utilized to insert loxP sites flanking the 3rd and 4th exons of the il1r1 gene in 129S6 embryonic stem cells. Quantitative RT-PCR and synaptosomal uptake assays were utilized to ensure normal physiologic levels of IL- 1R mRNA and 5-HT uptake, respectively. IL-1Rflox/flox animals were crossed to B6.C-Tg (CMV-cre) animals to ensure adequate excision of the floxed IL-1R allele. Results: IL-1Rflox/flox animals are congenic on a 129S6 background and a C57BL/6J background. Initial characterization reveals that these animals are viable, reproduce normally, and display no gross abnormalities. Studies reveal no alterations of IL-1R mRNA levels in midbrain or spleen, consistent with the benign nature of inserted loxP sites. Ex vivo assays revealed that IL-1Rflox/flox animals demonstrate normal synaptosomal SERT activity in the midbrain and frontal cortex. Additionally, we found that floxed IL-1R alleles are excised in animals expressing CMV-cre. Our animals are now being crossed to afford 5- HT neuron specific elimination of IL-1Rs to determine the immune/5- HT connection in anxiety and depressive behavior. Conclusions: Generation of IL-1Rflox/flox animals provides a critical opportunity to evaluate IL-1beta-mediated p38 MAPK signaling in the activation of SERT, and the role of immune modulation of SERT in 5- HT signaling and behavior. Given the comorbidity between immune system activation and neuropsychiatric disorders, these mice should also afford a translational opportunity to develop immune system based medications for the treatment of depression" 0 460 O. H. Setty and U. K. Misra 1975 Upake of plasma lipids by extrahepatic tissues of vitamin A fed rats Int.J.Vitam.Nutr.Res. 45 2 107-112 "The uptake of newly synthesized plasma lipids from intraportally injected palmitate 1(-14)C by heart, kidney and adipose tissues of rats fed 33 mg retinol for 2 days have been studied. The uptake of plasma lipids by adipose tissues and heart was decreased and that by kidney increased in rats fed retinol as compared to the controls" http://www.ncbi.nlm.nih.gov/pubmed/1165157 0 461 "Y. Lavi-Avnon, G. Yadid, D. H. Overstreet and A. Weller" 2005 Abnormal patterns of maternal behavior in a genetic animal model of depression Physiol Behav. 84 4 607-615 "The Flinders Sensitive Line (FSL) model is considered a genetic animal model of depression. Among other characteristics, FSL rats express stress-induced anhedonia and an abnormal dopaminergic system. Our hypothesis was that FSL rats would show abnormal maternal behaviors, especially reduced motivation to reach and care for pups and reduced licking and non-nutritive contact, based on their anhedonic characteristics. Mother-infant interactions were assessed by time limited observations in FSL and Sprague-Dawley (SD) controls. In study 1, differences were found in consummatory behaviors: FSL dams compared to SD dams showed less licking and significant decrease in non-nutritive contact from the first to the third postpartum weeks. In addition, shorter duration of nursing postures was seen in FSL compared to SD dams in the first week postpartum, and this difference was significantly increased by the third week postpartum. In study 2, after exposure to acute swim stress, differences emerged in appetitive behaviors: latencies to reach and care for pups were longer in FSL dams compared to controls, suggesting a stress-induced motivational deficit in FSL dams. Possible explanations, especially regarding the FSL dams' reward system are discussed" http://www.ncbi.nlm.nih.gov/pubmed/15811396 1 462 "M. Suzuki, R. A. Li, T. Miki, H. Uemura, N. Sakamoto, Y. Ohmoto-Sekine, M. Tamagawa, T. Ogura, S. Seino, E. Marban and H. Nakaya" 2001 Functional roles of cardiac and vascular ATP-sensitive potassium channels clarified by Kir6.2-knockout mice Circ.Res. 88 6 570-577 "-ATP-sensitive potassium (K(ATP)) channels were discovered in ventricular cells, but their roles in the heart remain mysterious. K(ATP) channels have also been found in numerous other tissues, including vascular smooth muscle. Two pore-forming subunits, K" http://www.ncbi.nlm.nih.gov/pubmed/11282890 0 463 "Y. H. Li, J. Wang and G. Zhang" 2011 Involvement of synaptic NR2B-containing NMDA receptors in long-term depression induction in the young rat visual cortex in vitro Chin J.Physiol 54 3 190-195 "Activation of N-methyl-D-aspartate receptors (NMDARs) has been implicated in various forms of synaptic plasticity depending on the receptor subtypes involved. However, the contribution of NR2A and NR2B subunits in the induction of long-term depression (LTD) of excitatory postsynaptic currents (EPSCs) in layer II/III pyramidal neurons of the young rat visual cortex remains unclear. The present study used whole-cell patch-clamp recordings in vitro to investigate the role of" http://www.ncbi.nlm.nih.gov/pubmed/21789901 0 464 D. F. Dowling 1979 Effect of birth weight on efficiency of beef production Aust.Vet.J. 55 4 167-169 "The large 'lean beef' breeds are vulnerable to calving difficulties and losses. Dystocia is related to high birth weight. Data recorded from evaluation experiments show that the birth weight of the 'lean beef' taurus crossbreeds was high (39+/-2.1 kg). Indicus beef genotypes were selected with the birth weight (29+/-1.9 kg) significantly lower (P is less than 0.01) without a depression in the final yield of beef. To increase efficiency of beef production the lower birth weight factor needs be incorporated into genotypes for high viability and growth. Profitability depends on output per dam, in relation to inputs, on a herd basis. Hence, progress may depend on the application of such changes of genotype" http://www.ncbi.nlm.nih.gov/pubmed/464937 0 465 V. A. Kostenko 1998 [Effects of hyperbaric oxygenation on oxidative phosphorylation in post-nephrotomy tissues sutured with different surgical threads (an experimental study)] Urol.Nefrol.(Mosk) 6 07-Aug "The activity of mitochondrial respiration and oxidative phosphorylation (OP) was studied in white rats subjected to nephrotomy. The suture was made with absorbable surgical threads such as catgut plain, biofil (from dura mater spinalis of the cattle), dexon II (polyglycolic acid). The use of catgut plain inhibits biosynthetic processes 7 and 14 days after operation. Hyperbaric oxygenation enhances oxidative phosphorylation in postoperative renal tissue sutured with different biological and synthetic absorbable surgical threads (catgut, biofil, dexon II) and prevents sharp depression of the above processes in the course of catgut biodegradation. This fact is of great importance for reduction of normal functional and metabolic activity of the operated kidney" http://www.ncbi.nlm.nih.gov/pubmed/10051816 0 466 "D. M. Lyons, O. J. Wang, S. E. Lindley, S. Levine, N. H. Kalin and A. F. Schatzberg" 1999 Separation induced changes in squirrel monkey hypothalamic-pituitary-adrenal physiology resemble aspects of hypercortisolism in humans Psychoneuroendocrinology 24 2 131-142 "When separated from groups, squirrel monkeys respond with significant increases in plasma cortisol and adrenocorticotropic hormone (ACTH). While cortisol remains elevated above pre-separation levels, significant reductions occur in ACTH. Monkeys that respond with greater increases in cortisol subsequently exhibit greater reductions in ACTH, which suggests that reductions in ACTH are mediated by corticosteroid feedback. Monkeys that respond with greater increases in cortisol also tend to exhibit greater cerebrospinal fluid levels of the dopamine metabolite HVA, but not the norepinephrine metabolite MHPG, or corticotropin-releasing factor (CRF). Attenuation of corticosteroid feedback with metyrapone results in significant increases in circulating ACTH, and in older monkeys increases plasma HVA. Similar findings in humans have been reported in clinical studies of hypercortisolism and major depression" http://www.ncbi.nlm.nih.gov/pubmed/10101722 0 467 "G. T. Berry, R. Buccafusca, J. J. Greer and E. Eccleston" 2004 Phosphoinositide deficiency due to inositol depletion is not a mechanism of lithium action in brain Mol.Genet.Metab 82 1 87-92 "The ""inositol depletion hypothesis"" has been widely held to be the explanation for both the effect of lithium on brain function, apropos of its use in mood disorders, and on the impairment of development and induction of embryonic malformations in diverse organisms. The essence of the hypothesis is that a deficiency in cellular myo-inositol (Ins), secondary to lithium inhibition of inositol monophosphatase and/or multiple inositol polyphosphate phosphatase activities with trapping of Ins as inositol phosphates, leads to a depression of phosphatidylinositol (PtdIns) and a secondary impairment in inositide signaling. However, the ability of relatively low micromolar levels of Ins to reduce mammalian PtdIns synthetase activity in vivo has never been adequately tested. We have generated a lethal murine brain Ins deficiency model and measured PtdIns content using a novel MALDI-TOF MS method. Our results show that in the most severe Ins deficiency ever recorded in a mammal, the brain PtdIns levels do not decrease. We conclude that PtdIns deficiency due to ""inositol depletion"" is not a mechanism of lithium action in brain, and that Ins plays another unidentified role in the mammalian brain" http://www.ncbi.nlm.nih.gov/pubmed/15110328 0 468 "K. W. Stewart, J. P. Coghlan, D. A. Denton, R. T. Mason, B. A. Scoggins and J. A. Whitworth" 1983 The baroreceptor-heart rate reflex in ACTH hypertension in sheep Clin.Exp.Hypertens.A 5 1 21-29 "ACTH administration in sheep produces an adrenally dependent rise in blood pressure. Cardiac output and heart rate are usually increased. The precise mechanisms involved in the genesis of the hypertension are unclear. This study examines the sensitivity of the baroreflex heart rate response to phenylephrine hydrochloride and sodium nitroprusside before, during and after ACTH administration in sheep. During ACTH administration there was a sustained rise in blood pressure within 24 hours, whereas heart rate rose gradually. There was a sustained fall in baroreflex sensitivity to sodium nitroprusside within 24 hours, whereas baroreflex sensitivity to phenylephrine fell gradually over the first three days. The different time course of the change in sensitivity suggests that two different mechanisms are influenced by ACTH administration, for instance, changes in function in both cardiac vagal efferents and sympathetic pathways" http://www.ncbi.nlm.nih.gov/pubmed/6299627 0 469 "R. R. Lamberts, E. Caldenhoven, M. Lansink, G. Witte, R. J. Vaessen, J. A. St Cyr and G. J. Stienen" 2007 Preservation of diastolic function in monocrotaline-induced right ventricular hypertrophy in rats Am.J.Physiol Heart Circ.Physiol 293 3 H1869-H1876 "During ischemic heart diseases and when heart failure progresses depletion of myocardial energy stores occurs. D-Ribose (R) has been shown to improve cardiac function and energy status after ischemia. Folic acid (FA) is an essential cofactor in the formation of adenine nucleotides. Therefore, we assessed whether chronic R-FA administration during the development of hypertrophy resulted in an improved cardiac function and energy status. In Wistar rats (n = 40) compensatory right ventricular (RV) hypertrophy was induced by monocrotaline (30 mg/kg; MCT), whereas saline served as control. Both groups received a daily oral dose of either 150 mg.kg(-1).day(-1) dextrose (placebo) or R-FA (150 and 40 mg.kg(-1).day(-1), respectively). In Langendorff-perfused hearts, RV and left ventricular (LV) pressure development and collagen content as well as total RV adenine nucleotides (TAN), creatine content, and RV and LV collagen content were determined. In the control group R-FA had no effect. In the MCT-placebo group, TAN and creatine content were reduced, RV and LV diastolic pressure-volume relations were steeper, RV systolic pressures were elevated, RV and LV collagen content was increased, and RV-LV diastolic interaction was altered compared with controls. In the MCT-R-FA group, TAN, RV and LV diastolic stiffness, RV and LV collagen content, and RV-LV diastolic interaction were normalized to the values in the control group while creatine content remained depressed and RV systolic function remained elevated. In conclusion, the depression of energy status in compensated hypertrophic myocardium observed was partly prevented by chronic R-FA administration and accompanied by a preservation of diastolic function and collagen deposition" http://www.ncbi.nlm.nih.gov/pubmed/17604325 0 470 "X. M. Ou, J. M. Storring, N. Kushwaha and P. R. Albert" 2001 Heterodimerization of mineralocorticoid and glucocorticoid receptors at a novel negative response element of the 5-HT1A receptor gene J.Biol.Chem. 276 17 14299-14307 "Negative regulation of neuronal serotonin (5-HT1A) receptor levels by glucocorticoids in vivo may contribute to depression. Both types I (mineralocorticoid) and II (glucocorticoid) receptors (MR and GR, respectively) participate in corticosteroid-induced transcriptional repression of the 5-HT1A gene; however, the precise mechanism is unclear. A direct repeat 6-base pair glucocorticoid response element (GRE) half-site 5'-TGTCCT separated by 6 nucleotides was conserved in human, mouse, and rat 5-HT1A receptor promoters. In SN-48 neuronal cells that express MR, GR, and 5-HT1A receptors, deletion or inactivation of the nGRE (negative GRE) eliminated negative regulation of the rat 5-HT1A or heterologous promoters by corticosteroids, whereas its inclusion conferred corticosteroid-induced inhibition to a heterologous promoter. Bacterially expressed recombinant MR and GR preferentially bound to the nGRE as a heterodimer, as identified in nuclear extracts of MR/GR-transfected COS-7 cells, and with higher affinity than MR or GR homodimers. In SN48 and COS-7 cells, concentration-dependent coactivation of MR and GR was required for maximal inhibitory action by corticosteroids and was abrogated in the L501P-GR mutant lacking DNA binding activity. Corticosteroid-mediated transcriptional inhibition was greater for MR/GR in combination than for MR or GR alone. These data represent the first identification of an nMRE/GRE and indicate that heterodimerization of MR and GR mediates direct corticosteroid-induced transrepression of the 5-HT1A receptor promoter" http://www.ncbi.nlm.nih.gov/pubmed/11278286 0 471 "H. H. Webster, G. Flores, E. R. Marcotte, D. Cecyre, R. Quirion and L. K. Srivastava" 2000 Olfactory bulbectomy alters NMDA receptor levels in the rat prefrontal cortex Synapse 37 2 159-162 "Olfactory bulbectomized (OBX) rats show a variety of behavioral and biochemical deficits that parallel human depression. We investigated the expression of glutamate receptor subtypes in cortical and subcortical brain regions following bilateral olfactory bulbectomy in adult rats. Quantitative receptor autoradiography using [(125)I]MK-801 (NMDA receptor), [(3)H]AMPA (AMPA receptor), and [(3)H]kainate (kainate receptor) was performed on brain sections at 1-5 weeks following olfactory bulbectomy. Our results show an elevation of NMDA receptors in the medial prefrontal cortex within 1 week following bulbectomy, which persisted up to at least 5 weeks post-bulbectomy. Neither kainate nor AMPA receptors were altered in any brain region examined. The potential significance of these results is discussed in light of experimental findings supporting a role for NMDA receptors in the mechanism of action of antidepressant drugs and the pathophysiology of major depression" http://www.ncbi.nlm.nih.gov/pubmed/10881036 1 472 R. Kinkead and G. S. Mitchell 1999 Time-dependent hypoxic ventilatory responses in rats: effects of ketanserin and 5-carboxamidotryptamine Am.J.Physiol 277 3 Pt 2 R658-R666 "We hypothesized that the 5-hydroxytryptamine (5-HT) active drugs ketanserin and 5-carboxamidotryptamine (5-CT) would modulate time-dependent hypoxic phrenic and hypoglossal responses, including 1) short-term hypoxic response, 2) posthypoxia frequency decline (PHFD), and 3) long-term facilitation (LTF) of respiratory motor output. Phrenic and hypoglossal nerve activities were recorded in urethan-anesthetized, paralyzed, vagotomized, and artificially ventilated rats pretreated either with ketanserin (5-HT(2A/C) antagonist; 2 mg/kg iv), 5-CT (5-HT(1A/B) agonist; 10 microg/kg iv), or saline (sham). Rats were exposed to three 5-min episodes of hypoxia [fractional inspired O(2) (FI(O2)) = 0.11], separated by 5 min of hyperoxia (FI(O2) = 0.5). During hypoxia, ketanserin augmented phrenic but not hypoglossal burst amplitude; 5-CT had no effect. Both drugs accentuated PHFD. Ketanserin blocked phrenic LTF; hypoglossal LTF was not apparent, even in sham-treated rats. 5-CT reversed LTF, resulting in a long-lasting depression of phrenic burst frequency and amplitude without effect on hypoglossal burst amplitude. The data suggest that 1) 5-HT(2A/C) receptor activation modulates the short-term hypoxic phrenic response and PHFD and is necessary for LTF; and 2) 5-CT may affect time-dependent hypoxic ventilatory responses by reducing serotonin release via 5-HT(1A/B) autoreceptor activation" http://www.ncbi.nlm.nih.gov/pubmed/10484481 0 473 A. B. DeAngelo and J. Gorski 1970 Role of RNA synthesis in the estrogen induction of a specific uterine protein Proc.Natl.Acad.Sci.U.S.A 66 3 693-700 "The rate of amino acid incorporation into a specific uterine protein (induced protein band) isolated by gel electrophoresis has been shown to be markedly stimulated within an hour after estrogen administration. Injection of actinomycin D (8 mg/kg) prior to estrogen blocks the synthesis of induced protein. The accumulation of the product of the actinomycin D-sensitive step (induced protein band RNA) is significant 15 minutes after estrogen, and its synthesis would appear to be initiated as soon as the estrogen-receptor complex reaches the nucleus. Blocking protein synthesis with puromycin or cycloheximide did not affect the accumulation of induced protein band RNA, indicating that this is one of the earliest macromolecular synthetic events to occur after estrogen administration" http://www.ncbi.nlm.nih.gov/pubmed/5269235 0 474 P. Rigas and M. A. Castro-Alamancos 2009 Impact of persistent cortical activity (up States) on intracortical and thalamocortical synaptic inputs J.Neurophysiol. 102 1 119-131 "The neocortex generates short epochs of persistent activity called up states, which are associated with changes in cellular and network excitability. Using somatosensory thalamocortical slices, we studied the impact of persistent cortical activity during spontaneous up states on intrinsic cellular excitability (input resistance) and on excitatory synaptic inputs of cortical cells. At the intrinsic excitability level, we found that the expected decrease in input resistance (high conductance) resulting from synaptic barrages during up states is counteracted by an increase in input resistance due to depolarization per se. The result is a variable but on average relatively small reduction in input resistance during up states. At the synaptic level, up states enhanced a late synaptic component of short-latency thalamocortical field potential responses but suppressed intracortical field potential responses. The thalamocortical enhancement did not reflect an increase in synaptic strength, as determined by measuring the evoked postsynaptic current, but instead an increase in evoked action potential (spike) probability due to depolarization during up states. In contrast, the intracortical suppression was associated with a reduction in synaptic strength, apparently driven by increased presynaptic intracortical activity during up states. In addition, intracortical suppression also reflected a reduction in evoked spike latency caused by depolarization and the abolishment of longer-latency spikes caused by stronger inhibitory drive during up states. In conclusion, depolarization during up states increases the success of excitatory synaptic inputs to reach firing. However, activity-dependent synaptic depression caused by increased presynaptic firing during up states and the enhancement of evoked inhibitory drive caused by depolarization suppress excitatory intracortical synaptic inputs" http://www.ncbi.nlm.nih.gov/pubmed/19403750 0 475 "H. Kohl, N. J. De Souza and P. D. Desai" 1973 Synthesis and biological activity of quinolyl acetic acid derivatives J.Pharm.Sci. 62 12 2028-2030 http://www.ncbi.nlm.nih.gov/pubmed/4202681 0 476 "A. Knapman, J. M. Heinzmann, R. Hellweg, F. Holsboer, R. Landgraf and C. Touma" 2010 Increased stress reactivity is associated with cognitive deficits and decreased hippocampal brain-derived neurotrophic factor in a mouse model of affective disorders J.Psychiatr.Res. 44 9 566-575 "Cognitive deficits are a common feature of major depression (MD), with largely unknown biological underpinnings. In addition to the affective and cognitive symptoms of MD, a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is commonly observed in these patients. Increased plasma glucocorticoid levels are known to render the hippocampus susceptible to neuronal damage. This structure is important for learning and memory, creating a potential link between HPA axis dysregulation and cognitive deficits in depression. In order to further elucidate how altered stress responsiveness may contribute to the etiology of MD, three mouse lines with high (HR), intermediate (IR), or low (LR) stress reactivity were generated by selective breeding. The aim of the present study was to investigate whether increased stress reactivity is associated with deficits in hippocampus-dependent memory tests. To this end, we subjected mice from the HR, IR, and LR breeding lines to tests of recognition memory, spatial memory, and depression-like behavior. In addition, measurements of brain-derived neurotrophic factor (BDNF) in the hippocampus and plasma of these animals were conducted. Our results demonstrate that HR mice exhibit hippocampus-dependent memory deficits along with decreased hippocampal, but not plasma, BDNF levels. Thus, the stress reactivity mouse lines are a promising animal model of the cognitive deficits in MD with the unique feature of a genetic predisposition for an altered HPA axis reactivity, which provides the opportunity to explore the progression of the symptoms of MD, predisposing genetic factors as well as new treatment strategies" http://www.ncbi.nlm.nih.gov/pubmed/20035953 1 477 "R. B. Walker, J. W. Ayres, J. H. Block and A. Lock" 1978 tert-Butoxycarbanyl as a convenient protecting group in synthesis of potential centrally active dopamine derivatives J.Pharm.Sci. 67 4 558-559 "Several pivaloyl and pivaloyloxy esters and amides of dopamine were synthesized for possible antiparkinson activity. The compounds were synthesized by select O- and N-acylation and N-methylation procedures. The tert-butoxycarbonyl function is an effective and easily removed nitrogen-protecting group for dopamine. Preliminary biological testing results showed that all compounds tested elicited a hypothermic response in mice, while only O,O-dipivaloyl-N,N-dimethyldopamine reversed reserpine-induced motor depression in mice. However, it is difficult to conclude from the preliminary data that the observed biological effects were due to central dopaminergic receptor stimulation" http://www.ncbi.nlm.nih.gov/pubmed/641771 0 478 "K. Adachi, C. Ueno and S. Makimura" 1993 Immunosuppression in dogs naturally infected with Babesia gibsoni J.Vet.Med.Sci. 55 3 503-505 We examined lymphoproliferative response to phytohemagglutinin and anti-parasite antibody level in dogs naturally infected with Babesia gibsoni. The dogs with subclinical B. gibsoni infection exhibited suppressed lymphocyte blastogenesis. Prominent depression of lymphocyte blastogenesis and anti-parasite antibody production was observed in dogs suffering from relapses of clinical B. gibsoni infection http://www.ncbi.nlm.nih.gov/pubmed/8357932 0 479 "M. Bernard, P. Menasche, P. Canioni, C. Grousset, E. Fontanarava, R. P. Geyer, A. Piwnica and P. J. Cozzone" 1985 Enhanced cardioplegic protection by a fluorocarbon-oxygenated reperfusate: a phosphorus-31 nuclear magnetic resonance study J.Surg.Res. 39 3 216-223 "Prolonged global ischemia results in a defect in oxygen extraction during early reperfusion. This study was thus undertaken to assess the effects of maintaining cardioplegia at the onset of reoxygenation in view of channeling available energy toward reparative cell processes rather than mechanical activity. Twenty-four isolated perfused rat hearts were subjected to 120 min of 15 degrees C ischemia. Group I (control) was reperfused with the standard Krebs perfusion medium whereas in groups II and III the initial reperfusate consisted of an oxygenated alkaline cardioplegic solution prior to the resumption of Krebs perfusion. Oxygenation of the cardioplegic reperfusate was ensured by fluorocarbons at a concentration of 10% (O2 content: 5.5 vol %; group II) or 20% (O2 content: 9 vol %; group III). In addition to hemodynamical determinations, high-energy phosphates and intracellular pH were monitored serially by phosphorus-31 nuclear magnetic resonance spectroscopy. After 30 min of reperfusion postischemic recovery of aortic flow was better in group II (74.0 +/- 5.9% of control) than in group I (59.1 +/- 5.4% of control, P less than 0.05). This functional improvement correlated with a higher postischemic increase in phosphocreatine levels (103.21 +/- 11.21% vs 74.12 +/- 3.59%, at 3 min of reperfusion, P less than 0.05) without significant differences in total ATP content. Group III hearts exhibited a slow recovery as evidenced by a severe depression in aortic flow, coronary arteriovenous difference, and total phosphate content during the 15 initial minutes of reperfusion. These results show that the protection provided by cardioplegia can be improved by a fluorocarbon-oxygenated cardioplegic reperfusate.(ABSTRACT TRUNCATED AT 250 WORDS)" http://www.ncbi.nlm.nih.gov/pubmed/4033105 0 480 "B. A. Henriksson, B. Biber, J. Martner, J. Ponten and O. Werner" 1985 Cardiovascular studies during controlled baroreflex activation in the dog: I. Effects of enflurane Acta Anaesthesiol.Scand. 29 1 90-94 "In chloralose-anaesthetized dogs the carotid sinuses were bilaterally perfused with blood from a femoral artery, either at systemic arterial pressure through a direct by-pass or with a pump in order to control the sinus pressure. Influences from cardiac receptors and aortic baroreceptors were eliminated by denervation. Administration of enflurane (1.6% end-tidal concentration) with the presence of barostatic modulation, i.e. the carotid sinuses were perfused at prevailing systemic arterial pressure, reduced cardiac performance (cardiac output, cardiac contractility, heart rate and left ventricular stroke work) and mean arterial pressure. When barostatic compensation of enflurane-induced circulatory changes was prevented by maintaining sinus perfusion pressure constant at the pre-enflurane level, these haemodynamic alterations, with the exception of cardiac output, were significantly more pronounced. Furthermore, systemic vascular resistance decreased. We conclude that barostatic reflexes significantly modify cardiovascular depressive effects of enflurane" http://www.ncbi.nlm.nih.gov/pubmed/3976327 0 481 "G. Bignami, V. Giardini and M. Scorrano" 1985 Behaviorally augmented versus other components in organophosphate tolerance: the role of reinforcement and response factors Fundam.Appl.Toxicol. 5 6 Pt 2 S213-S224 "Male Wistar-derived rats were used to assess the behaviorally augmented component of tolerance to paraoxon depression of a feeding response. Separate groups of animals were treated daily by 0.125 mg/kg of the compound given sc either 1 hr before the start or 45 min after the end of a 90-min feeding session. However, the dose was reduced to 0.0625 mg/kg from Day 9 to Day 12 of the treatment series if animals showed too severe a reduction in food consumption. After development of tolerance by the presession treatment group, the animals treated after feeding were shifted to treatment before feeding. This shift produced a marked depression in food consumption. This confirms similar data previously obtained by a different test (two-way avoidance), and indicates that behaviorally augmented tolerance to paraoxon related to practice factors may be a fairly general phenomenon. Other experiments were to assess the effects of paraoxon in the conditioned taste aversion (CTA) paradigm. These showed the development of an aversion only at high dosage levels (two pairings between the flavor cue and 0.25 mg/kg sc, or four pairings with a 0.17-mg/kg dose). However, the failure of lower doses to produce CTA may have depended on the relatively slow onset of the intoxication, producing an extended interval between the end of cue exposure and the development of malaise or illness. Two pretreatments given 6 and 3 days before the first conditioning session in an experiment using the 2 X 0.25-mg/kg schedule did not affect the development of CTA as measured by a conventional double-bottle test. However, a typical interference effect produced by prior exposure was shown by a substantial acceleration of subsequent CTA extinction in pretreated animals" http://www.ncbi.nlm.nih.gov/pubmed/4092889 0 482 "G. I. Mashanov, P. B. Tsyvian and O. G. Artemeva" 1992 [Early hypoxic contracture of the myocardium in adult and newborn rats] Fiziol.Zh. 38 6 36-41 "The effect of 30 min substrate free hypoxia (H) on isometric tension was studied in isolated myocardium (M) of adult (A) and newborn (N) rats. The perfusion with 50% Na+ H solution caused in AM the development of H contracture which was more than 50% higher than control contracture. H perfusion with 0.1 mM Ca2+, 1.0 mM La3+, and 10.0 mM of caffeine provides the discrimination of control and hypoNa+ contractures. It is assumed that early H contracture in AM is a result of inability of Ca-sequestering system to accumulate intracellular Ca2+ and Ca2+ influxing through the sarcolemma. In myocardium of N rats Na-Ca exchange is proposed as a main source of Ca2+ for H contracture development" http://www.ncbi.nlm.nih.gov/pubmed/1340450 0 483 "F. Trebak, A. Alaoui, D. Alexandre, O. S. El, Y. Anouar, N. Chartrel and R. Magoul" 2015 Impact of aflatoxin B1 on hypothalamic neuropeptides regulating feeding behavior Neurotoxicology 49 165-173 "The presence of mycotoxins in food is a major problem of public health as they produce immunosuppressive, hepatotoxic and neurotoxic effects. Mycotoxins also induce mutagenic and carcinogenic effects after long exposure. Among mycotoxins that contaminate food are aflatoxins (AF) such as AFB1, which is the most powerful natural carcinogen. The AF poisoning results in symptoms of depression, anorexia, diarrhea, jaundice or anemia that can lead to death, but very few studies have explored the impact of AF on neuroendocrine regulations. To better understand the neurotoxic effects of AF related to anorexia, we explored in rat the impact of AFB1 on the major hypothalamic neuropeptides regulating feeding behavior, either orexigenic (NPY, Orexin, AgRP, MCH) or anorexigenic (alpha-MSH, CART, TRH). We also studied the effect of AFB1 on a novel neuropeptide, the secretogranin II (SgII)-derived peptide EM66, which has recently been linked to the control of food intake. For this, adult male rats were orally treated twice a week for 5 weeks with a low dose (150 mug/kg) or a high dose (300 mug/kg) of AFB1 dissolved in corn oil. Repeated exposure to AFB1 resulted in reduced body weight gain, which was highly significant for the high dose of AF. Immunocytochemical and quantitative PCR experiments revealed a dose-related decrease in the expression of all the hypothalamic neuropeptides studied in response to AFB1. Such orexigenic and anorexigenic alterations may underlie appetite disorders as they are correlated to a dose-dependent decrease in body weight gain of treated rats as compared to controls. We also found a decrease in the number of EM66-containing neurons in the arcuate nucleus of AFB1-treated animals, which was associated with a lower expression of its precursor SgII. These findings show for the first time that repeated consumption of AFB1 disrupts the hypothalamic regulation of neuropeptides involved in feeding behavior, which may contribute to the lower body weight gain associated to AF exposure" http://www.ncbi.nlm.nih.gov/pubmed/26141519 0 484 "J. Drimal, V. Knezl, J. Navarova, J. Nedelcevova, E. Paulovicova, R. Sotnikova, V. Snirc and D. Drimal" 2008 Role of inflammatory cytokines and chemoattractants in the rat model of streptozotocin-induced diabetic heart failure Endocr.Regul. 42 4 129-135 "OBJECTIVE: It is not yet clear how oxidative stress, free radicals, inflammatory cytokines and chemoattractants produced in the heart induce chronic heart failure. The myocardial damage caused by chronic diabetes results either from the persistence of inflammatory signaling directly in the heart or from the dysregulation of anti-inflammatory signaling systems. In the rat model of streptozotocin-induced diabetes (STZD) we investigated 1/ the concentration of free radicals (FR), 2/ reduced glutathione (GSH), 3/ lysozomal enzymes, 4/ inflammatory cytokines (tumor necrosis factor-? (TNF-?) and interleukin-6 (IL-6)), and monocyte chemoattractant protein-1 (mcp-1) in the myocardium. METHODS: Diabetes was induced in 12 male Wistar rats by injection of streptozotocin (STZ). The free radical scavenger and cardiac protectant SMe1EC2 (10 mg/kg/d.) was given orally for 5 days and 5 weeks and these animals were compared with the diabetic and non-diabetic controls. RESULTS: We found reduced heart rate and rate dependent functions of the rat heart, early release of free radicals triggering the release of cytotoxic inflammatory cytokines (like TNF-? and IL-6) and chemoattractants (mcp-1) as an example of this type of pathogens, resulting in the initiation and progression of cardiac pathology. The reduced myocardial contractility after STZD was accompanied with the increased reactive responsiveness of isolated aorta and mesenteric artery to phenylephrine, with increased production of chemoattractive proteins directly in the myocardium, with increased activity of peripheral beta-N-acetyl-glucosaminidase (NAGA), as representative of lysosomal activation processes. The pretreatment of SME1EC2 reduced increase in vascular reactivity, reduced myocardial depression and protected against myocardial toxicity. CONCLUSION: The newly identified and specific cardiac protectant SMe1EC2 could serve as a prospective target in the treatment of increased myocardial cytokine and chemoattractive proteins in diabetic cardiomyopathy" http://www.ncbi.nlm.nih.gov/pubmed/18999900 0 485 "B. Dubrovsky, J. Harris, K. Gijsbers and A. Tatarinov" 2002 Oxytocin induces long-term depression on the rat dentate gyrus: possible ATPase and ectoprotein kinase mediation Brain Res.Bull. 58 2 141-147 "We studied the effects of the neuropeptide oxytocin (OT) on the long-term potentiation (LTP) paradigm in the dentate gyrus (DG) of urethane anesthetized rats. Intracerebroventricular injection of 1 microg of the hormone in 1 microl of physiological solution 2min before tetanization produced a significant decrease in both components of the perforant path evoked potentials (EP) in the DG. The effects appeared right after the tetanization stimuli and were more pronounced in the excitatory postsynaptic components of the EPs. The decrements lasted for the 2h of recording time. We concluded that OT induced and maintained long-term depression on the DG. In contrast, injection of OT in the absence of tetanic stimulation did not significantly affect perforant path EP in the DG. The results are discussed taking particular consideration of the inhibitory effects the OT has on (Ca(2+)+Mg(2+)) ATPase at membrane levels and the potential interference that this action may have with phosphorylation processes via an ectoprotein kinase isolated from membranes of hippocampal pyramidal neurons. Blocking of this ectoprotein kinase in vitro significantly impairs establishment and maintenance of LTP" http://www.ncbi.nlm.nih.gov/pubmed/12127011 0 486 V. S. Rotenberg 1984 "Search activity in the context of psychosomatic disturbances, of brain monoamines and REM sleep function" Pavlov.J.Biol.Sci. 19 1 Jan-15 "The author discusses a number of controversial aspects of the search activity concept. This concept, based on an analysis of data cited by other researchers and the results of the author's own investigation, performed together with V. V. Arshavsky, postulates that search activity raises the body's resistance to stress and experimentally induced pathology whereas renunciation of search forms a nonspecific predisposition to somatic disturbances (e.g., psychosomatic disease). REM sleep is regarded as a specific form of search activity aimed at compensating for the state of renunciation of search in walking. In this paper the author argues that 1) renunciation of search can be accompanied either by anxiety or by depression, 2) REM sleep deprivation on a ""small platform"" raises the requirement in REM sleep by producing renunciation of search, 3) during search activity brain catecholamine synthesis is stimulated by catabolism whereas a state of renunciation of search upsets this feedback system. The actuation of the brain mechanisms of search in REM sleep necessitates a certain brain catecholamine level. If the brain catecholamine level is very high during waking behavior due to intensive search activity, the REM sleep requirement is low, REM sleep becoming reduced. After a moderate drop in the brain catecholamine level at the initial stage of renunciation of search the requirement in REM sleep rises and this phase grows longer. But at the late stage of renunciation of search the brain catecholamine level drops extremely, REM sleep shrinking in spite of the great appropriate requirement, and 4) the functional insufficiency of REM sleep invites various forms of pathology" http://www.ncbi.nlm.nih.gov/pubmed/6709399 0 487 "C. D. Conrad, K. J. McLaughlin, J. S. Harman, C. Foltz, L. Wieczorek, E. Lightner and R. L. Wright" 2007 Chronic glucocorticoids increase hippocampal vulnerability to neurotoxicity under conditions that produce CA3 dendritic retraction but fail to impair spatial recognition memory J.Neurosci. 27 31 8278-8285 "We previously found that chronic stress conditions producing CA3 dendritic retraction and spatial memory deficits make the hippocampus vulnerable to the neurotoxin ibotenic acid (IBO). The purpose of this study was to determine whether exposure to chronic corticosterone (CORT) under conditions that produce CA3 dendritic retraction would enhance CA3 susceptibility to IBO. Male Sprague Dawley rats were chronically treated for 21 d with CORT in drinking water (400 microg/ml), and half were given daily injections of phenytoin (40 mg/kg), an antiepileptic drug that prevents CA3 dendritic retraction. Three days after treatments stopped, IBO was infused into the CA3 region. Conditions producing CA3 dendritic retraction (CORT and vehicle) exacerbated IBO-induced CA3 damage compared with conditions in which CA3 dendritic retraction was not observed (vehicle and vehicle, vehicle and phenytoin, CORT and phenytoin). Additionally, spatial recognition memory was assessed using the Y-maze, revealing that conditions producing CA3 dendritic retraction failed to impair spatial recognition memory. Furthermore, CORT levels in response to a potentially mild stressor (injection and Y-maze exposure) stayed at basal levels and failed to differ among key groups (vehicle and vehicle, CORT and vehicle, CORT and phenytoin), supporting the interpretations that CORT levels were unlikely to have been elevated during IBO infusion and that the neuroprotective actions of phenytoin were not through CORT alterations. These data are the first to show that conditions with prolonged glucocorticoid elevations leading to structural changes in hippocampal dendritic arbors can make the hippocampus vulnerable to neurotoxic challenges. These findings have significance for many disorders with elevated glucocorticoids that include depression, schizophrenia, Alzheimer's disease, and Cushing's disease" http://www.ncbi.nlm.nih.gov/pubmed/17670974 0 488 "J. L. Barker, J. W. Crayton and R. A. Nicoll" 1971 Supraoptic neurosecretory cells: adrenergic and cholinergic sensitivity Science 171 3967 208-210 "Adrenergic and cholinergic agonists and antagonists were applied microelectrophoretically to over 700 neurons in the cat supraoptic nucleus, 20 percent of which were antidromically identified as neurosecretory cells. Norepinephrine uniformly depressed all sensitive cells. Acetylcholine caused both muscarinic depression and nicotinic excitation which were antagonized by atropine and dihydro-beta-erythroidine, respectively. These results support the hypothesis that norepinephrine and acetylcholine are directly involved in controlling the release of antidiuretic hormone" http://www.ncbi.nlm.nih.gov/pubmed/4395231 0 489 J.-T. Zhang 2015 Epigenetic mechanism in cognitive function "Chinese Pharmacological Bulletin.31 (1) ()(pp 1-7), 2015.Date of Publication: 01 Jan 2015." 1 01-Jul "The definition of epigenetics and its cellular basis are introduced firstly in the paper. Then, the research progress on the relationship between cognition and epigenetic changes is reviewed in detail. In conclusion, epigenetic modifications occurring in hippocampus, cortex and other brain areas such as methylation, phosphorylation, ubiquitination, poly (ADP-ribos) polymerases and DNA methylation may certainly change animal behaviors including learning, memory, synaptic plasticity, depression, drug abuse and so on. Long-term memory and long-term potentiation (LTP), activation of AMPK-ERK signal transduction path-way and activation of key gene regulated by CREB-ABP transcriptional complex as well as transcription and expression of memory and synaptic plasticity related genes (Zif/268, Creb, Bdnf, reelin) are required. In contrast, epigenetic abnormal changes such as histone and DNA hypomethylation and increase of HDAC activity are observed in brains of aging and neurodegenerative diseases. Therefore, the main epigenetic treatments for cognitive impairments are increasing histone and DNA methylation, using HDAC inhibitors and RNA interference (RNAi) to promote formation of long term memory and long term potentiation, block learning and memory decline" DO - http://dx.doi.org/10.3969/j.issn.1001-1978.2015.01.001 0 490 "D. K. Rorie, L. W. Hunter and J. J. Lunn" 1990 "Halothane decreases the release of neuropeptide Y and 3,4-dihydroxyphenylglycol from superfused segments of dog pulmonary artery" Anesthesiology 73 4 722-730 "Neuropeptide Y (NPY), norepinephrine (NE), and 3,4-dihydroxyphenylglycol (DOPEG), the metabolite of NE that arises intraneuronally, were measured in superfusates before, during, and after nerve stimulation and in extracts of dog pulmonary artery after superfusion and electrical stimulation (ES) at 12, 6, and 1 Hz. NE and DOPEG were quantified by high-pressure liquid chromatography with electrochemical detection; peptides were quantified by radioimmunoassay. The rate of overflow of NPY, NE, and DOPEG into superfusate was measured over time. The overflow of DOPEG into superfusate during basal conditions was 3.0 times that of NE. Efflux of DOPEG and NPY increased during ES; peak effluxes were not reached, however, until after cessation of stimulation. NE efflux peaked during ES. Effluxes of NE, NPY, and DOPEG were frequency-dependent at 12 and 6 Hz; at 1 Hz efflux of only NE was greater than basal. Halothane decreased significantly the rates of NPY and DOPEG efflux during and after 12 Hz ES; DOPEG efflux evoked by 6 Hz stimulation was also decreased by halothane. The percentage of the total tissue content of NPY that overflowed was decreased by halothane. Halothane did not affect the molar ratios of NE:DOPEG or NE:NPY during basal conditions or ES. These studies provide evidence that halothane slows efflux of NPY that is released along with NE from dog pulmonary artery during high frequencies of stimulation. Halothane also reduces the metabolism of NE to DOPEG" http://www.ncbi.nlm.nih.gov/pubmed/2221441 0 491 "A. A. Bilgin, A. Yesilada, E. Palaska and R. Sunal" 1992 "Synthesis and antidepressant activity of some new 8-thiocarbamoyl-7,8-diazabicyclo[4.3.0]non-6-ene derivatives" "Arzneimittel-Forschung/Drug Research.42 (11) ()(pp 1271-1273), 1992.Date of Publication: 1992." 11 1271-1273 "Several 8-thiocarbamoyl-7,8-diazabicyclo[4.3.0]non-6-enes were prepared by condensing two alpha,beta-unsaturated ketones (2-benzylidene and 2,6-dibenzylidene cyclohexanones) with hydrazine hydrate and reacting the resulting compounds with various isothiocyanates. The structures of the synthesized compounds were confirmed by spectra (IR, 1H-NMR) and microanalysis, they were tested for antidepressant activity using Porsolt's behavioural despair test" 1 492 "K. H. Reid, R. Marrannes, P. E. De and A. Wauquier" 1987 Potassium translocation and spreading depression induced by electrical stimulation of the brain Exp.Neurol. 97 2 345-364 "Cathodal current pulses with durations from 20 ms to 80 s were applied to the surface of rat parietal neocortex, and the strength-duration properties of the threshold stimulus for initiation of spreading depression was determined. In one series, extradural stimulation was used. In a second series, a liquid electrode was used, the dura was opened, and K+-sensitive microelectrodes were used to determine the time course of extracellular K+ concentration during and after each stimulus pulse. With the dura open, the strength-duration curve was of the form It0.55 = constant. With extradural stimulation, the slope of the log-log plot relating current intensity to pulse duration changed gradually as the pulse duration increased, averaging 0.63. Theoretical analysis suggests that diffusion of K+ away from a zone of current-induced accumulation can account for these slope data. Applicability of this mechanism of K+ accumulation to observed changes in sensitivity of neurons to repeated stimulation at subcortical sites is considered" http://www.ncbi.nlm.nih.gov/pubmed/3609218 0 493 "H. J. Jeong, S. Y. Yang, H. Y. Kim, N. R. Kim, J. B. Jang and H. M. Kim" 2016 Chelidonic acid evokes antidepressant-like effect through the up-regulation of BDNF in forced swimming test Exp.Biol.Med.(Maywood.) "Depression is usually accompanied by neuro-inflammatory reactions. Chelidonic acid, in particular, has shown anti-inflammatory effects. The objective of this study was to evaluate the anti-depressant effects of chelidonic acid and to discuss the potential mechanisms of a forced swimming test. Chelidonic acid was administered orally once a day for 14 days. On the 14th day, chelidonic acid resulted in a significant decrease in immobility time during the forced swimming test without alteration of locomotor activity, in an open field test. Chelidonic acid also increased the number of nissl bodies in the hippocampus. Brain-derived neurotrophic factor expression and extracellular signal-regulated protein kinase phosphorylation in the hippocampus were up-regulated by the administration of chelidonic acid. Chelidonic acid administration significantly increased the mRNA expression of hippocampal estrogen receptor-beta. The levels of hippocampal interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha were effectively attenuated by the administration of chelidonic acid. In addition, chelidonic acid significantly increased the levels of 5-hydroxytryptamine (serotonin), dopamine, and norepinephrine compared with those levels for the mice that were administered distilled water in the hippocampus. These results suggest that chelidonic acid might serve as a new therapeutic strategy for the regulation of depression associated with inflammation" http://www.ncbi.nlm.nih.gov/pubmed/27037280 1 494 "O. Selbach, C. Bohla, A. Barbara, N. Doreulee, K. S. Eriksson, O. A. Sergeeva and H. L. Haas" 2010 Orexins/hypocretins control bistability of hippocampal long-term synaptic plasticity through co-activation of multiple kinases Acta Physiol (Oxf) 198 3 277-285 "AIM: Orexins/hypocretins (OX/Hcrt) are hypothalamic neuropeptides linking sleep-wakefulness, appetite and neuroendocrine control. Their role and mechanisms of action on higher brain functions, such as learning and memory, are not clear. METHODS: We used field recordings of excitatory post-synaptic potentials (fEPSP) in acute mouse brain slice preparations to study the effects of orexins and pharmacological inhibitors of multiple kinases on long-term synaptic plasticity in the hippocampus. RESULTS: Orexin-A (OX-A) but not orexin-B (OX-B) induces a state-dependent long-term potentiation of synaptic transmission (LTP(OX)) at Schaffer collateral-CA1 synapses in hippocampal slices from adult (8- to 12-week-old) mice. In contrast, OX-A applied to slices from juvenile (3- to 4-week-old) animals causes a long-term depression (LTD(OX)) in the same pathway. LTP(OX) is blocked by pharmacological inhibition of orexin receptor-1 (OX1R) and plasticity-related kinases, including serine/threonine- (CaMKII, PKC, PKA, MAPK), lipid- (PI3K), and receptor tyrosine kinases (Trk). Inhibition of OX1R, CaMKII, PKC, PKA and Trk unmasks LTD(OX) in adult animals. CONCLUSION: Orexins control not only the bistability of arousal states and threshold for appetitive behaviours but, in an age- and kinase-dependent manner, also bidirectional long-term synaptic plasticity in the hippocampus, providing a possible link between behavioural state and memory functions" http://www.ncbi.nlm.nih.gov/pubmed/19624551 0 495 "G. C. Luketic, R. Santini, Jr. and C. E. Butterworth, Jr." 1965 Depression of whole blood folate activity by colchicine Proc.Soc.Exp.Biol.Med. 120 1 13-16 http://www.ncbi.nlm.nih.gov/pubmed/4954939 0 496 "A. O. Rosa, M. P. Kaster, R. W. Binfare, S. Morales, E. Martin-Aparicio, M. L. Navarro-Rico, A. Martinez, M. Medina, A. G. Garcia, M. G. Lopez and A. L. Rodrigues" 2008 Antidepressant-like effect of the novel thiadiazolidinone NP031115 in mice Prog.Neuropsychopharmacol.Biol.Psychiatry 32 6 1549-1556 "Glycogen synthase kinase-3beta (GSK-3beta) is an enzyme that phosphorylates glycogen synthase, thereby inhibiting glycogen synthesis. Besides this role, it is now believed that this enzyme plays an important role in the pathophysiology of many brain diseases including depression. Some inhibitors of this enzyme have shown antidepressant effects in animal models. This study investigated the effects of a novel thiadiazolidinone NP031115, a putative GSK-3beta inhibitor, and the well-established GSK-3beta inhibitor AR-A014418 in the mouse forced swimming test (FST), a model widely used to evaluate antidepressant activity. We found that NP031115 had an IC50 of 1.23 and 6.5 microM for GSK-3beta and GSK-3alpha, respectively. NP031115 (0.5 and 5 mg/kg, i.p.), in a way similar to imipramine (15 mg/kg, i.p), fluoxetine (32 mg/kg, i.p), AR-A014418 (9 mg/kg, i.p.), and rosiglitazone (5 microg/site, i.c.v.), significantly reduced immobility time in the FST. NP031115 at the higher dose and AR-A014418 (9 mg/kg, i.p.) reduced locomotion in the open-field test. Rosiglitazone (30 microM), AR-A014418 (1 microM), PG(J2) (10 microM), and NP031115 (1, 10 and 25 microM) activate PPARgamma in CHO transfected cells. GW-9662 (10 microg/site, i.c.v, a PPARgamma antagonist) administered 15 min before NP03115 (5 mg/kg, i.p.) or co-administered with rosiglitazone (5 microg/site, i.c.v.) prevented the antidepressant-like effect of these drugs in the FST. The results of this study show that NP031115 can exhibit an antidepressant effect, likely by inhibiting GSK-3beta and enhancing PPARgamma activity" http://www.ncbi.nlm.nih.gov/pubmed/18579278 1 497 "H. D. Colby, R. J. Witorsch, J. L. Caffrey and J. I. Kitay" 1973 Effects of steroid suppression and gonadectomy on adrenal 5alpha-reductase activity and corticosterone production in rats Acta Endocrinol.(Copenh) 74 3 568-575 http://www.ncbi.nlm.nih.gov/pubmed/4800855 0 498 "G. Ulak, O. Mutlu, C. Komsuoglu, I, F. Akar and F. Erden" 2012 The antidepressant agomelatine improves unpredictable chronic mild stress-induced memory deterioration in mice "European Neuropsychopharmacology.Conference: 25th European College of Neuropsychopharmacology, ECNP Congress Vienna Australia.Conference Start: 20121013 Conference End: 20121017.Conference Publication: (var.pagings).22 ()(pp S182-S183), 2012.Date of" var.pagings S182-S183 "Agomelatine, a novel antidepressant with established clinical efficacy, acts as an agonist of melatonergic MT1 and MT2 receptors and as an antagonist of 5-HT2C receptors. Since stress plays an important role in the development of depression, the present study was undertaken to investigate whether chronic treatment of agomelatine would block unpredictable chronic mild stressinduced cognition deterioration in mice. Unpredictable chronic mild stres (UCMS) is a promising and valuable animal model of depression which shows similar features to the depressive symptoms seen in human beings. The aim of this study was to investigate the effect of agomelatine (10 mg/kg; 5 weeks) in comparison with melatonin (10 mg/kg; 5 weeks) on learning and memory in nonstressed and UCMS exposed Balb-c mice (n = 8 per group). Male inbred BALB/c mice were subjected to different kinds of stressors several times a day for 7 weeks in a chronic, inevitable and unpredictable way or no stress was applied to another group. Stressors were damp sawdust, changing the sawdust, placement in an empty cage or empty cage with water on the bottom, periods of soiled cage with aversive odour, social stress, cage tilting, predator sounds for 15 min, inversion of light/dark cycle, confinement in tube. To determine the effects of UCMS regimen and drug treatment on cognitive functions, elevated plus maze (EPM), passive avoidance (PA), novel object recognition (NOR) and Morris water maze (MWM) tests were used. This study includes no potential conflict of interest. The results of this study revealed that: (1) In the EPM test, there was no significant difference between the tranfer latency 1 values of all groups while transfer latency 2 was significantly increased in UCMS exposed mice (p<0.05); this effect was significantly reversed by melatonin (p<0.05) while agomelatine partially decreased this value but it failed to reach a significant level. (2) In the PA test, there was no significant difference between the first day latency of animals while retention latency significanly decreased in UCMS exposed mice (p <0.05); this effect was reversed by melatonin (p<0.05) but agomelatine exerted no effect in this test. (3) In the NOR test, ratio index significantly decreased in UCMS exposed mice (p<0.001) and this effect was reversed both by melatonin and agomelatine (p<0.001). (4) In the MWM test, the escape latency significantly increased in acquisition sessions and the time spent in escape platform's quadrant in the probe trial significantly decreased in UCMS exposed mice (p<0.001); both melatonin and agomelatine reversed these effects (p<0.05). There was no significant difference between the swimming speed of the animals (p>0.05) while mean distance to platform significantly increased in the probe trial in UCMS exposed mice; both melatonin (p <0.05) and agomelatine (p<0.01) improved this effect. The results of our study confirm that chronic stress causes cognition impairment and both agomelatine and melatonin had beneficial effects on learning and memory in stressed mice although agomelatine failed to improve cognitive functions in some tests" 0 499 "T. Sakurai, B. Yang, T. Takata and K. Yokono" 2002 Synaptic adaptation to repeated hypoglycemia depends on the utilization of monocarboxylates in Guinea pig hippocampal slices Diabetes 51 2 430-438 "This report provides in vitro evidence that synaptic activity becomes resistant to repeated hypoglycemia, i.e., hypoglycemic synaptic adaptation occurs. Synaptic function was estimated by the amplitude of the postsynaptic population spike (PS) recorded in the granule cell layer of guinea pig hippocampal slices. ATP, phosphocreatine (PCr), glycogen, and glucose concentrations were measured to investigate energy metabolism homeostasis. Glucose deprivation produced a complete elimination of the PS amplitude, with a 50% inhibition by 10.6 min, and a approximately 15% reduction in ATP and PCr concentrations. Low-glucose (0.5-1 mmol/l) medium gradually depressed the PS. After recovery from glucose depletion, repeated glucose deprivation produced a slowly developing depression of PS, with a 50% inhibition by 36.5 min. However, ATP and PCr concentrations were maintained. Incubation in secondary low-glucose medium maintained PS amplitude. Hippocampal glycogen and glucose concentrations promptly decreased during repeated glucose deprivation, indicating that glycogenolysis does not fuel synaptic adaptation to repeated hypoglycemia. Synaptic function during repeated glucose depletion was reversibly depressed by addition of alpha-cyano-4-hydroxycinnamic acid or 3-isobutyl-1-methylxanthine, inhibitors of the monocarboxylate transporter. Replacement of extracellular glucose with Na-lactate or Na-pyruvate sustained synaptic transmission after transient glucose depletion. These results indicate that synaptic utilization of monocarboxylates sustains hypoglycemic synaptic adaptation" http://www.ncbi.nlm.nih.gov/pubmed/11812751 0 500 T. Hiraga and M. Abe 1987 Anatomical observation of six calves affected with segmental aplasia of the spinal cord Anat.Rec. 219 4 402-408 "Four male and two female Holstein-Friesian calves with segmental aplasia of the spinal cord were examined macroscopically and radiographically, and in some cases also histologically. External symptoms included inability to stand, deep depression of the body near the middle of the back but without any blemish in the skin, and slight reduction of the body length. Both hind limbs were almost normal. In every case segmental aplasia of the spinal cord was observed between the caudal thoracic and the cranial lumbar region. Owing to this defect, the vertebrae of that limited area consisted only of the body and the ribs fused on both sides. The sternum showed abnormal ossification at its caudal part. Other defects were observed such as kyphoscoliosis (six cases), polycystic kidney (one case), cryptorchidism (one case), and XX/XY chimerism (one case). From these findings it was apparent that this anomaly was uniquely different from the other two main spinal cord anomalies, spina bifida and perosomus elumbis. One conceivable pathogenesis of this rare anomaly, it was conjectured, is as follows: This anomaly results primarily from a segmental disorder of the neural tube, probably due to vascular problems, whereby a part of the spinal cord fails to develop properly from its normal genesis. Anomalous shapes of the vertebral column and ribs are perhaps secondary defects caused by aplasia of the spinal cord" http://www.ncbi.nlm.nih.gov/pubmed/3448955 0 501 "P. D'Ocon, M. A. Blazquez, A. Bermejo and E. Anselmi" 1992 "Tetrandrine and isotetrandrine, two bisbenzyltetrahydroisoquinoline alkaloids from Menispermaceae, with rat uterine smooth muscle relaxant activity" J.Pharm.Pharmacol. 44 7 579-582 "The effects of two bisbenzyltetrahydroisoquinoline alkaloids, 1S,1'S tetrandrine and its isomer 1R,1'S isotetrandrine, were investigated in rat isolated uterus in order to identify the mechanism of relaxant action and to study the influence of the absolute configuration on the activity of these alkaloids. Both inhibited the uterine contraction induced by high K+, acetylcholine and oxytocin. In Ca(2+)-free medium, isotetrandrine relaxed the sustained contraction induced by oxytocin but tetrandrine did not. The relaxant effects of the alkaloids may be due to blockade of calcium influx through specific channels. Tetrandrine and isotetrandrine modify the calcium channel in a nonreversible manner whilst only isotetrandrine acts intracellularly. Tetrandrine shows a more specific relaxant activity as a calcium entry blocker" http://www.ncbi.nlm.nih.gov/pubmed/1357138 0 502 "V. Parsons, C. Davies and M. Jenkins" 1969 The effects of actinomycin D on the increased total hydroxyprolinuria in healing rachitic rats Biochim.Biophys.Acta 192 2 252-257 http://www.ncbi.nlm.nih.gov/pubmed/5370019 0 503 "Y. Z. Qu, Y. E. Wang and X. X. Li" 1996 "Effects of thiofedrine on platelet aggregation, thromboxane B2 and 6-keto-PGF1 alpha in rats" Methods Find.Exp.Clin.Pharmacol. 18 5 297-300 "Thiofedrine inhibited rat platelet aggregation and intraplatelet thromboxane B2 (TxB2) generation induced by arachidonic acid. The IC50 values were 0.18 and 0.21 mmol/l, respectively. Thiofedrine, 1.25-5.00 mg/kg i.v., showed a significant inhibition of rat platelet aggregation and intraplatelet TxB2 generation induced by arachidonic acid, with ID50 values of 2.4 and 3.3 mg/kg. Thiofedrine, 0.5-2.0 mg/kg i.v., reduced TxB2 generation but increased 6-keto-PGF1 alpha formation in rat plasma" http://www.ncbi.nlm.nih.gov/pubmed/8817463 0 504 "G. H. Seol, H. S. Shim, P. J. Kim, H. K. Moon, K. H. Lee, I. Shim, S. H. Suh and S. S. Min" 2010 Antidepressant-like effect of Salvia sclarea is explained by modulation of dopamine activities in rats J.Ethnopharmacol. 130 1 187-190 "AIM OF THE STUDY: The purpose of the present study was to screen aromatic essential oils that have antidepressant effects to identify the regulatory mechanisms of selected essential oils. MATERIALS AND METHODS: The antidepressant effects of essential oils of Anthemis nobilis (chamomile), Salvia sclarea (clary sage; clary), Rosmarinus officinalis (rosemary), and Lavandula angustifolia (lavender) were assessed using a forced swim test (FST) in rats. Rats were treated with essential oils by intraperitoneal injection or inhalation. Serum levels of corticosterone were assessed by enzyme-linked immunosorbent assay (ELISA). RESULTS: Among the essential oils tested, 5% (v/v) clary oil had the strongest anti-stressor effect in the FST. We further investigated the mechanism of clary oil antidepression by pretreatment with agonists or antagonists to serotonin (5-HT), dopamine (DA), adrenaline, and GABA receptors. The anti-stressor effect of clary oil was significantly blocked by pretreatment with buspirone (a 5-HT(1A) agonist), SCH-23390 (a D(1) receptor antagonist) and haloperidol (a D(2), D(3), and D(4) receptor antagonist). CONCLUSIONS: Our findings indicate that clary oil could be developed as a therapeutic agent for patients with depression and that the antidepressant-like effect of clary oil is closely associated with modulation of the DAnergic pathway" http://www.ncbi.nlm.nih.gov/pubmed/20441789 1 505 "T. Bhattacharyya, A. Sarkar and A. Ghosh" 1967 Effect of hydroxylation blocking agents on corticoids concentration in the pigeon adrenals Endocrinol.Jpn. 14 3 265-268 http://www.ncbi.nlm.nih.gov/pubmed/5630632 0 506 S. H. Koh and J. S. Noh 2014 A study of antidepressant and mood stabilizer's effect on phase of peripheral circadian rhythm in rat fibroblast "European Neuropsychopharmacology.Conference: 27th European College of Neuropsychopharmacology, ECNP Congress Berlin Germany.Conference Start: 20141018 Conference End: 20141021.Conference Publication: (var.pagings).24 ()(pp S223), 2014.Date of Publica" var.pagings S223 "Objective: Circadian rhythm is 24 hours cyclic variation in biological activity, which is crucial for physiology in mammals associated with sleep-wake cycles, circulation system, endocrinologic change, metabolic activity and thermal regulation. The center of circadian rhythm in mammals is located on suprachiasmatic nucleus of hypothalamus and plays crucial role to synchronize circadian rhythms among internal organs and hormonal activity. Alterations in circadian rhythm may be related to mood disorders and reported that especially phase change is closely related to depressive disorder and bipolar disorder. However, most studies focused on effect to diurnal variation and sleep wake cycle, but the effect of medications used for mood disorders such as antidepressant, mood stabilizer and atypical antipsychotics on peripheral tissue is less understood. Lithium is reported that act as inhibitor of GSK-3-beta activity which is key modulation factor of biological clock and recent study showed that paroxetine can modulate circadian rhythm directly on peripheral tissue and which implies that conventional selective serotonin receptor antagonists used on depressive disorder can modulate circadian rhythm on cellular level. In this study, we investigated whether treatment with antidepressants, antipsychotics, and mood stabilizers in rat fibroblast influenced circadian rhythm. Methods: NIH3T3, peripheral rat fibroblast was cultured in Dulbecco's Modified Eagle Medium with 10% Fetal Bovine Serum for 24 hours and induced serum starvation state by 1% fetal bovine serum media for 48 hours. 1uM dexamethasone was applied to induce synchronization of circadian rhythm and changed to 10% serum containing media after 2 hours. Per2 mRNA was measured every 6 hours by conventional PCR and BMAL1, CRY1, CLK protein was measured every 6 hours by Western blot for 24 hours. Lithium, bupropion, risperidone, lamotrigine, and paroxetine were applied on NIH3T3, in low and high concentration (lithium 10mM, 20mM; bupropion 10uM, 50uM; risperidone 10uM, 50uM; paroxetine 10uM; lamotrigine 50uM, 100uM). Per2 and Bmal1 activity was assessed by real-time qPCR to observe periodic oscillation and rhythmicity for 48 hours. Results: Oscillation, peak, and amplitude of Per2 activity were observed by 24 hour period and amplitude of oscillation dampened as time. Lithium showed a dose-dependent effect on phase delaying change of circadian rhythm. Bupropion, risperidone, lamotrigine, and paroxetine showed no changes on circadian rhythmic activity but buproipion showed a tendency to dampen the amplitude of Per2 oscillation compared to lithium, risperidone, lamotrigine, and paroxetine. Oscillation amplitude of Bmal1 is relatively lower than Per2, but showed reciprocal phase to Per2 activity. Conclusion: These results showed lithium treatment may have an effect on circadian rhythm lengthening in peripheral fibroblast tissue and also suggest that medications conventionally used on mood disorder have various pathway to modulate circadian rhythm from cellular level to organ and subject level. Results also imply that circadian rhythm change are closely related to neurovegetative symptoms, diurnal variations of mood disorders" 0 507 "E. Thiels, G. Barrionuevo and T. W. Berger" 1994 Excitatory stimulation during postsynaptic inhibition induces long-term depression in hippocampus in vivo J.Neurophysiol. 72 6 3009-3016 "1. As part of an effort to evaluate the biological plausibility of theoretically derived principles of synaptic modification, we studied activity-dependent long-term depression (LTD) of glutamatergic transmission in the hippocampus of anesthetized adult rats. Field potentials of CA1 pyramidal cells evoked by single-pulse stimulation (0.1 Hz) of the commissural afferents were recorded before and after paired-pulse stimulation (0.5 Hz) of the same pathway. A train of 150 or 200 paired pulses produced robust LTD of the commissural input to the CA1 pyramidal neurons when the interstimulus interval (ISI) of the pairs was short (25 ms) but not when the ISI was long (1,000 ms). 2. Paired-pulse stimulation with the short but not with the long ISI also was associated with pronounced inhibition of pyramidal cell firing upon the second pulse of a pair, despite the fact that the excitatory input was facilitated with the short-ISI paradigm. The inhibition of pyramidal cell activity was mediated by input to the pyramidal cells from local gamma-aminobutyric acid (GABA)-releasing interneurons activated by commissural fibers and/or CA1 recurrent collaterals, because the inhibition was eliminated by local administration of the selective GABAA receptor antagonist, bicuculline (50 microM), near the recording site. 3. Postsynaptic input from GABAergic interneurons was necessary for the induction of LTD, because short-ISI paired-pulse stimulation failed to produce LTD in the presence of bicuculline. 4. N-methyl-D-aspartate (NMDA) receptor-mediated excitation also was necessary for the induction of LTD, because administration of the selective NMDA receptor antagonist, D-2-amino-5-phosphonvaleric acid (100 microM), near the recording site prevented the development of LTD.(ABSTRACT TRUNCATED AT 250 WORDS)" http://www.ncbi.nlm.nih.gov/pubmed/7897506 0 508 "M. C. Cassone, A. Fundaro' and L. Molinengo" 1974 "Action of 5-hydroxytryptamine, histamine and methergoline on phagocytosis" Pharmacology 11 4 199-206 http://www.ncbi.nlm.nih.gov/pubmed/4218646 0 509 "A. C. Smith, S. A. Shah, A. E. Hudson, K. P. Purpura, J. D. Victor, E. N. Brown and N. D. Schiff" 2009 A Bayesian statistical analysis of behavioral facilitation associated with deep brain stimulation J.Neurosci.Methods 183 2 267-276 "Deep brain stimulation (DBS) is an established therapy for Parkinson's Disease and is being investigated as a treatment for chronic depression, obsessive compulsive disorder and for facilitating functional recovery of patients in minimally conscious states following brain injury. For all of these applications, quantitative assessments of the behavioral effects of DBS are crucial to determine whether the therapy is effective and, if so, how stimulation parameters can be optimized. Behavioral analyses for DBS are challenging because subject performance is typically assessed from only a small set of discrete measurements made on a discrete rating scale, the time course of DBS effects is unknown, and between-subject differences are often large. We demonstrate how Bayesian state-space methods can be used to characterize the relationship between DBS and behavior comparing our approach with logistic regression in two experiments: the effects of DBS on attention of a macaque monkey performing a reaction-time task, and the effects of DBS on motor behavior of a human patient in a minimally conscious state. The state-space analysis can assess the magnitude of DBS behavioral facilitation (positive or negative) at specific time points and has important implications for developing principled strategies to optimize DBS paradigms" http://www.ncbi.nlm.nih.gov/pubmed/19576932 0 510 "J. M. Jung, S. J. Park, Y. W. Lee, H. E. Lee, S. I. Hong, J. H. Lew, E. Hong, J. S. Shim, J. H. Cheong and J. H. Ryu" 2013 The effects of a standardized Acanthopanax koreanum extract on stress-induced behavioral alterations in mice J.Ethnopharmacol. 148 3 826-834 "ETHNOPHARMACOLOGICAL RELEVANCE: The roots and stem bark of Acanthopanax koreanum Nakai (Araliaceae), a well-known herbal medicine in Jeju Island, Korea, has been used as a tonic agent in treating stress-related states. Despite its popular application, the anti-anxiety or anti-depressive action of Acanthopanax koreanum is not yet known. AIM OF THE STUDY: This study aimed to determine the effects of Acanthopanax koreanum on stress-induced behavioral alterations such as anxiety and depression. MATERIALS AND METHODS: Mice in the acute stress group were exposed to immobilization stress for 2h followed by electric foot shocks (0.5 mA in 1 s duration with a 10 s inter-shock interval) for 2 min, while sub-chronically stressed mice were exposed to these stresses for 2 weeks, once per day. 70% ethanolic extract of Acanthopanax koreanum (EEAK) (25, 50, 100, or 200 mg/kg) was administered once or sub-chronically (for 2 weeks) 1h prior to stress induction. Anxiety- or depression-like behavioral changes were evaluated using the elevated plus-maze (EPM) test and the forced swimming test (FST) a day after the final stress induction. Corticosterone levels and spleen weight were measured after conducting all the behavioral assays. The numbers of BrdU- or DCX-immunopositive cells in the hippocampal region of sub-chronically stressed mice were measured 2 days after EEAK treatment. RESULTS: The percentage of time spent in the open arms was decreased in both the acutely and chronically stressed mice. In the FST, the immobility time was increased by only chronic stress, but not by acute stress. Acute or sub-chronic administration of EEAK significantly prevented the anxiety- or depression-like behavioral changes caused by stress. EEAK also attenuated stress-induced decrease and increase of spleen weight and corticosterone levels, respectively. Furthermore, the sub-chronic administration of EEAK (100 or 200 mg/kg, for 2 weeks) increased the number of BrdU-, doublecortin-, and neuropeptide Y-positive cells in the hippocampal region of the sub-chronically stressed mice. CONCLUSION: EEAK attenuated the behavioral and biochemical changes in acute or sub-chronic stressed mice. These results suggest the therapeutic potential of Acanthopanax koreanum for the treatment of stress-related neuropsychiatric disorders including anxiety disorders or major depressive disorder" http://www.ncbi.nlm.nih.gov/pubmed/23721913 0 511 N. N. Zislina 1977 [Effect of early visual deprivation on the recovery cycle of evoked potentials to photic stimuli in the rabbit cortex] Zh.Vyssh.Nerv.Deiat.Im I.P.Pavlova 27 5 1068-1074 "The influence of visual deprivation on the recovery cycle of the primary positive component (P1) of the visual evoked potential under conditions of dark or light adaptation was studied on eight adult unanaesthetized rabbits raised in darkness. The EP recovery cycle of visually deprived animals, studied in conditions of dark adaption, reveals a significant shortening (as compared with normal) of the initial depression period of testing responses. At the same time a significant lengthening of the facilitation phase and a sharp exaltation of the testing responses is observed. Unlike the norm, transition from dark- to light-adaptation of the deprived animals does not bring about any essential changes in the recovery cycle. An assumption is made that visual deprivation leads to a reduced effectiveness of the processes of successive inhibition. It is also assumed that enhanced excitabilty of a part of the cortical elements, apparently in the system of recurrent excitation, is likely to be one of the consequences of deprivation" http://www.ncbi.nlm.nih.gov/pubmed/930403 0 512 "H. S. Orer, G. L. Gebber and S. M. Barman" 2008 Role of serotonergic input to the ventrolateral medulla in expression of the 10-Hz sympathetic nerve rhythm Am.J.Physiol Regul.Integr.Comp Physiol 294 5 R1435-R1444 "We studied the changes in inferior cardiac sympathetic nerve discharge (SND) produced by unilateral microinjections of 5-hydroxytryptamine (5-HT) receptor agonists and antagonists into the ventrolateral medulla (VLM) of urethane-anesthetized, baroreceptor-denervated cats. Microinjection of the 5-HT2 receptor antagonist LY-53857 (10 mM) into either the rostral or caudal VLM significantly reduced (P < or = 0.05) the 10-Hz rhythmic component of basal SND without affecting its lower-frequency, aperiodic component. The selective depression of 10-Hz power was accompanied by a statistically significant decrease in mean arterial pressure (MAP). Microinjection of LY-53857 into the VLM also attenuated the increase in 10-Hz power that followed tetanic stimulation of depressor sites in the caudal medullary raphe nuclei. Microinjection of the 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)2-amino-propane (DOI; 10 microM) into the VLM selectively enhanced 10-Hz SND, and intravenous DOI (1 mg/kg) partially reversed the reduction in 10-Hz SND produced by 5-HT2 receptor blockade in the VLM. Microinjection of the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT; 10 mM), into either the rostral or caudal VLM also selectively attenuated 10-Hz SND and significantly reduced MAP. The reduction in 10-Hz SND produced by 8-OHDPAT was partially reversed by intravenous WAY-100635 (1 mg/kg), which selectively blocks 5-HT1A receptors. These results support the view that serotonergic inputs to the VLM play an important role in expression of the 10-Hz rhythm in SND" http://www.ncbi.nlm.nih.gov/pubmed/18337315 0 513 E. A. Young and M. Altemus 2004 "Puberty, ovarian steroids, and stress" "Annals of the New York Academy of Sciences.1021 ()(pp 124-133), 2004.Date of Publication: 2004." 124-133 "Puberty is accompanied by a number of changes, among them increased risk for development of major depression. The most common etiology of major depression is stressful life events, being present in approximately 90% of first episodes of depression. The hypothalamic-pituitary-adrenal (HPA) axis is one of the major systems involved in responses to stress, and this system is clearly influenced by ovarian hormones. Normal women demonstrate resistance to negative feedback of both cortisol in the fast-feedback paradigm and dexamethasone in the standard delayed-feedback paradigm. Depressed premenopausal women show greater increases in baseline cortisol than postmenopausal depressed women and than depressed men. Studies in rodents suggest a similar resistance to glucocorticoid feedback but suggest that estradiol can function to inhibit stress responsiveness. Studies of premenopausal depressed women demonstrate lower estradiol, which suggests that there is less inhibitory feedback of estradiol on the HPA axis, while normal progesterone continues to augment stress responses further. The onset of these reproductive hormonal changes modulating stress systems at puberty may sensitize girls to stressful life events, which become more frequent at the transition to puberty and young adulthood" DO - http://dx.doi.org/10.1196/annals.1308.013 0 514 "K. R. Urban, B. D. Waterhouse and W. J. Gao" 2012 Distinct age-dependent effects of methylphenidate on developing and adult prefrontal neurons Biol.Psychiatry 72 10 880-888 "BACKGROUND: Methylphenidate (MPH) has long been used to treat attention-deficit/hyperactivity disorder (ADHD); however, its cellular mechanisms of action and potential effects on prefrontal cortical circuitry are not well understood, particularly in the developing brain system. A clinically relevant dose range for rodents has been established in the adult animal; however, how this range will translate to juvenile animals has not been established. METHODS: Juvenile (postnatal day [PD] 15) and adult (PD90) Sprague Dawley rats were treated with MPH or saline. Whole-cell patch clamp recording was used to examine the neuronal excitability and synaptic transmission in pyramidal neurons of prefrontal cortex. Recovery from MPH treatment was also examined at 1, 5, and 10 weeks following drug cessation. RESULTS: A dose of 1 mg/kg intraperitoneal MPH, either single dose or chronic treatment (well within the accepted therapeutic range for adults), produced significant depressive effects on pyramidal neurons by increasing hyperpolarization-activated currents in juvenile rat prefrontal cortex, while exerting excitatory effects in adult rats. Minimum clinically-relevant doses (.03 to .3 mg/kg) also produced depressive effects in juvenile rats, in a linear dose-dependent manner. Function recovered within 1 week from chronic 1 mg/kg treatment, chronic treatment with 3 and 9 mg/kg resulted in depression of prefrontal neurons lasting 10 weeks and beyond. CONCLUSIONS: These results suggest that the juvenile prefrontal cortex is supersensitive to methylphenidate, and the accepted therapeutic range for adults is an overshoot. Juvenile treatment with MPH may result in long-lasting, potentially permanent, changes to excitatory neuron function in the prefrontal cortex of juvenile rats" http://www.ncbi.nlm.nih.gov/pubmed/22609367 0 515 "R. Meller, J. M. Babity and D. G. Grahame-Smith" 2002 5-HT2A receptor activation leads to increased BDNF mRNA expression in C6 glioma cells Neuromolecular.Med. 1 3 197-205 "It has recently been suggested that an increase in brain-derived neurotrophic factor (BDNF) expression may mediate some of the therapeutic effect of antidepressant drugs, via their effects on the neurotransmitter 5-hydroxytryptamine (5-HT). However, because it is unclear whether 5-HT manipulations directly affect BDNF expression, we examined BDNF mRNA levels in C6 glioma cells following incubation with 5-HT using reverse transcription polymerase chain reaction (RT-PCR) and Northern blot analysis. Incubation of C6 glioma cells with 5-HT increased the BDNF mRNA expression approx twofold. The effect of 5-HT (100 microM) was inhibited by a 5-HT2A receptor antagonist (ketanserin; 1 microM). The RNA synthesis inhibitor (actinomycin D; 10 microg/mL), but not a protein synthesis inhibitor (cycloheximide; 0.5 microg/mL) blocked the effect of 5-HT. Furthermore, incubation of C6 glioma cells with EGTA (1 mM), a protein kinase inhibitor (staurosporine; 1 microM), the Ca2+ ATPase inhibitor thapsigargin (1 microM), or a calcium/calmodulin-dependent kinase inhibitor (KN 62; 1 microM) inhibited the response to 5-HT. Our data show that 5-HT increases de novo BDNF mRNA synthesis following direct activation of the 5-HT2A receptor, via a calcium-dependent and protein kinase-dependent pathway" http://www.ncbi.nlm.nih.gov/pubmed/12095161 0 516 "K. Kapornai, I. Baji, E. Kiss, R. Dochnal, M. Kovacs and A. Vetro" 2015 Atypical early neurodevelopmental characteristics in childhood onset depression-two case-control studies "European Child and Adolescent Psychiatry.Conference: 16th International Congress of European Society for Child and Adolescent Psychiatry, ESCAP 2015 Madrid Spain.Conference Start: 20150620 Conference End: 20150624.Conference Publication: (var.pagings)." var.pagings S134 "Introduction: Early difficult temperament has been documented as risk for psychopathology later in life and there are studies documenting the role of perinatal problems and developmental delay in the development of different psychiatric disorders in children and in depressed adults. We aimed to extend our understanding about the etiology of childhood onset depression (COD) by comparing clinically depressed kids to healthy controls and to their unaffected siblings regarding atypical early temperamental and neurodevelopmental characteristics. Hypothesis: (1) Perinatal problems, developmental delay, and difficult temperament are more frequent in children with COD than in community control kids and (2) in their unaffected siblings. Method: Participants were children with COD (N = 648 and N = 95 in case of the comparison to siblings), their unaffected siblings (N = 97) and community control kids (N = 648) from elementary schools. Diagnoses were based on DSM-IV criteria. In case of controls depressive symptoms were measured by self rating scale. Mothers provided developmental data in a face-to face structured interview (COD kids and unaffected siblings) and via self-rated version of the same interview about controls. Using the data from this interview we created four scales of atypical development: total neurodevelopmental problems, perinatal problems, developmental delay, and difficult temperament. Results: Comparing the depressed to the control group depression significantly associated with the perinatal (F = 10.73; p = 0.0011), the developmental (F = 21.73; p<0.0001), the temperamental (F = 90.38 p < 0.0001) and the total score (F = 80.09; p < 0.0001) as well. The difficult temperament scale differentiated significantly (F = 5.556; p = 0.019) between the depressed and unaffected siblings group as well. Regarding this scale significant depression status-Xsex interaction was found (F = 2.908; p = 0.036). Across our study groups the difference was the most robust regarding the item of hard to comfort, which was six times frequent in the depressed group (28.59 %) comparing to community controls (5.25 %) and about twice as frequent than in unaffected siblings (13.4 %), indicating that unaffected siblings were between the depressed and normal controls. Conclusions: Early neurodevelopmental characteristics elevated the risk for COD. The variables that refer to difficult temperament are emerged with significantly higher frequency in unaffected siblings than in community controls. Improving the support for mothers dealing with infants with difficult early temperament could have positive effect in the prevention of COD later in childhood" DO - http://dx.doi.org/10.1007/s00787-015-0714-4 0 517 "A. Cittadini, J. D. Grossman, H. Stromer, S. E. Katz, J. P. Morgan and P. S. Douglas" 2001 Importance of an intact growth hormone/insulin-like growth factor 1 axis for normal post-infarction healing: studies in dwarf rats Endocrinology 142 1 332-338 "Treatment with GH attenuates remodeling and improves left ventricular function in the setting of experimental heart failure following coronary ligation. This study was designed to test the hypothesis that an intact GH/insulin-like growth factor 1 (IGF-1) axis is required for normal myocardial infarction healing. Myocardial infarction was induced by coronary ligation in GH-deficient dwarf rats and in age-matched controls. In dwarf rats, serum IGF-1 levels were reduced by 50%, and grow rate was 50% less than normal littermates, although no differences in myocardial IGF-1 messenger RNA levels were observed compared with controls. All rats underwent transthoracic echocardiography at baseline, 2 weeks, and 6 weeks after myocardial infarction. Left ventricular end-diastolic pressure was obtained by in vivo closed chest catheterization. At 6 weeks, both infarcted groups exhibited similar myocardial infarction size at transthoracic echocardiography and at morphometric histology. In both groups with myocardial infarction, there was significant left ventricular dilation and reduced systolic function. However, the extent of remodeling as assessed by the increase in end-diastolic dimension (%Delta + 36 +/- 5 vs. +19 +/- 4; P: < 0.01) and depression of function (%Delta fractional shortening -12 +/- 2 vs. -7 +/- 1; P: < 0.01) were both greater in the dwarf group. Furthermore, dwarf rats failed to develop compensatory hypertrophy of noninfarcted posterior wall (%Delta posterior wall +5 +/- 1 vs. +15 +/- 3; P: < 0.01). Therefore, pathologic left ventricular remodeling and functional loss following myocardial infarction is more marked in conditions of GH deficiency. An intact GH/IGF-1 axis appears necessary for a normal response to myocardial infarction injury in the rat" http://www.ncbi.nlm.nih.gov/pubmed/11145596 0 518 C. Lopez-Rubalcava and I. Lucki 2000 Strain differences in the behavioral effects of antidepressant drugs in the rat forced swimming test Neuropsychopharmacology 22 2 191-199 "Wistar-Kyoto (WKY) rats provide a model of stress-induced depressive behavior, because they show enhanced vulnerability to the effects of stressors. The present study examined differences in the behavioral response to different types of antidepressant drugs between WKY and Sprague-Dawley (SD) rats in the forced swimming test (FST). WKY rats displayed significantly greater immobility than SD rats during their exposure to the FST. The noradrenergic antidepressant, desipramine, produced a dose-dependent reduction of immobility and increase of climbing behavior in the SD rats. In WKY rats, desipramine reduced immobility at a lower dose and produced increases of both swimming and climbing behavior. The serotonergic compounds, fluoxetine and 8-OH-DPAT, produced dose-dependent reductions of immobility and increases of swimming behavior in the FST in SD rats, but the response to the serotonergic drugs were blunted in WKY rats. These results indicate that genetic or constitutive differences may determine the distinct behavioral profiles for antidepressant compounds with selective pharmacological effects in different rat strains, and these effects may be related to genetic heterogeneity of antidepressant responses in depressed patients" http://www.ncbi.nlm.nih.gov/pubmed/10649831 1 519 S. v. O.-O. MM and H. C. Kalsbeek 1988 Ureteropyelonephritis in a Friesian mare Vet.Rec. 122 25 609-610 "A 14-year-old Friesian breeding mare had strangury, depression, inappetence, neutrophilia and uraemia. Its urine had a low specific gravity and contained protein, blood cells and bacteria. Rectal examination showed that both kidneys and ureters were enlarged. Post mortem examination confirmed the diagnosis of pyelonephritis and revealed that small tumours in the vulva were probably the cause of the uropathy" http://www.ncbi.nlm.nih.gov/pubmed/3407117 0 520 T. J. Crowley 1972 "Dose-dependent facilitation or supression of rat fighting by methamphetamine, phenobarbital, or imipramine" Psychopharmacologia. 27 3 213-222 http://www.ncbi.nlm.nih.gov/pubmed/4674515 0 521 "M. Iqbal, E. Ezzeldin, K. A. Al-Rashood and A. A. Bajrai" 2015 A simple and fast UHPLC-MS-MS assay for rapid determination of vilazodone in plasma sample J.Anal.Toxicol. 39 2 106-112 "Vilazodone is a novel antidepressant agent, approved by the US Food and Drug Administration (US FDA) for the treatment of major depressive disorder. In this study, a fast sensitive ultra-high performance liquid chromatography-tandem mass spectroscopy method was developed and validated for the determination of vilazodone in human plasma. After a simple protein precipitation by acetonitrile, both vilazodone and risperidone (internal standard, IS) were separated on an Acquity UPLC BEH C18 column (50 x 2.1 mm, 1.7 microm). An isocratic mobile phase of acetonitrile:10 mM ammonium acetate (80:20, v/v) was used at the 0.3 mL/min flow rate. Both vilazodone and IS were eluted at 0.44 and 0.47 min, respectively, having a run time of 1.0 min. Detection and quantification were performed using an electrospray ionization source in positive mode by multiple reaction monitoring. The precursor to product ion transitions were monitored at m/z 442.19 > 154.99 for vilazodone and m/z 411.18 > 191.07 for IS, respectively. The standard curve (0.40-500 ng/mL) was found to be linear with a lower limit of quantification 0.40 ng/mL. All validation results were found to be within acceptable limits as per guidelines for bioanalytical method validation (US FDA and European Medicines Agency). To the best of our knowledge, this is the first fully validated assay for the determination of vilazodone in human plasma and was successfully applied to an oral pharmacokinetic study in rats" http://www.ncbi.nlm.nih.gov/pubmed/25404657 0 522 "C. E. Green, C. B. Higgins, M. J. Kelley, J. D. Newell, W. S. Schmidt and F. Haigler" 1981 Effects of intracoronary administration of contrast materials on left ventricular function in the presence of severe coronary artery stenosis Cardiovasc.Intervent.Radiol. 4 2 110-116 "The effects of intracoronary administration of contrast materials on regional and global left ventricular (LV) function were assessed in anesthetized dogs with segmental myocardial ischemia produced by critical stenosis of the circumflex coronary artery. Effects caused by sodium meglumine diatrizoate (R76), sodium meglumine calcium metrizoate (ISO), and metrizamide were evaluated. In the nonischemic state R76 produced an early (0-10 seconds) decrease in LV contractility followed by a late (10-20 seconds) positive inotropic effect. In the presence of regional ischemia there was prolongation of the negative inotropic effect. ISO produced only positive inotropic effects without significant differences between responses in the nonischemic and ischemic states. Metrizamide produced almost no alterations in LV function" http://www.ncbi.nlm.nih.gov/pubmed/7249015 0 523 R. J. Coppola and D. F. Rolek 1975 A neuropharmacologic approach to self-mutilating behavior J.Am.Osteopath.Assoc. 74 6 555-557 http://www.ncbi.nlm.nih.gov/pubmed/1039013 0 524 J. N. Nobrega and D. V. Coscina 1983 Central injections of the GABA-transaminase inhibitor ethanolamine-O-sulfate (EOS): effects on brain [14C]2-deoxy-D-glucose uptake and behavior in rats Brain Res. 262 2 243-252 "Brain glucose utilization was examined 24 h after single intracisternal injections of the GABA-transaminase inhibitor ethanolamine-O-sulfate (EOS) in rats. Qualitative autoradiography indicated a pronounced and homogeneous depression in [14C]2-deoxy-D-glucose ([14C]2DG) uptake throughout the brains of rats treated with 200 or 400 micrograms EOS. Quantitative scintillation counting of 14C in 9 brain areas of other rats confirmed the marked, generalized decrease in label uptake 24 h after EOS. Food intake measurements confirmed previous reports of dose-dependent anorexia after EOS. Rats treated with the 200 micrograms dose showed decreased open-field activity 24 h after injection but no other deficits in various tests of sensorimotor function or in tail-pinch-induced feeding. Rats treated with the 400 micrograms dose also showed deficits in open-field activity, plus deficits in orientation to touch stimuli, longer latencies than controls in catalepsy tests, and faster habituation of startle responses to sound. This group showed normal feeding responses to tail-pinch stimulation in the presence of solid food but not in the presence of liquid food. It was concluded that sensorimotor deficits may play some role in the anorexigenic effects of EOS but are probably not their primary cause. The discrepancy between the apparent degree of depression of brain glucose utilization and the comparatively mild behavioral deficits observed would suggest the possibility that metabolic fuels other than glucose may be mobilized following central EOS treatment" http://www.ncbi.nlm.nih.gov/pubmed/6839155 0 525 "D. Teran-Escandon, L. Teran-Ortiz, C. Ormsby-Jenkins, M. L. Evia-Viscarra, D. J. White and R. Valdes-Gonzalez-Salas" 2005 Psychosocial aspects of xenotransplantation: survey in adolescent recipients of porcine islet cells Transplant.Proc. 37 1 521-524 "INTRODUCTION: Transplantation is a process with several psychosocial challenges. Regarding the case of xenotransplantation, the perceived similarity between humans and pigs may be stressful. Adjustment disorders have been reported among transplantation recipients. We sought to assess the psychosocial aspects of xenotransplantation among porcine islet-cell recipients and their efforts to adapt themselves to this condition. MATERIAL AND METHODS: Ten insulin-dependent diabetes mellitus patients aged 14.58 +/- 7.93 who received porcine islet-cells were included. The bioartificial steel/fibrous tissue chamber method was used. All patients and their relatives were interviewed about their expectations, overall functioning, and experiences. The quality of life, enjoyment, and satisfaction scale and the hospital anxiety and depression scales were used. A 1-year follow-up was done. RESULTS: Their motivation was centered on autonomy; there were no troubles regarding the graft origin. Xenotransplantation was perceived with pragmatism, seeing pigs as an unlimited resource. The patients with best outcomes also had the greatest improvements in several quality of life areas (QOL) while the medium responders had fewer QOL improvements. The nonresponders experienced mainly frustration. Parents' concerns were not related to their children's health but to their recently gained autonomy. CONCLUSIONS: In addition to enthusiasm, the perception of animals as an unlimited source of organs may affect patient compliance; in this group, xenotransplantation was seen as using as a long-lasting drug, with chamber walls considered as a physical, immunologic, and, in certain manner, a psychological barrier" http://www.ncbi.nlm.nih.gov/pubmed/15808697 0 526 "E. V. Gurevich, N. V. Bobkova, I. Katkov, N. A. Otmakhova and I. V. Nesterova" 1992 [The behavioral and biochemical sequelae of the removal of the olfactory bulbs in C57Bl/6j mice] Zh.Vyssh.Nerv.Deiat.Im I.P.Pavlova 42 4 779-787 "Ablation of the olfactory bulbs in mice C57Bl/6j was accompanied by motor and orienting-exploratory activity augmentation in the ""open field"" test and deterioration of the learning ability to active and passive avoidance. The most expressed behavioural changes developed in four weeks after the surgery. Chronic administration of antidepressants (amitriptyline, 20 mg/kg; trazodone, 20 mg/kg; imipramine, 10 mg/kg; intraperitoneally) normalized behaviour of bulbectomized animals, trazodone being the most effective. In the biochemical studies the brainstem serotonin level was found to be decreased and the density of 5HT2-receptors in the cerebral cortex increased in bulbectomized mice. Only trazodone was able to correct the biochemical indices. The state of the bulbectomized mice is supposed to serve a model of a depression with hypo-function of serotonergic system of the brain" http://www.ncbi.nlm.nih.gov/pubmed/1332299 1 527 A. E. Autry and L. M. Monteggia 2009 Epigenetics in suicide and depression Biol.Psychiatry 66 9 812-813 http://www.ncbi.nlm.nih.gov/pubmed/19833253 0 528 "G. Fernandez, M. C. Villarruel, E. C. de Ferreyra, O. M. de Fenos, A. S. Bernacchi, C. R. de Castro and J. A. Castro" 1984 Carbon tetrachloride-induced early biochemical alterations but not necrosis in pigeon's liver Agents Actions 15 03-Apr 463-466 "In contrast to what is well known to occur in rats, pigeons receiving CCl4 (1 ml/kg i.p.) were not susceptible to necrogenic effects of the hepatotoxin at 24 h. There were, however, other early biochemical alterations observable, such as depression of glucose 6 phosphatase activity, decrease in the cytochrome P-450 content and in aminopyrine-N-demethylase activity in pigeon liver microsomes at 3 and 6 h after CCl4 administration. Pigeon liver was able to activate CCl4 to reactive metabolites that bind covalently to lipids, but no CCl4-induced lipid peroxidation was proved by the diene hyperconjugation technique in pigeon liver microsomes at 1, 3 or 6 h after administration. Results suggest that covalent binding of CCl4-reactive metabolites are more relevant to early biochemical alterations induced by CCl4 than is lipid peroxidation. Absence of CCl4-induced necrosis in pigeon liver could be attributable to a smaller intensity of covalent binding interactions observed, when compared to susceptible species, and to absence of lipid peroxidation" http://www.ncbi.nlm.nih.gov/pubmed/6098176 0 529 "M. H. Bassant, A. Jobert, P. Dutar and Y. Lamour" 1988 Effect of psychotropic drugs on identified septohippocampal neurons Neuroscience 27 3 911-920 "The effects of various psychotropic drugs (benzodiazepines, antidepressants, neuroleptics and nootropic drugs, a family of cognition activator agents) on firing rates of septohippocampal neurons, identified by electrical antidromic stimulation, were studied in the medial septum-nucleus of the diagonal band of Broca of rats anaesthetized with urethan. Extracellular potentials from single septohippocampal neurons were recorded using glass pipettes. Drugs were applied by either microiontophoresis or intravenous injections (i.v.). Benzodiazepines produced a marked depression of spontaneous firing rates of septohippocampal neurons whether applied i.v. (diazepam) or iontophoretically (flurazepam, midazolam). In addition, diazepam had a potent depressant effect on the rhythmically bursting activity of the septohippocampal neurons. Baclofen also had an inhibitory effect. Antidepressant drugs (applied by iontophoresis) as well as amphetamine, had a depressant effect on spontaneous firing rates. Neuroleptics (i.v.) had less significant or consistent effects on septohippocampal neurons, although the effects of haloperidol were usually inhibitory. Nootropic drugs were generally ineffective. These data indicate that most psychotropic drugs tested (with the exception of nootropic drugs) have an inhibitory effect on the spontaneous activity of septohippocampal neurons. However, benzodiazepines seem to be more active than antidepressants or neuroleptics. Oxotremorine (i.v.) had a potent excitatory effect on septohippocampal neurons. Atropine (i.v.) increased the septohippocampal neurons' firing rate in some cases. These results are discussed in view of the possible implication of the involvement of septohippocampal neurons in the mediation of the effects of psychotropic drugs on the central nervous system and, more specifically, on the cholinergic systems" http://www.ncbi.nlm.nih.gov/pubmed/2908059 0 530 "Y. Legrand, J. P. Caen and L. Robert" 1968 Effect of glucosamine on platelet-collagen reaction Proc.Soc.Exp.Biol.Med. 127 3 941-943 http://www.ncbi.nlm.nih.gov/pubmed/5651155 0 531 K. Kozlowska 1968 The effect of cortisone and ACTH on behaviour of beta-glucuronidase and beta-galactosidase in stomach mucosa of white rat Acta Histochem. 30 2 380-385 http://www.ncbi.nlm.nih.gov/pubmed/4302063 0 532 "T. Hedner, J. Hedner, B. Bergman, K. Iversen and J. Jonason" 1983 Effects of GABA and some GABA analogues on respiratory regulation in the preterm rabbit Biol.Neonate 43 03-Apr 134-145 "Preterm neonatal rabbits (gestational age 29 days) were given GABA (750 mg/kg) or the GABA-like drugs muscimol (2 mg/kg) and GHBA (375 mg/kg) intraperitoneally. Basal respiration and the ventilatory response to 10% CO2 were studied, before and after drug administration, in a whole body plethysmograph during halothane anesthesia. The three drugs tested all caused a decrease in minute volume. The decrease in minute volume was mainly due to a decrease in tidal volume after GABA and muscimol, while GHBA reduced minute volume due to a decrease in respiratory frequency. A decrease in respiratory frequency was also seen after muscimol administration. Changes in the respiratory time intervals were seen after muscimol and GHBA both causing significant increases in expiratory and respiratory time. 'Inspiratory drive' and 'respiratory timing mechanisms' were evaluated by VT/TI and TI/TTOT, respectively. GABA and muscimol reduced both VT/TI and TI/TTOT while GHBA only reduced TI/TTOT. Addition of 10% CO2 to the inhalation gas caused an increase in tidal volume and minute volume during control conditions. This response to CO2 was abolished by GABA and GHBA treatment. Our findings demonstrate that GABA and GABA-like drugs cause respiratory depression in the preterm neonate. Central mechanisms are most likely involved in this response. These findings may be relevant to the irregular or apneic breathing sometimes seen in the preterm human infant" http://www.ncbi.nlm.nih.gov/pubmed/6407536 0 533 "I. M. Dixon, T. Hata and N. S. Dhalla" 1992 Sarcolemmal Na(+)-K(+)-ATPase activity in congestive heart failure due to myocardial infarction Am.J.Physiol 262 3 Pt 1 C664-C671 "Because the Na+ pump is considered to modulate the contractile force development by the cardiac muscle and depressed cardiac pump function is the hallmark of congestive heart failure, we characterized the sarcolemmal Na(+)-K(+)-ATPase activity in failing rat hearts after myocardial infarction. For this purpose, the left ventricular coronary artery was ligated, and hearts were examined 4, 8, and 16 wk later; sham-operated animals served as controls. Hemodynamic assessment revealed the presence of abnormal cardiac function at 4, 8, and 16 wk. Although accumulation of ascites in the abdominal cavity was present in experimental animals at 4 wk, other clinical signs of congestive heart failure in experimental rats including lung congestion and cardiac dilatation were evident 8 and 16 wk after induction of myocardial infarction. The depression in Na(+)-K(+)-ATPase activity in purified sarcolemmal membrane from the uninfarcted experimental left ventricle at 8 wk was associated with depressed Vmax without any changes in the affinities for Mg-ATP, Na+, and K+ or the pH optimum for the enzyme. The Kd values of both the high- and low-affinity binding sites for [3H]ouabain, which is believed to interact with Na(+)-K(+)-ATPase, were increased; however, no change in the density of either class of ouabain binding site was evident. The depression of Na(+)-K(+)-ATPase activity in failing hearts at 16 wk of myocardial infarction was not different from that observed at 8 wk but the enzyme activity was not altered at 4 wk of coronary occlusion. These data support the view that depression of Na(+)-K(+)-ATPase activity may serve as an adaptive mechanism during the development of congestive heart failure" http://www.ncbi.nlm.nih.gov/pubmed/1312780 0 534 A. H. Miller 2010 Peripheral activation of the kynurenine pathway by interferon-alpha leads to altered csf concentrations of kynurenine and its metabolites which correlate with depression "Neuropsychopharmacology.Conference: 49th Annual Conference of the American College of Neuropsychopharmacology, ACNP 2010 Miami Beach, FL United States.Conference Start: 20101205 Conference End: 20101209.Conference Publication: (var.pagings).35 ()(pp S" var.pagings S60 "Background: Converging evidence suggests that activation of the innate immune, inflammatory response including the release of cytokines of the innate immune system may contribute to the pathogenesis of major depression in certain depressed patients. One pathway that may be relatively unique to the mechanisms by which inflammatory stimuli contribute to the symptoms of depression is cytokine-induced activation of the enzyme, indoleamine 2,3-dioxygenase (IDO). IDO catabolizes L-tryptophan (TRP) into L-kynurenine (KYN), which is metabolized to quinolinic acid (QUIN) and kynurenic acid (KA). QUIN and KA are both neuroactive and may contribute to the behavioral changes experienced by patients during chronic exposure to inflammatory stimuli such as the innate immune cytokine, interferon (IFN)-alpha. Of note, activation of IDO appears to play a critical role in the development of depressive-like symptoms in laboratory animals following exposure to inflammatory stimuli such as lipopolysaccharide and bacille Calmette-Guerin, an attenuated form of Mycobacterium bovis. A relationship between depressive symptoms and peripheral blood TRP, KYN and KA during IFN-alpha treatment in humans has been described. However, whether peripheral blood changes in these IDO catabolites are manifest in the brain and whether they are related to central nervous system cytokine responses and/or behavior is unknown. Methods: TRP, KYN, QUIN and KA were measured in cerebrospinal fluid (CSF) and blood along with CSF concentrations of relevant cytokines, chemokines and soluble cytokine receptors in 27 patients with hepatitis C after B12 weeks of either treatment with IFN-alpha (n=16) or no treatment (n=11). Depressive symptoms were assessed using the Montgomery Asberg Depression Rating Scale. Results: IFN-alpha significantly increased peripheral blood KYN, which was accompanied by marked increases in CSF KYN (IFN-alphatreated: 111.5nM SD 32.6 versus controls: 76.6nM SD 19.2, t=2.36, p=0.03). Increased CSF KYN was in turn associated with significant increases in CSF QUIN and KA (Spearman's rho=0.72, p<0.001, and Spearman's rh=0.48, p=0.001, respectively). Despite significant decreases in peripheral blood TRP, IFN-alpha had no effect on CSF TRP concentrations. Increases in CSF KYN and QUIN were correlated with increased CSF IFN-alpha, soluble tumor necrosis factor-alpha receptor 2 (sTNFR2) and monocyte chemoattractant protein (MCP)-1 as well as increased depressive symptoms (Spearman's rho=0.47, p=0.019 and Spearman's rho=0.39, p=0.043, respectively). Discussion: These data demonstrate that peripheral administration of a cytokine of the innate immune system can activate IDO in concert with central nervous system cytokine responses, resulting in increased brain KYN, QUIN, KA, and ultimately depressive symptoms" DO - http://dx.doi.org/10.1038/npp.2010.215 0 535 T. W. Stone 1973 Actions of some 3-methoxyphenylethylamine derivatives on cortical neurones Arch.Int.Pharmacodyn.Ther. 205 1 29-39 http://www.ncbi.nlm.nih.gov/pubmed/4757846 0 536 "D. R. Curtis, L. Hosli and G. A. Johnston" 1968 [Inhibitory effect of glycine and similar amino acids on spinal neurons] Helv.Physiol Pharmacol.Acta 26 2 CR-6 http://www.ncbi.nlm.nih.gov/pubmed/5697775 0 537 "O. Mutlu, E. Gumuslu, G. Ulak, I. K. Celikyurt, S. Kokturk, H. M. Kir, F. Akar and F. Erden" 2012 "Effects of fluoxetine, tianeptine and olanzapine on unpredictable chronic mild stress-induced depression-like behavior in mice" Life Sci. 91 25-26 1252-1262 "AIMS: Tianeptine is an atypical antidepressant drug that has a different mechanism of action than other antidepressants. Olanzapine is an atypical antipsychotic drug used for the treatment of schizophrenia. The present study was undertaken to investigate effects of chronic administration of tianeptine or olanzapine on unpredictable chronic mild stress (UCMS)-induced depression-like behavior in mice compared to a widely used SSRI antidepressant, fluoxetine. MAIN METHODS: Male inbred BALB/c mice were subjected to different kinds of stressors several times a day for 7weeks and were treated intraperitoneally with tianeptine (5mg/kg), olanzapine (2.5mg/kg), fluoxetine (15mg/kg) or vehicle for 5weeks (n=7-8 per group). KEY FINDINGS: All the drugs tested prevented stress-induced deficit in coat state during UCMS procedure, in grooming behavior in the splash test, decreased the attack frequency in the resident intruder test and decreased the immobility time in the tail suspension test. In the open field test olanzapine had anxiolytic-like effects in both stressed and non-stressed mice. Tianeptine, olanzapine and fluoxetine decreased the enhanced levels of plasma ACTH and IL-6. Chronic treatment with tianeptine resulted in a significant increase in both total number and density of BrdU-labeled cells in stressed animals, while fluoxetine and olanzapine had a partial effect. SIGNIFICANCE: The results of this study support the hypothesis that tianeptine can be as effective as fluoxetine for the treatment of depression in spite of the differences in the mechanism of action of these drugs. Moreover, olanzapine could be used effectively in psychotic patients with depression" http://www.ncbi.nlm.nih.gov/pubmed/23069580 1 538 "R. A. Del, M. M. McDermott and J. Panee" 2012 Effects of a high-fat diet and bamboo extract supplement on anxiety- and depression-like neurobehaviours in mice Br.J.Nutr. 108 7 1143-1149 "High-fat diet is a major causative factor of overweight and obesity, which are associated with an increased risk of neuropsychiatric diseases, such as anxiety and depression. In the present study, we investigated the protective effects of bamboo extract (BEX) on anxiety- and depression-like neurobehaviours in mice treated with a high-fat diet. Male mice with CD-1 genetic background were treated for 2 months with either a standard or a high-fat diet (10 or 45 % energy from fat, respectively), with or without the BEX supplement (11 g dry mass per 17 MJ). The anxiety levels of mice were evaluated using open-field and hole-board tests, and depression was measured using the force-swimming test. The anxiety responses of the animals were found significantly increased after the high-fat diet treatment, and this elevation was effectively abolished by the BEX supplement. The high-fat diet seemed to have an anti-depressive effect in mice at the tested time point, but the effect of the BEX supplement on the depression level of the animals was not conclusive. The high-fat diet significantly decreased total glutathione content in the blood while the BEX supplement increased glutathione oxidation. In summary, the present study shows that decreased total glutathione concentration in the blood co-occurred with a high-fat treatment, high anxiety level and low depression level in mice, and when supplemented in a high-fat diet, BEX had an anxiolytic effect in mice" http://www.ncbi.nlm.nih.gov/pubmed/22313665 1 539 A. K. Abbas 2013 Evidence for constitutive protein synthesis in hippocampal LTP stabilization Neuroscience 246 301-311 "The notion that blockade of constitutive protein synthesis underlies the effect of protein synthesis inhibitors (PSIs) on long-term potentiation (LTP) stabilization was examined using the rat hippocampal CA3-CA1 synapse. Using a biochemical assay we found protein synthesis rate largely recovered 1h after wash-out of cycloheximide (CHX). Nonetheless, a 4-h CHX application followed by wash-out 1h prior to LTP resulted in a significant decrement of LTP stabilization. Wash-out initiated just prior to LTP, thus extending protein synthesis inhibition well into the post-LTP period, resulted in no further effect on LTP. However, short pre- and continuous post-tetanization application of PSIs failed to influence LTP persistence for up to 7 h. Addition of hydrogen peroxide (H(2)O(2)) 5-25 min following LTP induction resulted in parallel depression of potentiated and non-potentiated inputs, leaving LTP seemingly unaltered. However, in the presence of cyxloheximide the H(2)O(2) application resulted in a significant reduction of LTP. IN CONCLUSION: LTP stabilization was impaired by pre-LTP application of protein synthesis inhibition but not by post-LTP application unless the slices were exposed to oxidative stress. We submit that these results favor the notion that constitutive rather than triggered protein synthesis is important for LTP stabilization" http://www.ncbi.nlm.nih.gov/pubmed/23685165 0 540 S. V. Goswami and B. I. Sundararaj 1973 "Effect of actinomycin D, mitomycin C, puromycin, and cycloheximide on desoxycorticosterone-induced in vitro maturation in oocytes of the catfish, Heteropneustes fossilis (Bloch)" J.Exp.Zool. 185 3 327-332 http://www.ncbi.nlm.nih.gov/pubmed/4748951 0 541 L. Vinay and F. Clarac 1996 CGP 35348 and CGP 55845A block the baclofen-induced depression of dorsal root evoked potentials in lumbar motoneurons of the neonatal rat Neurosci.Lett. 214 02-Mar 103-106 "In vitro brainstem-spinal cord preparations isolated from neonatal (0-5 days old) rats were used to investigate the GABAB receptor-mediated modulation of the dorsal root evoked potentials in lumbar motoneurons recorded intracellularly. The GABAB receptor agonist, baclofen, at low concentrations (1-10 microM), caused a reduction of the amplitude of the monosynaptic excitatory postsynaptic potential (EPSP), in a concentration-dependent manner. The depression of EPSPs was likely exerted at a presynaptic level since it occurred without any significant change of the passive membrane properties of the motoneurons. The two GABAB receptor antagonists, CGP 35348 and CGP 55845A blocked the effects of baclofen. These two compounds may be useful tools to study the evolution of GABAB receptor-mediated presynaptic inhibition during ontogenesis" http://www.ncbi.nlm.nih.gov/pubmed/8878094 0 542 "Y. Ago, T. Harasawa, S. Itoh, S. Nakamura, A. Baba and T. Matsuda" 2005 Antidepressant-like effect of coadministration of sulpiride and fluvoxamine in mice "European Journal of Pharmacology.520 (1-3) ()(pp 86-90), 2005.Date of Publication: 27 Sep 2005." 01-Mar 86-90 "We have recently reported that coadministration of sulpiride, an antipsychotic drug, and fluvoxamine, a selective serotonin (5-HT) reuptake inhibitor, selectively increases in vivo dopamine release in the prefrontal cortex. This study examined the effects of coadministration of these drugs on duration of immobility in the tail suspension test using mice. Neither sulpiride (3 or 10 mg/kg) nor fluvoxamine (10 or 20 mg/kg) alone affected immobility time, whereas coadministration significantly reduced immobility time. WAY100635, a 5-HT1A receptor antagonist, did not affect the effects of sulpiride and fluvoxamine coadministration, but reduced immobility time in combination with fluvoxamine (20 mg/kg). A high dose of fluvoxamine alone (60 mg/kg) also reduced immobility time. These results suggest that the antidepressant-like effects of fluvoxamine in combination with sulpiride or WAY100635 in the tail suspension test are mediated by the activation of dopamine or 5-HT systems, respectively. © 2005 Elsevier B.V. All rights reserved" DO - http://dx.doi.org/10.1016/j.ejphar.2005.08.011 1 543 "S. Atal, P. Phadnis, S. Vyas, G. Gudsurkar and R. Churihar" 2016 "Evaluation of the interaction of piperine with antidepressant sertraline and analgesic pentazocine, using different routes of administration in albino mice" "Asian Journal of Pharmaceutical and Clinical Research.9 (1) ()(pp 178-182), 2016.Date of Publication: January 2016." 1 178-182 "Objective: To evaluate the effect of piperine on the antidepressant activity of sertraline and analgesic activity of pentazocine and to explore the effect of using oral and parenteral routes of administration on the possible interactions. Methods: Piperine was isolated from commercially obtained Piper nigrum extract. Swiss albino mice of either sex were divided into 8 groups (n=6) receiving: 2% gum acacia (oral, intraperitoneally [i.p.]), standard drug (oral, i.p.), standard drug + piperine (oral, i.p.), piperine (oral, i.p.). Tail suspension test (TST) was used for antidepressant effect and Eddy's hot plate method for analgesic effect. Sertraline and pentazocine were used as standard drugs (5 mg/kg) and piperine at 10 mg/kg. Result: In the TST, piperine alone (both routes) decreased immobility time, but the effect was statistically insignificant. Both combination groups (oral and i.p.) showed significantly better activity compared to sertraline oral and i.p. groups, respectively (p<0.05). Oral combination showed activity comparable to i.p. combination (p>0.05). Piperine did not show any analgesic activity of its own (both routes). Piperine with pentazocine orally showed significantly better activity compared to pentazocine (oral) at 1, 2, and 4 hrs, and analgesia at 0.5 hr which pentazocine oral did not. Parenteral combination was significantly better than pentazocine (i.p.) group at 2 and 4 hrs and better than oral combination at 4 hrs. Conclusion: Piperine has potential to be used in combination with pentazocine due to its bioenhancing effect and with sertraline due to a potentiating/ additive effect which can help reduce dose and adverse effects of these drugs" 1 544 "d. van, V, B. Vanheel and I. Leusen" 1992 Endothelium-dependent relaxation and hyperpolarization in aorta from control and renal hypertensive rats Circ.Res. 70 1 42583 "Endothelium-dependent relaxations are depressed in hypertension. In this study we investigated the possible involvement of endothelium-dependent smooth muscle hyperpolarization in this phenomenon. In isolated aortic segments from control rats, acetylcholine (10(-8)-10(-5) M) elicits relaxations after precontraction with norepinephrine (10(-7) M), and acetylcholine or carbachol (10(-5) M) induce smooth muscle hyperpolarization (10.6 +/- 0.9 mV). Both effects disappear after removal of the endothelium and are depressed by tetraethylammonium (3 x 10(-3) M), a rather nonspecific blocker of K+ channels, but not by glibenclamide (10(-5) M), a potent blocker of the ATP-regulated K+ channels, which has a marked effect on the relaxation induced by BRL 38227. The relaxation effect of acetylcholine is impaired in norepinephrine-contracted preparations from hypertensive rats but is not further depressed by tetraethylammonium. In aorta from hypertensive rats, hyperpolarization induced by carbachol was significantly reduced to a mean of only 21.8% of the values obtained in preparations from normotensive rats. From the relaxation-hyperpolarization relation obtained with BRL 38227 (opening K+ channels), it is derived that the endothelium-dependent hyperpolarization (approximately 10 mV) contributes for at least 20-30% of the maximal relaxation effect of acetylcholine on rat aorta. It is concluded that the diminished endothelium-dependent hyperpolarization may contribute to the depression of the endothelium-dependent relaxation in hypertension" http://www.ncbi.nlm.nih.gov/pubmed/1727681 0 545 "J. D. Ireson, R. Ford and C. Loveday" 1969 The neuromuscular blocking action of suxamethonium in the anaesthetised rat Arch.Int.Pharmacodyn.Ther. 181 2 283-286 http://www.ncbi.nlm.nih.gov/pubmed/5403606 0 546 "T. Nagao, S. Nishio, H. Kato and K. Takagi" 1972 Coronary vasodilating effect of some chromanone derivatives Chem.Pharm.Bull.(Tokyo) 20 1 82-87 http://www.ncbi.nlm.nih.gov/pubmed/4622566 0 547 L. D. Klimovskaia and S. B. Krotova 1979 [Bioelectrical activity of the neuromuscular and sympathetic systems exposed to a constant magnetic field] Kosm.Biol.Aviakosm.Med. 13 6 58-61 "The experiments on an isolated frog neuromuscular preparation gave evidence that an exposure to stable magnetic fields of 1000-4000 Oe did not influence the time parameters, amplitude and pattern of the action potentials of the gastrocnemius muscle induced by ischiatic nerve stimulation with single impulses. Similar results were obtained from an analysis of electric responses of the upper cervical sympathetic mode to the stimulation of preganglionar fibers in in situ experiments on urethane anesthesized rabbits subjected to a total exposure of a stable magnetic field (500-3000 Oe). In addition, an exposure to a stable magnetic field of 4000 Oe brought about a decrease of the level of depression of the action potential of muscles after conditioning tetanus" http://www.ncbi.nlm.nih.gov/pubmed/502428 0 548 "T. P. Wong, J. G. Howland, J. M. Robillard, Y. Ge, W. Yu, A. K. Titterness, K. Brebner, L. Liu, J. Weinberg, B. R. Christie, A. G. Phillips and Y. T. Wang" 2007 Hippocampal long-term depression mediates acute stress-induced spatial memory retrieval impairment Proc.Natl.Acad.Sci.U.S.A 104 27 11471-11476 "Acute stress impairs memory retrieval and facilitates the induction of long-term depression (LTD) in the hippocampal CA1 region of the adult rodent brain. However, whether such alterations in synaptic plasticity cause the behavioral effects of stress is not known. Here, we report that two selective inhibitors of the induction or expression of stress-enabled, N-methyl-D-aspartate receptor-dependent hippocampal LTD also block spatial memory retrieval impairments caused by acute stress. Additionally, we demonstrate that facilitating the induction of hippocampal LTD in vivo by blockade of glutamate transport mimics the behavioral effects of acute stress by impairing spatial memory retrieval. Thus, the present study demonstrates that hippocampal LTD is both necessary and sufficient to cause acute stress-induced impairment of spatial memory retrieval and provides a new perspective from which to consider the nature of cognitive deficits in disorders whose symptoms are aggravated by stress" http://www.ncbi.nlm.nih.gov/pubmed/17592137 1 549 M. Felder 1975 Vinblastine: influence on nerve conduction and synaptic transmission J.Neurosci.Res. 1 2 121-129 "Vinblastine injected into the eyes of pigeons had a detrimental effect on the amplitude of the postsynaptic evoked potential in the optic tectum; impulse conduction of the optic nerve was not influenced. The depression of the postsynaptic evoked potential was dependent on the dosage. Only 20 and 100 mug vinblastine had an influence; no influence was observed with 10 mug vinblastine. The reversible depression was seen from the third day after injection to between the 21st and the 28th day after injection, and in that period it remained constant. The latency of the response was not influenced by vinblastine" http://www.ncbi.nlm.nih.gov/pubmed/177789 0 550 "C. A. Shively, T. C. Register, S. E. Appt and T. B. Clarkson" 2015 Effects of long-term sertraline treatment and depression on coronary artery atherosclerosis in premenopausal female primates Psychosom.Med. 77 3 267-278 "OBJECTIVES: Major depressive disorder and coronary heart disease often co-occur in the same individuals. Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed for depression and other disorders, but their effects on coronary heart disease risk remain unclear. We determined the effects of an SSRI on coronary artery atherosclerosis (CAA) in an established nonhuman primate model used to clarify the association between depression and CAA. METHODS: Forty-two adult female cynomolgus macaques consuming a Western diet were characterized during an 18-month pretreatment phase and assigned to SSRI (sertraline hydrochloride 20 mg/kg, per os, once a day) or placebo balanced on pretreatment depression, body weight (BW), and iliac artery atherosclerosis extent measured via biopsy. After 18 months, CAA extent was measured using histomorphometry. RESULTS: Before and during treatment, depressed monkeys had lower BW, body mass index, and plasma high-density lipoprotein cholesterol, and higher heart rates during the pretreatment (p < .01) but not the treatment phase (p = .17). There were no pretreatment differences between the sertraline and placebo groups. Sertraline reduced anxious behavior but had no effect on BW, body mass index, heart rate, plasma lipids, or depression. CAA, analyzed by a 2 (depressed, nondepressed) x 2 (placebo, sertraline) x 3 (coronary arteries) analysis of covariance adjusted for pretreatment iliac atherosclerosis, was greater in depressed than in nondepressed monkeys (p < .036), and in sertraline than in placebo-treated monkeys (p = .040). The observed CAA extent in depressed monkeys treated with sertraline was 4.9 times higher than that in untreated depressed monkeys, and 6.5 times higher than that in nondepressed monkeys, on average. CONCLUSIONS: Depressed animals developed more CAA, and long-term treatment with sertraline resulted in more extensive CAA" http://www.ncbi.nlm.nih.gov/pubmed/25829239 1 551 "L. Y. Wang, M. W. Salter and J. F. Macdonald" 1991 Regulation of kainate receptors by cAMP-dependent protein kinase and phosphatases Science 253 5024 1132-1135 "In the mammalian central nervous system, receptors for excitatory amino acid neurotransmitters such as the alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA)-kainate receptor mediate a large fraction of excitatory transmission. Currents induced by activation of the AMPA-kainate receptor were potentiated by agents that specifically stimulate adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase A (PKA) activity or were supported by intracellular application of the catalytic subunit of PKA by itself or in combination with cAMP. Furthermore, depression of these currents by a competitive inhibitor of PKA indicates that AMPA-kainate receptors are regulated by endogenous PKA. Endogenous protein phosphatases also regulate these receptors because an inhibitor of cellular phosphates enhanced kainate currents. Modulation of PKA and phosphatases may regulate the function of these receptors and thus contribute to synaptic plasticity in hippocampal neurons" http://www.ncbi.nlm.nih.gov/pubmed/1653455 0 552 E. Mezey 1984 Commentary on the hypermetabolic state and the role of oxygen in alcohol-induced liver injury Recent Dev.Alcohol 2 135-141 "Centrilobular hypoxia has been postulated as a mechanism for the development of hepatocellular necrosis and fibrosis in alcoholic liver disease. Chronic ethanol ingestion in rodents results in increased hepatic oxygen consumption and in a steeper fall in oxygen tension between the periportal and the pericentral area of the lobule, rendering the pericentral area susceptible to hypoxia. Hepatocellular necrosis occurs when ethanol-fed animals are exposed to low atmospheric oxygen. In man, the existence of a hypermetabolic state is more tenuous, but suggested by an increased rate of ethanol elimination after chronic ethanol consumption that has been linked to increased oxygen consumption in animals. Also, decreases in hepatic blood flow and hepatic vein oxygen tension were found in alcoholics with histological evidence of liver-cell necrosis as compared to those without necrosis. It is postulated that in man, reduction in the availability of oxygen to the liver may be caused by miscellaneous conditions such as anemia, respiratory depression or infection, cigarette-smoking, or reduction of hepatic blood flow, but the contribution of one or more of these factors remains to be proven. Trials of the effect of propylthiouracil (PTU) on alcoholic hepatitis are based on the effect of this drug in decreasing the ethanol-induced hypermetabolic state and in preventing hepatocellular necrosis in animals exposed to low atmospheric oxygen. A tentative conclusion of the two small trials that have been completed is that PTU may be beneficial in moderately ill patients with a low mortality, but not useful in severely ill patients with a high mortality" http://www.ncbi.nlm.nih.gov/pubmed/6374779 0 553 R. W. Gange and I. R. Mendelson 1981 Photoaugmentation in the hairless mouse: a study using ornithine decarboxylase activity and alteration of DNA synthesis as markers of epidermal response J.Invest Dermatol. 77 5 393-396 "Photoaugmentation is the potentiation of UVB-induced cutaneous erythema by UV irradiation. We have examined other cutaneous responses to UVB irradiation-the 4 hr depression of DNA synthesis, the 48 hr stimulation of DNA synthesis, and the induction of ornithine decarboxylase (ODC), to determine whether these were also susceptible to augmentation by UVA, which does not cause these responses when administered alone. No photoaugmentation of DNA synthesis, stimulation or ODC induction occurred. The early depression of DNA synthesis was slightly augmented for this did not consistently reach significance" http://www.ncbi.nlm.nih.gov/pubmed/7288205 0 554 "H. J. Jeong, J. H. Kim, N. R. Kim, M. S. Yoou, S. Y. Nam, K. Y. Kim, Y. Choi, J. B. Jang, I. C. Kang, N. I. Baek and H. M. Kim" 2015 Antidepressant effect of Stillen Arch.Pharm.Res. 38 6 1223-1231 "Stillen has been used to treat patients with gastric mucosal ulcers and has an anti-inflammatory effect. It is well-known that neuro-inflammatory reactions are related to depression. Here we evaluated the antidepressant-like effect of Stillen on mice subjected to the forced swimming test (FST). Stillen and eupatilin (a major component of Stillen) significantly decreased immobility times compared with the FST control group. In the Stillen-administered group, increased levels of 5-hydroxytryptamine (serotonin) and brain-derived neurotrophic factor protein were observed in the hippocampus. Nissl bodies also increased in the hippocampus neuronal cytoplasm of the Stillen-administered group. Stillen decreased levels of interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha (at the mRNA and protein levels) in the hippocampus and serum, compared with the control group. In addition, the mRNA expression of estrogen receptor-beta increased after Stillen administration in the hippocampus. These findings suggest that Stillen should be viewed as a candidate antidepressant" http://www.ncbi.nlm.nih.gov/pubmed/25163682 1 555 "J. M. Cantor, Y. M. Binik and J. G. Pfaus" 1999 Chronic fluoxetine inhibits sexual behavior in the male rat: reversal with oxytocin Psychopharmacology (Berl) 144 4 355-362 "RATIONALE: Selective serotonin reuptake inhibitors, used widely in the treatment of depression, progressively inhibit sexual orgasm in many patients and induce a transient inhibition of sexual desire. OBJECTIVES: We attempted to model the effects of these drugs in sexually experienced male rats during tests of copulation in bilevel chambers. These chambers allow the study of both appetitive and consummatory sexual responses of male rats. METHODS: Males were treated daily with fluoxetine hydrochloride (0, 1, 5, or 10 mg/kg) and tested for sexual behavior with receptive females at 4-day intervals. Rats were treated with oxytocin (200 ng/kg) or saline after ejaculations had decreased. RESULTS: Fluoxetine decreased ejaculatory responses of male rats in a dose- and time-dependent fashion, but left the copulatory efficiency of the males intact. In contrast, conditioned level changing, a measure of appetitive sexual excitement, was inhibited following acute and chronic treatment with 10 mg/kg, although tolerance may have developed to the effect of 5 mg/kg. Subsequent administration of oxytocin restored the ejaculatory response but not the measure of sexual excitement to baseline levels. CONCLUSIONS: The reversal by oxytocin of the fluoxetine-induced deficit in ejaculations is consistent with the hypothesis that serotonin suppresses ejaculatory mechanisms by interrupting the action of oxytocin, which normally accompanies sexual behavior. Co-administration of oxytocin may help to alleviate the predominant sexual side effect of serotonin reuptake blockers" http://www.ncbi.nlm.nih.gov/pubmed/10435408 0 556 "I. Branchi, I. D'Andrea, F. Cirulli, H. P. Lipp and E. Alleva" 2010 Shaping brain development: mouse communal nesting blunts adult neuroendocrine and behavioral response to social stress and modifies chronic antidepressant treatment outcome Psychoneuroendocrinology 35 5 743-751 "Early experiences shape brain function and behavior and, consequently, vulnerability to psychopathology at adulthood. Here we exploited the mouse communal nest (CN) paradigm in order to investigate the effect of the early social environment on the emergence of endophenotypes of depression and on antidepressant efficacy at adulthood. CN, which consists in a single nest where three mothers keep their pups together and share care-giving behavior until weaning, is characterized by high levels of maternal behavior and peer interactions, thus representing an highly stimulating environment. Our results show that, when compared to mice reared in standard laboratory conditions (SN), adult CN mice exhibited greater sucrose preference on the first days of the test, displayed reduced anhedonia during social stress and had lower corticosterone levels after acute and prolonged social stress. Furthermore, in line with previous work, CN displayed longer immobility than SN mice in the forced swim test. Here we show that such behavioral response is differently affected by antidepressants according to early experiences. A 3-week fluoxetine treatment affected only SN mice, leading to an increase of immobility duration up to the levels showed by CN mice, while acute fluoxetine administration decreased immobility duration in both groups. These results show that being reared in a CN profoundly changes developmental trajectories, reducing the adult display of endophenotypes of depression and modifying response to antidepressants. The present findings suggest that early experiences represent one of those factors to be taken into account to identify the appropriate individual pharmacological strategy to treat depression in patients" http://www.ncbi.nlm.nih.gov/pubmed/19945226 1 557 "C. H. Davies, S. N. Davies and G. L. Collingridge" 1990 Paired-pulse depression of monosynaptic GABA-mediated inhibitory postsynaptic responses in rat hippocampus J.Physiol 424 513-531 "1. Intracellular recording techniques were used to characterize monosynaptic inhibitory postsynaptic potentials (IPSPs) and currents (IPSCs) in rat hippocampal slices and to study the mechanism of paired-pulse depression of these synaptic responses. This was achieved by stimulation in stratum radiatum close (less than 0.5 mm) to an intracellularly recorded CA1 neurone after pharmacological blockade of all excitatory synaptic transmission. 2. Under these conditions, low-frequency stimulation (0.033 Hz) evoked a pure biphasic IPSP, which had a short and constant latency to onset. This IPSP was blocked by tetrodotoxin (1 microM) suggesting that it resulted from the electrical stimulation of the axons and/or cell bodies of a monosynaptic inhibitory pathway. 3. Picrotoxin (100 microM) abolished the early component of the biphasic IPSP/C. It left an intact, pure late IPSP/C (IPSP/CB) which had a latency to onset of 29 +/- 2 ms, latency to peak of 139 +/- 4 ms, a duration of 723 +/- 135 (range 390-1730) ms and a reversal potential of -93 +/- 2 mV. The duration was highly dependent on the stimulus intensity whereas the latency to onset was largely independent of the stimulus intensity. The IPSP/CB was reduced or abolished by 1 mM-phaclofen. 4. Phaclofen (1 mM) and 2-hydroxy-saclofen (0.1-1.0 mM) reversibly depressed (60-100%) the late component of the biphasic IPSP/C and, where maximally effective, left a pure, early IPSP/C (IPSP/CA). The IPSP/CA had a latency to onset of 3 ms or less, a latency to peak of 17 +/- 1 ms, a duration of 225 +/- 3 ms and a reversal potential of -75 +/- 2 mV. 5. Two shocks of identical strength were applied in close succession to characterize, and to study the mechanisms underlying, frequency-dependent depression of inhibitory synaptic responses. Paired-pulse depression was seen for both phases of the biphasic IPSP/C and of the pure IPSP/CB, recorded in the presence of picrotoxin. Paired-pulse depression was not accompanied by changes in the reversal potential of either component, indicating that it was caused by a reduction in the two synaptic conductances. Paired-pulse depression was greater when high stimulus intensities were employed. 6. Paired stimuli were applied at separation intervals of between 5 ms and 10 s to determine the temporal profile of frequency-dependent depression. Paired-pulse depression of both IPSCA and IPSCB was most pronounced at an interstimulus interval of 100-125 ms and ceased to occur at intervals greater than 5 10s.(ABSTRACT TRUNCATED AT 400 WORDS)" http://www.ncbi.nlm.nih.gov/pubmed/2167975 0 558 "D. A. Scholnick, K. G. Burnett and L. E. Burnett" 2006 Impact of exposure to bacteria on metabolism in the penaeid shrimp Litopenaeus vannamei Biol.Bull. 211 1 44-49 "We hypothesized that aggregation of bacteria and hemocytes at the gill, which occurs as part of the shrimp's antibacterial immune defenses, would impair normal respiratory function and thereby disrupt aerobic metabolism. Changes in oxygen uptake and lactate accumulation were determined in Litopenaeus vannamei, the Pacific white shrimp, following injection with either saline (control) or a strain of the gram-negative bacterium Vibrio campbellii that is pathogenic in crustaceans. The rate of oxygen uptake was determined during the first 4 h after injection and after 24 h. Injection of bacteria decreased oxygen uptake by 27% (from 11.0 to 8.2 micromol g-1 h-1) after 4 h, while saline-injected shrimp showed no change. Decreased oxygen uptake persisted 24 h after Vibrio injection. In well-aerated water, resting whole-animal lactic acid levels increased in shrimp injected with bacteria (mean=2.59 micromol lactate g-1+/-0.39 SEM, n=8) compared to saline-injected control shrimp, but this difference did not persist at 24 h. Exposure to hypercapnic hypoxia (PCO2=1.8 kPa, PO2=6.7 kPa) also resulted in significant whole-body lactic acid differences (mean=3.99 and 1.8 micromol g-1 tissue in Vibrio and saline-injected shrimp, respectively). Our results support the hypothesis that the crustacean immune response against invading bacteria impairs normal metabolic function, resulting in depression of oxygen uptake and slightly increased anaerobic metabolism" http://www.ncbi.nlm.nih.gov/pubmed/16946240 0 559 R. Onur and S. O. Kayaalp 1972 "The neuromuscular blocking properties of 4,4'(2-(4-methyl-piperidyl)-1-hydroxyethyl) biphenyl" Arch.Int.Pharmacodyn.Ther. 198 2 305-311 http://www.ncbi.nlm.nih.gov/pubmed/5054738 0 560 M. Rigbi and L. J. Greene 1968 Limited proteolysis of the bovine pancreatic secretory trypsin inhibitor at acid pH J.Biol.Chem. 243 20 5457-5464 http://www.ncbi.nlm.nih.gov/pubmed/5750336 0 561 "M. E. Costlow, R. A. Buschow and W. L. McGuire" 1976 "Prolactin receptors in 7,12-dimethylbenz(a) anthracene-induced mammary tumors following endocrine ablation" Cancer Res. 36 11 Pt 1 3941-3943 "We have determined the effect of ovariectomy and hypophysectomy on prolactin receptors in 7,12-dimethylbenz(a)anthracene-induced mammary tumors. Growing tumors from intact rats show a wide range in the number of prolactin receptors. Ovariectomy causes a slight (approximately 30%) decrease in receptors regardless of whether tumors regress or continue to grow, while the affinity of the receptor for prolactin remains unchanged. Hypophysectomy, which causes a prompt 10-fold decrease in prolactin receptors in rat liver, causes only a slight reduction in prolactin receptors in tumors from these same animals. We conclude that autonomous and ovariectomy responsive 7,12-dimethylbenz(a)anthracene-induced mammary tumors cannot be distinguished on the basis of prolactin receptor sites and that endocrine regulation of prolactin receptors is distinctly different in normal liver and neoplastic mammary tissue" http://www.ncbi.nlm.nih.gov/pubmed/184919 0 562 "D. Gupta, M. Radhakrishnan, D. Thangaraj and Y. Kurhe" 2015 "Pharmacological evaluation of novel 5-HT3 receptor antagonist, QCM-13 (N-cyclohexyl-3-methoxyquinoxalin-2-carboxamide) as anti-anxiety agent in behavioral test battery" "Journal of Pharmacy and Bioallied Sciences.7 (2) ()(pp 103-108), 2015.Date of Publication: 01 Apr 2015." 2 103-108 "Objective: In the last few decades, serotonin type-3 (5-HT3 ) receptor antagonists have been identified as potential targets for anxiety disorders. In preclinical studies, 5-HT3 antagonists have shown promising antianxiety effects. In this study, a novel 5-HT3 receptor antagonist, QCM-13(N-cyclohexyl-3-methoxyquinoxalin-2-carboxamide) was evaluated for anxiolytic-like activity in rodent behavioral test battery. Materials and Methods: Mice were given QCM-13 (2 and 4 mg/kg, intraperitoneally [i.p.]) or diazepam (2 mg/kg, i.p.) or vehicle and after 30 min, mice were subjected to four validated behavioral test batteries viz. elevated plus maze, hole board, light-dark and open field tests. Interaction study of QCM-13 with m-chlorophenyl piperazine (mCPP) (mCPP, a 5-HT2A/2C receptor agonist, 1 mg/kg, i.p.) and buspirone (BUS, a partial 5-HT1A agonist, 10 mg/kg, i.p.) were performed to assess the pharmacological mechanism of the drug. Results: QCM-13 expressed potential anxiolytic effect with significant (P < 0.05) increase in behavioral parameters measured in aforementioned preliminary models. Besides, QCM-13 was unable to reverse the anxiogenic effect of mCPP, but potentiated anxiolytic affect of BUS. Conclusion: The results suggest that QCM-13 can be a potential therapeutic candidate for the management of anxiety-like disorders and combination doses of novel 5-HT3 receptor antagonist with standard anxiolytics may improve therapeutic efficacy" DO - http://dx.doi.org/10.4103/0975-7406.154429 0 563 "S. Papa, N. E. Lofrumento, G. Paradies and E. Quagliariello" 1968 The inhibition of succinate oxidation in isolated mitochondria by uncouplers Biochim.Biophys.Acta 153 1 306-308 http://www.ncbi.nlm.nih.gov/pubmed/4170446 0 564 N. K. Karimullina and A. A. Gizatullina 1969 [On the liver condition in animals under the effect of bromic ether] Farmakol.Toksikol. 32 2 165-167 http://www.ncbi.nlm.nih.gov/pubmed/5772141 0 565 E. Ohe 1994 [Effects of aromatase inhibitor on sexual differentiation of SDN-POA in rats] Nihon Sanka Fujinka Gakkai Zasshi 46 3 227-234 "The sexually dimorphic nucleus of the preoptic area (SDN-POA) of male rats is larger than that of females, the difference being caused by the perinatal effect of estrogen converted from androgen. To investigate the role of estrogen formation in the SDN-POA during the critical period of this sexual differentiation, CGS16949A (0.5 mg/kg, sc) was injected into the mothers in the late gestational age(F) or into neonates for 14 days from birth(N). Animals were sacrificed on the 20th. day of gestation and 7 days after birth, and fetal and neonatal brain aromatase activities (AA) as well as serum levels of testosterone(T) and corticosterone(B) were measured. On the 30th day after birth, the offspring of treated mothers and neonatally treated rats were sacrificed and the cross-sectional areas of the SDN-POA were evaluated by image processor NEXUS 6800. In group F, CGS16949A markedly suppressed brain AA in vitro (fetal hypothalamus: IC50 1.4nM) and in vivo in both the hypothalamus and amygdala. However, the levels of T and B did not show any significant change in group F. The same depression of AA was also observed in group N on the 7th day after birth. In CGS-treated males in groups F and N, the SDN-POA area markedly decreased to that of control females. The area in males in group F was not significantly different from that in females. These results suggest that estrogen converted from androgen plays a dominant role in the development of sexual dimorphism of the SDN-POA, and that the brain AA in the pre- and postnatal period is important in this process" http://www.ncbi.nlm.nih.gov/pubmed/8133132 0 566 J. Sam 1968 "Preparation of 2,2-Diethyl-3-(3,4,5-trimethoxybenzoyloxy)propyl carbamate" J.Pharm.Sci. 57 4 707 http://www.ncbi.nlm.nih.gov/pubmed/5652170 0 567 "B. Escalante, D. Erlij, J. R. Falck and J. C. McGiff" 1991 Ion transport inhibition in the medullary thick ascending limb of Henle's loop by cytochrome P450-arachidonic acid metabolites Adv.Prostaglandin Thromboxane Leukot.Res. 21A 209-212 http://www.ncbi.nlm.nih.gov/pubmed/1847767 0 568 "M. Pettersson, B. M. Campbell, A. B. Dounay, D. L. Gray, L. Xie, C. J. O'Donnell, N. C. Stratman, K. Zoski, E. Drummond, G. Bora, A. Probert and T. Whisman" 2011 "Design, synthesis, and pharmacological evaluation of azetedine and pyrrolidine derivatives as dual norepinephrine reuptake inhibitors and 5-HT(1A) partial agonists" Bioorg.Med.Chem.Lett. 21 2 865-868 "Compounds with combined norepinephrine reuptake inhibitor (NRI) and serotonin 1A (5-HT(1A)) partial agonist pharmacology may offer a new therapeutic approach for treating symptoms of neuropsychiatric disorders including ADHD, depression, and anxiety. Herein we describe the design and optimization of novel chemical matter that exhibits favorable dual NRI and 5-HT(1A) partial agonist activity. Lead compounds in this series were found to be devoid of activity at the dopamine transporter and were shown to be brain penetrant with high receptor occupancy" http://www.ncbi.nlm.nih.gov/pubmed/21185183 0 569 "J. P. Gardner, C. A. Fornal and B. L. Jacobs" 1997 Effects of sleep deprivation on serotonergic neuronal activity in the dorsal raphe nucleus of the freely moving cat Neuropsychopharmacology 17 2 72-81 "Total sleep deprivation (TSD) for one or more nights produces a rapid antidepressant response in humans. Since most pharmacological treatments for depression increase brain serotonin neurotransmission, the purpose of the present study was to determine whether TSD increases the activity of serotonergic neurons in the dorsal raphe nucleus (DRN) in cats. Cats were prevented from sleeping by the experimenter, who monitored the behavioral state of each animal on a polygraph. Firing rates during quiet waking (QW) and active waking (AW) were obtained throughout a 24-h sleep deprivation period and subsequent 6-h recovery period. During the experiments, unit activity was also recorded during exposure to loud white noise, which elicited strong behavioral arousal. The inhibitory response of serotonergic DRN neurons to systemic administration of the selective 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was determined before and after TSD to assess possible changes in 5-HT1A autoreceptor sensitivity. TSD increased mean firing rates by as much as 18% during both AW and white noise exposure. Maximal effects were observed after 15 h of TSD for AW, and after 18 h for white noise. QW firing rates also tended to be elevated throughout TSD. Firing rates for all conditions during the recovery period were not significantly different from baseline. The neuronal inhibition produced by 8-OH-DPAT was significantly diminished after TSD. Overall, these results indicate that TSD increases the firing rate of serotonergic DRN neurons during AW and arousal. This effect may be attributable to a decrease in the sensitivity of 5-HT1A autoreceptors. These findings are consistent with the hypothesis that TSD exerts its antidepressant action, at least in part, through an activation of brain serotonergic neurons" http://www.ncbi.nlm.nih.gov/pubmed/9252982 0 570 "T. Bilde, Y. Lubin, D. Smith, J. M. Schneider and A. A. Maklakov" 2005 The transition to social inbred mating systems in spiders: role of inbreeding tolerance in a subsocial predecessor Evolution 59 1 160-174 "The social spiders are unusual among cooperatively breeding animals in being highly inbred. In contrast, most other social organisms are outbred owing to inbreeding avoidance mechanisms. The social spiders appear to originate from solitary subsocial ancestors, implying a transition from outbreeding to inbreeding mating systems. Such a transition may be constrained by inbreeding avoidance tactics or fitness loss due to inbreeding depression. We examined whether the mating system of a subsocial spider, in a genus with three social congeners, is likely to facilitate or hinder the transition to inbreeding social systems. Populations of subsocial Stegodyphus lineatus are substructured and spiders occur in patches, which may consist of kin groups. We investigated whether male mating dispersal prevents matings within kin groups in natural populations. Approximately half of the marked males that were recovered made short moves (< 5m) and mated within their natal patch. This potential for inbreeding was counterbalanced by a relatively high proportion of immigrant males. In mating experiments, we tested whether inbreeding actually results in lower offspring fitness. Two levels of inbreeding were tested: full sibling versus non-sib matings and matings of individuals within and between naturally occurring patches of spiders. Neither full siblings nor patch mates were discriminated against as mates. Sibling matings had no effect on direct fitness traits such as fecundity, hatching success, time to hatching and survival of the offspring, but negatively affected offspring growth rates and adult body size of both males and females. Neither direct nor indirect fitness measures differed significantly between within patch and between-patch pairs. We tested the relatedness between patch mates and nonpatch mates using DNA fingerprinting (TE-AFLP). Kinship explained 30% of the genetic variation among patches, confirming that patches are often composed of kin. Overall, we found limited male dispersal, lack of kin discrimination, and tolerance to low levels of inbreeding. These results suggest a history of inbreeding which may reduce the frequency of deleterious recessive alleles in the population and promote the evolution of inbreeding tolerance. It is likely that the lack of inbreeding avoidance in subsocial predecessors has facilitated the transition to regular inbreeding social systems" http://www.ncbi.nlm.nih.gov/pubmed/15792236 0 571 "F. N. Jacka, J. A. Pasco, M. J. Hensry, M. A. Kotowicz, G. C. Nicholson and M. Berk" 2004 Dietary omega-3 fatty acids and depression in a community sample "Nutritional Neuroscience.7 (2) ()(pp 101-106), 2004.Date of Publication: April 2004." 2 101-106 "To evaluate the association between omega-3 polyunsaturated essential fatty acids and depression, data regarding prevalence rates of self-reported depression and median daily dietary intakes of these fatty acids were obtained from an age-stratified, population-based sample of women (n = 755; 23 97 year) in the Barwon Statistical Division of south-eastern Australia. A self-report questionnaire based on Diagnostic and Statistical Manual-IV criteria was utilised to determine 12-month prevalence rates of depression in this sample, and data from biennial food frequency questionnaires examining seafood and fish oil consumption over a 6-year period were examined. Differences in median dietary intakes of omega-3 fatty acids between the depressed and non-depressed cohorts were analysed and results were adjusted for age, weight and smoking status. No significant differences in median intakes were identified between the two groups of women (median, interquartile range; depressed = 0.09 g/day, 0.04 0.18 versus non-depressed = 0.11 g/day, 0.05 0.22, p = 0.3), although overall average intakes of omega-3 fatty acids were lower than recommended and rates of depression within this sample higher than expected, based on previous data. Further research that takes into account ratios of omega-6 to omega-3 polyunsaturated essential fatty acids, as well as other dietary sources of omega-3 fatty acids, is warranted. © 2004 Taylor & Francis Ltd" DO - http://dx.doi.org/10.1080/10284150410001710438 0 572 "O. Nemoto, J. Takeda, K. Adachi, K. M. Halprin, C. W. Woodyard and V. Levine" 1983 Reversal of beta-agonist-induced refractoriness in skin by tetracaine and mepacrine J.Invest Dermatol. 80 4 237-240 "We previously reported that in skin slices stimulated by a beta-adrenergic agonist, the intracellular cyclic AMP level increased transiently. The level returned to a low steady state in 20-30 min and further stimulation by the agonist did not increase the cyclic AMP level. This state of ""refractoriness"" was found to be specific to the initial stimulator, i.e., histamine but not epinephrine could restimulate the cyclic AMP system after an initial exposure to epinephrine (Biochim Biophys Acta 497:428-436, 1977). We now report that incubation of skin with mepacrine or tetracaine after beta-adrenergic stimulation caused partial recovery from the refractoriness. Neither the simultaneous incubation of skin with epinephrine plus mepacrine (or tetracaine) nor preincubation of skin with mepacrine (or tetracaine) before the beta-adrenergic stimulation prevented the development of the refractoriness. Mepacrine inhibited the skin adenylate cyclase catalytic (or the complex of GTP-regulatory protein and catalytic) unit. The available data suggest that mepacrine and tetracaine interacted with the agonist-receptor complex at the cell membrane" http://www.ncbi.nlm.nih.gov/pubmed/6131924 0 573 "J. Schmidt, H. Fischer and A. Buschges" 2001 Pattern generation for walking and searching movements of a stick insect leg. II. Control of motoneuronal activity J.Neurophysiol. 85 1 354-361 "In the stick insect, Cuniculina impigra, intracellular recordings from mesothoracic motoneurons that control flexion and extension of the tibia and depression and levation of the trochantero-femur were made while the leg performed walking-like movements on a treadband or stereotyped rhythmic searching movements. We were interested in how synaptic input and intrinsic properties contribute to form the activity pattern of motoneurons during rhythmic leg movements without sensory feedback from other legs. During searching and walking, motoneurons expressed a rhythmic bursting pattern that was formed by a depolarizing input followed by a hyperpolarizing input in the inter-burst interval. This basic pattern was similar in all fast, semi-fast, and slow motoneurons that were recorded. Hyperpolarizations were in synchrony with activity in the antagonistic motoneurons. De- and hyperpolarizations were associated with a decrease in input resistance. All motoneurons showed spike frequency adaptation when depolarized by current injection to a membrane potential similar to that observed during walking. In the hyperpolarizing phase of fast flexor motoneurons, the initial maximum hyperpolarization was followed by a sag in potential toward more depolarized values. Consistent with this observation, only fast flexor motoneurons developed a depolarizing sag potential when hyperpolarized by injection of constant negative current" http://www.ncbi.nlm.nih.gov/pubmed/11152735 0 574 A. Stadnicka and Z. J. Bosnjak 2003 Isoflurane decreases ATP sensitivity of guinea pig cardiac sarcolemmal KATP channel at reduced intracellular pH Anesthesiology 98 2 396-403 "BACKGROUND: Volatile anesthetics can protect the myocardium against ischemic injury by opening the adenosine triphosphate (ATP)-sensitive potassium (K(atp)) channels. However, direct evidence for anesthetic-channel interaction is still limited, and little is known about the role K(atp) channel modulators play in this effect. Because pH is one of the regulators of K(atp) channels, the authors tested the hypothesis that intracellular pH (pHi) modulates the direct interaction of isoflurane with the cardiac K(atp) channel. METHODS: The effects of isoflurane on sarcolemmal K(atp) channels were investigated at pHi 7.4 and pHi 6.8 in excised inside-out membrane patches from ventricular myocytes of guinea pig hearts. RESULTS: At pHi 7.4, intracellular ATP (1-1,000 microm) inhibited K(atp) channels and decreased channel open probability (Po) in a concentration-dependent manner with an IC(50) of 8 +/- 1.5 microm, and isoflurane (0.5 mm) either had no effect or decreased channel activity. Lowering pHi from 7.4 to 6.8 enhanced channel opening by increasing Po and reduced channel sensitivity to ATP, with IC shifting from 8 +/- 1.2 to 45 +/- 5.6 microm. When applied to the channels activated at pHi 6.8, isoflurane (0.5 mm) increased Po and further reduced ATP sensitivity, shifting IC(50) to 110 +/- 10.0 microm. CONCLUSIONS: Changes in pHi appear to modulate isoflurane interaction with the cardiac K(atp) channel. At pHi 6.8, which itself facilitates channel opening, isoflurane enhances channel activity by increasing Po and reduces sensitivity to inhibition by ATP without changing the unitary amplitude of single channel current or the conductance. These results support the hypothesis of direct isoflurane-K(atp) channel interaction that may play a role in cardioprotection by volatile anesthetics" http://www.ncbi.nlm.nih.gov/pubmed/12552199 0 575 "O. Strubelt, F. Wegener and C. P. Siegers" 1970 [Hepatotoxicity of caffeine and theophylline] Arzneimittelforschung. 20 4 473-476 http://www.ncbi.nlm.nih.gov/pubmed/5467807 0 576 "W. Glinski, A. Langner, S. Obalek and F. N. Marzulli" 1975 "Immunological phenomena in harmless mice during experimental carcinogenesis induced with long-term topical application of 7, 12-dimethylbenzanthracene (DMBA)" Acta Derm.Venereol. 55 1 15-19 "To estimate the influence of topical treatment with DMBA and induced tumors on delayed hypersensitivity, the response of spleen lymphocytes to PHA in vitro and macrophage migration inhibition with PHA were studied in DMBA-treated hairless mice. DNA synthesis and blastic transformation of cultured lymphocytes decreased after 6-12 weeks of DMBA application. Lymphocyte response to PHA gradually diminished during the experiment, as compared with control animals. Since the malignant transformation of skin tumors was not observed before 16 weeks of DMBA carcinogenesis, it seems that derangements in cellular immunity preceded the malignant proliferation. The increase in spleen weight and the absence of PHA-induced inhibition of macrophage migration in hairless mice with malignant tumors may also be related to the influence of the tumor itself on the lymphatic system of experimental animals" http://www.ncbi.nlm.nih.gov/pubmed/46667 0 577 "A. Roepstorff, H. Bjorn and P. Nansen" 1987 Resistance of Oesophagostomum spp. in pigs to pyrantel citrate Vet.Parasitol. 24 03-Apr 229-239 "This study was undertaken to determine whether anthelmintic-resistant Oesophagostomum spp. populations occur in Danish swine herds. A controlled field trial on selected sow herds suggested resistance to pyrantel citrate in a herd where faecal egg count depression in response to treatment was only 28.3%. This was confirmed by subsequent experimental infection of pigs where the suspected resistant Oesophagostomum isolate was compared with a susceptible worm isolate. After treatment with the recommended dose of the drug, worm burdens of the suspected isolate were only reduced by 42.6% (p greater than 0.05) in contrast to the susceptible isolate, which was reduced by 94.6% (p less than 0.01). Differential counts of the resistant isolate suggested that O. dentatum might be more resistant than O. quadrispinulatum. The resistant isolate originated from a herd, where the anthelmintic had been administered four times a year over a period of 7 years. The potential for development of anthelmintic resistance in Oesophagostomum spp. under management practices in our country is discussed in the light of the current views on predisposing factors" http://www.ncbi.nlm.nih.gov/pubmed/2956755 0 578 "C. Schnell, O. A. Janc, B. Kempkes, C. A. Callis, G. Flugge, S. Hulsmann and M. Muller" 2012 Restraint Stress Intensifies Interstitial K(+) Accumulation during Severe Hypoxia Front Pharmacol. 3 53 "Chronic stress affects neuronal networks by inducing dendritic retraction, modifying neuronal excitability and plasticity, and modulating glial cells. To elucidate the functional consequences of chronic stress for the hippocampal network, we submitted adult rats to daily restraint stress for 3 weeks (6 h/day). In acute hippocampal tissue slices of stressed rats, basal synaptic function and short-term plasticity at Schaffer collateral/CA1 neuron synapses were unchanged while long-term potentiation was markedly impaired. The spatiotemporal propagation pattern of hypoxia-induced spreading depression episodes was indistinguishable among control and stress slices. However, the duration of the extracellular direct current potential shift was shortened after stress. Moreover, K(+) fluxes early during hypoxia were more intense, and the postsynaptic recoveries of interstitial K(+) levels and synaptic function were slower. Morphometric analysis of immunohistochemically stained sections suggested hippocampal shrinkage in stressed rats, and the number of cells that are immunoreactive for glial fibrillary acidic protein was increased in the CA1 subfield indicating activation of astrocytes. Western blots showed a marked downregulation of the inwardly rectifying K(+) channel Kir4.1 in stressed rats. Yet, resting membrane potentials, input resistance, and K(+)-induced inward currents in CA1 astrocytes were indistinguishable from controls. These data indicate an intensified interstitial K(+) accumulation during hypoxia in the hippocampus of chronically stressed rats which seems to arise from a reduced interstitial volume fraction rather than impaired glial K(+) buffering. One may speculate that chronic stress aggravates hypoxia-induced pathophysiological processes in the hippocampal network and that this has implications for the ischemic brain" http://www.ncbi.nlm.nih.gov/pubmed/22470344 0 579 "I. N. Maiskii, G. P. Airapet'ian, A. I. Maiskii, R. B. Gudkova and E. G. Skriabina" 1979 [Analysis of the effect of morphine on the reproductive capacity and immunological status of mice] Biull.Eksp.Biol.Med. 88 10 465-467 Embryogenesis process is disturbed under the action of prolonged morphine administration to CBA mice. Simultaneously a decrease in the level of antibody-synthesizing cells and a significant reduction in the cooperating interaction of T and B lymphocytes in response to the injection of sheep red blood cells are noted. At the same time stimulation of bone marrow cells and specific sensitization of MIF-inducers to the antigen from the brain of morphinized mice are revealed http://www.ncbi.nlm.nih.gov/pubmed/574028 0 580 T. P. Vertogradova 1969 [Effect of rubomycin C and B on hemopoiesis in rabbits and rats] Antibiotiki. 14 12 1092-1096 http://www.ncbi.nlm.nih.gov/pubmed/5371176 0 581 "M. Melzig, H. Michalski and E. Teuscher" 1989 [The ectophosphatase activity of cultured endothelial cells of calf aorta and the effect of drugs on ecto-ATPase] Biomed.Biochim.Acta 48 7 431-436 "Cultivated endothelial cells of calf aorta (line BKEz-7) possess an effective ectophosphatase system (enzyme activities: ATPase 38.0 +/- 10.2; ADPase 9.2 +/- 4.2; 5'-nucleotidase 4.1 +/- 2.6 fmol/cell.min). Drugs with central depressive activity such as promazine, chlorpromazine, and meprobamate inhibit the activity of the ecto-ATPase. A possible connection between the inhibitory activity on the ecto-ATPase and their central depressive effects is discussed" http://www.ncbi.nlm.nih.gov/pubmed/2553007 0 582 "I. Koyama, H. Yamagami, T. Kuwae and M. Kurata" 1982 [Inhibition of adherence and phagocytosis of zymosan particles by mouse peritoneal macrophages with hydrocortisone] Yakugaku Zasshi 102 7 698-700 http://www.ncbi.nlm.nih.gov/pubmed/7153858 0 583 "F. T. Crump, K. S. Dillman and A. M. Craig" 2001 cAMP-dependent protein kinase mediates activity-regulated synaptic targeting of NMDA receptors J.Neurosci. 21 14 5079-5088 "Chronic activity blockade increases synaptic levels of NMDA receptor immunoreactivity in hippocampal neurons. We show here that blockade-induced synaptic NMDA receptors are functional and mediate enhanced excitotoxicity in response to synaptically released glutamate. Activity blockade increased the cell surface association of NMDA receptors. Blockade-induced synaptic targeting of NMDA receptors did not require protein synthesis but required phosphorylation and specifically cAMP-dependent protein kinase (PKA). Furthermore, activation of PKA was sufficient to induce synaptic targeting of NMDA receptors regardless of receptor activity status. These results implicate PKA activity downstream of receptor blockade as a mediator of enhanced synaptic transport or stabilization of NMDA receptors. Synaptic clustering of NR1-green fluorescent protein was observed in living neurons in response to NMDA receptor and cAMP phosphodiesterase antagonists and occurred gradually over the course of a day. This pathway represents a cellular mechanism for synaptic homeostasis and is likely to function in metaplasticity, long-term regulation of the ability of a synapse to undergo potentiation or depression" http://www.ncbi.nlm.nih.gov/pubmed/11438583 0 584 "N. D. Giadinis, V. Psychas, Z. Polizopoulou, E. Papadopoulos, N. Papaioannou, A. T. Komnenou, A. L. Thomas, E. J. Petridou, M. Kritsepi-Konstantinou, S. Q. Lafi and G. D. Brellou" 2012 Acute coenurosis of dairy sheep from 11 flocks in Greece N.Z.Vet.J. 60 4 247-253 "CASE HISTORY: A syndrome of acute neurological dysfunction with increased mortality was observed in lambs of 10 dairy sheep flocks and adult animals in one flock in Central and Northern Greece. Each farmer completed a questionnaire regarding the management and feeding of their flocks. In seven of the 11 flocks the affected animals were grazing pasture, while in the remaining four flocks (5, 8, 9, 10) the animals were fed alfalfa hay (Medicago sativa) and concentrates indoors. A follow-up study of the affected flocks was conducted during the next 12 months. CLINICAL FINDINGS: Of 42 sheep with acute coenurosis that were examined, the most prominent neurological abnormalities were ataxia, depression, blindness, scoliosis, coma and dysmetria. Except for the four sheep that were comatose, all other animals had normal body temperatures and their appetites remained normal or were slightly decreased. Haematological findings of 15 examined sheep were within normal limits. The affected sheep were subject to euthanasia. A histopathological examination was performed in 13 cases. Faecal samples from dogs associated with these flocks were negative for taeniid infections. During the following 12 months cases of chronic coenurosis in these flocks were observed. PATHOLOGICAL FINDINGS: In the 42 animals that were necropsied, the main gross findings were cystic formations between 0.5-1 cm in diameter with translucent walls that were seen lying free on the leptomeninges or partly penetrating the brain tissue, sterile microabscecess and brain necrosis. Histopathological evaluation of tissue sections of 13 brains showed multifocal purulent or pyogranulomatous meningoencephalitis, accompanied by eosinophilic infiltrations. No bacteria were isolated following bacterial culture of brain tissue Parasitological examination of the cysts from five cases revealed whitish specks on the transparent cyst wall and germination membrane representing the scolices. DIAGNOSIS: Acute coenurosis was diagnosed in all cases studied. CLINICAL RELEVANCE: Acute coenurosis can be one of the causes of acute encephalopathy mainly in lambs, but also in adult sheep. This condition is incurable, but can be controlled by changing the feeding regime. Cases of chronic coenurosis may be seen a few months later in the same flock" http://www.ncbi.nlm.nih.gov/pubmed/22506508 0 585 I. P. Lapin and G. F. Oxenkrug 1969 Intensification of the central serotoninergic processes as a possible determinant of the thymoleptic effect Lancet 1 7586 132-136 http://www.ncbi.nlm.nih.gov/pubmed/4178247 0 586 S. Endo and T. Launey 2003 ERKs regulate PKC-dependent synaptic depression and declustering of glutamate receptors in cerebellar Purkinje cells Neuropharmacology 45 6 863-872 "Phorbol esters, such as tetradecanoylphorbol 13-acetate (TPA), have been used extensively in studies of cerebellar long-term depression (LTD), based on the hypothesis that activated protein kinase C (PKC) directly mediates alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor phosphorylation. Here, we show that TPA-induced depression of synaptic transmission between granule cells and Purkinje cells in culture is mediated through activation of the MEK1/2-ERK1/2 pathway. Phosphorylation of ERK1/2 induced by TPA and co-application of high potassium and glutamate was greatly attenuated by preincubating Purkinje cells with the MEK1/2 (MAPK ERK kinase 1/2) inhibitor PD98059. TPA-induced depression of synaptic transmission between granule cells and Purkinje cells was attenuated by PD98059. The MEK1/2 inhibitor also suppressed declustering of the ionotropic glutamate receptor subunit 2/3 (GluR2/3) induced by TPA and co-application of high potassium and glutamate, even though phosphorylation of Ser880 of GluR2/3 was not inhibited significantly in the presence of PD98059. These results suggest that ERK1/2 plays an essential role in TPA-induced depression via regulation of GluR2/3 declustering at the synapse" http://www.ncbi.nlm.nih.gov/pubmed/14529724 0 587 "K. Ouriel, M. E. Ginsburg, C. S. Patti, F. J. Pearce and G. L. Hicks" 1987 Verapamil crystalloid cardioplegia: an experimental evaluation of dose-response relationships J.Surg.Res. 43 2 164-171 "Calcium channel blockers have been advocated as agents which enhance myocardial protection during ischemia and reperfusion. Unfortunately, while cellular integrity is preserved, myocardial function is depressed as a result of the negative inotropic effects of these agents. In order to assess the efficacy of verapamil cardioplegia, 25 isolated perfused rabbit hearts were studied. A model of normothermic ischemic arrest was utilized, employing either verapamil-free crystalloid cardioplegia or cardioplegia containing verapamil in concentrations of 0.5, 1.0, or 5.0 mg/liter. All three verapamil-treated groups demonstrated increased postischemic left ventricular developed pressure and improved postischemic compliance when compared with the untreated group (P less than 0.05). However, myocardial function was significantly depressed at 15 min of reperfusion in the 1.0 and 5.0 mg/liter verapamil-treated groups when compared with the 0.5 ml/liter group (P less than 0.05). These data suggest that the addition of verapamil to crystalloid cardioplegia results in enhanced myocardial function while minimizing the early reperfusion depression associated with higher dose therapy" http://www.ncbi.nlm.nih.gov/pubmed/3626538 0 588 K. P. Skibicka and S. L. Dickson 2013 Enteroendocrine hormones - Central effects on behavior "Current Opinion in Pharmacology.13 (6) ()(pp 977-982), 2013.Date of Publication: 2013." 6 977-982 "A number of appetite-regulating gut hormones alter behaviors linked to reward, anxiety/mood, memory and cognitive function, although for some of these (notably GLP-1 and CCK) the endogenous signal may be CNS-derived. From a physiological perspective it seems likely that these hormones, whose secretion is altered by nutritional status and by bariatric weight loss surgery, orchestrate neurobiological effects that are integrated and linked to feeding/metabolic control. Consistent with a role in hunger and meal initiation, ghrelin increases motivated behavior for food and, when food is not readily available, decreases behaviors in anxiety tests that would otherwise hinder the animal from finding food. Of the many anorexigenic signals, GLP-1 and PYY have been linked to a suppressed reward function and CCK (and possibly GLP-1) to increased anxiety-like behavior. © 2013 The Authors. Published by Elsevier Ltd. All rights reserved" DO - http://dx.doi.org/10.1016/j.coph.2013.09.004 0 589 "N. R. Holm, P. Christophersen, J. Hounsgaard, S. Gammeltoft and S. P. Olesen" 2002 CNTF inhibits high voltage activated Ca2+ currents in fetal mouse cortical neurones J.Neurochem. 82 3 495-503 "Neurotrophic factors yield neuroprotection by mechanisms that may be related to their effects as inhibitors of apoptosis as well as their effects on ion channels. The effect of ciliary neurotrophic factor (CNTF) on high-threshold voltage-activated Ca channels in cultured fetal mouse brain cortical neurones was investigated. Addition of CNTF into serum-free growth medium resulted in delayed reduction of the Ca2+ currents. The currents decreased to 50% after 4 h and stabilized at this level during incubation with CNTF for 48 h. Following removal of CNTF the inhibition was completely reversed after 18 h. CNTF reduced the current of all pharmacological subtypes of Ca channels as shown by use of selective blockers of L, N, and P/Q type Ca channels (nifedipine, omega-conotoxin MVIIA, omega-agatoxin IVA). The Ca channel depression was mediated via the CNTF receptor, because enzymatic cleavage of the alpha-subunit glycerophosphatidylinositol anchor of the receptor eliminated the response. The CNTF effect was not elicited through pertussis toxin-sensitive G proteins. Other neurotrophic factors like neurotrophin-3 and insulin-like growth factor-I had no effect on the Ca2+ currents. These results may have important implications for the possible functions of CNTF in the nervous system, such as altered synaptic activity, neuronal excitability and susceptibility to brain ischaemia" http://www.ncbi.nlm.nih.gov/pubmed/12153474 0 590 "M. Hasbani, J. H. Pincus and S. H. Lee" 1974 Diphenylhydantoin and calcium movement in lobster nerves Arch.Neurol. 31 4 250-254 http://www.ncbi.nlm.nih.gov/pubmed/4412829 0 591 "A. J. Severance, R. V. Parsey, J. S. Kumar, M. D. Underwood, V. Arango, V. J. Majo, J. Prabhakaran, N. R. Simpson, R. L. Van Heertum and J. J. Mann" 2006 In vitro and in vivo evaluation of [11C]MPEPy as a potential PET ligand for mGlu5 receptors Nucl.Med.Biol. 33 8 1021-1027 "Excessive activation via the metabotropic glutamate receptor subtype 5 (mGluR(5)) has been implicated in depression, neuropathic pain and other psychiatric, neurological and neurodegenerative diseases. A mGluR(5) radioligand for in vivo quantification by positron emission tomography (PET) would facilitate studies of the role of this receptor in disease and treatment. 3-Methoxy-5-pyridin-2-ylethynylpyridine (MPEPy), a selective and high-affinity antagonist at the mGluR(5) receptor was selected as a candidate ligand; a recent publication by Yu et al. [Nucl Med Biol 32 (2005) 631-640] presented initial micro-PET results for [(11)C]MPEPy with enthusiasm. Building on their efforts, we report as unique contributions (1) an improved chemical synthesis method, (2) the first data using human tissue, (3) phosphor images for rat brain preparations, (4) a novel comparison of anesthetic agents and (5) in vivo data in baboon. In vitro phosphor imaging studies of this ligand using human and rat brain tissue demonstrated high specific binding in the hippocampus, striatum and cortex with minimal specific binding in the cerebellum. In contrast, in vivo micro-PET studies in rats using urethane anesthesia, PET studies in baboons using isoflurane anesthesia and ex vivo micro-PET studies in unanesthetized rats each showed little specific binding in the brain. Despite the promising in vitro results, the low signal-to-noise ratio found in vivo does not justify the use of [(11)C]MPEPy as a PET radiotracer in humans" http://www.ncbi.nlm.nih.gov/pubmed/17127176 0 592 "D. M. Gatlin, III and R. P. Wilson" 1984 Dietary selenium requirement of fingerling channel catfish J.Nutr. 114 3 627-633 "Two experiments were conducted in aquaria to determine the minimum dietary selenium requirement of fingerling channel catfish (Ictalurus punctatus). Casein-gelatin diets containing graded levels of supplemental selenium (as Na2SeO3) ranging from 0 to 15 mg/kg were fed to catfish for 15 weeks in experiment 1 to broadly define their selenium requirement and toxicity levels. Although growth of catfish was affected by dietary selenium level, significant differences in weight gain were not easily discernible due to variability among the groups of fish. Weight gain data generally indicated that the basal diet containing 0.06 mg Se/kg diet caused growth depression, and a supplemental selenium level of 15 mg/kg also caused a reduced growth response, which indicated selenium toxicity. Selenium concentrations in edible muscle tissue increased almost linearly with increasing dietary selenium levels. Liver and plasma selenium-dependent glutathione peroxidase (Se GSH-Px) activities indicated the selenium requirement of fingerling channel catfish was between 0.1 and 0.5 mg Se/kg diet. In experiment 2, casein-gelatin diets containing incremental levels of supplemental selenium were fed to catfish for 14 weeks to more precisely determine their minimum dietary selenium requirement. Growth data and liver and plasma Se GSH-Px activities indicated that the minimum selenium requirement of fingerling channel catfish fed adequate vitamin E was 0.25 mg Se/kg dry diet. Based on these data, it appears that selenium supplementation of commercial catfish feeds is warranted" http://www.ncbi.nlm.nih.gov/pubmed/6699743 0 593 "B. Kadriu, A. Guidotti, E. Costa and J. Auta" 2009 "Imidazenil, a non-sedating anticonvulsant benzodiazepine, is more potent than diazepam in protecting against DFP-induced seizures and neuronal damage" Toxicology 256 3 164-174 "Organophosphate (OP)-nerve agent poisoning may lead to prolonged epileptiform seizure activity, which can result in irreversible neuronal brain damage. A timely and effective control of seizures with pharmacological agents can minimize the secondary and long-term neuropathology that may result from this damage. Diazepam, the current anticonvulsant of choice in the management of OP poisoning, is associated with unwanted effects such as sedation, amnesia, cardio-respiratory depression, anticonvulsant tolerance, and dependence liabilities. In search for an efficacious and safer anticonvulsant benzodiazepine, we studied imidazenil, a potent anticonvulsant that is devoid of sedative action and has a low intrinsic efficacy at alpha1- but is a high efficacy positive allosteric modulator at alpha5-containing GABA(A) receptors. We compared the potency of a combination of 2 mg/kg, i.p. atropine with: (a) imidazenil 0.05-0.5 mg/kg i.p. or (b) equipotent anti-bicuculline doses of diazepam (0.5-5 mg/kg, i.p.), against diisopropyl fluorophosphate (DFP; 1.5 mg/kg, s.c.)-induced status epilepticus and its associated neuronal damage. The severity and frequency of seizure activities were determined by continuous radio telemetry recordings while the extent of neuronal damage and neuronal degeneration were assessed using the TUNEL-based cleaved DNA end-labeling technique or neuron-specific nuclear protein (NeuN)-immunolabeling and Fluoro-Jade B (FJB) staining, respectively. We report here that the combination of atropine and imidazenil is at least 10-fold more potent and longer lasting than the combination with diazepam at protecting rats from DFP-induced seizures and the associated neuronal damage or ongoing degeneration in the anterior cingulate cortex, CA1 hippocampus, and dentate gyrus. While 0.5 mg/kg imidazenil effectively attenuated DFP-induced neuronal damage and the ongoing neuronal degeneration in the anterior cingulate cortex, dentate gyrus, and CA1 hippocampus, 5 mg/kg or a higher dose of diazepam is required to produce similar protective effects. These finding suggests that imidazenil, a non-sedating anticonvulsant BZ ligand, is a more potent, effective, and safer drug than diazepam in protecting rats from DFP-induced seizures and the associated neuronal damage and/or ongoing neuronal degeneration" http://www.ncbi.nlm.nih.gov/pubmed/19111886 0 594 "T. Ide, Y. Sakurai, M. Aono and T. Nishino" 1999 Contribution of peripheral chemoreception to the depression of the hypoxic ventilatory response during halothane anesthesia in cats Anesthesiology 90 4 1084-1091 "BACKGROUND: The effects of inhalational anesthetics on the hypoxic ventilatory response are complex. This study was designed to determine the contribution of peripheral chemoreception to the depression of hypoxic ventilatory response seen with halothane anesthesia. METHODS: Cats were anesthetized with pentobarbital sodium and alpha-chloralose and artificially ventilated. Respiratory output was evaluated by phasic inspiratory activity of the phrenic nerve. In 12 cats, this activity was measured during inhalation of an hypoxic gas mixture with halothane, 0, 0.1, and 0.8%, with intact or denervated carotid bodies. In 10 cats, a carotid body was isolated from the systemic circulation and perfused with hypoxic Krebs-Ringer solution equilibrated with halothane, 0, 0.1, and 0.8%. RESULTS: The hypoxic ventilatory response was depressed in a dose-dependent manner during halothane anesthesia. In carotid body perfusion studies, the response was significantly depressed only with halothane, 0.80%. CONCLUSION: The hypoxic ventilatory response is depressed by a high dose of halothane through a peripheral effect at the carotid body" http://www.ncbi.nlm.nih.gov/pubmed/10201681 0 595 "D. M. Lovinger, E. C. Tyler and A. Merritt" 1993 Short- and long-term synaptic depression in rat neostriatum J.Neurophysiol. 70 5 1937-1949 "1. We have examined plasticity at glutamatergic synapses on neurons in slices of neostriatum, a forebrain area involved in movement and cognitive function. 2. High-frequency stimulation of afferent inputs to neostriatal neurons induced depression of glutamatergic synaptic transmission. Depression could be induced using either prolonged trains or short repetitive bursts of high-frequency stimulation. Depression developed within seconds after such stimulation. Responses recovered to baseline levels within 10 min in most slices but persisted for up to 60 min in others. 3. Postsynaptic passive electrical properties and the ability to elicit action potentials by postsynaptic depolarization were not altered during depression. 4. The magnitude and time course of depression was similar whether postsynaptic responses were mediated by alpha amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) or N-methyl-D-aspartate (NMDA) type glutamate receptors. Depression was not altered by antagonism of AMPA or NMDA receptors or potentiation of AMPA receptor function with aniracetam. 5. Depression was blocked by treatments that increase transmitter release including increased extracellular Ca2+, application of 4-aminopyridine, or application of phorbol ester. 6. Our findings indicate that glutamatergic synapses in neostriatum are capable of expressing a form of synaptic depression that may involve decreased glutamate release" http://www.ncbi.nlm.nih.gov/pubmed/7905031 0 596 "J. B. Rhodes, A. Eichholz and R. K. Crane" 1967 Studies on the organization of the brush border in intestinal epithelial cells. IV. Aminopeptidase activity in microvillus membranes of hamster intestinal brush borders Biochim.Biophys.Acta 135 5 959-965 http://www.ncbi.nlm.nih.gov/pubmed/4965166 0 597 G. Hennighausen and P. Lange 1979 Toxic effects of di-n-octyltin dichloride on the thymus in mice Arch.Toxicol.Suppl 2 315-320 "The effects of di-n-octyltin dichloride (DOTC) on the thymus in mice were studied in dependence on the route of administration. Single administrations of 30, 60 and 120 mg/kg of DOTC i.m. induced a dose-related decrease of the thymus weight and of the number of nucleated cells in the thymus of male mice. 4 days after intravenous injection of 8 mg/kg of DOTC the thymus weight and the number of thymocytes were reduced to 50 percent of the control. In oral route of administration higher doses of DOTC (300 mg/kg) were necessary to provoke a thymus atrophy. After pretreatment of mice with carbon tetrachloride the toxic effects of orally administered DOTC were increased. The reduction of the thymus weight and of the number of thymocytes in mice after parenteral administration was accompanied by a depression of thymus-dependent antibody formation against sheep red blood cells" http://www.ncbi.nlm.nih.gov/pubmed/288338 0 598 "C. L. Su, C. W. Su, Y. H. Hsiao and P. W. Gean" 2016 Epigenetic regulation of BDNF in the learned helplessness-induced animal model of depression J.Psychiatr.Res. 76 101-110 "Major depressive disorder (MDD), one of the most common mental disorders, is a significant risk factor for suicide and causes a low quality of life for many people. However, the causes and underlying mechanism of depression remain elusive. In the current work, we investigated epigenetic regulation of BDNF in the learned helplessness-induced animal model of depression. Mice were exposed to inescapable stress and divided into learned helplessness (LH) and resilient (LH-R) groups depending on the number they failed to escape. We found that the LH group had longer immobility duration in the forced swimming test (FST) and tail suspension tests (TST), which is consistent with a depression-related phenotype. Western blotting analysis and enzyme-linked immunosorbent assay (ELISA) revealed that the LH group had lower BDNF expression than that of the LH-R group. The LH group consistently had lower BDNF mRNA levels, as detected by qPCR assay. In addition, we found BDNF exon IV was down-regulated in the LH group. Intraperitoneal injection of imipramine or histone deacetylase inhibitors (HDACi) to the LH mice for 14 consecutive days ameliorated depression-like behaviors and reversed the decrease in BDNF. The expression of HDAC5 was up-regulated in the LH mice, and a ChIP assay revealed that the level of HDAC5 binding to the promoter region of BDNF exon IV was higher than that seen in other groups. Knockdown of HDAC5 reduced depression-like behaviors in the LH mice. Taken together, these results suggest that epigenetic regulation of BDNF by HDAC5 plays an important role in the learned helplessness model of depression" http://www.ncbi.nlm.nih.gov/pubmed/26921875 1 599 "R. Bressler, M. Vargas-Cordon and K. Brendel" 1969 Inhibition of insulin secretion by aryl-substituted secondary aminoethanols Diabetes 18 5 262-267 http://www.ncbi.nlm.nih.gov/pubmed/4307639 0 600 "H. Y. Huang, H. W. Lee, S. D. Chen and F. Z. Shaw" 2012 Lamotrigine ameliorates seizures and psychiatric comorbidity in a rat model of spontaneous absence epilepsy Epilepsia 53 11 2005-2014 "PURPOSE: Lamotrigine (LTG) is an effective clinical treatment for epilepsy associated with absence seizures. However, the impact of LTG administration in studies employing various animal models of epilepsy remains controversial. This study aimed to clarify the outcomes of LTG treatment on absence seizures and comorbid anxiety and depression disorders in Long-Evans rats with spontaneous spike-wave discharges (SWDs). METHODS: LTG (10 mg/kg) or water vehicle was chronically administered perorally to Long-Evans rats (twice daily for 35 days). Cortical activities were recorded to assess the presence of SWDs. Five behavioral tests, including the open field (OF), elevated plus maze (EPM), sucrose consumption (SC), sucrose preference, and forced swimming (FS) tests, were performed after LTG/vehicle treatment. The behavioral indexes of these tests were designed to assess anxiety (OF and EPM tests), depression (SC and FS tests), and preference for hedonistic stimuli (sugar preference test). KEY FINDINGS: Total SWD duration, SWD number, and mean SWD duration were significantly decreased in rats that received 35-day LTG treatment compared with rats that received vehicle treatment. Rats with spontaneous SWDs versus rats with no SWDs showed significant levels of anxiety and depression in the OF, EPM, and SC tests. Rats with SWDs also showed longer immobility in the FS test. However, the LTG-treated group compared with the vehicle group presented with significantly lower manifestations of anxiety and depression in the OF, EPM, SC, and sucrose preference tests and shorter immobility in the FS test. SIGNIFICANCE: The results of this study suggest that chronic LTG treatment can benefit patients with epilepsy via suppression of absence seizures and amelioration of comorbid anxiety and depression" http://www.ncbi.nlm.nih.gov/pubmed/22988820 1 601 S. Haj-Dahmane and R. Y. Shen 2010 Regulation of plasticity of glutamate synapses by endocannabinoids and the cyclic-AMP/protein kinase A pathway in midbrain dopamine neurons J.Physiol 588 Pt 14 2589-2604 "Endocannabinoids (eCBs) are lipid signalling molecules which play a key role in the regulation of synaptic transmission and plasticity in the central nervous system. Previous studies have reported that eCBs are released 'on demand' in the ventral tegmental area (VTA), a brain region critical for reward learning. However, their role in modulating the long-term plasticity of glutamate synapses of VTA dopamine (DA) neurons remains unknown. In the present study, we showed that low frequency afferent stimulation paired with moderate postsynaptic depolarization elicited an N-methyl-d-aspartate (NMDA) receptor-independent long-term depression (LTD) at glutamate synapses of VTA DA neurons. This form of LTD was caused by a decrease in the probability of glutamate release. Examination of the mechanisms underlying this form of LTD revealed that it was mediated by retrograde eCB signalling. In addition, we found that inhibition of 2-arachidonoyl glycerol biosynthesis blocked LTD induction, suggesting that 2-arachidonoyl glycerol is the most likely retrograde eCB messenger mediating LTD. The eCB-LTD induced at glutamate synapses of VTA DA neurons also required the inhibition of the presynaptic cAMP/PKA pathway. Taken together, these results reveal a critical role of eCBs in controlling the long-term plasticity of glutamate synapses in VTA DA neurons" http://www.ncbi.nlm.nih.gov/pubmed/20498231 0 602 "T. Kameyama, H. Fukuda and H. Kato" 1976 Effects of carbenoxolone sodium on animal behavior and central nervous system (Japanese) "Pharmacometrics.11 (2) ()(pp 275-281), 1976.Date of Publication: 1976." 2 275-281 1 603 "D. Demontis, C. Pertoldi, V. Loeschcke, K. Mikkelsen, T. Axelsson and T. N. Kristensen" 2009 "Efficiency of selection, as measured by single nucleotide polymorphism variation, is dependent on inbreeding rate in Drosophila melanogaster" Mol.Ecol. 18 22 4551-4563 "It is often hypothesized that slow inbreeding causes less inbreeding depression than fast inbreeding at the same absolute level of inbreeding. Possible explanations for this phenomenon include the more efficient purging of deleterious alleles and more efficient selection for heterozygote individuals during slow, when compared with fast, inbreeding. We studied the impact of inbreeding rate on the loss of heterozygosity and on morphological traits in Drosophila melanogaster. We analysed five noninbred control lines, 10 fast inbred lines and 10 slow inbred lines; the inbred lines all had an expected inbreeding coefficient of approximately 0.25. Forty single nucleotide polymorphisms in DNA coding regions were genotyped, and we measured the size and shape of wings and counted the number of sternopleural bristles on the genotyped individuals. We found a significantly higher level of genetic variation in the slow inbred lines than in the fast inbred lines. This higher genetic variation was resulting from a large contribution from a few loci and a smaller effect from several loci. We attributed the increased heterozygosity in the slow inbred lines to the favouring of heterozygous individuals over homozygous individuals by natural selection, either by associative over-dominance or balancing selection, or a combination of both. Furthermore, we found a significant polynomial correlation between genetic variance and wing size and shape in the fast inbred lines. This was caused by a greater number of homozygous individuals among the fast inbred lines with small, narrow wings, which indicated inbreeding depression. Our results demonstrated that the same amount of inbreeding can have different effects on genetic variance depending on the inbreeding rate, with slow inbreeding leading to higher genetic variance than fast inbreeding. These results increase our understanding of the genetic basis of the common observation that slow inbred lines express less inbreeding depression than fast inbred lines. In addition, this has more general implications for the importance of selection in maintaining genetic variation" http://www.ncbi.nlm.nih.gov/pubmed/19780974 0 604 "R. P. Swenson, Jr." 1981 Inactivation of potassium current in squid axon by a variety of quaternary ammonium ions J.Gen.Physiol 77 3 255-271 "The characteristics of potassium channel block by a diverse group of quaternary ammonium (QA) ions was examined in squid axons. Altering the size and nature of the head and/or tail groups of the QA ions applied internally produced only quantitative differences in the potassium current block. Although their entry rate is diminished, compounds with head groups as large as 11 X 12 A are capable of occluding the channel, whereas the smallest QA ions, with head groups approximately 5 X 6 A, are not potent blockers. When one or three terminal hydrogens of the head group were replaced by hydroxyl moieties, the compound's blocking ability was diminished, suggesting that QA binding is not improved by hydrogen bonding at these positions. QA ions bound to their site within the potassium channel with 1:1 stoichiometry, and the site is perhaps 20% or more of the distance through the membrane electric field. Raising external potassium concentration did not alter the steady-state or kinetic features of the QA block of outward potassium currents; however, increasing temperature or adding Ba2+ internally increased the rate of decay of the QA-blocked currents. From the structure-function analysis of the QA ions, projections concerning both the architecture of the potassium channel's inner mouth and the significance of various chemical constituents of the ions were made. The potassium channel may now be pictured as having a wider mouth (up to 11 X 12 A) extending to the QA binding site and then narrowing quickly to the region of channel selectivity. Important alterations that improve the blocking ability of the compounds include: (a) lengthening the alkyl hydrocarbon tail group (up to 10 carbon), (b) lengthening a second hydrocarbon chain of the head group (e.g., decyldimethylphenylammonium bromide [C10DM phi]), and (c) adding a carbonyl moiety to the tail (e.g., ambutonium)" http://www.ncbi.nlm.nih.gov/pubmed/6265591 0 605 "C. Montalban, R. Martinez-Fernandez, J. L. Calleja, J. D. Garcia-Diaz, R. Rubio, F. Dronda, S. Moreno, M. Yebra, C. Barros, J. Cobo and ." 1989 Visceral leishmaniasis (kala-azar) as an opportunistic infection in patients infected with the human immunodeficiency virus in Spain Rev.Infect.Dis. 11 4 655-660 "In an area endemic for visceral leishmaniasis, 16 patients with human immunodeficiency virus (HIV) infection developed the disease. All belonged to populations at risk for AIDS (15 were intravenous drug abusers). Five patients fulfilled the criteria for full-blown AIDS, and two more fulfilled them after diagnosis of leishmaniasis. All presented with the classic manifestations of visceral leishmaniasis, but leishmania serology was negative in 15 patients (93%). Leishmania donovani amastigotes were identified in the bone marrow in all cases. Most patients responded initially to treatment with pentavalent antimonial drugs, but seven (43%) followed a chronic course, with multiple relapses in five, despite alternative treatments. Visceral leishmaniasis occurred in patients with different levels of depression of the CD4 to CD8 lymphocyte ratio. Mortality was 37% (six patients) and was independent of the chronic-relapsing course of the disease. In no case was leishmaniasis the primary cause of death. Our data establish that visceral leishmaniasis is an opportunistic infection in HIV-infected patients, and we suggest that in endemic areas it should be considered an indicator disease for the diagnosis of AIDS" http://www.ncbi.nlm.nih.gov/pubmed/2672242 0 606 L. Smith and B. J. Meyerson 1981 Long-term effect of two tricyclic antidepressants "Neuroscience Letters.24 (SUPPL.7) ()(pp S257), 1981.Date of Publication: 1981." Suppl7 S257 1 607 A. Scublinsky and H. H. Wotiz 1971 The contraceptive action of impeding oestrogens. VII. Effectiveness of oestriol in the rabbit and the hamster J.Reprod.Fertil. 26 3 365-367 http://www.ncbi.nlm.nih.gov/pubmed/5569651 0 608 J. Baron and T. R. Tephly 1969 The role of heme synthesis during the induction of hepatic microsomal cytochrome P-450 and drug metabolism produced by benzpyrene Biochem.Biophys.Res.Commun. 36 4 526-532 http://www.ncbi.nlm.nih.gov/pubmed/4390185 0 609 M. N. Perkins and T. W. Stone 1980 Aminophylline and theophylline derivatives as antagonists of neuronal depression by adenosine: a microiontophoretic study Arch.Int.Pharmacodyn.Ther. 246 2 205-214 "Aminophylline, theophylline, etamiphylline and diprophylline have been tested as antagonists of neuronal inhibition produced by microiontophoretically applied adenosine, when ejected as cations or anions. Aminophylline proved to be an effective adenosine antagonist when ejected as an anion, especially from alkaline solution. Anionic theophylline was also effective but less so, and on a smaller proportion of neurones. Ethylenediamine and hydroxyl ions had no effect on adenosine responses. GABA depressions were unaffected by any of the methylxanthines at the time of adenosine blockade. Cationic ejection from aminophylline or ethylenediamine barrels produced a depression of unit firing on about one third of the cells tested, but no antagonism of adenosine was observed. It is concluded that the anionic ejection of aminophylline from alkaline solution, or of etamiphylline of diprophylline, yields potentially useful antagonists of adenosine for iontophoretic experiments" http://www.ncbi.nlm.nih.gov/pubmed/7436627 0 610 "I. Bashmakov, T. V. Sidorenko and L. A. Diugovskaia" 1991 [The role of tissue basophils in the regulation of the secretory activity of macrophages] Fiziol.Zh. 37 1 89-94 "Mast cells and macrophages isolated from sensitized rats are unequivalent producer of enzymes in systems in vitro. Allergen intensifies exocytosis of acid phosphatase in them but the activity of allergen-induced enzyme secretion by macrophages ++ in immunized rats is lower than the activity of spontaneous secretion of acid phosphatase in suspensions of macrophages + in nonimmunized rats. Macrophages rather than mast cells show the ability for exocytosis of C4-gamma-glutamyltranspeptidase, leukotriene++ catabolism enzyme. Cocultivation of immune macrophages with syngeneic mast cells in the presence of allergen is followed with sharp depression of the activity of this enzyme secretion, that can create conditions for prolongation of eicosanoid effects in allergy" http://www.ncbi.nlm.nih.gov/pubmed/1676002 0 611 "T. F. Yuan, A. Li, X. Sun, O. Arias-Carrion and S. Machado" 2016 Vagus nerve stimulation in treating depression: A tale of two stories Curr.Mol.Med. 16 1 33-39 "Vagus nerve stimulation (VNS) has been widely used to treat different neurological disorders, especially epilepsy. Accumulating evidence also suggests its potential application in antidepressive therapy, given that VNS has been confirmed by several clinical trials to exert long-term effects on mitigating depression and reducing the risk of relapse in depressed patients. Likewise, VNS has also proven to ameliorate the behavioral deficits in a rat model of depression. While the influences of VNS on monoamine metabolism and mood improvement are well-recognized, the underlying mechanisms mediating its antidepressive action remain poorly understood. Recent findings suggest that VNS-enhanced proliferation of hippocampal neural progenitor cells (NPCs) and synaptic transmission might serve as a monoamine-independent pathway contributive to the beneficial effects of VNS on depression. Here we briefly reviewed the recent progress in this field, based on which we propose that there might be, at least, two little-overlapped, and yet interactive pathways mediating the antidepressive action of VNS" http://www.ncbi.nlm.nih.gov/pubmed/26695696 0 612 "D. C. Clark, R. D. Gibbons, J. Fawcett and W. A. Scheftner" 1989 What is the mechanism by which suicide attempts predispose to later suicide attempts? A mathematical model "Journal of abnormal psychology.98 (1) ()(pp 42-49), 1989.Date of Publication: Feb 1989." 1 42-49 "A state dependence model of serial behavior suggests that each occurrence increases the subsequent likelihood of that behavior being repeated. A heterogeneity model, by contrast, suggests that the likelihood of a behavior occurring is predetermined, and uninfluenced by intervening occurrences. We have applied the random-effects probit model of Gibbons and Bock (1987) to examine the fit of the state dependence and heterogeneity models to longitudinal data on suicide attempts by 928 patients with affective disorder. Heterogeneity but not state dependence was required to model these data. The findings suggest that when considering patients with moderate to severe major affective disorder, the clinician should not interpret the absence of any recent suicide attempts to mean that the patient is at relatively low risk for attempting suicide in the future. An implication of the heterogeneity model is that suicide attempts made many years ago may have equal value to recent attempts when estimating an individual's ""predisposition"" to nonlethal attempts in the future" 0 613 P. Klubes and I. Cerna 1974 Effects of 5-fluorouracil on drug-metabolizing enzymes in the rat Cancer Res. 34 5 927-931 http://www.ncbi.nlm.nih.gov/pubmed/4823903 0 614 "F. Mosca, V. Narcisi, A. Calzetta, L. Gioia, M. G. Finoia, M. Latini and P. G. Tiscar" 2013 "Effects of high temperature and exposure to air on mussel (Mytilus galloprovincialis, Lmk 1819) hemocyte phagocytosis: modulation of spreading and oxidative response" Tissue Cell 45 3 198-203 "Hemocytes are a critical component of the mussel defense system and the present study aims at investigating their spreading and oxidative properties during phagocytosis under in vivo experimental stress conditions. The spreading ability was measured by an automated cell analyzer on the basis of the circularity, a parameter corresponding to the hemocyte roundness. The oxidative activity was investigated by micromethod assay, measuring the respiratory burst as expression of the fluorescence generated by the oxidation of specific probe. Following the application of high temperature and exposure to air, there was evidence of negative modulation of spreading and oxidative response, as revealed by a cell roundness increase and fluorescence generation decrease. Therefore, the fall of respiratory burst appeared as matched with the inhibition of hemocyte morphological activation, suggesting a potential depression of the phagocytosis process and confirming the application of the circularity parameter as potential stress marker, both in experimental and field studies" http://www.ncbi.nlm.nih.gov/pubmed/23375726 0 615 "M. Naim, A. Gertler and Y. Birk" 1982 "The effect of dietary raw and autoclaved soya-bean protein fractions on growth, pancreatic enlargement and pancreatic enzymes in rats" Br.J.Nutr. 47 2 281-288 "1. Raw soya-bean meal (RS) was fractionated into soya-bean lyophilized extract (SLE), soya-bean lyophilized residue (SLR), acid-precipitated proteins (APP) and whey proteins. 2. Trypsin (EC 3. 4. 21. 4)and chymotrypsin (EC 3. 4. 21.1) inhibitors (TI) were soluble at pH 8 and remained soluble after the extract was acidified to pH 4.4 Except for whey, heating abolished, almost totally, their inhibiting activity. 3. Feeding SLE diet (high TI content) and APP diet (low TI content) resulted in growth depression below the RS level. Feeding the SLR diet resulted in an optimal growth. Feeding diets containing heated fractions improved the growth rate though not to the level observed with heated RS (HS) diet. 4. RS, SLE, APP and whey diets produced similar pancreatic enlargement which could be totally (RS, whey) or partially (SLE, APP) abolished by heating. 5. Feeding the RS diet reduced pancreatic amylase content. The factor responsible for this effect cofractionated with SLE and whey proteins. 6. Two groups of factors in the various diets were probably responsible for the elevation in pancreatic proteases. The first group were the heat-labile factors present in RS, SLE and whey whereas the second group resisted the heat treatment and were found in APP and SLR. 7. The results suggest that for optimal growth rate of rats, heat treatment should be given to the unfractionated soya-bean proteins rather than to the isolated fractions. The results further indicated that TI are not the only factors that can lead to pancreatic enlargement and changes in pancreatic enzymes composition" http://www.ncbi.nlm.nih.gov/pubmed/7199936 0 616 "H. J. Seo, E.-J. Park, M. J. Kim, S. Y. Kang, S. H. Lee, H. J. Kim, K. N. Lee, M. E. Jung, M. Lee, M.-S. Kim, E.-J. Son, W.-K. Park, J. Kim and J. Lee" 2011 Design and synthesis of novel arylpiperazine derivatives containing the imidazole core targeting 5-HT2A receptor and 5-HT transporter "Journal of Medicinal Chemistry.54 (18) ()(pp 6305-6318), 2011.Date of Publication: 22 Sep 2011." 18 6305-6318 "Serotonin antagonist reuptake inhibitor (SARI) drugs that block both 5-HT2 receptors and the serotonin transporters have been developed. The human 5-HT2A/2C receptor has been implicated in several neurological conditions, and potent selective 5-HT2A/2C ligands may have therapeutic potential for treatment of CNS diseases such as depression. An imidazole moiety usually provides good pharmacokinetic properties as a drug substance, and thus considerable efforts have been devoted to develop imidazole derivatives into drug candidates. The imidazole series of compounds was evaluated against 5-HT2A/2C and serotonin reuptake inhibition. A few of the compounds in the series showed promising IC50 values and antidepressant-like effect in in vivo forced swimming test (FST). On the basis of these results, further lead optimization studies resulted in identifying promising compounds potentially for therapeutic use. © 2011 American Chemical Society" DO - http://dx.doi.org/10.1021/jm200682b 1 617 B. M. Altura 1976 DPAVP: a vasopressin analog with selective microvascular and RES actions for the treatment of circulatory shock in rats Eur.J.Pharmacol. 37 1 155-167 "The present study indicates that: (a) local administration of low concentrations of an analog of vasopressin, 1-deamino-[2-phenylalanine, 8-arginine]-vasopressin (DPAVP), constricts venules in the rat splanchnic terminal vascular bed of normal animals, unlike that seen for catecholamines; (b) maximal concentrations of DPAVP narrow but do not occlude both arterioles and venules: (c) microscopic muscular venules (31-39 mu i.d.) do not narrow more than 20% in response to the vasopressin analog DPAVP; and (d) terminal arterioles (17-23 mu i.d.) do not narrow more than 50% in response to DPAVP. Systemic administration of DPAVP to rats subjected to hemorrhage or bowel ischemia shock more than doubles survival rates over control rats receiving Ringer solution. Infusion of DPAVP produces a dose-dependent effect on arterial blood pressure, microscopic capacitance vessels, large arterioles and small arteries. In addition, i.v. administration of DPAVP: (a) returns arterial hematocrit towards normal after shock; and (b) regenerates and sustains vasomotion and venular tone, decreases microvascular hyperreactivity characteristic of shock syndromes, restores constricted arteriolar lumen sizes towards normal, predisposes to a splanchnic microbed virtually free of stasis, petechiae and leukocytic sticking, and restores capillary perfusion and outflow to near-normal. Further, DPAVP effectively restores the early reticuloendothelial system (RES) phagocytic depression, characteristic of shock syndromes, to normal; the latter eventuating in RES hyper-phagocytic activity. These findings indicate it is possible to synthesize vasoactive molecules which: (a) exert selective microvascular and RES phagocytic effects; and (b) are highly beneficial in the therapy of low-flow states, at least in rats" http://www.ncbi.nlm.nih.gov/pubmed/1278238 0 618 "R. Ramamoorthy, M. Radhakrishnan and M. Borah" 2008 "Antidepressant-like effects of serotonin type-3 antagonist, ondansetron: An investigation in behaviour-based rodent models" "Behavioural Pharmacology.19 (1) ()(pp 29-40), 2008.Date of Publication: February 2008." 1 29-40 "The present behavioural investigation evaluates the antidepressant potential of ondansetron (OND), a widely used (in management of cancer chemotherapy-induced nausea and emesis) 5-HT3 receptor antagonist. Separate groups of mice received acute or chronic treatment of OND (0.005-1000 mug/kg), and were subjected to spontaneous locomotor activity test or antidepressant assays, namely, the forced swim and tail suspension tests. Interaction studies with fluoxetine, venlafaxine, desipramine and 8-hydroxy-2-(di-n-propylamino) tetralin were conducted in the forced swim test. The effect of OND (0.01-1000 mug/kg) in combination with paroxetine (10 mg/kg, for 14 days) on the behaviour of male bulbectomized or sham-operated rats was also assessed. The postbulbectomy behavioural analysis included exploration in the open field and elevated plus maze. OND exhibited a biphasic dose-response profile, with antidepressant-like effects peaking at 0.1 mug/kg, in the forced swim and tail suspension tests. None of the tested doses influenced spontaneous locomotor activity. Chronic OND pretreatment augmented the antidepressant effects of fluoxetine and venlafaxine but did not influence the effects of desipramine or 8-hydroxy-2-(di-n-propylamino) tetralin. Chronic OND (10 mug/kg) reversed hyperactivity in the open field, and decreased the percentage entry and time spent in open arms in the elevated plus maze. Summing up, it is observed that OND exhibits antidepressant-like effects, possibly mediated through postsynaptic 5-HT3 receptors. © 2008 Lippincott Williams & Wilkins, Inc" DO - http://dx.doi.org/10.1097/FBP.0b013e3282f3cfd4 1 619 "G. E. Batrak, S. I. Khrustalev and A. K. Iarosh" 1977 "[Comparative reactivity of the neo-, paleo- and archicortex of the brain under conditions of ether and hexanal anesthesia]" Farmakol.Toksikol. 40 2 137-141 "In acute experiments on dogs subject to investigation under ether- and hexobarbital sodium-induced anesthesia was comparative reactivity of the neo-(sensomotor region), paleo-(hippocampus) and archicortex (olfactory lobe) of the brain. It was found that following administration of low and medium doses of general anesthetics more marked EEG changes, with but an insignificant inhibition of respirations and a slight fall in arterial pressure, were observed to occur in the hippocampus and in the olfactory lobe, as against the biocurrents in the sensomotor region. Such a regularity continued for as long as the oxygen tension in the neocortex was maintained at a level higher than in the paleo-and archicortex. Upon introduction of toxic ether and hexobarbital doses the oxygen tension in the neocortex dropped earlier and the inhibition of its bioelectric activity would set in concurrently or sooner than in the olfactory lobe and in the hippocampus" http://www.ncbi.nlm.nih.gov/pubmed/852555 0 620 "F. Delwiche, M. J. Garrity, J. S. Powell, R. P. Robertson and J. W. Adamson" 1983 High levels of the circulating form of parathyroid hormone do not inhibit in vitro erythropoiesis J.Lab Clin.Med. 102 4 613-620 "Either primary or secondary hyperparathyroidism may be associated with anemia. The pathogenesis of this anemia remains obscure, but parathyroid hormone may directly suppress erythropoiesis or anemia may result from myelofibrosis. Previously reported in vitro studies of a direct inhibitory effect of PTH on erythroid progenitor growth were carried out with crude hormone preparations and appeared nonspecific. We have studied simultaneously the in vitro effects of pure (greater than 6000 U/mg) and crude (130 U/mg) preparations of PTH on murine and human hematopoietic progenitor growth. Increasing concentrations (2.5 to 20 U/ml) of crude PTH produced a dose-dependent inhibition of early erythroid (BFU-E) and granulocyte/macrophage progenitor (CFU-GM) growth in human and mouse marrow cell cultures. However, the biologically active N-terminal fragment containing amino acids 1-34 and the pure intact molecule of 84 amino acids failed to significantly inhibit hematopoietic colony growth. These observations demonstrate that in vitro inhibitory effects described with parathyroid gland extracts are not specific for erythropoiesis and may not be related to the circulating form of PTH" http://www.ncbi.nlm.nih.gov/pubmed/6311928 0 621 M. Pospisil and I. Zakopalova 1971 Differences in the sensitivity to hydrocortisone of erythropoiesis in the bone marrow and the spleen of fasting adrenalectomized mice Folia Biol.(Praha) 17 1 33-36 http://www.ncbi.nlm.nih.gov/pubmed/5550396 0 622 "M. Kanarik, A. Alttoa, D. Matrov, K. Koiv, T. Sharp, J. Panksepp and J. Harro" 2011 "Brain responses to chronic social defeat stress: effects on regional oxidative metabolism as a function of a hedonic trait, and gene expression in susceptible and resilient rats" Eur.Neuropsychopharmacol. 21 1 92-107 "Chronic social defeat stress, a depression model in rats, reduced struggling in the forced swimming test dependent on a hedonic trait-stressed rats with high sucrose intake struggled less. Social defeat reduced brain regional energy metabolism, and this effect was also more pronounced in rats with high sucrose intake. A number of changes in gene expression were identified after social defeat stress, most notably the down-regulation of Gsk3b and Map1b. The majority of differences were between stress-susceptible and resilient rats. Conclusively, correlates of inter-individual differences in stress resilience can be identified both at gene expression and oxidative metabolism levels" http://www.ncbi.nlm.nih.gov/pubmed/20656462 1 623 "T. J. Martin, J. Suchocki, E. L. May and B. R. Martin" 1990 Pharmacological evaluation of the antagonism of nicotine's central effects by mecamylamine and pempidine J.Pharmacol.Exp.Ther. 254 1 45-51 "The nature of mecamylamine's and pempidine's antagonism of nicotine in the central nervous system has not been defined clearly. Although these compounds are thought to be noncompetitive antagonists in the brain due to the fact that they do not compete effectively for agonist binding to brain tissue in vitro, pharmacological evidence is lacking. The alteration of nicotine's dose-response curves for depression of spontaneous activity and antinociception was determined in the presence of increasing concentrations of pempidine. Pempidine was found to increase the ED50 of nicotine (0.73 mg/kg) for depression of spontaneous activity in a dose-related manner. At a dose of 3 mg/kg, pempidine increased nicotine's ED50 4.7-fold. The maximum effect of nicotine was achieved in the presence of the highest dose of pempidine, suggesting competitive antagonism. However, pempidine did decrease the maximum effect of nicotine in producing antinociception at doses that increased the ED50 13.7-fold which suggests a noncompetitive action. The structural requirements for mecamylamine's antagonism of these nicotine effects was also determined in order to address the question of whether the antagonists are interacting at a receptor site. The structure-activity relationships of the mecamylamine analogs revealed that the N-, 2- and 3-methyl groups were important for optimal potency. Optical isomerism was found to have little effect on potency. Addition of pyridinyl groups to the nitrogen abolished the activity of these compounds. The structural requirements for the agonists and antagonists therefore appear to be quite different. The alterations produced similar results for antagonism of both effects of nicotine. Mecamylamine and pempidine therefore appear to exhibit both competitive and noncompetitive properties in antagonizing the central effects of nicotine" http://www.ncbi.nlm.nih.gov/pubmed/2366189 0 624 "K. Huang, S. Y. Im, W. E. Samlowski and R. A. Daynes" 1989 Molecular mechanisms of lymphocyte extravasation. III. The loss of lymphocyte extravasation potential induced by pertussis toxin is not mediated via the activation of protein kinase C J.Immunol. 143 1 229-238 "The present study evaluated whether protein kinase C (PKC) activation was involved in the lymphocytosis promoting properties of pertussis toxin (Ptx). The exposure of mouse lymphocytes to phorbol esters (as a means to selectively activate PKC) caused a depression in their subsequent capacity to localize into lymph nodes and Peyer's patches in vivo. This pattern of inhibition was quite similar to that observed with lymphocytes treated with Ptx. The mechanisms responsible for the observed decreases in localization to lymphoid organs caused by these two agents, however, appeared to be distinct. Exposure of lymphocytes to PMA was followed by a time and dosage-dependent decrease in the surface density of MEL-14 defined homing receptors. Ptx-treated lymphocytes retained normal density of this homing receptor. Consequently, PMA-treated lymphocytes lost their capacity to bind to high-endothelial venules in in vitro lymph node binding assays while Ptx-treated cells retained normal high-endothelial venule binding potential. We conclude from this study that: 1) the activation of PKC in lymphocytes by PMA can alter their recirculation properties via mechanisms that diminish their expression of surface receptors which support extravasation into lymph node and mucosal lymphoid tissues, and 2) even though Ptx has been reported to elevate the rate of inositol phosphate turnover in lymphocytes, the loss of extravasation potential of Ptx-treated lymphocytes is not mediated via the modification of surface homing receptors as observed in cells exposed to the known PKC activator, PMA" http://www.ncbi.nlm.nih.gov/pubmed/2732469 0 625 "D. M. Hills, V. P. Gerskowitch, S. P. Roberts, N. J. Welsh, N. P. Shankley and J. W. Black" 1996 Pharmacological analysis of the CCKB/gastrin receptors mediating pentagastrin-stimulated gastric acid secretion in the isolated stomach of the immature rat Br.J.Pharmacol. 119 7 1401-1410 "1. The CCKB/gastrin receptors mediating pentagastrin stimulation of gastric acid secretion by histamine release and by direct stimulation of oxyntic cells have been characterized in the immature rat isolated stomach assay. This was achieved by estimating antagonist affinity values for competitive antagonists from three distinct chemical classes (L-365,260, PD134,308 and JB93190) in the absence and presence of a high concentration of the histamine H2-receptor antagonist, famotidine (30 microM). 2. Pentagastrin produced concentration-dependent stimulation of gastric acid secretion in the absence and presence of famotidine. Famotidine depressed the maximum secretory response to pentagastrin although the degree of depression varied between experimental replicates (25-60%). This variation was attributed to the histamine-release mediated component of acid secretion, as judged by the consistency of the maximum responses obtained in the presence, but not absence, of famotidine. 3. All three CCKB/gastrin receptor antagonists behaved as surmountable antagonists in the absence and presence of famotidine. JB93190 (pKB approximately 9.1, approximately 8.9, in the absence and presence of famotidine, respectively) was approximately 30 fold more potent than either L-365,260 (pKB approximately 7.4, approximately 7.1) or PD134,308 (pKB approximately 7.6, approximately 7.4). 4. It was assumed that the famotidine treatment converted pentagastrin-stimulated acid secretion from a combination of an indirect action due to the release of histamine and a direct action on the oxyntic cell to solely a direct action on the oxyntic cell. A simple mathematical model of this two-receptor system was developed. The direct and indirect components were assumed to sum to produce the total response to pentagastrin obtained in the absence of famotidine. It was found that this model could account quantitatively for the behaviour of the three antagonists without invoking a difference in antagonist affinity for the CCKB/gastrin receptors mediating the direct and indirect actions of pentagastrin. However, a conclusion of receptor homogeneity has to be qualified because the model was also used to generate simulations which indicated that the analysis could only detect antagonist affinity differences of greater than one log-unit between enterochromaffin-like (ECL) and oxyntic cell CCKB/gastrin receptor populations" http://www.ncbi.nlm.nih.gov/pubmed/8968549 0 626 "H. Nagasawa, R. Yanai and K. Yamanouchi" 1976 Inhibition of pituitary prolactin secretion by human placental lactogen in rats J.Endocrinol. 71 1 115-120 "Intact female rats given twice daily injections of 1 mg human placental lactogen (HPL) showed continued dioestrous vaginal smears and their ovarian corpora lutea were found to be hypertrophied and functiona. The serum prolactin level was significantly lower in these rats than in the controls at dioestrus as well as at pro-oestrus. Twice-daily injections of 0.5 or 2 mg HPL to ovariectomized rats decreased serum and pituitary levels of prolactin and increased hypothalamic activity of prolactin inhibiting hormone, although the effect was less at the lower dose. Human placental lactogen had no direct effect on pituitary prolactin secretion in vitro. These findings have demonstrated that HPL, like prolactin itself, inhibits prolactin secretion by actin" http://www.ncbi.nlm.nih.gov/pubmed/10338 0 627 "K. Mlyniec, B. Ostachowicz, A. Krakowska, W. Reczynski, W. Opoka and G. Nowak" 2014 Chronic but not acute antidepressant treatment alters serum zinc/copper ratio under pathological/zinc-deficient conditions in mice "Journal of Physiology and Pharmacology.65 (5) ()(pp 673-678), 2014.Date of Publication: 01 Oct 2014." 5 673-678 "Depression is the leading psychiatric disorder with a high risk of morbidity and mortality. Clinical studies report lower serum zinc in depressed patients, suggesting a strong link between zinc and mood disorders. Also copper as an antagonistic element to zinc seems to play a role in depression, where elevated concentration is observed. In the present study we investigated serum copper and zinc concentration after acute or chronic antidepressant (AD) treatment under pathological/zinc-deficient conditions. Zinc deficiency in mice was induced by a special diet administered for 6 weeks (zinc adequate diet - ZnA, contains 33.5 mgZn/kg; zinc deficient diet - ZnD, contains 0.2 mgZn/kg). Animals received acute or chronically saline (control), imipramine, escitalopram, reboxetine or bupropion. To evaluate changes in serum copper and zinc concentrations the total reflection X-ray fluorescence (TXRF) and flame atomic absorption spectrometry (FAAS) was performed. In ZnD animals serum zinc level was reduced after acute ADs treatment (similarly to vehicle treatment), however, as demonstrated in the previous study after chronic ADs administration no differences between both ZnA and ZnD groups were observed. Acute ADs in ZnD animals caused different changes in serum copper concentration with no changes after chronic ADs treatment. The calculated serum Zn/Cu ratio is reduced in ZnD animals (compared to ZnA subjects) treated with saline (acutely or chronically) and in animals treated acutely with ADs. However, chronic treatment with ADs normalized (by escitalopram, reboxetine or bupropion) or increased (by imipramine) this Zn/Cu ratio. Observed in this study normalization of serum Zn/Cu ratio in depression-like conditions by chronic (but not acute) antidepressants suggest that this ratio may be consider as a marker of depression or treatment efficacy" 1 628 "C. Rozas, H. Frank, A. J. Heynen, B. Morales, M. F. Bear and A. Kirkwood" 2001 Developmental inhibitory gate controls the relay of activity to the superficial layers of the visual cortex J.Neurosci. 21 17 6791-6801 "A developmental reduction in the radial transmission of synaptic activity has been proposed to underlie the end of the critical period for experience-dependent modification in layers II/III of the visual cortex. Using paired-pulse stimulation, we investigated in visual cortical slices how the propagation of synaptic activity to the superficial layers changes during development and how this process is affected by sensory experience. The results can be summarized as follows. (1) Layers II/III responses to repetitive stimulation of the white matter become increasingly depressed between the third and sixth week of postnatal development, a time course that parallels the end of the critical period. (2) Paired-pulse depression is reduced after dark rearing and also by blocking inhibitory synaptic transmission. (3) Paired-pulse depression and its regulation by age and sensory experience is more pronounced when stimulation is applied to the white matter than when applied to layer IV. Together, these results are consistent with the idea that the maturation of intracortical inhibition reduces the capability of the cortex to relay incoming high-frequency patterns of activity to the supragranular layers" http://www.ncbi.nlm.nih.gov/pubmed/11517267 0 629 "M. Szymanska, B. Budziszewska, L. Jaworska-Feil, A. Basta-Kaim, M. Kubera, M. Leskiewicz, M. Regulska and W. Lason" 2009 "The effect of antidepressant drugs on the HPA axis activity, glucocorticoid receptor level and FKBP51 concentration in prenatally stressed rats" Psychoneuroendocrinology 34 6 822-832 "Dysregulation of hypothalamic-pituitary-adrenal (HPA) axis activity is thought to be an important factor in pathogenesis of depression. In animals, stress or glucocorticoids given in prenatal period lead to long-lasting behavioral and neuroendocrine changes similar to those observed in depressed patients. However, molecular basis for HPA disturbances in animals exposed to prenatal stress - a model of depression - have been only partially recognized. Therefore, in the present study we investigated the effect of prenatal stress on behavioral changes, blood corticosterone level, concentrations of glucocorticoid receptor (GR) and its cochaperone, FKBP51, in the hippocampus and frontal cortex in adult rats. It has been found that prenatally stressed rats display high level of immobility in the Porsolt test and anxiety-like behavior. The HPA axis hyperactivity in theses animals was evidenced by corticosterone hypersecretion at the end of the light phase and 1h following acute stress. Western blot study revealed that GR level was significantly elevated in the hippocampus but not in the frontal cortex of prenatally stressed rats, whereas concentration of FKBP51 was decreased only in the former brain structure. Chronic treatment with imipramine, fluoxetine, mirtazapine and tianeptine have diminished both behavioral and biochemical alterations observed in this animal model of depression. These data indicate that the increase in hippocampal GR level and low concentration of FKBP51 in the frontal cortex may be responsible for enhanced glucocorticoid action in depression" http://www.ncbi.nlm.nih.gov/pubmed/19195790 0 630 "H. Y. Zhou, S. R. Chen, H. Chen and H. L. Pan" 2010 Opioid-induced long-term potentiation in the spinal cord is a presynaptic event J.Neurosci. 30 12 4460-4466 "Opioids remain the mainstay of treatment for severe pain, but the associated hyperalgesia and tolerance are significant impediments to achieving adequate pain relief with opioids. Here we show that in the spinal cord, brief application of the mu-opioid receptor agonist (D-Ala(2),N-Me-Phe(4),Gly-ol(5))-enkephalin (DAMGO) at 1 mum, but not at 1-10 nm, caused an initial decrease followed by a large and long-lasting increase in the amplitude of monosynaptic EPSCs evoked from the dorsal root in approximately 50% of lamina I and II neurons. However, postsynaptic dialysis of the G-protein inhibitor had no effect on DAMGO-induced initial inhibition and long-term potentiation (LTP) in either lamina I or II neurons. DAMGO-induced LTP was associated with an increase in the paired-pulse depression ratio. Furthermore, DAMGO application and washout induced an initial decrease followed by a persistent increase in the frequency of miniature EPSCs. Bath application, but not postsynaptic dialysis, of an NMDA receptor antagonist or a calcium chelator abolished DAMGO-induced LTP. Strikingly, ablation of TRPV1-expressing primary afferents not only eliminated DAMGO-induced LTP but also prolonged DAMGO-induced inhibition of the miniature and evoked EPSCs (i.e., long-term depression). Thus, our study strongly suggests that TRPV1-expressing primary afferents play a prominent role in opioid-induced presynaptic LTP, which challenges a previous report suggesting the postsynaptic nature of this opioid-induced LTP. This excitatory effect of opioids on primary afferents can counteract the inhibitory effect of opioids on synaptic transmission at the spinal level and is likely involved in opioid-induced hyperalgesia and tolerance" http://www.ncbi.nlm.nih.gov/pubmed/20335482 0 631 Z. Ahmed and A. Wieraszko 2009 The influence of pulsed magnetic fields (PMFs) on nonsynaptic potentials recorded from the central and peripheral nervous systems in vitro Bioelectromagnetics 30 8 621-630 "The influence of pulsed magnetic fields (PMFs) on nonsynaptic potentials recorded from the central and peripheral nervous system in vitro has been investigated. The population spikes (PSs) recorded from hippocampal slices during antidromic stimulation and compound action potentials (CAPs) recorded from the segments of the sciatic nerve were used as indicators of neuronal activity. The potentials recorded from both preparations were significantly and permanently enhanced following PMF (0.16 Hz, 15 mT) exposure. The increase in the antidromic PS occurred even in the presence of potassium channel blocker tetraethylammonium (TEA) and was accompanied by multiple spiking. Among all frequencies of PMF tested (0.5, 0.16, 0.07, 0.03, 0.0 Hz), the frequency of 0.5 Hz was the most effective in enhancement of potential amplitude. The influence of PMF on the amplitude of two CAPs evoked by the pair of electrical stimuli applied in rapid succession has also been evaluated. In control conditions the potential triggered by the second stimuli was slightly smaller expressing the phenomenon of short-term depression (STD). Although PMF exposure amplified the amplitude of both potentials, the increase in the size of the first potential was significantly greater increasing further the magnitude of STD. The blocking of potassium channels reversed STD into facilitation. One of the possible mechanisms involved in PMF action could be the modification of the axonal threshold, which was significantly reduced following exposure to PMF" http://www.ncbi.nlm.nih.gov/pubmed/19551768 0 632 "L. Cattarossi, B. Haxhiu-Poskurica, M. A. Haxhiu and W. A. Carlo" 1993 Response of upper airway and chest wall muscles to selective brain stem hypoxia in the newborn J.Appl.Physiol (1985.) 74 5 2443-2449 "In animals with intact peripheral chemosensory afferents, hypoxia differentially affects upper airway (UA) and chest wall muscles. To determine the contribution of brain stem (BS) hypoxia to the response of UA and chest wall muscles during early life, we perfused the BS through a vertebral artery intermittently with blood from an extracorporeal circuit in nine newborn piglets (age 1-5 days). BS perfusions were performed with hypoxemic blood (arterial PO2 32 +/- 6 to 38 +/- 8 Torr) with different levels of BS PCO2 (28 +/- 2, 37 +/- 4, and 56 +/- 5 Torr) while systemic normocapnic hyperoxia was maintained (arterial PCO2 36 +/- 3 to 40 +/- 6 Torr, arterial PO2 345 +/- 73 to 392 +/- 37 Torr). Electromyograms (EMGs) of alae nasi (AN), external intercostal (EI), and diaphragm (DIA) were recorded. Normocapnic hypoxia of the BS induced a sustained increase in AN EMG (P < 0.01, analysis of variance) and depression of EI and DIA EMGs without a transient increase. These contrasting responses were also observed during hypocapnic and hypercapnic hypoxia of the BS and were not affected by inputs from the peripheral chemoreceptors or rostral cerebral structures that were not exposed to hypoxia. We conclude that, despite eliciting the known central respiratory depression, BS hypoxia causes an increase in the respiratory drive to an UA airway muscle. Thus, BS hypoxia elicits a selective rather than a generalized respiratory muscle depression. The respiratory muscles with high energy expenditure (DIA and EI) are depressed while UA muscles are stimulated or disinhibited. This response is independent of the level of BS arterial PCO2" http://www.ncbi.nlm.nih.gov/pubmed/8335579 0 633 "S. L. Peters, C. Sand, H. D. Batinik, M. Pfaffendorf and P. A. van Zwieten" 2001 Reactive oxygen species potentiate the negative inotropic effect of cardiac M2-muscarinic receptor stimulation Naunyn Schmiedebergs Arch.Pharmacol. 364 2 166-171 "The aim of the present study was to investigate the influence of reactive oxygen species (ROS) on the contractile responses of rat isolated left atria to muscarinic receptor stimulation. ROS were generated by means of electrolysis (30 mA, 75 s) of the organ bath fluid. Twenty minutes after the electrolysis period, the electrically paced atria (3 Hz) were stimulated with the adenylyl cyclase activator forskolin (1 microM). Subsequently, cumulative acetylcholine concentration-response curves were constructed (0.01 nM-10 microM). In addition, phosphoinositide turnover and adenylyl cyclase activity under basal and stimulated conditions were measured. For these biochemical experiments we used the stable acetylcholine analogue carbachol. The atria exposed to reactive oxygen species were influenced more potently (pD2 control: 6.2 vs. 7.1 for electrolysis-treated atria, P<0.05) and more effectively (Emax control: 40% vs. 90% reduction of the initial amplitude, P<0.05) by acetylcholine. In contrast, ROS exposure did not alter the responses to adenosine, whose receptor is also coupled via a Gi-protein to adenylyl cyclase. The basal (40% vs. control, P<0.05) as well as the carbachol-stimulated (-85% vs. control, P<0.05) inositol-phosphate formation was reduced in atria exposed to ROS. The forskolin-stimulated adenylyl cyclase activity was identical in both groups but carbachol stimulation induced a more pronounced reduction in adenylyl cyclase activity in the electrolysis-treated atria. Accordingly we may conclude that ROS enhance the negative inotropic response of isolated rat atria to acetylcholine by both a reduction of the positive (inositide turnover) and increase of the negative (adenylyl cyclase inhibition) inotropic components of cardiac muscarinic receptor stimulation. This phenomenon is most likely M2-receptor specific, since the negative inotropic response to adenosine is unaltered by ROS exposure" http://www.ncbi.nlm.nih.gov/pubmed/11534856 0 634 "Z. Ren, H. Pribiag, S. J. Jefferson, M. Shorey, T. Fuchs, D. Stellwagen and B. Luscher" 2016 Bidirectional Homeostatic Regulation of a Depression-Related Brain State by Gamma-Aminobutyric Acidergic Deficits and Ketamine Treatment Biol.Psychiatry "BACKGROUND: Major depressive disorder is increasingly recognized to involve functional deficits in both gamma-aminobutyric acid (GABA)ergic and glutamatergic synaptic transmission. To elucidate the relationship between these phenotypes, we used GABAA receptor gamma2 subunit heterozygous (gamma2+/-) mice, which we previously characterized as a model animal with construct, face, and predictive validity for major depressive disorder. METHODS: To assess possible consequences of GABAergic deficits on glutamatergic transmission, we quantitated the cell surface expression of N-methyl-D-aspartate (NMDA)-type and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors and the function of synapses in the hippocampus and medial prefrontal cortex of gamma2+/- mice. We also analyzed the effects of an acute dose of the experimental antidepressant ketamine on all these parameters in gamma2+/- versus wild-type mice. RESULTS: Modest defects in GABAergic synaptic transmission of gamma2+/- mice resulted in a strikingly prominent homeostatic-like reduction in the cell surface expression of NMDA-type and AMPA-type glutamate receptors, along with prominent functional impairment of glutamatergic synapses in the hippocampus and medial prefrontal cortex. A single subanesthetic dose of ketamine normalized glutamate receptor expression and synaptic function of gamma2+/- mice to wild-type levels for a prolonged period, along with antidepressant-like behavioral consequences selectively in gamma2+/- mice. The GABAergic synapses of gamma2+/- mice were potentiated by ketamine in parallel but only in the medial prefrontal cortex. CONCLUSIONS: Depressive-like brain states that are caused by GABAergic deficits involve a homeostatic-like reduction of glutamatergic transmission that is reversible by an acute, subanesthetic dose of ketamine, along with regionally selective potentiation of GABAergic synapses. The data merge the GABAergic and glutamatergic deficit hypotheses of major depressive disorder" http://www.ncbi.nlm.nih.gov/pubmed/27062563 1 635 J. M. McMillan and D. J. Jollow 1992 Galactosamine hepatotoxicity: effect of galactosamine on glutathione resynthesis in rat primary hepatocyte cultures Toxicol.Appl.Pharmacol. 115 2 234-240 "The effect of galactosamine on the resynthesis of glutathione in rat primary hepatocyte cultures was investigated. Cultured rat hepatocytes were treated with galactosamine (4 mM) 1.5 hr prior to concurrent with, or 1.5 hr after cell attachment; total cellular glutathione was then measured over time. Addition of galactosamine at any of these times suppressed methionine-enhanced glutathione resynthesis in the cultures after a lag period of about 120 min. The lag period was not due to slow uptake of galactosamine by the cultured cells, since cellular UTP levels fell to less than 10% of controls within 60 min, a time frame comparable to that observed in vivo. Neither was the lag period a result of interference with cellular uptake of methionine or with conversion of methionine to cysteine, since the phenomenon was observed regardless of whether methionine or cysteine was used to promote glutathione resynthesis. Addition of uridine, which protects against galactosamine hepatotoxicity in vivo by replenishing hepatic UTP levels, did not prevent the suppression of glutathione resynthesis. The data indicate that (a) galactosamine inhibits the time-dependent resynthesis of glutathione in primary hepatocyte cultures, (b) a lag period exists for this response, and (c) this effect is not directly related to depletion of cellular UTP stores" http://www.ncbi.nlm.nih.gov/pubmed/1641857 0 636 "M. Ukai, S. Yamada and T. Kameyama" 1984 Naloxone reserves the inhibitory effects of dynorphin A on motor activity in the mouse Pharmacol.Biochem.Behav. 20 5 815-818 "Dynorphin-(1-17) (dynorphin A) significantly reduced the linear locomotion, rearing and grooming behaviors in mice using a newly devised multi-dimensional behavioral analyser. The behaviors inhibited by dynorphin A were dose-dependently antagonized by prior treatment with naloxone. The results suggest that dynorphin A-induced behavioral depression is mediated via opioid receptors in the mouse brain" http://www.ncbi.nlm.nih.gov/pubmed/6146145 1 637 D. K. Das and A. Neogi 1984 Effects of superoxide anions on the (Na + K)ATPase system in rat lung Clin.Physiol Biochem. 2 1 32-38 "Oxygen-derived free radicals have been shown to alter endothelial cell functions in lung. Enzymatically generated superoxide anions inactivated (Na + K)ATPase activity and caused lipid peroxidation in lung. Superoxide dismutase or allopurinol, but not ATP, protected this oxy radical-mediated depression of ATPase activity" http://www.ncbi.nlm.nih.gov/pubmed/6091979 0 638 "R. M. Bluthe, B. Michaud, K. W. Kelley and R. Dantzer" 1996 Vagotomy attenuates behavioural effects of interleukin-1 injected peripherally but not centrally Neuroreport 7 9 1485-1488 "Peripheral and central injections of recombinant rat interleukin-1 beta (IL-1 beta) have been shown to decrease social exploration in rats. To test the involvement of vagal afferents in the communication between the immune system and the brain, sham-operated and vagotomized rats were injected peripherally or centrally with physiological saline or IL-1 beta 4 weeks after surgery. Vagotomy attenuated the depression in social exploration induced by i.p. administration of IL-1 beta (15 micrograms) but did not alter the behaviour-depressing effects of an intracerebroventricular (i.c.v.) injection of IL-1 beta (45 ng). These results confirm the role of vagal afferent nerves in the transmission of an immune message from the periphery to the brain, and show that vagotomy does not impair the direct sensitivity of the brain itself to immune signals" http://www.ncbi.nlm.nih.gov/pubmed/8856703 0 639 K. Shimamoto and N. Toda 1968 Modifications by propranolol of the response of isolated rabbit atria to endogenous and exogenous noradrenaline Br.J.Pharmacol.Chemother. 32 3 539-545 http://www.ncbi.nlm.nih.gov/pubmed/5641948 0 640 "L. Chen, T. Z. Han and M. L. Jiang" 2008 Different glutamate receptor mechanisms in long-term depression induced by different stimulus patterns in the CA1 area of adult rat hippocampus Sheng Li Xue.Bao. 60 2 270-274 "Previous reports suggested that a novel stimulus pattern of multi-train stimulus at low-frequency (2-Hz or 5-Hz) could induce stable long-term depression (LTD) in the CA1 area of adult rat hippocampus. In the present study, in order to determine the mechanism in LTD induced by the two novel tetanus patterns, changes in the population spikes (PS) in the hippocampal CA1 area of adult rats following the multi-train stimulus in the presence of AP5 [antagonist of N-methyl-D-aspartate receptors (NMDARs)] or MCPG [antagonist of type I/II metabotropic glutamate receptors (mGluRs)] were recorded. The results showed that both AP5 and MCPG inhibited the LTD induced by 2-Hz multi-train stimulus. The mean amplitude of population spikes (PSA) normalized to the baseline was (96.0+/-3.5)% after applying AP5 (n=10) and (95.7+/-4.1)% after applying MCPG (n=8), respectively, measured at 20 min post-tetanus. While 5-Hz multi-train tetanus failed to induce LTD in the presence of MCPG. The mean PSA was (73.6+/-4.4)% (n=10) and (98.2+/-8.9)% (n=8) in the presence of AP5 and MCPG, respectively, measured at 35 min post-tetanus. So it is suggested that LTD induced by 2-Hz multi-train tetanus involves co-activation of NMDARs and mGluRs, while LTD induced by 5-Hz multi-train tetanus is only related to activation of mGluRs" http://www.ncbi.nlm.nih.gov/pubmed/18425317 0 641 "J. R. Sabater, R. Otero, W. M. Abraham, A. Wanner and T. G. O'Riordan" 1996 Endothelin-1 depresses tracheal mucus velocity in ovine airways via ET-A receptors Am.J.Respir.Crit Care Med. 154 2 Pt 1 341-345 "Endothelin-1 (ET-1) is a potent constrictor of bronchial smooth muscle, but there is limited information on its actions on the airway mucociliary clearance in vivo. The purpose of this study was to determine (1) the effect of aerosolized ET-1 on tracheal mucus velocity (TMV), a marker of mucociliary clearance, in sheep and (2) if the ET-1-induced effects were mediated by ET-A or ET-B receptors. To measure TMV, radiopaque teflon particles were insufflated into six intubated, spontaneously breathing, adult sheep, and the velocity at which these particles traveled up the trachea was measured using a previously reported roentgenographic technique. After baseline TMV measurements, 50 breaths of either ET-1 (10(-7) M) or vehicle (phosphate-buffered saline) were aerosolized into the airways. TMV measurements were then obtained over a 2-h period. After exposure to ET-1, mean TMV decreased significantly as compared with vehicle, the effects being most marked within 30 min after administration (54%, p < 0.05). On subsequent days, animals were pretreated with an aerosolized ET-A receptor antagonist (BQ-123) or an ET-B receptor antagonist (BQ-788) before exposure to ET-1. When ET-1 was given after BQ-123, no significant drop in TMV was noted. In contrast, pretreatment with BQ-788 exhibited no protective effect on the decrease in TMV. The ET-1 effects were not influenced by pretreatment with either the cyclo-oxygenase inhibitor indomethacin or the leukotriene receptor antagonist MK-571, indicating that ET-1-induced depression in TMV does not involve the activation of prostanoids or peptide leukotrienes. Thus, exogenous ET-1 reduces TMV, an in vivo effect that is mediated through stimulation of ET-A receptors" http://www.ncbi.nlm.nih.gov/pubmed/8756804 0 642 E. L. Tolman and R. Partridge 1975 Multiple sites of interaction between prostaglandins and non-steroidal anti-inflammatory agents Prostaglandins 9 3 349-359 "Several non-steroidal anti-inflammatory agents (NSAIA) are shown to inhibit the net production of prostaglandin (PG)- like activity from arachidonic acid by a cell-free preparation of guinea-pig lung. Moreover, these agents also antagonize PGE-1-induced contractions of the isolated gerbil colon. The anti-spasmogenic effects are reversible and specific. At high concentrations, indomethacin and mefenamic acid interfere with the binding of PGE-1 to a broken cell preparation of rat epididymal adipocytes. Taken together the data indicate that NSAIA interact with prostaglandins at multiple sites and are consistent with the suggestions reported previously that NSAIA may have multiple in vivo actions" http://www.ncbi.nlm.nih.gov/pubmed/1138291 0 643 "C. H. Bourke, Z. N. Stowe, G. N. Neigh, D. E. Olson and M. J. Owens" 2013 "Prenatal exposure to escitalopram and/or stress in rats produces limited effects on endocrine, behavioral, or gene expression measures in adult male rats" Neurotoxicol.Teratol. 39 100-109 "Stress and/or antidepressants during pregnancy have been implicated in a wide range of long-term effects in the offspring. We investigated the long-term effects of prenatal stress and/or clinically relevant antidepressant exposure on male adult offspring in a model of the pharmacotherapy of maternal depression. Female Sprague-Dawley rats were implanted with osmotic minipumps that delivered clinically relevant exposure to the antidepressant escitalopram throughout gestation. Subsequently, pregnant females were exposed on gestational days 10-20 to a chronic unpredictable mild stress paradigm. The male offspring were analyzed in adulthood. Baseline physiological measurements were largely unaltered by prenatal manipulations. Behavioral characterization of the male offspring, with or without pre-exposure to an acute stressor, did not reveal any group differences. Prenatal stress exposure resulted in a faster return towards baseline following the peak response to an acute restraint stressor, but not an airpuff startle stressor, in adulthood. Microarray analysis of the hippocampus and hypothalamus comparing all treatment groups revealed no significantly-altered transcripts. Real time PCR of the hippocampus confirmed that several transcripts in the CRFergic, serotonergic, and neural plasticity pathways were unaffected by prenatal exposures. This stress model of maternal depression and its treatment indicate that escitalopram use and/or stress during pregnancy produced no alterations in our measures of male adult behavior or the transcriptome, however prenatal stress exposure resulted in some evidence for increased glucocorticoid negative feedback following an acute restraint stress. Study design should be carefully considered before implications for human health are ascribed to prenatal exposure to stress or antidepressant medication" http://www.ncbi.nlm.nih.gov/pubmed/23906943 1 644 "S. J. Yang, H. Y. Yu, D. Y. Kang, Z. Q. Ma, R. Qu, Q. Fu and S. P. Ma" 2014 Antidepressant-like effects of salidroside on olfactory bulbectomy-induced pro-inflammatory cytokine production and hyperactivity of HPA axis in rats Pharmacol.Biochem.Behav. 124 451-457 "Salidroside (SA) is the primary bioactive marker compound in the standardized extracts from Rhodiola rosea. Although it has potential antidepressant activity in a rat behavioral despair model, the mechanisms of antidepressant effect for SA remain unclear. The objective of this study was to evaluate the antidepressant effects of SA and to discuss the potential mechanisms in olfactory bulbectomized (OBX) rats. SA of 20, 40 mg/kg (p.o.) for 2 weeks notably alleviated OBX-induced hyperactivity in open field test, decreased immobility time in TST and FST. Chronic treatment with SA could remarkably reduce TNF-alpha and IL-1beta levels in hippocampus. Western blot showed that SA could markedly increase glucocorticoid receptor (GR) and brain-derived neurotrophic factor (BDNF) expression in the hippocampus. Besides, SA could also attenuate corticotropin-releasing hormone (CRH) expression in hypothalamus, as well as reducing significantly the levels of serum corticosterone. In conclusion, this study demonstrated that OBX rats treated with SA could significantly improve the depressive-like behaviors. The antidepressant mechanisms of SA might be associated with its anti-inflammatory effects and the regulation of HPA axis activity. Reversal of abnormalities of GR may be partly responsible for those effects. These findings suggested that SA might become a beneficial agent to prevent and treat the depression" http://www.ncbi.nlm.nih.gov/pubmed/25101546 1 645 "J. L. Booker, Jr., H. H. Erickson and E. L. Fitzpatrick" 1982 Cardiodynamics in the rhesus macaque during dissociative anesthesia Am.J.Vet.Res. 43 4 671-675 "Effects of dissociative anesthesia on cardiovascular dynamics and respiration were investigated in rhesus macaques to determine its use in nonhuman primates for restraint and minor surgical procedures. Respiration was spontaneous, and premedicants or anesthetic adjuvants were not used. Two doses of the anesthetic were administered (IM): 1.5 and 3.0 mg/kg. Depressant effects were observed in all variables initially; some cardiovascular variables eventually exceeded preinjection values after the higher (3.0 mg/kg) dose level. At a dose of 1.5 mg/kg, significant depression in myocardial contractility persisted for 20 minutes, and at 3.0 mg/kg for 50 minutes. Stroke volume was minimally affected initially, although significant increases occurred at 40 and 50 minutes after the 3.0 mg/kg injections. Heart rate was depressed by 5% and 7% in the animals given the small and large doses. Values were within control levels by 90 minutes after the anesthetic was injected, except respiratory rate and body temperature. We conclude that the dissociative anesthetic used produces neither marked nor prolonged cardiovascular effects. Since cardiovascular effects are absent by 90 minutes after the anesthetic was injected, dissociative anesthesia is a desirable technique for minor surgical procedures and restraint, especially before physiologic studies" http://www.ncbi.nlm.nih.gov/pubmed/7073088 0 646 "A. Hennig, G. Hartmann, K. Gruhn and M. Anke" 1968 [Contraceptive action of cadmium in laying hens] Naturwissenschaften 55 11 551 http://www.ncbi.nlm.nih.gov/pubmed/5704510 0 647 "A. J. Nazarali, G. B. Baker, R. T. Coutts, J. M. Yeung and T. S. Rao" 1987 Rapid analysis of beta-phenylethylamine in tissues and body fluids utilizing pentafluorobenzoylation followed by electron-capture gas chromatography Prog.Neuropsychopharmacol.Biol.Psychiatry 11 02-Mar 251-258 "A rapid, sensitive gas chromatographic procedure for analysis of beta-phenylethylamine is reported. The procedure involves extraction with a liquid ion-pairing compound, back-extraction with HCl, basification and reaction with pentafluorobenzoyl chloride under aqueous conditions. The pentafluorobenzoyl derivative of beta-phenylethylamine is then separated and analyzed on a gas chromatograph equipped with a capillary column and an electron-capture detector. The procedure produces a derivative which has good chromatographic properties and a high degree of stability. The method has been applied to analysis of beta-phenylethylamine in a variety of tissues and body fluids" http://www.ncbi.nlm.nih.gov/pubmed/3628832 0 648 J. W. Phillis and R. E. Stair 1987 Ro 15-1788 both antagonizes and potentiates adenosine-evoked depression of cerebral cortical neurons Eur.J.Pharmacol. 136 2 151-156 "The effects of Ro 15-1788, a benzodiazepine antagonist with some agonist properties, were studied on adenosine and adenosine 5'-N-ethyl-carboxamide (NECA)-evoked depressions of rat cerebral cortical neuronal activity. Iontophoretically applied Ro 15-1788 had both antagonistic and potentiative interactions with adenosine. Reductions in the magnitude of adenosine-evoked depressions of firing were evident during the period of Ro 15-1788 application, with a long-lasting potentiative effect becoming apparent upon termination of the Ro 15-1788 application. Depressions of cell firing evoked by NECA, an uptake-resistant analog of adenosine, were antagonized by Ro 15-1788, with no subsequent potentiation. Larger applications of Ro 15-1788 had a depressant action on neuronal firing, which was antagonized by caffeine (20 mg/kg), an adenosine receptor blocker. These results indicate that Ro 15-1788 may be an antagonist at the adenosine receptor as well as a potentiator of the adenosine response. The prolongation of the adenosine depression is likely to be the result of a persistent inhibition of adenosine uptake by Ro 15-1788. These diverse effects on the adenosine response may account for some of the complex behavioral actions of Ro 15-1788" http://www.ncbi.nlm.nih.gov/pubmed/3109926 0 649 "P. Pedas, S. Husted, K. Skytte and J. K. Schjoerring" 2011 Elevated phosphorus impedes manganese acquisition by barley plants Front Plant Sci. 2 37 "The occurrence of manganese (Mn) deficiency in cereal crops has increased in recent years. This coincides with increasing phosphorus (P) status of many soils due to application of high levels of animal manure and P-fertilizers. In order to test the hypothesis that elevated P my lead to Mn deficiency we have here conducted a series of hydroponics and soil experiments examining how the P supply affects the Mn nutrition of barley. Evidence for a direct negative interaction between P and Mn during root uptake was obtained by on-line inductively coupled plasma mass spectrometry (ICP-MS). Addition of a pulse of KH(2)PO(4) rapidly and significantly reduced root Mn uptake, while a similar concentration of KCl had no effect. Addition of a P pulse to the same nutrient solution without plants did not affect the concentration of Mn, revealing that no precipitation of Mn-P species was occurring. Barley plants growing at a high P supply in hydroponics with continuous replenishment of Mn(2+) had up to 50% lower Mn concentration in the youngest leaves than P limited plants. This P-induced depression of foliar Mn accelerated the development of Mn deficiency as evidenced by a marked change in the fluorescence induction kinetics of chlorophyll a. Also plants growing in soil exhibited lower leaf Mn concentrations in response to elevated P. In contrast, leaf concentrations of Fe, Cu, and N increased with the P supply, supporting that the negative effect of P on Mn acquisition was specific rather than due to a general dilution effect. It is concluded that elevated P supply directly interferes with Mn uptake in barley roots and that this negative interaction can induce Mn deficiency in the shoot. This finding has major implications in commercial plant production where many soils have high P levels" http://www.ncbi.nlm.nih.gov/pubmed/22639592 0 650 H. Ellegren 1999 Inbreeding and relatedness in Scandinavian grey wolves Canis lupus Hereditas 130 3 239-244 "Management of small and threatened populations may require detailed knowledge about the genetic status of individuals and the genetic relatedness between individuals. I show here that individual heterozygosity at a set of 29 microsatellite loci correlates closely to the degree of inbreeding in a captive grey wolf population. Microsatellite allele sharing similarly correlates closely to known relatedness between pairs of individuals. Genotyping the same markers in a small (60-70 individuals) natural population of grey wolves in Sweden, low individual heterozygosities and high values of allele sharing between some animals were found. Since inbreeding depression has been documented in a captive grey wolf population of Scandinavian origin, the results point out an additional risk for the small Swedish wild population" http://www.ncbi.nlm.nih.gov/pubmed/10509138 0 651 "M. M. Mota, S. Takemoto, Y. Takeuchi, N. Hara and K. Futai" 2006 "Comparative Studies between Portuguese and Japanese Isolates of the Pinewood Nematode, Bursaphelenchus xylophilus" J.Nematol. 38 4 429-433 "Comparative studies between Portuguese (T and HF) and Japanese (S10, T4, C14-5 and OKD-1) isolates of the pinewood nematode Bursaphelenchus xylophilus have been made in order to provide information to better understand the possible origin of the Portuguese isolates, recently introduced in the European Union. The main comparative aspects investigated were pathogenicity (seedling mortality ratio), sexual compatibility, and DNA sequences of the rDNA region. Four-year-old Japanese black pine (Pinus thunbergii) seedlings were used as host plants for pathogenicity tests. The Portuguese isolates, and in particular isolate ""T,"" propagated in higher numbers than the Japanese isolates within pine seedlings. All combinations of crossings produced viable progeny, with higher numbers obtained when crossings were made between Japanese and Portuguese isolates, a possible situation of heterosis and/or inbreeding depression. Reciprocal crossings yielded different values, which may reflect a sex effect (maternal inheritance, mtDNA). Regarding DNA sequencing, both Portuguese isolates displayed nearly identical ITS 1, ITS2, and 5.8S rDNA base sequences as the Japanese isolates. Although biologically very similar, and possibly reflecting a common origin, the Portuguese isolates may present a serious threat to Japanese black pine, due to their higher virulence" http://www.ncbi.nlm.nih.gov/pubmed/19259459 0 652 K. E. Makhkamov 2001 [Cytochrome P-450 content and activity of NADPH-cytochrome P-450 c-reductase in experimental subarachnoid hemorrhage] Lik.Sprava. 3 114-115 "The condition was studied of the brain monooxigenase system (MOS) in experimental subarachnoidal hemorrhage in rats. The results show that the above hemorrhage leads to a significant depression of activity of brain MOS enzymes (cytochrome P-450, NADPN-cytochrome C-reductase). Depression of activity of the enzymic system is manifest from day 1 and has a tendency toward reduction but at day 14 and 21 the indices are still below the control values. Under the exposure to phenobarbital the reduction of activity of the enzyme system in subarachnoidal hemorrhage gets accelerated, with normalization of the indices occurring by day 7 after the hemorrhage" http://www.ncbi.nlm.nih.gov/pubmed/11559996 0 653 G. Conti and P. Portincasa 1987 Inhibitory effect of diamidinophenylindole on the replication of influenza virus in permissive cellular hosts. Brief report Arch.Virol. 94 01-Feb 149-157 "The production of avian and human strains of influenza virus was altered to various extents by treatment of various host cells with 40 micrograms/ml of diamidinophenylindole (DAPI). In infected LLC-MK 2 cells only an abortive replication cycle occurred; in other cell lines there was partial inhibition or no inhibition of replication. Virus polypeptide synthesis in LLC-MK 2 cells was confined to the early pattern of viral multiplication; only the P proteins, the nucleoprotein NP, and the non-structural protein NS 1 were synthesized. The stage of replication mainly affected by DAPI was between the fourth and the sixth hour after infection. The mode of action of the drug and its modulating effect on virus production is discussed" http://www.ncbi.nlm.nih.gov/pubmed/3579606 0 654 O. A. Karasik and P. G. Nazarov 1975 [Natural immune response and immunological memory in the effects of a 2d unrelated antigen] Zh.Mikrobiol.Epidemiol.Immunobiol. 12 106-111 "In combined administration of two nonaffiliated erythrocytic antigens there can be seen both depression and stimulation of the immunological response to the participating antigens. The end result of the interaction depended on the ""power"", the dose and the order of administration of the antigens. Distribution of the antigen in the animals whose immune response was depressed as a result of preliminary administration of the nonaffiliated antigen remained unchanged. The factor determining the effect on the immunological response to the other antigen did not serve as an antibody" http://www.ncbi.nlm.nih.gov/pubmed/1082695 0 655 "R. Gaggi, E. Beltrandi, R. Dall'Olio and S. Ferri" 1985 Relationships between hypocalcaemic and anorectic effect of calcitonin in the rat Pharmacol.Res.Commun. 17 3 209-215 "Salmon calcitonin (sCT, 2 and 20 U/kg), porcine calcitonin (pCT, 20 and 40 U/kg) and human calcitonin (hCT, 20 and 40 U/kg) were injected subcutaneously to rats trained to eat their food during two hours each day. Food intake and serum Ca++ concentrations were determined at the end of 2h-feeding period. A long lasting anorectic effect was observed for 20 U/kg of sCT with a parallelism between hypocalcaemia and anorexia in the first 8 hours after treatment; on the contrary, rats continued to eat less than controls in the following hours when their serum Ca++ concentrations had risen to normal or even higher levels. As regards pCT and hCT, it was shown that these peptides reduced significantly meal size only for 1-2 hours when serum Ca++ levels were at their lowest levels for these peptides" http://www.ncbi.nlm.nih.gov/pubmed/4011645 0 656 "D. F. Devereux, C. A. Michas and S. Rice" 1977 Heparin pretreatment suppresses norepinephrine concentrations in dogs in endotoxic shock Clin.Chem. 23 7 1346-1347 "Mongrel dogs were treated intravenously with either 1000 units of beef-lung heparin per kilogram of body weight or with isotonic saline, before intravenous administration of E. coli endotoxin. We found significant differences in circulating norepinephrine concentrations between a heparin-pretreatment group (1.89 +/- 0.39 microgram/liter) and the control group (9.83 +/- 4.64 microgram/liter), but none with respect to epinephrine. Systolic blood pressures at 360 min were also significantly (P less than 0.05) different, 148 +/- 6 mmHg as compared with 118 +/- 13.4 mmHg. Evidently heparin pretreatment can decrease circulating norepinephrine concentrations in the endotoxic state and changes in circulating catecholamine concentrations can affect physiological variables" http://www.ncbi.nlm.nih.gov/pubmed/872387 0 657 T. J. Tierney and M. W. Simpson-Morgan 1997 The proliferative responses of lymphocytes from foetal calves and adult cattle Vet.Immunol.Immunopathol. 59 01-Feb 49-64 "This paper describes the proliferative responses of prescapular lymph lymphocytes and peripheral blood lymphocytes of foetal calves compared with cells of similar origin from adult cattle. Lymph lymphocytes were collected continuously by means of cannulation of efferent lymphatic ducts of the prescapular lymph node of foetal calves and adult cattle. Peripheral blood lymphocytes were collected from the foetus by means of cannulation of superficial veins of the foetus or of the umbilical vessels and from the jugular vein of adults. Foetal lymphocytes in one-way mixed lymphocyte culture stimulated and responded as well as adult lymphocytes. Foetal cells stimulated and responded more to cells from unrelated animals than to cells from their dam. Lymph lymphocytes from foetal calves between 188 and 253 days of gestation proliferated as well as adult lymphocytes and at a high level after stimulation with concanavalin A, phytohaemagglutinin and pokeweed mitogen. Response to stimulation with lipopolysaccharide, soybean agglutinin and wheat-germ agglutinin was variable but generally low and within the same range recorded by adult cells. Proliferation by foetal and adult whole-blood cultures was on occasions as high as that recorded by separated lymphocytes, even though fewer lymphocytes were initially present in the whole-blood cultures. Foetal lymph lymphocytes exhibited lower proliferative responses in autologous lymph plasma than in foetal calf serum or pooled foetal lymph plasma. There was no consistent depression of proliferation by culture medium supplements from pregnant animals. Rabbit serum consistently abrogated responses. Fetuin at final concentrations of greater than 2.5 mg/ml significantly depressed proliferation in foetal and adult lymphocytes from efferent lymph and peripheral blood" http://www.ncbi.nlm.nih.gov/pubmed/9437825 0 658 "C. Rivadulla, K. L. Grieve, R. Rodriguez, S. Martinez-Conde, C. Acuna and J. Cuderio" 1997 An unusual effect of application of the amino acid L-arginine on cat visual cortical cells Neuroreport 8 4 863-866 "Iontophoretic application of L-arginine (L-Arg) resulted in a profound decrease in visually elicited and spontaneous activity in 22 of 77 (29%) cells in area 17 of the anaesthetized/paralysed cat. Duration was long, and cells did not recover pre-application activity levels, indicating permanent decline. This effect was obtained without change in the extracellularly recorded wave-form, demonstrating that this did not result from depolarization block. In the remaining 55 cells, application of L-Arg alone, at levels capable of eliciting inhibition as described above, was without effect. In 29 cells, L-Arg application was able to reverse the effect of inhibition of nitric oxide (NO) production. Populations of cells showing the depressive effect described above and those affected by NO modulation levels were mutually exclusive" http://www.ncbi.nlm.nih.gov/pubmed/9141053 0 659 "H. Nakao, K. Nakao, M. Kano and A. Aiba" 2007 Metabotropic glutamate receptor subtype-1 is essential for motor coordination in the adult cerebellum Neurosci.Res. 57 4 538-543 "We previously demonstrated that metabotropic glutamate receptor-subtype 1 knockout [mGluR1 (-/-)] mice showed ataxic gait, deficient long-term depression and impaired synapse elimination and these phenotypes were rescued by introduction of an mGluR1 transgene with Purkinje cell-specific promoter (mGluR1-rescue mice). However, roles of mGluR1 in the adult brain remain elusive, mainly due to lack of conventional and reproducible method to block mGluR1 expression at a certain developmental stage. Here, we established a versatile mouse line, mGluR1 conditional knockout (cKO) mice using the tetracycline-controlled gene expression system to understand the roles of mGluR1 in the adult brain. The mGluR1 cKO mice express mGluR1 only in Purkinje cells and show normal motor coordination. Blockade of expression of mGluR1 in the adult mGluR1 cKO mice led to impaired motor coordination, suggesting that mGluR1 is essential for cerebellar function in mice not only during postnatal development but also in adulthood" http://www.ncbi.nlm.nih.gov/pubmed/17270300 0 660 "M. Lagus, N. Gass, J. Saharinen, J. Saarela, T. Porkka-Heiskanen and T. Paunio" 2010 Gene expression patterns in a rodent model for depression Eur.J.Neurosci. 31 8 1465-1473 "Disturbances in sleep are encountered in the majority of patients with depression. To elucidate the possible molecular mechanisms behind this relationship we examined gene expression changes in a rodent model for depression and disturbed sleep. Animals were treated with daily injections of clomipramine in their early infancy, after which gene expression in basal forebrain was examined using Affymetrix Rat 230.2 chips. We tested the levels of both single transcripts and involved pathways, and searched for common nominators (i.e. transcription factors) that could explain these changes. We identified 72 differentially expressed gene transcripts, many of which are involved in epigenetic regulation, such as DNMT2. Analysis of functional pathways revealed statistically significant changes of the biological process of synaptic transmission, the cellular compartment of the synapse and the molecular function of GABA signalling, showing that transcripts with altered expression are functionally related. Finally, promoter analysis of the differentially expressed genes showed a clear enrichment of binding sites for the transcription factor CREB1, a molecule also involved in epigenetic regulation (cAMP response element-binding protein induces histone modifications). These results indicate that CREB1 may constitute one of the major links between disturbed sleep and mood. The results also highlight the molecular mechanisms in the murine clomipramine model, previously shown to be a valid model for depression" http://www.ncbi.nlm.nih.gov/pubmed/20384783 1 661 "V. V. Papilian, E. Carpen, D. Muresan, A. Olinic, M. E. Gocan and M. Radu-Toader" 1979 Spleen and lymph node changes in rats irradiated with X-rays and treated with testosterone Morphol.Embryol.(Bucur.) 25 2 163-166 "The authors have studied the effect of testosterone administration in male adult Wistar rats irradiated with a single total dose of 800 r X-rays. The results obtained show that testosterone exerts a double radioprotective action. This hormone prevents both the occurrence of the senile type spleen and lymph node changes and the depression of the colloidopexic capacity of the hepatosplenic macrophages. At the same time, these results suggest that testosterone induces hyperplasia of the lymphocytic elements, particularly of T lymphocytes" http://www.ncbi.nlm.nih.gov/pubmed/158136 0 662 "H. Wang, L. Song, F. Laird, P. C. Wong and H. K. Lee" 2008 BACE1 knock-outs display deficits in activity-dependent potentiation of synaptic transmission at mossy fiber to CA3 synapses in the hippocampus J.Neurosci. 28 35 8677-8681 "beta-Amyloid precursor protein cleavage enzyme 1 (BACE1) has been identified as a major neuronal beta-secretase critical for the formation of beta-amyloid (Abeta) peptide, which is thought responsible for the pathology of Alzheimer's disease (AD). Therefore, BACE1 is one of the key therapeutic targets that can prevent the progression of AD. Previous studies showed that knocking out the BACE1 gene prevents Abeta formation, but results in behavioral deficits and specific synaptic dysfunctions at Schaffer collateral to CA1 synapses. However, BACE1 protein is most highly expressed at the mossy fiber projections in CA3. Here, we report that BACE1 knock-out mice display reduced presynaptic function, as measured by an increase in paired-pulse facilitation ratio. More dramatically, mossy fiber long-term potentiation (LTP), which is normally expressed via an increase in presynaptic release, was eliminated in the knock-outs. Although long-term depression was slightly larger in the BACE1 knock-outs, it could not be reversed. The specific deficit in mossy fiber LTP was upstream of cAMP signaling and could be ""rescued"" by transiently elevating extracellular Ca2+ concentration. These results suggest that BACE1 may play a critical role in regulating presynaptic function, especially activity-dependent strengthening of presynaptic release, at mossy fiber synapses" http://www.ncbi.nlm.nih.gov/pubmed/18753368 0 663 "A. Viggiano, R. Seru, S. Damiano, L. B. De, M. Santillo and P. Mondola" 2012 Inhibition of long-term potentiation by CuZn superoxide dismutase injection in rat dentate gyrus: involvement of muscarinic M1 receptor J.Cell Physiol 227 8 3111-3115 "Long-term potentiation (LTP) and long-term depression represent important processes that modulate synaptic transmission that carries out a key role in neural mechanisms of memory. Many studies give strong evidences on a role of the reactive oxygen species in the induction of LTP in CA1 region of hippocampal slices that was inhibited by adding the scavenger enzyme superoxide dismutase (SOD1). Previous data showed that SOD1 is secreted by many cellular lines, including neuroblastoma SK-N-BE cells through microvesicles by an ATP-dependent mechanism; moreover, it has been shown that SOD1 interacts with human neuroblastoma cell membranes increasing intracellular calcium levels via a phospholipase C-protein kinase C pathway activation. The aim of this study was to investigate the effect of intracerebral injection of SOD1 or the inactive form of enzyme (ApoSOD) on the modulation of synaptic transmission in dentate gyrus of the hippocampus in urethane anesthetized rats. The results of the present research showed that intracerebral injection of SOD1 and ApoSOD in the dentate gyrus of the rat hippocampal formation inhibits LTP induced by high-frequency stimulation of the perforant path. This result cannot be only explained by the dismutation of oxygen radical induced by SOD1 since also ApoSOD, that lacks the enzymatic activity, carries out the same inhibitory effect on LTP induction" http://www.ncbi.nlm.nih.gov/pubmed/22015651 0 664 "S. B. Kombian, K. V. Ananthalakshmi, S. S. Parvathy and W. C. Matowe" 2005 Cholecystokinin inhibits evoked inhibitory postsynaptic currents in the rat nucleus accumbens indirectly through gamma-aminobutyric acid and gamma-aminobutyric acid type B receptors J.Neurosci.Res. 79 3 412-420 "We recently reported that cholecystokinin (CCK) excited nucleus accumbens (NAc) cells and depressed excitatory synaptic transmission indirectly through gamma-aminobutyric acid (GABA), acting on presynaptic GABAB receptors (Kombian et al. [2004] J. Physiol. 555:71-84). The present study tested the hypothesis that CCK modulates inhibitory synaptic transmission in the NAc. Using in vitro forebrain slices containing the NAc and whole-cell patch recording, we examined the effects of CCK on evoked inhibitory postsynaptic currents (IPSCs) recorded at a holding potential of -80 mV throughout CCK-8S caused a reversible inward current accompanied by a concentration-dependent decrease in evoked IPSC amplitude. Maximum IPSC depression was approximately 25% at 10 microM, with an estimated EC50 of 0.1 microM. At 1 microM, CCK-8S induced an inward current of 28.3 +/- 4.8 pA (n=6) accompanied by an IPSC depression of -18.8% +/- 1.6% (n=6). This CCK-induced IPSC depression was blocked by pretreatment with proglumide (100 microM; -3.7% +/- 6.9%; n=4) and by LY225910 (100 nM), a selective CCKB receptor antagonist (4.4% +/- 2.6%; n=4). It was not blocked by SCH23390 (10 microM; -23.5% +/- 1.3%; P < 0.05; n=7) or sulpiride (10 microM; -21.8% +/- 5.1%; P <0.05; n=4), dopamine receptor antagonists. By contrast, it was blocked by CGP55845 (1 microM; -0.4% +/- 3.4%; n=5) a potent GABAB receptor antagonist, and by forskolin (50 microM; 9.9% +/- 5.2%; n=4), an adenylyl cyclase activator, and H-89 (1 microM; 6.9% +/- 3.9%; n=4), a protein kinase A (PKA) inhibitor. These results indicate that CCK acts on CCKB receptors to increase extracellular levels of GABA, which then acts on GABAB receptors to decrease IPSC amplitude" http://www.ncbi.nlm.nih.gov/pubmed/15605383 0 665 R. S. Mehta and P. C. Wainwright 2007 Biting releases constraints on moray eel feeding kinematics J.Exp.Biol. 210 Pt 3 495-504 "We present an analysis of prey capture functional morphology in eels by comparing two species of moray eels, Muraena retifera and Echidna nebulosa (Family Muraenidae), to the American eel Anguilla rostrata (Family Anguillidae). The skulls of both moray species exhibited extreme reductions of several prominent components of the suction-feeding mechanism, including the hyoid bar, the sternohyoideus muscle and the pectoral girdle. Associated with these anatomical modifications, morays showed no evidence of using suction during prey capture. From 59 video sequences of morays feeding on pieces of cut squid we saw no hyoid depression and no movement of prey toward the mouth aperture during the strike, a widely used indicator of suction-induced water flow. This was in contrast to A. rostrata, which exhibited a robust hyoid, sternohyoideus muscle and pectoral girdle, and used suction to draw prey into its mouth. Average prey capture time in morays, about 500 ms, was roughly 10 times longer than in A. rostrata, and morays frequently reversed the direction of jaw and head rotation in the midst of the strike. We tested whether the absence of suction feeding reduces temporal constraints on feeding kinematics, permitting greater variance in traits that characterize timing and the extent of motion in the neurocranium, by comparing moray eel species with A. rostrata, two Centrarchids and a cichlid. Kinematic variance was roughly 5 times higher in morays than the suction-feeding species. Prey capture by suction demands a rapid, highly coordinated series of cranial movements and the loss of this mechanism appears to have permitted slower, more variable prey capture kinematics in morays. The alternative prey capture strategy in morays, biting, may be tied to their success as predators in the confined spaces of reef crevices where they hunt for cephalopods, crustaceans and fish" http://www.ncbi.nlm.nih.gov/pubmed/17234619 0 666 "J. C. LeDouarec, J. Duhault and M. Laubie" 1969 "[Pharmacological study of phenethyl-8-oxa-1-diaza-3,8-spiro(4,5)decanone-2 hydrochloride or fenspiride (JP 428)]" Arzneimittelforschung. 19 8 1263-1271 http://www.ncbi.nlm.nih.gov/pubmed/4390182 0 667 "V. I. Nazarenko, T. E. Pastukhova and I. Belik" 1983 "[Mechanism of ethonium effect on membrane preparations of brain Na+, K+-ATPase]" Ukr.Biokhim.Zh.(1978.) 55 4 398-402 "The effect of ethonium, a local anesthetic, on the membrane preparations of brain N+, K+-ATPase was studied by fluorescent, radioisotopic, electron-microscopic and electrophysiological methods. Ethonium is established to affect the formation of an intermediate phosphorylated product and has no pronounced destructive effect on the membrane. It changes the fluorescence intensity of 2-toluidinonaphthalen-6-sulphonate (TNS), astrafloxin (AF) and fluorene probes in a suspension of the Na+, K+-ATPase preparations, which evidences for ethonium-induced changes in the structure of membrane fragments" http://www.ncbi.nlm.nih.gov/pubmed/6312652 0 668 "G. O. Barbezat, M. W. Waterworth, M. Daniel, S. Bank and J. Terblanche" 1974 Effect of burimamide on histamine- and pentagastrin-stimulated acid and pepsin secretion in the pig S.Afr.Med.J. 48 47 1985-1990 http://www.ncbi.nlm.nih.gov/pubmed/4153649 0 669 "F. Duval, M. C. Mokrani, J. Monreal, T. Weiss, S. Fattah, B. Hamel and J. P. Macher" 2002 Interaction between the serotonergic system and HPA and HPT axes in patients with major depression: implications for pathogenesis of suicidal behavior Dialogues.Clin.Neurosci. 4 4 417 "Disturbances in the serotonin (5-hydroxytryptamine, 5-HT) system constitute the neurobiological abnormality most consistently associated with suicide. This abnormality could be a marker of vulnerability predisposing individuals to auto-aggressive and impulsive behavior. However, other abnormalities, such as hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, have also been described in suicide victims. While inhibitory effects of adrenocorticosteroids on 5-HT(1A) receptor function have been shown in animals, HPA axis hyperactivity does not seem to be responsible for the reduced 5-HT activity found in depressed patients with a history of suicidal behavior. On the other hand, hypothalamic-pituitarythyroid (HPT) axis dysfunction, frequently observed in depression, may represent a compensatory response to reduced central 5-HT neurotransmission. Moreover, in depressed patients with a history of suicidal behavior, the absence of a functional link between HPT and dopamine activity at the hypothalamic level may be implicated in the pathophysiology of suicidal behavior. Future research is needed to determine why compensatory mechanisms are not efficient in patients with suicidal behavior" http://www.ncbi.nlm.nih.gov/pubmed/22033833 0 670 "C. Wakabayashi, T. Numakawa, H. Odaka, Y. Ooshima, Y. Kiyama, T. Manabe, H. Kunugi and Y. Iwakura" 2015 IL-1 receptor-antagonist (IL-1Ra) knockout mice show anxiety-like behavior by aging Neurosci.Lett. 599 20-25 "Interleukin 1 (IL-1) plays a critical role in stress responses, and its mRNA is induced in the brain by restraint stress. Previously, we reported that IL-1 receptor antagonist (IL-1Ra) knockout (KO) mice, which lacked IL-1Ra molecules that antagonize the IL-1 receptor, showed anti-depression-like behavior via adrenergic modulation at the age of 8 weeks. Here, we report that IL-1Ra KO mice display an anxiety-like phenotype that is induced spontaneously by aging in the elevated plus-maze (EPM) test. This anxiety-like phenotype was improved by the administration of diazepam. The expression of the anxiety-related molecule glucocorticoid receptor (GR) was significantly reduced in 20-week-old but not in 11-week-old IL-1Ra KO mice compared to wild-type (WT) littermates. The expression of the mineralocorticoid receptor (MR) was not altered between IL-1Ra KO mice and WT littermates at either 11 or 20 weeks old. Analysis of monoamine concentration in the hippocampus revealed that tryptophan, the serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA), and the dopamine metabolite homovanillic acid (HVA) were significantly increased in 20-week-old IL-1Ra KO mice compared to littermate WT mice. These findings strongly suggest that the anxiety-like behavior observed in older mice was caused by the complicated alteration of monoamine metabolism and/or GR expression in the hippocampus" http://www.ncbi.nlm.nih.gov/pubmed/26002078 0 671 "H. Senn, L. Banfield, T. Wacher, J. Newby, T. Rabeil, J. Kaden, A. C. Kitchener, T. Abaigar, T. L. Silva, M. Maunder and R. Ogden" 2014 Splitting or lumping? A conservation dilemma exemplified by the critically endangered dama gazelle (Nanger dama) PLoS.One. 9 6 e98693 "Managers of threatened species often face the dilemma of whether to keep populations separate to conserve local adaptations and minimize the risk of outbreeding, or whether to manage populations jointly to reduce loss of genetic diversity and minimise inbreeding. In this study we examine genetic relatedness and diversity in three of the five last remaining wild populations of dama gazelle and a number of captive populations, using mtDNA control region and cytochrome b data. Despite the sampled populations belonging to the three putative subspecies, which are delineated according to phenotypes and geographical location, we find limited evidence for phylogeographical structure within the data and no genetic support for the putative subspecies. In the light of these data we discuss the relevance of inbreeding depression, outbreeding depression, adaptive variation, genetic drift, and phenotypic variation to the conservation of the dama gazelle and make some recommendations for its future conservation management. The genetic data suggest that the best conservation approach is to view the dama gazelle as a single species without subspecific divisions" http://www.ncbi.nlm.nih.gov/pubmed/24956104 0 672 "A. L. Frederick, T. P. Saborido and G. D. Stanwood" 2012 Neurobehavioral phenotyping of Galphaq knockout mice reve impairments in motor functions and spatial working memory without changes in anxiety or behavioral despai "Frontiers in Behavioral Neuroscience.(JUNE) (no pagination), 2012.Date of Publication: 19 Jun 2012." JUNE "Many neurotransmitters, hormones, and sensory stimuli elicit their cellular responses through the targeted activation of receptors coupled to the Galphaq family of heterotrimeric G proteins. Nevertheless, we still understand little about the consequences of loss of this signaling activity on brain function. We therefore examined the effects of genetic inactivation of Gnaq, the gene that encode for Galphaq, on responsiveness in a battery of behavioral tests in order to assess the contribution of Galphaq signaling capacity in the brain circuits mediating expression of affective behaviors (anxiety and behavioral despair), spatial working memory, and locomotor output (coordination, strength, spontaneous activity, and drug-induced responses). First, we replicated and extended findings showing clear motor deficits in Galphaq knockout mice as assessed on an accelerating rotarod and the inverted screen test. We then assessed the contribution of the basal ganglia motor loops to these impairments, using open field testing and analysis of drug-induced locomotor responses to the psychostimulant cocaine, the benzazepine D1 receptor agonists SKF83822 and SKF83959, and the NMDA receptor antagonist MK-801. We observed significant increases in drug-induced locomotor activity in Galphaq knockout mice from the dopaminergic agonists but not MK-801, indicating that basal ganglia locomotor circuitry is largely intact in the absence of Galphaq. Additionally, we observed normal phenotypes in both the elevated zero maze and the forced swim test indicating that anxiety and depression-related circuitry appears to be largely intact after loss of Gnaq expression. Lastly, use of the Y-maze revealed spatial memory deficits in Galphaq knockout mice, indicating that receptors signaling through Galphaq are necessary in these circuits for proficiency in this task" DO - http://dx.doi.org/10.3389/fnbeh.2012.00029 1 673 T. W. Stief 1991 Factor XIII of blood coagulation inhibits the oxidative phagocyte metabolism and suppresses the immune response in vivo Thromb.Res. 63 2 227-238 "Factor XIII of blood coagulation (F XIII) belongs to the family of transglutaminases and is a major cell product of certain subsets of macrophages. The gene for F XIIIA is coupled to the immune response genes of the HLA-region on chromosome 6. F XIII dose- dependently inhibits the in vitro chemiluminescence response of human phagocytes. About 0.1 units of F XIII/ml (final) decreased the chemiluminescence response to about 50%. In addition, about 0.6 units of F XIII/ml inhibits 50% of the release of the lysosomal hydrolase N-acetyl-beta glucosaminidase in both immune complex stimulated and unstimulated monocytes. Intraperitoneal application of F XIII reduced the activity of phagocytes in a F XIII dose dependent manner. 0.25 units of F XIII reduced the chemiluminescence reaction of murine peritoneal M phi to about 50% of the activity of PBS treated animals after 2 or 24 hours of in vivo incubation. In the Fisher/Lewis rats skin transplantation model, injections of 5 units of F XIII/animal on days 1-7 or on days 10-17 increased the survival times of the transplants from the control value of 17.0 +/- 1.4 to 26.0 +/- 2.0 and 23.0 +/- 2.4 days, respectively. F XIII may represent a novel and physiological immune suppressive agent for a broad range of human diseases of autoimmune character" http://www.ncbi.nlm.nih.gov/pubmed/1771628 0 674 "C. B. Hantler, N. C. Wilton and P. R. Knight" 1994 "Comparative effects of halothane, enflurane, and isoflurane on atrioventricular conductivity and subsidiary pacemaker function in dogs" Anesth.Analg. 79 3 455-459 "This study compares effects of equipotent concentrations of halothane, enflurane, and isoflurane on atrioventricular (AV) function in dogs. Enflurane anesthesia was associated with more AV nodal depression, only at faster heart rates than either halothane or isoflurane. These rate-related effects are important in the genesis of supraventricular reentrant tachyarrhythmias. Subsidiary pacemaker function exhibited marked variability between and within animals with no demonstrable difference between anesthetic drugs. Enflurane has more depressant effects on AV nodal recovery properties than halothane or isoflurane; however, there were no differences demonstrated on slow AV nodal conduction. This suggests that enflurane would be the most effective volatile anesthetic in converting or slowing supraventricular tachyarrhythmias, while carrying no more risk of causing advanced heart block" http://www.ncbi.nlm.nih.gov/pubmed/8067548 0 675 "K. Kanemaru, K. Nishi and M. Diksic" 2009 "AGN-2979, an inhibitor of tryptophan hydroxylase activation, does not affect serotonin synthesis in Flinders Sensitive Line rats, a rat model of depression, but produces a significant effect in Flinders Resistant Line rats" Neurochem.Int. 55 7 529-535 "The neurotransmitter, serotonin, is involved in several brain functions, including both normal, physiological functions, and pathophysiological functions. Alterations in any of the normal parameters of serotonergic neurotransmission can produce several different psychiatric disorders, including major depression. In many instances, brain neurochemical variables are not able to be studied properly in humans, thus making the use of good animal models extremely valuable. One of these animal models is the Flinders Sensitive Line (FSL) of rats, which has face, predictive and constructive validities in relation to human depression. The objective of this study was to quantify the effect of the tryptophan hydroxylase (TPH) activation inhibitor, AGN-2979, on the FSL rats (rats with depression-like behaviour), and compare it to the effect on the Flinders Resistant Line (FRL) of rats used as the control rats. The effect was evaluated by measuring changes in regional serotonin synthesis in the vehicle treated rats (FSL-VEH and FRL-VEH) relative to those measured in the AGN-2979 treated rats (FSL-AGN and FRL-AGN). Regional serotonin synthesis was measured autoradiographically in more than 30 brain regions. The measurements were performed using alpha-[(14)C]methyl-l-tryptophan as the tracer. The results indicate that AGN-2979 did not produce a significant reduction of TPH activity in the AGN-2979 group relative to the vehicle group (a reduction would have been observed if there had been an activation of TPH by the experimental setup) in the FSL rats. On the other hand, there was a highly significant reduction of synthesis in the FRL rats treated by AGN-2979, relative to the vehicle group. Together, the results demonstrate that in the FSL rats, AGN-2979 does not affect serotonin synthesis. This suggests that there was no activation of TPH in the FSL rats during the experimental procedure, but such activation did occur in the FRL rats. Because of this finding, it could be hypothesized that TPH in the FSL rats cannot be easily activated. This may contribute to the development of depressive-like symptoms in the FSL rats (""depressed"" rats), as they cannot easily modulate their need for elevated amounts of this neurotransmitter, and possibly other neurotransmitters. Further, because these rats represent a very good model of human depression, one can hypothesize that humans who do not have readily activated TPH may be more prone to develop depression" http://www.ncbi.nlm.nih.gov/pubmed/19463878 1 676 "A. Velasco-Martin, P. Lorenzo-Fernandez and P. D. Garcia de Jalon" 1973 Effect of sulpiride on oxygen uptake by rat's brain tissue in vitro Experientia 29 9 1100-1101 http://www.ncbi.nlm.nih.gov/pubmed/4744859 0 677 "D. A. Hoffman, M. Schiller, J. M. Greenblatt and D. V. Iosifescu" 2011 Polypharmacy or medication washout: An old tool revisited "Neuropsychiatric Disease and Treatment.7 (1) ()(pp 639-648), 2011.Date of Publication: 2011." 1 639-648 "There has been a rapid increase in the use of polypharmacy in psychiatry possibly due to the introduction of newer drugs, greater availability of these newer drugs, excessive confidence in clinical trial results, widespread prescribing of psychotropic medications by primary care, and pressure to augment with additional medications for unresolved side effects or greater efficacy. Even the new generation of medications may not hold significant advantages over older drugs. In fact, there may be additional safety risks with polypharmacy being so widespread. Washout, as a clinical tool, is rarely done in medication management today. Studies have shown that augmenting therapy with additional medications resulted in 9.1%-34.1% dropouts due to intolerance of the augmentation, whereas studies of medication washout demonstrated only 5.9%-7.8% intolerance to the washout procedure. These perils justify reconsideration of medication washout before deciding on augmentation. There are unwarranted fears and resistance in the medical community toward medication washout, especially at the moment a physician is trying to decide whether to washout or add more medications to the treatment regimen. However, medication washout provides unique benefits to the physician: it establishes a new baseline of the disorder, helps identify medication efficacy from their adverse effects, and provides clarity of diagnosis and potential reduction of drug treatments, drug interactions, and costs. It may also reduce overall adverse events, not to mention a potential to reduce liability. After washout, physicians may be able to select the appropriate polypharmacy more effectively and safely, if necessary. Washout, while not for every patient, may be an effective tool for physicians who need to decide on whether to add potentially risky polypharmacy for a given patient. The risks of washout may, in some cases, be lower and the benefits may be clearly helpful for diagnosis, understanding medication effects, the doctor/patient relationship, and safer use of polypharmacy if indicated. © 2011 Hoffman et al, publisher and licensee Dove Medical Press Ltd" 0 678 "L. B. De, M. Monda, M. P. Pellicano and A. Zenga" 1987 Cortical control of thermogenesis induced by lateral hypothalamic lesion and overeating Am.J.Physiol 253 4 Pt 2 R626-R633 "Increased O2 consumption was found in rats after bilateral lesions of the lateral hypothalamus (LH) or during voluntary overeating. This phenomenon appears to be mediated by the sympathetic nervous system (SNS) in both conditions, since it is blocked by the beta-blocker propranolol administration. In the first experiment we showed that the brain cortex is involved in the thermogenesis induced by LH lesion and this effect is mediated by SNS, since bilateral functional decortication induced by cortical-spreading depression (CSD) impaired the increase of O2 consumption to the same extent as administration of propranolol. In the second experiment the role played by the cerebral cortex on thermogenesis in rats during voluntary overeating of ""cafeteria"" diet and in control rats was investigated. Cafeteria rats showed a significantly higher colonic temperature, brown adipose tissue temperature (Tbat), and rate of O2 consumption than control animals. CSD led to a significant decrease of Tbat and O2 consumption in cafeteria rats but not in controls. On the basis of the results obtained in the two experiments, the possibility that the cerebral cortex could be involved in the metabolic responses for reduction of body weight to the ""set-point"" is hypothesized" http://www.ncbi.nlm.nih.gov/pubmed/2889375 0 679 L. D. Loose and N. R. Di Luzio 1976 A temporal relationship between reticuloendothelial system phagocytic alterations and antibody responses in mice infected with Plasmodium berghei (NYU-2 strain) Am.J.Trop.Med.Hyg. 25 2 221-228 "Malaria-induced immunosuppression has been demonstrated in humans and experimental animals. The suppressed immune response has been suggested to be primarily humoral and not cellular in nature, since classical lymphocytic cell-mediated responses have been reported to be normal. Since previous results have demonstrated that an impairment in macrophage antigen processing may be a contributing factor in malaria-induced immunosuppression, the present studies were conducted to determine if the macrophage/reticuloendothelial system (RES) alteration occurs parallel to the course of the malarial infection and if the impairment in antibody formation is temporally related to the RES alteration. The present study has demonstrated that a profound impairment in splenic direct plaque forming cell (PFC) formation occurs in malaria-infected Balb/c mice which had been immunized with sheep erythrocytes (SRBC) either 2 or 4 days after inoculation with Plasmodium berghei, NYU-2 strain. Serum hemagglutinin titers were significantly depressed in mice which received the SRBC 4 days post-inoculation; however, no alterations in antibody titers were observed in mice immunized with SRBC 2 days post-inoculation. Coincident with the depression of serum antibody titers at the day 4 immunization period was a profound increase in the vascular clearance of 51Cr-SRBC with an enhanced hepatic uptake of the 51Cr-SRBC and a decreased splenic localization of the labelled erythrocytes. It is suggested that a direct vascular exposure of the splenic lymphoid-macrophage elements to the parasite may be responsible for the initial early alterations in the PFC response while the impairment in serum antibody titers and splenic phagocytic activity may be a result of the pathological alterations occurring later in the infection, e.g., tissue anoxia, anemia, and hemolysis" http://www.ncbi.nlm.nih.gov/pubmed/769577 0 680 "W. D. Paton, E. S. Vizi and M. A. Zar" 1971 The mechanism of acetylcholine release from parasympathetic nerves J.Physiol 215 3 819-848 "1. The output of acetylcholine from the plexus of the guinea-pig ileum longitudinal strip has been used to study the mechanism of acetylcholine release. From the effects of hexamethonium and tetrodotoxin, it was inferred that 60% of the normal resting output is due to propagated activity in the plexus, and 40% to spontaneous release. Tetrodotoxin virtually abolishes the increase in output in response to electrical stimulation.2. Resting acetylcholine output is increased when the bathing medium is changed in the following ways:(a) sodium replacement by sucrose, trometamol or lithium;(b) addition of ouabain or p-hydroxymercuribenzoate (PHMB), or withdrawal of potassium;(c) the combination of PHMB and partial sodium replacement;(d) addition of potassium; this increase in output becomes greater in the absence of sodium.3. The resting output is virtually abolished by calcium withdrawal, and is restored by barium substitution for calcium. It is also reduced by raising the magnesium concentration.4. The enhanced resting output in response to sodium withdrawal also occurs in the absence of calcium.5. Cooling to 5 degrees C greatly reduces both the resting output and the output in response to raised potassium concentration or to electrical stimulation.6. The increase in resting output due to potassium excess is slight up to 25 mM [K(+)](o), but increases thereafter with about the fourth power of the potassium concentration; it is resistant to tetrodotoxin.7. Synthesis of acetylcholine by the longitudinal strip is increased when output is enhanced by electrical stimulation, by potassium excess or by addition of barium, so that the acetylcholine content of the strip is maintained approximately normal. Synthesis is reduced, in relation to output, by potassium lack or by treatment with ouabain, and is virtually abolished by sodium withdrawal.8. The theory is discussed that acetylcholine release depends on inhibition of the activity of a (Na(+) + K(+) + Mg(2+))-activated ATPase at the axonal membrane" http://www.ncbi.nlm.nih.gov/pubmed/4253676 0 681 "H. W. Ko, E. Y. Kim, J. Chiu, J. T. Vanselow, A. Kramer and I. Edery" 2010 A hierarchical phosphorylation cascade that regulates the timing of PERIOD nuclear entry reveals novel roles for proline-directed kinases and GSK-3beta/SGG in circadian clocks J.Neurosci. 30 38 12664-12675 "The daily timing of when PERIOD (PER) proteins translocate from the cytoplasm to the nucleus is a critical step in clock mechanisms underpinning circadian rhythms in animals. Numerous lines of evidence indicate that phosphorylation plays a prominent role in regulating various aspects of PER function and metabolism, including changes in its daily stability and subcellular distribution. In this report, we show that phosphorylation of serine 661 (Ser661) by a proline-directed kinase(s) is a key phospho-signal on the Drosophila PER protein (dPER) that regulates the timing of its nuclear accumulation. Mutations that block phosphorylation at Ser661 do not affect dPER stability but delay its nuclear entry in key pacemaker neurons, yielding longer behavioral rhythms. Intriguingly, abolishing phosphorylation at Ser661 also attenuates the extent of dPER hyperphosphorylation in vivo, suggesting the phosphorylated state of Ser661 regulates phosphorylation at other sites on dPER. Indeed, we identify Ser657 as a site that is phosphorylated by the glycogen synthase kinase GSK-3beta (SHAGGY; SGG) in a manner dependent on priming at Ser661. Although not as dramatic as mutating Ser661, mutations that abolish phosphorylation at Ser657 also lead to longer behavioral periods, suggesting that a multi-kinase hierarchical phosphorylation module regulates the timing of dPER nuclear entry. Together with evidence in mammalian systems, our findings implicate proline-directed kinases in clock mechanisms and suggest that PER proteins are key downstream targets of lithium therapy, a potent inhibitor of GSK-3beta used to treat manic depression, a disorder associated with clock malfunction in humans" http://www.ncbi.nlm.nih.gov/pubmed/20861372 0 682 "I. Z. Mathews, A. Wilton, A. Styles and C. M. McCormick" 2008 Increased depressive behaviour in females and heightened corticosterone release in males to swim stress after adolescent social stress in rats Behav.Brain Res. 190 1 33-40 "We previously reported that males undergoing chronic social stress (SS) (daily 1h isolation and new cage partner on days 30-45 of age) in adolescence habituated (decreased corticosterone release) to the homotypic stressor, but females did not. Here, we report that adolescent males exposed to chronic social stress had potentiated corticosterone release to a heterotypic stressor (15 min of swim stress) compared to acutely stressed and control males. The three groups of males did not differ in depressive-like behaviour (time spent immobile) during the swim stress. Corticosterone release in socially stressed females was elevated 45 min after the swim stress compared to acutely stressed and control females, and socially stressed females exhibited more depressive behaviour (longer durations of immobility and shorter durations of climbing) than the other females during the swim stress. Separate groups of rats were tested as adults several weeks after the social stress, and there were no group differences in corticosterone release after the swim stress. The only group difference in behaviour among the adults was more time spent climbing in socially stressed males than in controls. Thus, there are sex-specific effects of social stress in adolescence on endocrine responses and depressive behaviour to a heterotypic stressor, but, unlike for anxiety, substantial recovery is evident in adulthood in the absence of intervening stress exposures" http://www.ncbi.nlm.nih.gov/pubmed/18342957 1 683 "M. A. Hurle, A. Mediavilla and J. Florez" 1983 Participation of pontine structures in the respiratory action of opioids Life Sci. 33 Suppl 1 571-574 "The respiratory action of morphine, D-Ala2-D-Leu5-enkephalin, and D-Ala2-Me-Phe4-Met(O)ol5-enkephalin, restrictively applied to the dorso-rostral surface of the pons, was studied in anesthetized cats. Frequency was selectively and dose-dependently depressed, down to apnea, whereas tidal volume and its response to CO2 either remained unchanged or were increased. Similar effects were observed in vagotomized and decerebrate cats. From these and previous (1) results, it can be concluded that the medullary and pontine structures related to respiration are differentially affected by opioids. Pontine nuclei are more sensitive to opioid depression and account for changes in frequency, whereas medullary depression results in reduction of tidal volume and CO2 sensitivity" http://www.ncbi.nlm.nih.gov/pubmed/6363854 0 684 W. Y. Ahn and J. Vassileva 2016 Machine-learning identifies substance-specific behavioral markers for opiate and stimulant dependence Drug Alcohol Depend. 161 247-257 "BACKGROUND: Recent animal and human studies reveal distinct cognitive and neurobiological differences between opiate and stimulant addictions; however, our understanding of the common and specific effects of these two classes of drugs remains limited due to the high rates of polysubstance-dependence among drug users. METHODS: The goal of the current study was to identify multivariate substance-specific markers classifying heroin dependence (HD) and amphetamine dependence (AD), by using machine-learning approaches. Participants included 39 amphetamine mono-dependent, 44 heroin mono-dependent, 58 polysubstance dependent, and 81 non-substance dependent individuals. The majority of substance dependent participants were in protracted abstinence. We used demographic, personality (trait impulsivity, trait psychopathy, aggression, sensation seeking), psychiatric (attention deficit hyperactivity disorder, conduct disorder, antisocial personality disorder, psychopathy, anxiety, depression), and neurocognitive impulsivity measures (Delay Discounting, Go/No-Go, Stop Signal, Immediate Memory, Balloon Analogue Risk, Cambridge Gambling, and Iowa Gambling tasks) as predictors in a machine-learning algorithm. RESULTS: The machine-learning approach revealed substance-specific multivariate profiles that classified HD and AD in new samples with high degree of accuracy. Out of 54 predictors, psychopathy was the only classifier common to both types of addiction. Important dissociations emerged between factors classifying HD and AD, which often showed opposite patterns among individuals with HD and AD. CONCLUSIONS: These results suggest that different mechanisms may underlie HD and AD, challenging the unitary account of drug addiction. This line of work may shed light on the development of standardized and cost-efficient clinical diagnostic tests and facilitate the development of individualized prevention and intervention programs for HD and AD" http://www.ncbi.nlm.nih.gov/pubmed/26905209 0 685 "I. D. Johnsson, J. F. Hecker and M. Wodzicka-Tomaszewska" 1974 Proceedings: Effect of exogenous progesterone injected within the first 5 days after mating on conception in ewes J.Reprod.Fertil. 36 2 485-486 http://www.ncbi.nlm.nih.gov/pubmed/4856465 0 686 "G. W. Mello, D. M. Oliveira, C. J. Carvalho, M. V. Cavalcante, F. A. Costa, F. Riet-Correa and S. M. Silva" 2010 Poisoning of goats by the pods of Luetzelburgia auriculata Toxicon 55 6 1115-1118 "Farmers report that the pods of Luetzelburgia auriculata cause digestive signs and death when ingested by goats. To demonstrate the toxicity of the pods of this plant 12 goats were divided into 4 groups of 3 goats each. Groups 1, 2, 3 and 4 were administered 2.5, 1, 0.5 and nil g of pods per kg body weight, respectively. Goats in Groups 1 and 2 developed decreased ruminal movements followed by anorexia, depression and soft feces or diarrhea. Goats in Group 1 died 59-106 h after first showing clinical signs. Goats in Group 2 also regurgitated rumen content, but all recovered 65-90 h after first showing clinical signs. The only clinical sign shown by goats in Group 3 was regurgitation of rumen content, and all goats recovered 5.5-24 h after first regurgitating. All goats in Group 4 remained normal. The goats that died were necropsied and found to have a reddish mucosa of the forestomachs that detached easily from the underlying tissues. Other lesions included diffuse reddening of the mucosa of the abomasum and intestine. Histological examination of the mucosa of the forestomachs showed diffuse ballooning degeneration of keratinocytes, with necrosis and vesicle and pustule formation in the epithelium. In some areas there was sloughing of the ruminal epithelium. These results demonstrate that the pods of L. auriculata are toxic and responsible for field outbreaks of poisoning in goats in the state of Piaui" http://www.ncbi.nlm.nih.gov/pubmed/20043935 0 687 A. J. Hannan 2007 "International Brain Research Organization--Seventh World Congress of Neuroscience. 12-17 July 2007, Melbourne, Victoria, Australia" IDrugs. 10 10 690-692 http://www.ncbi.nlm.nih.gov/pubmed/17899483 0 688 A. P. Viana and W. Osswald 1970 Antiarrhythmic effects of proadifen hydrochloride (SKF 525-A) Arzneimittelforschung. 20 6 851-853 http://www.ncbi.nlm.nih.gov/pubmed/5468902 0 689 "M. R. Hayden, W. A. Banks, G. N. Shah, Z. Gu and J. R. Sowers" 2013 Cardiorenal metabolic syndrome and diabetic cognopathy "CardioRenal Medicine.3 (4) ()(pp 265-282), 2013.Date of Publication: December 2013." 4 265-282 "The prevalence of the cardiorenal metabolic syndrome (CRS) is increasing in parallel with obesity, type 2 diabetes mellitus, Alzheimer's disease, and other forms of dementia. Along with metabolic, inflammatory, and immunological abnormalities, there is maladaptive structural remodeling of the heart, kidney, and brain. The term 'diabetic cognopathy' (DC) may be used when discussing functional and structural changes in the brain of the diabetic patient. DC likely represents an advanced form of these changes in the brain that evolve with increasing duration of the CRS and subsequent clinical diabetes. We posit that DC develops due to a convergence of aging, genetic and lifestyle abnormalities (overnutrition and lack of exercise), which result in multiple injurious metabolic and immunologic toxicities such as dysfunctional immune responses, oxidative stress, inflammation, insulin resistance, and dysglycemia (systemically and in the brain). These converging abnormalities may lead to endothelial blood-brain barrier tight junction/adherens junction (TJ/AJ) complex remodeling and microglia activation, which may result in neurodegeneration, impaired cognition, and dementia. Herein, we describe the brain ultrastructural changes evolving from a normal state to maladaptive remodeling in rodent models of CRS including microglia activation/polarization and attenuation and/or loss of the TJ/AJ complexes, pericytes and astrocytes of the neurovascular unit. Further, we discuss the potential relationship between these structural changes and the development of DC, potential therapeutic strategies, and future directions. © 2013 S. Karger AG, Basel" DO - http://dx.doi.org/10.1159/000357113 0 690 "C. A. Grillo, P. Mulder, V. A. Macht, K. F. Kaigler, S. P. Wilson, M. A. Wilson and L. P. Reagan" 2014 Dietary restriction reverses obesity-induced anhedonia Physiol Behav. 128 126-132 "Obesity-induced changes in the metabolic and endocrine milieu elicit deficits in neuroplasticity, including increased risk for development of neuropsychiatric disorders such as depressive illness. We previously demonstrated that downregulation of hypothalamic insulin receptors (hypo-IRAS) elicits a phenotype that is consistent with features of the metabolic syndrome (MetS) and that rats with this phenotype exhibit deficits in neuronal plasticity, including depressive-like behaviors such as anhedonia. Since food restriction paradigms effectively inhibit obesity-induced neuroplasticity deficits, the aim of the current study was to determine whether food restriction could reverse obesity-induced anhedonia in hypo-IRAS rats. Compared to hypo-IRAS rats provided ad lib food access, food restriction paradigms that were initiated either prior to increases in body weight or following development of the MetS/obesity phenotype effectively restored sucrose intake in hypo-IRAS rats. Moreover, food restriction paradigms were able to prevent and reverse the changes in the endocrine/metabolic/inflammatory milieu observed in hypo-IRAS, such as increases in plasma leptin and triglyceride levels and increases in pro-inflammatory cytokines such as IL-1alpha, IL-6 and C-reactive protein (CRP). Collectively, these results demonstrate that obesity-induced anhedonia is a reversible process and identify some potential mechanistic mediators that may be responsible for co-morbid depression in obesity" http://www.ncbi.nlm.nih.gov/pubmed/24518861 1 691 "T. D. Perera, A. J. Dwork, K. A. Keegan, L. Thirumangalakudi, C. M. Lipira, N. Joyce, C. Lange, J. D. Higley, G. Rosoklija, R. Hen, H. A. Sackeim and J. D. Coplan" 2011 Necessity of hippocampal neurogenesis for the therapeutic action of antidepressants in adult nonhuman primates PLoS.One. 6 4 e17600 "BACKGROUND: Rodent studies show that neurogenesis is necessary for mediating the salutary effects of antidepressants. Nonhuman primate (NHP) studies may bridge important rodent findings to the clinical realm since NHP-depression shares significant homology with human depression and kinetics of primate neurogenesis differ from those in rodents. After demonstrating that antidepressants can stimulate neurogenesis in NHPs, our present study examines whether neurogenesis is required for antidepressant efficacy in NHPs. MATERIALS/METHODOLOGY: Adult female bonnets were randomized to three social pens (N = 6 each). Pen-1 subjects were exposed to control-conditions for 15 weeks with half receiving the antidepressant fluoxetine and the rest receiving saline-placebo. Pen-2 subjects were exposed to 15 weeks of separation-stress with half receiving fluoxetine and half receiving placebo. Pen-3 subjects 2 weeks of irradiation (N = 4) or sham-irradiation (N = 2) and then exposed to 15 weeks of stress and fluoxetine. Dependent measures were weekly behavioral observations and postmortem neurogenesis levels. RESULTS: Exposing NHPs to repeated separation stress resulted in depression-like behaviors (anhedonia and subordinance) accompanied by reduced hippocampal neurogenesis. Treatment with fluoxetine stimulated neurogenesis and prevented the emergence of depression-like behaviors. Ablation of neurogenesis with irradiation abolished the therapeutic effects of fluoxetine. Non-stressed controls had normative behaviors although the fluoxetine-treated controls had higher neurogenesis rates. Across all groups, depression-like behaviors were associated with decreased rates of neurogenesis but this inverse correlation was only significant for new neurons in the anterior dentate gyrus that were at the threshold of completing maturation. CONCLUSION: We provide evidence that induction of neurogenesis is integral to the therapeutic effects of fluoxetine in NHPs. Given the similarity between monkeys and humans, hippocampal neurogenesis likely plays a similar role in the treatment of clinical depression. Future studies will examine several outstanding questions such as whether neuro-suppression is sufficient for producing depression and whether therapeutic neuroplastic effects of fluoxetine are specific to antidepressants" http://www.ncbi.nlm.nih.gov/pubmed/21525974 1 692 "W. Xie, L. Cai, Y. Yu, L. Gao, L. Xiao, Q. He, Z. Ren and Y. Liu" 2014 "Activation of brain indoleamine 2,3-dioxygenase contributes to epilepsy-associated depressive-like behavior in rats with chronic temporal lobe epilepsy" J.Neuroinflammation. 11 41 "BACKGROUND: Depression has most often been diagnosed in patients with temporal lobe epilepsy (TLE), but the mechanism underlying this association remains unclear. In this study, we report that indoleamine 2,3-dioxygenase 1 (IDO1), a rate-limiting enzyme in tryptophan metabolism, plays a key role in epilepsy-associated depressive-like behavior. METHODS: Rats which develop chronic epilepsy following pilocarpine status epilepticus exhibited a set of interictal disorders consistent with depressive-like behavior. Changes of depressive behavior were examined by taste preference test and forced swim test; brain IL-1beta, IL-6 and IDO1 expression were quantified using real-time reverse transcriptase PCR; brain kynurenine/tryptophan and serotonin/tryptophan ratios were analyzed by liquid chromatography-mass spectrometry. Oral gavage of minocycline or subcutaneous injection of 1-methyltryptophan (1-MT) were used to inhibite IDO1 expression. RESULTS: We observed the induction of IL-1beta and IL-6 expression in rats with chronic TLE, which further induced the upregulation of IDO1 expression in the hippocampus. The upregulation of IDO1 subsequently increased the kynurenine/tryptophan ratio and decreased the serotonin/tryptophan ratio in the hippocampus, which contributed to epilepsy-associated depressive-like behavior. The blockade of IDO1 activation prevented the development of depressive-like behavior but failed to influence spontaneous seizures. This effect was achieved either indirectly, through the anti-inflammatory tetracycline derivative minocycline, or directly, through the IDO antagonist 1-MT, which normalizes kynurenine/tryptophan and serotonin/tryptophan ratios. CONCLUSION: Brain IDO1 activity plays a key role in epileptic rats with epilepsy-associated depressive-like behavior" http://www.ncbi.nlm.nih.gov/pubmed/24594021 1 693 "M. Gross, A. Sheinin, E. Nesher, T. Tikhonov, D. Baranes, A. Pinhasov and I. Michaelevski" 2015 Early onset of cognitive impairment is associated with altered synaptic plasticity and enhanced hippocampal GluA1 expression in a mouse model of depression Neurobiol.Aging 36 5 1938-1952 "Memory deficit is a common manifestation of age-related cognitive impairment, of which depression is a frequently occurring comorbidity. Previously, we developed a submissive (Sub) mouse line, validated as a model of depressive-like behavior. Using learning paradigms testing hippocampus-dependent spatial and nonspatial memory, we demonstrate here that Sub mice developed cognitive impairments at earlier age (3 months), compared with wild-type mice. Furthermore, acute hippocampal slices from Sub animals failed to display paired-pulse facilitation, whereas primed burst stimulation elicited significantly enhanced long-term potentiation in region CA1, relative to control mice. Changes in synaptic plasticity were accompanied by markedly reduced hippocampal messenger RNA expression of insulin-like growth factor and brain-derived neurotrophic factor. Finally, we identified markedly elevated protein levels of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluA1 in the hippocampi of Sub mice, which was exacerbated with age. Taken together, the results point to a linkage between depressive-like behavior and the susceptibility to develop age-related cognitive impairment, potentially by hippocampal alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated glutamatergic signaling" http://www.ncbi.nlm.nih.gov/pubmed/25796132 1 694 H. C. Rosenberg and T. H. Chiu 1979 Decreased 3H-diazepam binding is a specific response to chronic benzodiazepine treatment Life Sci. 24 9 803-807 http://www.ncbi.nlm.nih.gov/pubmed/36541 0 695 "M. D. Roberts, T. E. Childs, J. D. Brown, J. W. Davis and F. W. Booth" 2012 Early depression of Ankrd2 and Csrp3 mRNAs in the polyribosomal and whole tissue fractions in skeletal muscle with decreased voluntary running J.Appl.Physiol (1985.) 112 8 1291-1299 "The wheel-lock (WL) model for depressed ambulatory activity in rats has shown metabolic maladies ensuing within 53-173 h after WL begins. We sought to determine if WL beginning after 21-23 days of voluntary running in growing female Wistar rats affected the mRNA profile in the polyribosomal fraction from plantaris muscle shortly following WL. In experiment 1, WL occurred at 0200 and muscles were harvested at 0700 daily at 5 h (WL5h, n = 4), 29 h (WL29h, n = 4), or 53 h (WL53h, n = 4) after WL. Affymetrix Rat Gene 1.0 ST Arrays were used to test the initial question as to whether WL affects mRNA occupancy on skeletal muscle polyribosomes. Using a false discovery rate of 15%, no changes in mRNAs in the polyribosomal fraction were observed at WL29h and eight mRNAs (of over 8,200 identified targets) were altered at WL53h compared with WL5h. Interestingly, two of the six downregulated genes included ankyrin repeat domain 2 (Ankrd2) and cysteine-rich protein 3/muscle LIM protein (Csrp3), both of which encode mechanical stretch sensors and RT-PCR verified their WL-induced decline. In experiment 2, whole muscle mRNA and protein levels were analyzed for Ankrd2 and Csrp3 from the muscles of WL5h (4 original samples + 2 new), WL29h (4 original), WL53h (4 original + 2 new), as well as WL173 h (n = 6 new) and animals that never ran (SED, 4-5 new). Relative to WL5h controls, whole tissue Ankrd2 and Csrp3 mRNAs were lower (P < 0.05) at WL53h, WL173h, and SED; Ankrd2 protein tended to decrease at WL53h (P = 0.054) and Csrp3 protein was less in WL173h and SED rats (P < 0.05). In summary, unique early declines in Ankrd2 and Csrp3 mRNAs were identified with removal of voluntary running, which was subsequently followed by declines in Csrp3 protein levels during longer periods of wheel lock" http://www.ncbi.nlm.nih.gov/pubmed/22282489 0 696 "M. Vervliet, J. Lammertyn, E. Broekaert and I. Derluyn" 2014 Longitudinal follow-up of the mental health of unaccompanied refugee minors "European Child and Adolescent Psychiatry.23 (5) ()(pp 337-346), 2014.Date of Publication: May 2014." 5 337-346 "Despite growing numbers of unaccompanied refugee minors (UMs) in Europe, and evidence that this group is at risk of developing mental health problems, there still remain important knowledge gaps regarding the development of UMs' mental health during their trajectories in the host country and, in particular, the possible influencing role of traumatic experiences and daily stressors therein. This study therefore followed 103 UMs from the moment they arrived in Belgium until 18 months later. Traumatic experiences (SLE), mental health symptoms (HSCL-37A, RATS) and daily stressors (DSSYR) were measured at arrival in Belgium, after 6 and 18 months. UMs reported generally high scores on anxiety, depression and post-traumatic stress disorder (PTSD). Linear mixed model analysis showed no significant differences in mental health scores over time, pointing towards the possible long-term persistence of mental health problems in this population. The number of traumatic experiences and the number of daily stressors leaded to a significant higher symptom level of depression (daily stressors), anxiety and PTSD (traumatic experiences and daily stressors). European migration policies need to reduce the impact of daily stressors on UMs' mental health by ameliorating the reception and care facilities for this group. Moreover, regular mental health screenings are needed, in combination with, if needed, adapted psychosocial and therapeutic care. © 2013 Springer-Verlag" DO - http://dx.doi.org/10.1007/s00787-013-0463-1 0 697 "M. Jonker, W. Slingerland, G. Treacy, E. P. van, K. Y. Pak, E. Wilson, S. Tam, K. Bakker, A. F. Lobuglio, P. Rieber and ." 1993 In vivo treatment with a monoclonal chimeric anti-CD4 antibody results in prolonged depletion of circulating CD4+ cells in chimpanzees Clin.Exp.Immunol. 93 3 301-307 "Chimeric M-T412 (cM-T412), an anti-CD4 antibody, was tolerated in chimpanzees at a dosage of 5 mg/kg per day for up to 7 consecutive days, or 5 mg/kg per dose, twice weekly for 4 weeks. All cM-T412-treated chimpanzees showed a prolonged CD4-cell depression. Weak chimpanzee antibody responses to chimeric M-T412 were observed. One of the chimpanzees on the biweekly dosage regimen exhibited a hypersensitivity reaction immediately after receiving its seventh dose. Following supportive treatment, the animal recovered and remained asymptomatic during the non-treatment observation period. The hypersensitivity reaction was not an unexpected response considering the animal received repeated intermittent i.v. administration of a foreign protein. This animal also showed a chimpanzee antibody response to chimeric M-T412 after the seventh dose. Chimeric M-T412 also induced an anti-cM-T412 response in some of the other animals. The level of this response was lower than the anti-mouse responses observed in animals treated with murine anti-CD4. Moreover, the anti-cM-T412 response was mainly directed to idiotypic determinants. The decrease in CD4+ cells observed for all chimeric M-T412-treated chimpanzees is an expected effect of the anti-CD4 antibody. The duration of this CD4+ cell decrease is, however, much longer than observed for other CD4-specific MoAbs described. No selective loss of either memory or naive CD4+ cells was observed after either the single, 7-day or twice-weekly treatments. The CD4+ cell depression was reversible, although individual variation in time to recovery was observed. Therefore, cM-T412 could be a good candidate for clinical use in autoimmune conditions" http://www.ncbi.nlm.nih.gov/pubmed/8103714 0 698 M. Muftic and G. Hoyer 1968 "Alkylaminoalkyl-dithiocarbamic acids, new drugs against Pityrosporum ovale" Arzneimittelforschung. 18 9 1205-1207 http://www.ncbi.nlm.nih.gov/pubmed/4237099 0 699 "H. W. Chen, A. A. Kandutsch and C. Waymouth" 1974 Inhibition of cell growth by oxygenated derivatives of cholesterol Nature 251 5474 419-421 http://www.ncbi.nlm.nih.gov/pubmed/4472548 0 700 "Q. Q. Lv, W. J. Wu, X. L. Guo, R. L. Liu, Y. P. Yang, D. S. Zhou, J. X. Zhang and J. Y. Liu" 2014 Antidepressant activity of astilbin: involvement of monoaminergic neurotransmitters and BDNF signal pathway Biol.Pharm.Bull. 37 6 987-995 "Depression and related mood disorders are among the world's greatest public health problems. Previous studies have demonstrated that astilbin (AST) has broad pharmacological functions which may modulate numerous pathways, such as antioxidant, scavenging free radicals, anti-inflammatory and so on, similarly to some of other flavonoids. In this study, the antidepressant-like effect of AST was investigated using chronic unpredictable mild stress (CUMS) model of depression in mice. The results showed that chronic administration of AST at doses of 10, 20 and 40 mg/kg (intraperitoneally (i.p.), 21 d) reduced depressive-like behaviors of mice in the forced swim test (FST), tail suspension test (TST) and sucrose preference test (SPT) without affecting locomotor activity. AST increased the contents of serotonin (5-HT) and dopamine (DA) in the frontal cortex of CUMS mice. Additionally, it was shown that AST treatment restored the CUMS-induced inhibition of extracellular signal-regulated kinase (ERK) 1/2 and AKT phosphorylation in the frontal cortex, conformed to the brain-derived neurotrophic factor (BDNF) expression. Our findings suggest that AST has antidepressant activities and the mechanisms, at least in part, relate to up-regulation of monoaminergic neurotransmitters (5-HT and DA) and activation of the BDNF signaling pathway" http://www.ncbi.nlm.nih.gov/pubmed/24681540 1 701 C. Kiselycznyk and P. Svenningsson 2010 Mice lacking two key phosphorylation sites on the GluR1 subunit exhibit decreased anxiety-like behaviour "European Neuropsychopharmacology.Conference: 2010 ECNP Workshop on Neuropsychopharmacology for Young Scientists in Europe Nice France.Conference Start: 20100304 Conference End: 20100307.Conference Publication: (var.pagings).20 ()(pp S42-S43), 2010.Da" var.pagings S42-S43 "Phosphorylation of the AMPA receptor subunit GluR1 has been implicated in the treatment response of various mood disorders. Chronic administration with a diverse set of antidepressants has been shown to increase phosphorylation of this subunit [1], while chronic antimanics have decreased this same phosphorylation [2]. It is not known, however, if these phosphorylation sites are a side effect of treatment or if they are involved in basal anxious or depressive states. To evaluate this, mutant mice were generated with a knockin mutation replacing the functional serine 831 and serine 845 with alanine residues on a C57BL/6 background as previously described [3]. Wildtype littermates and GluR1 phosphomutant mice at 4 months of age were phenotyped on a battery of tests of anxiety-like (elevated-plus maze, light-dark emergence task, novelty-induced hypophagia) and depressive-like behavior (sucrose preference, forced swim test) with one week between each test. In the five minute elevated plus maze, glur1 double phosphomutant mice spent significantly more time in the open arms of the maze (students ttest p = 0.016; t = 2.702; df = 15). Mutant mice also spent significantly more time in the light section of the light-dark box during the first 5 minutes of the test (students ttest p = 0.027; t = 2.685 df = 8), and had a significant increase in the amount of exits from the shelter into the light area (students ttest p = 0.005; t = 5.568 df = 8). In novelty-induced hypophagia, mutant mice were presented with a sweetened condensed milk in their homecage for fifteen minutes and the latency to drink the milk and amount of milk consumed was measured. After four days of milk presentations in the homecage, mice were placed in a novel cage and drinking was measured. Mutant mice showed significantly less difference in their latency to drink the sweetened milk between the home and novel cage days (students ttest p = 0.035; t = 2.225 df = 27), however, there was no difference between the two genotypes in their change in milk consumption over the two days. In the sucrose preference test, mice were single-housed and given a two-bottle choice between water and 1% sucrose for 3 days. No significant difference was found between wildtype and mutant mice in the percent of sucrose consumed. A six minute forced swim test also revealed no significant difference in depressivelike behavior as mutant mice showed no change in the amount of time spent immobile in the last four minutes of the test. Overall, there was a significant reduction in anxiety-like behavior in the GluR1 phosphomutant mice in three separate tests (elevated plus maze, lightdark emergence, and novelty-induced hypophagia), but no significant change in depressive-like behavior (sucrose preference and forced swim test). This suggests that basal decrease of glur1 phosphorylation could be important for anxiety-like phenotypes. Future studies might investigate these animals response to chronic stress or try to block these same phosphorylation sites in a region-specific manner" DO - http://dx.doi.org/10.1016/S0924-977X%2810%2970051-1 0 702 M. Spedding and P. Lestage 2005 [Synaptic plasticity and neuropathology: new approaches in drug discovery] Med.Sci.(Paris) 21 1 104-109 "Neuronal plasticity is now known to be very important in the adult, both in the formation of new synaptic connections and of new neurones (neurogenesis) and of glial cells. However, old age and stress can inhibit this plasticity and lead to cerebral atrophy. The time course of changes in neuronal plasticity involves, in the first milliseconds to seconds, changes in synaptic strength (long term potentialisation, LTP, or long term depression, LTD), then, over minutes to hours, changes in the number of synaptic connections (linked to changes in neurotrophic factors), and over weeks to months, to changes in neuronal reconfiguration. These changes in brain systems are particularly targeted in psychiatric disorders to the areas which are sensitive to stress and play roles in memory and emotion (hippocampus, amygdala and prefrontal cortex). The discovery and development of drugs modifying neuronal plasticity and neurotrophins production has been a priority for Servier research for the last ten years; Servier has a clinically effective antidepressant, tianeptine (Stablon), with a favourable side effect profile, but which does not inhibit the uptake of serotonin, or other monoamines. However, this drug can reverse the deleterious effects of stress on neuronal plasticity, thereby acting on the causes of psychiatric disorders. Furthermore, a new research area is being investigated - facilitation of AMPA receptors, favouring the production of neurotrophic factors" http://www.ncbi.nlm.nih.gov/pubmed/15639031 0 703 "H. Castel, S. Jegou, M. C. Tonon and H. Vaudry" 2000 Regulation of the GABA(A) receptor by nitric oxide in frog pituitary melanotrophs Endocrinology 141 9 3451-3460 "Nitric oxide (NO) is implicated in the regulation of various endocrine functions, but the effect of NO on GABA(A) receptor transmission has never been reported in endocrine cells. In the present study, we have investigated the effects of various agents acting on the NO transduction pathway on GABA(A) receptor function in frog pituitary melanotrophs. Histochemical studies using the NADPH-diaphorase reaction and immunohistochemical labeling with antibodies against neuronal NO synthase (nNOS) revealed that nNOS is expressed in the intermediate lobe of the pituitary and in cultured melanotrophs. Whole-cell patch-clamp recordings showed that the specific substrate of NOS L-arginine (L-Arg, 10(-4) M) or the NO donor sodium nitroprusside (10(-5) M) provoked a long-lasting inhibition of the current evoked by GABA (5 x 10(-6) M). The NOS inhibitor L-nitroarginine (10(-5) M) produced a biphasic effect, i.e. a transient decrease followed by a delayed increase of the GABA-evoked current amplitude. Similarly, the specific nNOS inhibitor 7-nitroindazole and the specific inducible NOS (iNOS) inhibitor aminoguanidine (10(-5) M each) provoked a transient depression of the current followed by a sustained potentiation. Formation of cGMP in neurointermediate lobes was enhanced by L-Arg (10(-4) M) and by the calcium-releasing agent caffeine (10(-4) M), and inhibited by the calmodulin (CaM)/Ca2+ complex blocker W7 (10(-5) M). The GABA-evoked current was potentiated by the guanylyl cyclase inhibitor ODQ (10(-8)-10(-7) M) and inhibited by the protein kinase G (PKG) activator 8pCPT-cGMP (3 x 10(-7)-3 x 10(-5) M). The present data indicate that NO, produced by a CaM/Ca2+-dependent NOS in frog melanotrophs, exerts an autocrine inhibitory effect on the GABA-evoked current. The action of NO on the GABA(A) receptor function is mediated through activation of the cGMP/PKG pathway" http://www.ncbi.nlm.nih.gov/pubmed/10965918 0 704 F. M. Hilker 2010 Population collapse to extinction: the catastrophic combination of parasitism and Allee effect J.Biol.Dyn. 4 1 86-101 "Infectious diseases are responsible for the extinction of a number of species. In conventional epidemic models, the transition from endemic population persistence to extirpation takes place gradually. However, if host demographics exhibits a strong Allee effect (AE) (population decline at low densities), extinction can occur abruptly in a catastrophic population crash. This might explain why species suddenly disappear even when they used to persist at high endemic population levels. Mathematically, the tipping point towards population collapse is associated with a saddle-node bifurcation. The underlying mechanism is the simultaneous population size depression and the increase of the extinction threshold due to parasite pathogenicity and Allee effect. Since highly pathogenic parasites cause their own extinction but not that of their host, there can be another saddle-node bifurcation with the re-emergence of two endemic equilibria. The implications for control interventions are discussed, suggesting that effective management may be possible for (0)>>1" http://www.ncbi.nlm.nih.gov/pubmed/22881072 0 705 "S. P. Nordt, J. Wu, S. Zahller, R. F. Clark and F. L. Cantrell" 2011 Palytoxin poisoning after dermal contact with zoanthid coral J.Emerg.Med. 40 4 397-399 "BACKGROUND: Palytoxin is most commonly reported after ingestion of seafood. We report a case of palytoxin poisoning from dermal absorption with local toxicity from zoanthid coral in a patient with intact skin. CASE REPORT: A 25-year-old previously healthy woman handled a zoanthid coral from a home aquarium without any barrier protection. The patient manifested neurologic symptoms of perioral paresthesia and dysguesia. In addition, there was local dermatologic toxicity that persisted for several days. The patient was treated supportively with corticosteroids and a histamine antagonist. CONCLUSION: We report a case of palytoxin poisoning from dermal absorption after handling a zoanthid coral. Palytoxin is a potent marine toxin that affects the sodium-potassium ATPase (adenosinetriphosphatase) pump and can cause multiple clinical effects, including paresthesia, dysguesia, hypertension, respiratory depression, coma, and death" http://www.ncbi.nlm.nih.gov/pubmed/19545971 0 706 "H. J. Seo, E. J. Park, M. J. Kim, S. Y. Kang, S. H. Lee, H. J. Kim, K. N. Lee, M. E. Jung, M. Lee, M. S. Kim, E. J. Son, W. K. Park, J. Kim and J. Lee" 2011 Design and synthesis of novel arylpiperazine derivatives containing the imidazole core targeting 5-HT(2A) receptor and 5-HT transporter J.Med.Chem. 54 18 6305-6318 "Serotonin antagonist reuptake inhibitor (SARI) drugs that block both 5-HT(2) receptors and the serotonin transporters have been developed. The human 5-HT(2A/2C) receptor has been implicated in several neurological conditions, and potent selective 5-HT(2A/2C) ligands may have therapeutic potential for treatment of CNS diseases such as depression. An imidazole moiety usually provides good pharmacokinetic properties as a drug substance, and thus considerable efforts have been devoted to develop imidazole derivatives into drug candidates. The imidazole series of compounds was evaluated against 5-HT(2A/2C) and serotonin reuptake inhibition. A few of the compounds in the series showed promising IC(50) values and antidepressant-like effect in in vivo forced swimming test (FST). On the basis of these results, further lead optimization studies resulted in identifying promising compounds potentially for therapeutic use" http://www.ncbi.nlm.nih.gov/pubmed/21823597 1 707 R. Cacabelos 2007 Donepezil in Alzheimer's disease: From conventional trials to pharmacogenetics "Neuropsychiatric Disease and Treatment.3 (3) ()(pp 303-333), 2007.Date of Publication: 2007." 3 303-333 "Donepezil is the leading compound for the treatment of Alzheimer's disease (AD) in more than 50 countries. As compared with other conventional acetyleholinesterase inhibitors (AChEIs), donepezil is a highly selective and reversible piperidine derivative with AChEI activity that exhibits the best pharmacological profile in terms of cognitive improvement, responders rate (40%-58%), dropout cases (5%-13%), and side-effects (6%-13%) in AD. Although donepezil represents a non cost-effective treatment most studies convey that this drug can provide a modest benefit on cognition, behavior, and activities of the daily living in both moderate and severe AD, contributing to slow down disease progression and, to a lesser exetnt, to delay institutionalization. Patients with vascular dementia might also benefit from donepezil in a similar fashion to AD patients. Some potential effects of donepezil on the AD brain, leading to reduced cortico-hippocampal atrophy, include the following: AChE inhibition, enhancement of cholinergic neurotransmission and putative modulation of other neurotransmitter systems, protection against glutamate-induced excitotoxicity, activation of neurotrophic mechanisms, promotion of non-amyloidodgenic pathways for APP processing, and indirect effects on cerebrovascular function improving brain perfusion. Recent studies demonstrate that the therapeutic response in AD is genotype-specific. Donepezil is metabolized via CYP-related enzymes, especially CYP2D6, CYP3A4, and CYPIA2. Approximately, 15%-20% of the AD population may exhibit an abnormal metabolism of AChEIs; about 50% of this population cluster would show an ultrarapid metabolism, requiring higher doses of AChEIs to reach a therapeutic threshold, whereas the other 50% of the cluster would exhibit a poor metabolism, displaying potential adverse events at low doses. In AD patients treated with a multifactorial therapy, including donepezil, the best responders are the CYP2D6-related extensive (EM)(*1/*1, *1/* 10) (57.47%) and intermediate metabolizers (IM)(* 1/*3, *1/* 5, *1/*6, *7/*10) (25.290/6), and the worst responders are the poor (PM) (*4/*4)(9.20%) and ultra-rapid metabolizers (UM) (* 1xN/* 1) (8.04%). Pharmacogenetic and pharmacogenomic factors may account for 755-85% of the therapeutic response in AD patients treated with donepezil and other AChEIs metabolized via enzymes of the CYP family. The implementation of pharmacogenetic protocols can optimize AD therapeutics. © 2007 Dove Medical Press Limited. All rights reserved" 0 708 "H. S. Menezes, B. B. Bueno, L. Ciulla, A. Schuh, F. F. Luz, R. J. Alves, M. P. Abegg and S. L. Cirino" 2008 Antidepressant behavioral effects of duloxetine and amitriptyline in the rat forced swimming test Acta Cir.Bras. 23 5 447-450 "PURPOSE: To compare the effects of the antidepressant drugs duloxetine and amitriptyline on depressive behaviors in rats. METHODS: Fifteen male Wistar rats were given systemic injections of duloxetine, amitriptyline or saline prior to a Forced Swimming Test (FST). Immobility and number of stops were measured. Data were analyzed by one-way ANOVA and Kruskall-Wallis. RESULTS: Rats given injections of duloxetine displayed fewer stops than the amitriptyline and control group (p< 0.05). The control group and Amitriptyline showed no difference (p=0.8). CONCLUSION: Duloxetine reduced depressive behaviors in the Forced Swimming Test been more effective than amitriptyline" http://www.ncbi.nlm.nih.gov/pubmed/18797690 1 709 "H. S. Foyet, D. E. Tsala, A. A. Bouba and L. Hritcu" 2012 Anxiolytic and Antidepressant-Like Effects of the Aqueous Extract of Alafia multiflora Stem Barks in Rodents Adv.Pharmacol.Sci. 2012 912041 "The present study examined the anxiolytic and antidepressant effects of the aqueous extract of Alafia multiflora Stapf (AM) stem barks (150 and 300 mg/kg, 7 days administration) on rats and mice, using experimental paradigms of anxiety and depression. In the open field, the aqueous extract increased significantly the number of center square crossed and the time spent at the center of the field as well as the rearing time, while the grooming time was reduced significantly. In the elevated plus maze, the aqueous extract increased the time spent and the number of entries in the open arms. All these effects were also completely reversed by flumazenil, an antagonist of benzodiazepine receptors and pindolol a beta-adrenoceptors blocker/5-HT 1A/1B receptor antagonist. The time spent in the light compartment, the latency time, and the number of the light-dark transitions increased significantly in the light/dark exploration test after the treatment with AM. The extract was able to reduce significantly the immobility time and increase swimming as well as climbing duration. Taken together, the present work evidenced anxiolytic effects of the aqueous extract of AM that might involve an action on benzodiazepine-type receptors and an antidepressant effect where noradrenergic mechanisms will probably play a role" http://www.ncbi.nlm.nih.gov/pubmed/23125853 1 710 "X. X. Qin, K. J. Coyne and J. H. Waite" 1997 Tough tendons. Mussel byssus has collagen with silk-like domains J.Biol.Chem. 272 51 32623-32627 "The primary structure of the alpha-chain of preCol-D (molecular mass = 80 kDa), a tanned collagenous protein predominating in the distal portion of the byssal threads of the mussel Mytilus edulis, was deduced from cDNA to encode an unprecedented natural block copolymer with three major domain types: a central collagen domain flanked by fibroin-like domains and followed by histidine-rich termini. The fibroin-like domains have sequence motifs that strongly resemble the crystalline polyalanine-rich and amorphous glycine-rich regions of spider dragline silk fibroins. The terminal regions resemble the histidine-rich domains of a variety of metal-binding proteins. The silk domains may toughen the collagen by increasing its strength and extensibility. PreCol-D expression is limited to the mussel foot, which contains a longitudinal gradient of preCol-D mRNA. This gradient increases linearly in the proximal to distal direction and reaches a maximum just before the distal depression of the foot" http://www.ncbi.nlm.nih.gov/pubmed/9405478 0 711 U. Baumfalk and K. Albus 1987 Baclofen inhibits the spontaneous and visually evoked responses of neurones in the striate cortex of the cat Neurosci.Lett. 75 2 187-192 The effects of iontophoretic application of gamma-aminobutyric acid (GABA) and beta-p-chlorophenyl-GABA (baclofen) on the activity of single neurones in the striate cortex of anaesthetized and paralysed cats were compared. Both compounds inhibited the spontaneous and the visually evoked responses of 92% of the neurones tested (n = 75) and they also eliminated the enhancement of the spontaneous and the evoked responses induced by the microiontophoretic application of glutamate. Bicuculline methiodide (BMI) antagonized the GABA-induced inhibition but did not significantly alter the effectiveness of baclofen for most neurones tested. The findings suggest that GABAB receptors are ubiquitous in the striate cortex of the cat. Evidence is presented to suggest that the GABAA and GABAB receptor subtypes differ in their distribution on some striate neurons http://www.ncbi.nlm.nih.gov/pubmed/2883615 0 712 "X. Zhang, M. Jakubowski, C. Buettner, V. Kainz, M. Gold and R. Burstein" 2013 Ezogabine (KCNQ2/3 channel opener) prevents delayed activation of meningeal nociceptors if given before but not after the occurrence of cortical spreading depression Epilepsy Behav. 28 2 243-248 "We proposed recently that induction of delayed activation of trigeminovascular neurons by cortical spreading depression (CSD) can explain the delayed onset of headache after the migraine aura (""aura""). This prompted us to search for ways to block the neuronal activation by" http://www.ncbi.nlm.nih.gov/pubmed/23562239 0 713 I. Liberzon and S. A. George 2010 SSRI-enhanced locus coeruleus activity and adolescent suicide: Lessons from animal models Neuropsychopharmacology 35 8 July 0 714 "C. Devader, A. Khayachi, J. Veyssiere, M. H. Moha Ou, M. Roulot, S. Moreno, M. Borsotto, S. Martin, C. Heurteaux and J. Mazella" 2015 In vitro and in vivo regulation of synaptogenesis by the novel antidepressant spadin "British Journal of Pharmacology.172 (10) ()(pp 2604-2617), 2015.Date of Publication: 01 May 2015." 10 2604-2617 "Background and Purpose We have described a novel antidepressant peptide, spadin, that acts by blocking the TWIK-related-potassium channel, type 1 (TREK-1). Here, we examined possible mechanisms of action of spadin at both molecular and cellular levels. Experimental Approaches Effects of spadin were measured in primary cultures of neurons or tissues from mice injected i.v. with spadin. Western blots, qPCR, histochemical and electrophysiological techniques were used. Key Results In vitro, spadin increased neuronal membrane potential and activated both the MAPK and PI3K signalling pathways, in a time- and concentration-dependent manner. The latter pathway was involved in the protective effect of spadin against staurosporine-induced apoptosis. Also, spadin enhanced both mRNA expression and protein of two markers of synaptogenesis, the post-synaptic density protein of 95 kDalton (PSD-95) and synapsin. We confirmed these effects on synaptogenesis by the observation that spadin treatment significantly increased the proportion of mature spines in cortical neurons. Finally, in vivo injections of spadin led to a rapid increase in both mRNA expression and protein level of brain-derived neurotrophic factor (BDNF) in the hippocampus, confirming the antidepressant action of the peptide. We argue for a new role of spadin in synaptogenesis as both PSD-95 and synapsin mRNA expression and protein levels were further enhanced in the hippocampus, following treatment in vivo with the peptide. Conclusions and Implications These findings provide new mechanisms of action for the rapidly acting antidepressant peptide spadin by stimulating expression of BDNF and synaptic proteins, both in vitro and in vivo" DO - http://dx.doi.org/10.1111/bph.13083 0 715 "M. Berg-Candolfi, E. Candolfi and L. Z. Benet" 1996 Suppression of intestinal and hepatic cytochrome P4503A in murine Toxoplasma infection. Effects of N-acetylcysteine and N(G)-monomethyl-L-arginine on the hepatic suppression Xenobiotica 26 4 381-394 "1. Cytochrome P4503A (CYP3A) expression was studied in a murine model of infection. Mice were infected with a cystogenic strain of Toxoplasma gondii and microsomes were prepared for liver homogenates and jejunum villus tip enterocytes on day 10 postinfection. Total cytochrome P450 (CYP) and CYP3A were quantitated, and CYP3A activity was determined. 2. In the infected mouse, total CYP and CYP3A contents fell in the liver (-39 and - 49% respectively) and intestine (-43 and - 48 % respectively), as did the rate of metabolism of erythromycin (Ery) and cyclosporine A (CyA), two markers of CYP3A activity (-36 and -26% in the liver, -35 and -58% in the intestine). 3. To determine the mechanism(s) involved in the depression of hepatic CYP3A, infected mice were treated on day 7.5 post-infection with a monoclonal antibody raised against interferon-gamma (anti-IFN-gamma, or from days 7.5 to 10 post-infection with either N(G)-monomethyl-L-arginine (NMMA), an inhibitor of reactive nitrogen intermediates (RNI) production, or N-acetylcysteine (NAC), a reactive oxygen intermediates (ROI) scavenger. 4. Total CYP content was restored in the liver of infected mice treated with anti-IFN-gamma, but with marked interindividual variability. NAC treatment led to a recovery in the liver of total CYP content (+35 %), CYP3A content (total recovery), and the rates of Ery (+59%) and CyA (+87%) metabolism, whereas inconsistent results were obtained with NMMA. These results suggest that NAC, but probably not NMMA, partially protects hepatic CYP3A from Toxoplasma-mediated suppression in mouse" http://www.ncbi.nlm.nih.gov/pubmed/9173679 0 716 "R. Eitan, G. Landshut, T. Lifschytz, O. Einstein, T. Ben-Hur and B. Lerer" 2010 "The thyroid hormone, triiodothyronine, enhances fluoxetine-induced neurogenesis in rats: possible role in antidepressant-augmenting properties" Int.J.Neuropsychopharmacol. 13 5 553-561 "The thyroid hormone triiodothyronine (T3) may accelerate and augment the action of antidepressants. Antidepressants up-regulate neurogenesis in adult rodent hippocampus. We studied the effect of T3 and T3+fluoxetine in enhancement of hippocampal neurogenesis beyond that induced by fluoxetine alone and the correlation with antidepressant behaviour in the novelty suppressed feeding test (NSFT). Rats were administered fluoxetine (5 mg/kg.d), T3 (50 mug/kg.d), fluoxetine (5 mg/kg.d)+T3 (50 mug/kg.d) or saline, for 21 d. Neurogenesis was studied by doublecortin (DCX) immunohistochemistry in the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ). In the NSFT, latency to feeding in animals deprived of food was measured. Fluoxetine and fluoxetine+T3 increased the number of doublecortin-positive (DCX+) cells in the SGZ compared to saline (p=0.00005, p=0.008, respectively). There was a trend towards an increased number of DCX+ cells by T3 compared to saline (p=0.06). Combined treatment with fluoxetine+T3 further increased the number of DCX+ cells compared to T3 or fluoxetine alone (p=0.001, p=0.014, respectively). There was no effect of any of the treatments on number of DCX+ cells in the SVZ. In the NSFT, all treatments (T3, fluoxetine+T3 and fluoxetine) reduced latency to feeding compared to saline (p=0.0004, p=0.00001, p=0.00009, respectively). Fluoxetine+T3 further reduced latency to feeding compared to T3 alone (p=0.05). The results suggest that enhancement of antidepressant action by T3 may be related to its effect of increasing hippocampal neurogenesis and that the antidepressant effect of these treatments is specific to the hippocampus and does not represent a general effect on cell proliferation" http://www.ncbi.nlm.nih.gov/pubmed/19835665 1 717 "G. Eisenhofer, D. S. Goldstein, R. Stull, H. R. Keiser, T. Sunderland, D. L. Murphy and I. J. Kopin" 1986 "Simultaneous liquid-chromatographic determination of 3,4-dihydroxyphenylglycol, catecholamines, and 3,4-dihydroxyphenylalanine in plasma, and their responses to inhibition of monoamine oxidase" Clin.Chem. 32 11 2030-2033 "This is a reversed-phase liquid-chromatographic method, with electrochemical detection, for simultaneously measuring, in plasma, the concentrations of the catecholamine precursor dihydroxyphenylalanine (DOPA); the endogenous catecholamines norepinephrine, epinephrine, and dopamine; and the deaminated catecholamine metabolites dihydroxyphenylacetic acid (DOPAC) and dihydroxyphenylglycol (DHPG). We used this method to assess effects of monoamine oxidase (EC 1.4.3.4) inhibition in humans. Plasma DHPG concentrations as determined by the present method (mean 826, SEM 61 ng/L) were similar to those found by other methods. Inhibition of monoamine oxidase (by administering deprenyl or tranylcypromine) decreased plasma DHPG by greater than 65%, plasma DOPAC by greater than 50%, and plasma DOPA by about 20%, without consistently affecting norepinephrine or epinephrine. Simultaneous measurement of DOPA, catecholamines, and DHPG may be useful for examining the synthesis, release, and intraneuronal metabolism of norepinephrine. The assay method is rapid, reliable, and simple, and it provides a more comprehensive assessment of noradrenergic nervous function than does measurement only of catecholamines" http://www.ncbi.nlm.nih.gov/pubmed/3096593 0 718 "G. Kukes, V. J. De and R. Elul" 1976 A linked active transport system for Na+ and K+ in a glial cell line Brain Res. 104 1 93-105 "Ouabain (5 X 10(-4) M) induced a 6-fold increase in intracellular Na+ and a 65% loss of cellular K+ in C6 glial cells which was accompanied by a 12 mV decrease in the resting membrane potential. Following ouabain washout intracellular ion concentrations and the membrane potential returned to control levels suggesting that C6 is capable of active Na+ transport which is linked to uptake of K+. A portion of K+ uptake under steady-state conditions is also active since K+ influx was reduced 32% by ouabain. Five mM cyanide significantly increased cell Na+ and significantly decreased cell K+ and the membrane potential. The similarity in the ratio of Na+ gained/K+ lost (ouabain 1.24, cyanide 1.41) suggests that the two agents inhibit the same ion transport system. Decreased temperature had the paradoxical effect of increasing intracellular K+ while significantly decreasing both membrane potential and K+ influx. Part of this effect may be due to the marked reduction in K+ efflux at low temperature. At 6 degrees C cell loss of K+ was much less than loss of K+ with ouabain at 37 degrees C. The observation of a linked Na+-K+ transport system in C6 cell confirms the hypothesis that coupled active Na+-K+ exchange occurs in glial cells and suggests that ionic transport may regulate certain aspects of glial metabolism" http://www.ncbi.nlm.nih.gov/pubmed/1247910 0 719 C. Harrison 2013 Trial watch: opioid receptor blocker shows promise in Phase II depression trial Nat.Rev.Drug Discov. 12 6 415 http://www.ncbi.nlm.nih.gov/pubmed/23722336 0 720 "L. Daristotle, A. D. Berssenbrugge, M. J. Engwall and G. E. Bisgard" 1990 The effects of carotid body hypocapnia on ventilation in goats Respir.Physiol 79 2 123-135 "This study was designed to examine the influence of carotid body (CB) hypocapnia on ventilation by selectively perfusing the CB through an extracorporeal circuit in 19 goats. When PcbCO2 was decreased from normocapnic levels in 14 awake goats (delta PcbCO2 = 10.9 Torr), PaCO2 increased 5.6 Torr (P less than 0.05) and VE decreased 24% (P less than 0.001) (mean values). The ventilatory sensitivity to inspired CO2 was not changed by CB hypocapnia in 5 of these goats, but the response was shifted to the right. During CB hypocapnia, ventilatory instability, including apnea, was observed in 4 of 14 goats; this irregular breathing continued at elevated levels of PaCO2. In 5 anesthetized goats, CB hypocapnia (delta PcbCO2 = 18.0 Torr) decreased VE by 70% in the intact state, but produced no significant ventilatory depression after CB denervation. We conclude that CB hypocapnia depresses ventilation in both awake and anesthetized goats mostly through CB chemoreceptor effects, and suggest that this hypoventilation may predispose to ventilatory instability in some animals" http://www.ncbi.nlm.nih.gov/pubmed/2110682 0 721 "K. Weissenborn, A. B. Tryc, M. Heeren, H. Worthmann, H. Pflugrad, G. Berding, M. Bokemeyer, H. L. Tillmann and A. Goldbecker" 2009 Hepatitis C virus infection and the brain "Metabolic Brain Disease.24 (1) ()(pp 197-210), 2009.Date of Publication: March 2009." 1 197-210 "There is growing evidence that hepatitis C virus (HCV)-infection may affect the brain. About half of the HCV-infected patients complain of chronic fatigue irrespective of their stage of liver disease or virus replication rate. Even after successful antiviral therapy fatigue persists in about one third of the patients. Many patients, in addition, report of deficits in attention, concentration and memory, some also of depression. Psychometric testing revealed deficits in attention and verbal learning ability as characteristic for HCV-afflicted patients with normal liver function. Magnetic resonance spectroscopic studies showed alterations of the cerebral choline, N-acetyl-aspartate, and creatine content in the basal ganglia, white matter and frontal cortex, respectively. Recently, pathologic cerebral serotonin and dopamine transporter binding and regional alterations of the cerebral glucose utilisation compatible with alterations of the dopaminergic attentional system were observed. Several studies detected HCV in brain samples or cerebro-spinal fluid. Interestingly, viral sequences in the brain often differed from those in the liver, but were closely related to those found in lymphoid tissue. Therefore, the Trojan horse hypothesis emerged: HCV-infected mononuclear blood cells enter the brain, enabling the virus to reside within the brain (probably in microglia) and to infect brain cells, especially astrocytes. © 2008 Springer Science+Business Media, LLC" DO - http://dx.doi.org/10.1007/s11011-008-9130-5 0 722 "A. Kageyama, H. Sakakibara, W. Zhou, M. Yoshioka, M. Ohsumi, K. Shimoi and H. Yokogoshi" 2010 Genistein regulated serotonergic activity in the hippocampus of ovariectomized rats under forced swimming stress Biosci.Biotechnol.Biochem. 74 10 2005-2010 "The mortality of individuals suffering from depression has been increasing, especially post-menopausal women; therefore, their care and treatment are important to maintain a high quality of life. In the present study, we evaluated the antidepressant-like effects of a major isoflavonoid, genistein (4',5,7-trihydroxyisoflavone), using a behavioral model of depression, the forced swimming test (FST), in ovariectomized rats. Daily administration of genistein to ovariectomized rats at a dosage of 10 mg/kg of body weight/d for 14 d significantly reduced the immobility time during the FST without changing motor dysfunction. On the other hand, a higher dosage, 100 mg/kg/d, did not have any effects on the immobility time compared with the vehicle control. Repeated administration of genistein at 10 mg/kg of body weight did not affect serotonergic activities in the hippocampus compared to the vehicle control in ovariectomized rats. A 5-min FST trial stimulated these activities. On the other hand, repeated pretreatment with genistein protected against changes in activity during the FST trial. These results suggest that daily consumption of genistein 10 mg/kg/d might have antidepressant-like effect on ovariectomized rats by regulating changes in serotonergic metabolism in the hippocampus under stressful conditions" http://www.ncbi.nlm.nih.gov/pubmed/20944428 1 723 "S. S. Negus, E. M. Morrissey, M. Rosenberg, K. Cheng and K. C. Rice" 2010 Effects of kappa opioids in an assay of pain-depressed intracranial self-stimulation in rats Psychopharmacology (Berl) 210 2 149-159 "RATIONALE: Selective, centrally acting kappa opioid agonists produce antinociception in a wide range of preclinical assays, but these compounds perform poorly as analgesics in humans. This discrepancy may be related to the behavioral depressant effects of kappa agonists. Kappa antagonists do not typically produce antinociception, but they produce antidepressant-like effects in some preclinical assays. OBJECTIVE: The objective of this study was to test the hypothesis that the kappa agonist U69,593 and the kappa antagonist norbinaltorphimine would produce pronociceptive and antinociceptive effects, respectively, in an assay of pain-depressed behavior. METHODS: Effects of U69,593 (0.056-0.56 mg/kg), norbinaltorphimine (10-32 mg/kg), and morphine (3.2 mg/kg) were evaluated on the stimulation of a stretching response and the depression of intracranial self-stimulation (ICSS) of the medial forebrain bundle produced in rats by a common noxious stimulus (intraperitoneal administration of dilute lactic acid). RESULTS: U69,593 produced a dose-dependent blockade of acid-stimulated stretching but only exacerbated acid-induced depression of ICSS. Thus, U69,593 produced antinociception in the assay of pain-stimulated behavior but pronociceptive effects in the assay of pain-depressed behavior. Norbinaltorphimine did not alter acid-stimulated stretching or acid-induced depression of ICSS. The mu opioid agonist morphine blocked both acid-stimulated stretching and acid-induced depression of ICSS. CONCLUSIONS: These results support the hypothesis that prodepressant effects of kappa agonists may limit their clinical utility as analgesics. These results do not support the use of kappa antagonists to treat depressant effects of pain. These findings illustrate the potential value of using complementary assays of pain-stimulated and pain-depressed behaviors for preclinical evaluation of candidate analgesics" http://www.ncbi.nlm.nih.gov/pubmed/20101391 0 724 "T. M. Griffith, A. T. Chaytor, L. M. Bakker and D. H. Edwards" 2005 5-Methyltetrahydrofolate and tetrahydrobiopterin can modulate electrotonically mediated endothelium-dependent vascular relaxation Proc.Natl.Acad.Sci.U.S.A 102 19 7008-7013 "We have investigated the ability of 5-methyltetrahydrofolate (5-MTHF) and tetrahydrobiopterin (BH(4)) to modulate nitric oxide (NO)-independent vascular relaxations that are mediated by the sequential spread of endothelial hyperpolarization through the wall of the rabbit iliac artery by means of myoendothelial and homocellular smooth muscle gap junctions. Relaxations and subintimal smooth muscle hyperpolarizations evoked by cyclopiazonic acid were depressed by the gap junction inhibitor 2-aminoethoxydiphenyl borate, whose effects were prevented by 5-MTHF and BH(4), but not by their oxidized forms folic acid and 7,8-dihydrobiopterin. Analogously, 5-MTHF and BH(4), but not folic acid or 7,8-dihydrobiopterin, attenuated the depression of subintimal hyperpolarization by a connexin-mimetic peptide targeted against Cx37 and Cx40 ((37,40)Gap 26) and the depression of subadventitial hyperpolarization by a peptide targeted against Cx43 ((43)Gap 26), thus reflecting the known differential expression of Cx37 and Cx40 in the endothelium and Cx43 in the media of the rabbit iliac artery. The inhibitory effects of 2-aminoethoxydiphenyl borate and (37,40)Gap 26 against subintimal hyperpolarization were prevented by catalase, which destroys H(2)O(2). 5-MTHF and BH(4) thus appear capable of modulating electrotonic signaling by means of myoendothelial and smooth muscle gap junctions by reducing oxidant stress, potentially conferring an ability to reverse the endothelial dysfunction found in disease states through mechanisms that are independent of NO" http://www.ncbi.nlm.nih.gov/pubmed/15867155 0 725 "A. J. Eisch, H. A. Cameron, J. M. Encinas, L. A. Meltzer, G.-L. Ming and L. S. Overstreet-Wadiche" 2008 "Adult neurogenesis, mental health, and mental illness: Hope or hype?" "Journal of Neuroscience.28 (46) ()(pp 11785-11791), 2008.Date of Publication: 12 Nov 2008." 46 11785-11791 "Psychiatric and neurologic disorders take an enormous toll on society. Alleviating the devastating symptoms and consequences of neuropsychiatric disorders such as addiction, depression, epilepsy, and schizophrenia is a main force driving clinical and basic researchers alike. By elucidating these disease neuromechanisms, researchers hope to better define treatments and preventive therapies. Research suggests that regulation of adult hippocampal neurogenesis represents a promising approach to treating and perhaps preventing mental illness. Here we appraise the role of adult hippocampal neurogenesis in major psychiatric and neurologic disorders within the essential framework of recent progress made in understanding ""normal"" adult neurogenesis. Topics addressed include the following: the life cycle of an adult hippocampal stem cell and the implications for aging; links between learning and hippocampal neurogenesis; the reciprocal relationship between cocaine self-administration and adult hippocampal neurogenesis; the role of adult neurogenesis in an animal model of depression and response to antidepressant exposure; the impact of neonatal seizures on dentate gyrus neurogenesis; and the contribution of a schizophrenia-susceptibility gene to adult hippocampal neurogenesis. These topics are discussed in light of the regulation of adult neurogenesis, the relationship to normal neurogenesis in adulthood and aging, and, importantly, the manipulation of neurogenesis to promote mental health and treat mental illness. Copyright © 2008 Society for Neuroscience" DO - http://dx.doi.org/10.1523/JNEUROSCI.3798-08.2008 0 726 "D. Patschke, H. J. Eberlein, W. Hess, J. Tarnow and G. Zimmermann" 1977 Antagonism of morphine with naloxone in dogs: cardiovascular effects with special reference to the coronary circulation Br.J.Anaesth. 49 6 525-533 "The cardiovascular effects of naloxone 15 microgram/kg following morphine 2.0 mg/kg were studied in closed-chest dogs during light nitrous oxide-halothane anaesthesia. The bolus injection of naloxone caused an increase in heart rate (73%), cardiac output (20%) and mean arterial pressure (20%). Total peripheral resistance was unaffected. LV dP/dt max and LV dP/dt max/IP increased by 25% and 14% respectively, but positive inotropic effects could not be shown when load data, heart rate and the decrease in left ventricular ejection fraction (22%) were taken into consideration. The cardiovascular stimulation resulted in an increase in myocardial oxygen demand (66%) which was met by an increase in coronary blood flow (59%). The data suggest that the antagonism of narcotics with high doses of naloxone may impair the myocardial oxygen supply in patients suffering from coronary insufficiency. It is concluded that naloxone should be titrated for each patient to ensure adequate reversal of respiratory depression and to avoid circulatory stress" http://www.ncbi.nlm.nih.gov/pubmed/871349 0 727 P. Willner 1983 "Dopamine and depression: A review of recent evidence, II. Theoretical approaches" "Brain Research Reviews.6 (3) ()(pp 235-236), 1983.Date of Publication: 1983." 3 235-236 "This paper discusses 3 behavioural approaches to depression, 'learned helplessness', reward system dysfunction and reduced responsiveness to the environment, and the role of dopamine (DA) in their related animal models. The meso-limbic and nigrostriatal DA system appears to be related primarily to responsiveness to the environment. This conclusion is discussed in relation to the clinical symptomatology of depression" 0 728 "K. Kajiyama, D. F. Pauly, H. Hughes, S. B. Yoon, M. L. Entman and J. B. McMillin-Wood" 1987 Protection by verapamil of mitochondrial glutathione equilibrium and phospholipid changes during reperfusion of ischemic canine myocardium Circ.Res. 61 2 301-310 "Pretreatment of the ischemic myocardium with verapamil protects against mitochondrial respiratory depression observed during ischemic arrest as well as during reperfusion. Since ischemic mitochondrial function appears not to be altered further by reperfusion, the purpose of this study is to identify a biochemical event affecting mitochondria that is specifically associated with reperfusion injury. It has been proposed that increased cellular Ca2+ influx and oxygen toxicity may result from reintroduction of coronary flow. Increased cytosolic Ca2+ is transmitted to the mitochondria with subsequent activation of Ca2+-dependent events, including phospholipase A2. Net production of lysophospholipids (and loss of total diacylphospholipids from the mitochondria) will proceed when reacylation mechanisms are inhibited. Since acyl-CoA:lysophospholipid acyltransferase is a sulfhydryl-sensitive enzyme and since increased activity of glutathione peroxidase shifts the levels of the mitochondrial sulfhydryl buffer, glutathione, towards oxidation, levels of glutathione and its oxidation state were measured during reperfusion in the absence or presence of verapamil pretreatment. Ischemia lowers total glutathione and reduces the redox ratio (reduced glutathione: oxidized glutathione) by 85%. Reperfusion partially returns the redox ratio to control by causing oxidized glutathione to disappear from the matrix. Verapamil maintains both the concentration and the redox potential of glutathione at control levels. Concomitant with alterations in reduced glutathione:oxidized glutathione is a decrease in ischemic mitochondrial phospholipid content. During reperfusion, phosphatidylethanolamine and its major constituent fatty acids (C 18:0 and C 20:4) are specifically lost from the mitochondrial membrane. Accompanying the significant loss of arachidonic acid during reperfusion is the decreased content of 11-OH, 12-OH, and 15-OH arachidonate. These lipid peroxidation products are not increased in ischemia. It is proposed that oxidation of matrix glutathione to glutathione disulfide during ischemia results in formation of glutathione-protein mixed disulfides and inhibition of sulfhydryl-sensitive proteins, including acyl-CoA lysophosphatide acyltransferase. Thus, metabolic events occurring within the ischemic period set the stage for prolonged dysfunction during reperfusion" http://www.ncbi.nlm.nih.gov/pubmed/3621493 0 729 "S.-L. Cheng, H.-C. Wang and P.-C. Yang" 2005 Acute respiratory distress syndrome and lung fibrosis after ingestion of a high dose of ortho-phenylphenol "Journal of the Formosan Medical Association.104 (8) ()(pp 585-587), 2005.Date of Publication: 2005." 8 585-587 "Ortho-phenylphenol (OPP) and its sodium salt are used as fungicides and antibacterial agents, ingestion of which has been found to cause liver toxicity, renal toxicity and carcinomas in the urinary tract of rats. Lung damage due to OPP ingestion has not been reported in humans. We report a suicidal 39-year-old woman with stage II cervical cancer who drank a potentially lethal dose of OPP in the form of a commercial antiseptic, which led to the complication of liver and renal function impairment, severe lung damage with acute respiratory distress syndrome and subsequent severe lung fibrosis. Open lung biopsy showed diffuse alveolar damage. She was discharged after 34 days of hospitalization with continuing domiciliary oxygen therapy" 0 730 "S. Authier, P. Haefner, S. Fournier, E. Troncy and L. B. Moon" 2010 Combined cardiopulmonary assessments with implantable telemetry device in conscious freely moving cynomolgus monkeys J.Pharmacol.Toxicol.Methods 62 1 06-Nov "Female cynomolgus monkeys were surgically implanted with telemetry transmitters recording ECG (DII), arterial pressure, physical activity, body temperature, and tidal volume. Respiratory rate (RR) and tidal volume (TV) were monitored simultaneously with the telemetry transmitter using impedance. Impedance-based monitoring of RR and TV by telemetry correlated with controlled TV and with pneumotachometer (>98%) in restrained animals. Control drugs with cardiovascular and respiratory effects, including saline, medetomidine (0.01, 0.02 and 0.04mg/kg) and cocaine (0.5, 1.0 and 1.5mg/kg) were administered intravenously. An averaging epoch of 5min was used for analysis of respiratory data. Medetomidine induced significant respiratory depression with decrease in RR and TV in freely moving animals while cocaine increased TV, RR and minute ventilation (MV) with concomitant increase in heart rate when compared with time matched values from saline-treated animals. The onset, duration and magnitude of cardiovascular and respiratory changes were correlated. This highlights the dependency of the cardiovascular and respiratory systems. The use of cardiopulmonary monitoring can allow continuous monitoring including during night time when variability of respiratory parameters is lower. Monitoring of cardiovascular and respiratory parameters in the same animals could also help to decrease the number of animals used in research" http://www.ncbi.nlm.nih.gov/pubmed/20570745 0 731 F. A. Wali and A. H. Suer 1987 Effect of verapamil on Ca2+ influx to rat phrenic nerve-diaphragm preparation Br.J.Anaesth. 59 12 1571-1578 "The effect of verapamil on contractility and on influx of calcium (Ca2+) to the rat phrenic nerve-hemidiaphragm preparation was studied in vitro, at rest and during electrical stimulation at 0.2-100 Hz. Calcium content of the bathing solution was measured using the Technicon method (SMAC, Sequential Multiple Analyser/Computer). The results showed that verapamil (a) reduced the twitch and tetanic contractions in a non-competitive manner, and (b) reduced the influx of Ca2+ to the rat hemidiaphragm preparation. Greater reductions occurred as the rate of stimulation increased" http://www.ncbi.nlm.nih.gov/pubmed/3426912 0 732 "H. Winterhoff, M. Hambrugge and U. Vahlensieck" 1993 Pharmacological screening of hypericum perforatum L. in animals "Nervenheilkunde.12 (6 A) ()(pp 341-345), 1993.Date of Publication: 1993." 6:00 AM 341-345 0 733 "F. Priviero, N. G. De, E. Antunes and A. Zanesco" 2004 Negative chronotropic response to adenosine receptor stimulation in rat right atria after run training Clin.Exp.Pharmacol.Physiol 31 10 741-743 "The aim of the present study was to evaluate the potency and maximal responses (E(max)) to the adenosine receptor agonists N(6)-cyclopentyladenosine (CPA), N-ethylcarboxamidoadenosine (NECA) and N(6)-(3-iodobenzyl)-5'-N-methylcarbaxamidoadenosine (IB-MECA) in right atria from trained rats. We also investigated the interaction between the training bradycardia and the sensitivity of the chronotropic response mediated by adenosine receptor stimulation. Animals were submitted to run training for 60 min, 5 days a week, over a period of 8 weeks. Mean blood pressure and heart rate were measured in conscious animals. Right atria were isolated and concentration-response curves to CPA, NECA and IB-MECA were obtained. A reduction in heart rate was found in trained rats, indicating that the training programme was successful in inducing physical conditioning. The three adenosine receptor agonists induced a concentration-dependent negative chronotropic response. The rank order of potency and E(max) for the three adenosine receptor agonists was CPA > NECA > IB-MECA. Dynamic exercise for 8 weeks did not alter the E(max) for CPA, NECA and IB-MECA. Similarly, the potencies of CPA and NECA were not affected by run training, whereas the potency of IB-MECA was reduced (6.10 +/- 0.09 vs 5.66 +/- 0.10 for sedentary and trained groups, respectively). In conclusion, run training for 8 weeks induced a desensitization of the chronotropic response to IB-MECA without changing the potency of CPA and NECA. These findings exclude the participation of adenosine receptors in the training bradycardia" http://www.ncbi.nlm.nih.gov/pubmed/15554918 0 734 "O. Reikeras, P. Gunnes, D. Sorlie, R. Ekroth, R. Jorde and O. D. Mjos" 1985 Haemodynamic effects of high doses of insulin during acute left ventricular failure in dogs Eur.Heart J. 6 5 451-457 "Haemodynamic effects of pharmacological doses of insulin during acute ischaemic heart failure were studied in 8 dogs. Severe depression of left ventricular function was induced by the injection of 50 micron plastic microspheres into the left main coronary artery. This was demonstrated by a significant increase in left ventricular end-diastolic pressure and a significant decrease in the maximum rate of left ventricular pressure rise (LVdP/dtmax), stroke volume and cardiac output. Eighty-five minutes after the embolization procedure, 300 IU of insulin free of glucagon and calcium was injected as a bolus. This was followed by infusion of glucose and potassium to maintain physiological levels of these factors. Five minutes after insulin administration, there was a significant improvement in left ventricular performance as shown by decreased left ventricular end-diastolic pressure (P less than 0.01) and increased LVdP/dtmax (P less than 0.01), stroke volume (P less than 0.05) and cardiac output (P less than 0.05). A significant reduction in heart rate occurred. A non-significant increase in mean aortic blood pressure and reduction in total peripheral resistance were seen. In conclusion, pharmacological doses of insulin significantly improve cardiac pump function during acute ischaemic left ventricular failure in dogs" http://www.ncbi.nlm.nih.gov/pubmed/3899650 0 735 G. Pogatsa and E. Dubecz 1979 Effect of propranolol on drug-induced and physiological glycogenolysis in the liver Arzneimittelforschung. 29 8 1104-1107 "The beta-adrenergic blocking agent propranolol had in itself no notable influence on the blood glucose level in rats, but in combination with chlorpropamide it considerably delayed and enhanced the hypoglycaemic and liver glycogenolysis depressing actions of chlorpropamide. This effect was still more pronounced when the rats were treated in addition to propranolol and chlorpropamide with thyroxine or glanduitrine, which in themselves act as stimulators of liver glycogenolysis. The simultaneous administration of propranolol and chlorpropamide depressed considerably the liver glycogenolysis induced by prolonged fasting and inhibited completely the liver glycogenolysis observed after hepatectomy. The reports available in the literature on propranolol-precipitated hypoglycaemia in patients are surveyed and it is supposed that the beta-adrenergic blocking agent produces hypoglycaemia primarily through the depression of liver glycogenolysis. This observation supports the hypothesis that the adrenergic beta-receptors play an important role in the sympathetic control of liver glycogenolysis" http://www.ncbi.nlm.nih.gov/pubmed/583007 0 736 "T. Akema, A. Chiba, R. Shinozaki, M. Oshida, F. Kimura and J. Toyoda" 1996 Acute immobilization stress and intraventricular injection of CRF suppress naloxone-induced LH release in ovariectomized estrogen-primed rats J.Neuroendocrinol. 8 8 647-652 "The present study was undertaken to evaluate the role and possible interaction of the endogenous opioid peptide (EOP) and corticotropin-releasing factor (CRF) in the acute stress-induced suppression of gonadotropin secretion in ovariectomized estrogen-primed rats. An intravenous (i.v.) injection of naloxone (10 or 20 mg/kg), an EOP antagonist, significantly elevated serum luteinizing hormone (LH) levels within 10 min in non-stressed animals. The naloxone-induced LH release was completely eliminated when tested 30 min after the onset of acute immobilization. In a subsequent study, it was found that suppression of the naloxone-induced LH release occurred as early as 5 min after the stress onset, and was still evident 60 min after the end of a 30-min period of immobilization. The effect of naloxone was restored 3 h after liberation of the animal from the 30-min immobilization. An intraventricular (i.c.v.) injection of CRF (1 or 5 micrograms) also significantly suppressed, in a dose-related manner, the effect of a subsequent i.v. injection of naloxone. However, an i.c.v. injection of alpha-helical CRF(9-41) (25 or 50 micrograms), a CRF antagonist, prior to immobilization, could not interfere with the suppressive effect of stress on naloxone-induced LH release. These results suggest that both acute immobilization stress and CRF can inhibit the LH secretory activity without mediation by EOP neurons. However, the stress-related suppression may involve non-CRF mechanism(s)" http://www.ncbi.nlm.nih.gov/pubmed/8866253 0 737 H. Petzold and A. Ziegler 1967 [The effect of prednisone and turinabol on the tissue phosphatases in experimental fatty liver in rats] Z.Gesamte Inn.Med. 22 21 654-657 http://www.ncbi.nlm.nih.gov/pubmed/4233509 0 738 G. G. Chichkanov 1968 [Effect of reserpine on the heart blood supply] Farmakol.Toksikol. 31 3 269-273 http://www.ncbi.nlm.nih.gov/pubmed/5698104 0 739 "H. Fromm and J. B. Rodgers, Jr." 1971 Effect of aminopterin on lipid absorption: depression of lipid-reesterifying enzymes Am.J.Physiol 221 4 998-1003 http://www.ncbi.nlm.nih.gov/pubmed/5111267 0 740 "S. Bhavsar, J. Watkins and A. Young" 1998 Synergy between amylin and cholecystokinin for inhibition of food intake in mice Physiol Behav. 64 4 557-561 "Several gastrointestinal peptides which are secreted in response to nutrients have been reported to suppress food intake. Amylin is a peptide hormone co-secreted with insulin from pancreatic beta-cells in response to nutrient stimuli. Cholesystokinin (CCK) is secreted from duodenal and jejunal mucosal cells in response to fat and protein. Amylin and CCK-8 have been reported to reduce food intake in rodents when given centrally as well as peripherally. Amylin injected intraperitoneally (i.p.) reduced food intake over the subsequent 30 min in overnight fasted mice by a maximum of 57 +/- 6% with an ED50 of 0.93 nmol/kg (3.63 microg/kg) +/- 0.34 log units. On a molar basis, this potency was similar to that of CCK-8 (ED50 0.85 nmol/kg (0.97 microg/kg) +/- 0.28 log units; p = 0.93) which inhibited food intake by a maximum of 71 +/- 7%. When amylin and CCK-8 were injected i.p. as an amylin:CCK-8 mixture, immediately before presentation of food in overnight fasted mice, food intake in the subsequent 30 min was reduced by a maximum of 91%, an amount that was greater than that producable by i.p. injection of amylin or CCK-8 alone. Isobolar analysis revealed a marked synergy between amylin and CCK-8 in reducing food intake, such that statistically ineffective doses of amylin and CCK, when combined, evoked near-maximal inhibition of food intake. Because the typical physiological event is for amylin and CCK both to be secreted in response to mixed meals, the synergy between them could indicate a shared role in physiological appetite control" http://www.ncbi.nlm.nih.gov/pubmed/9761232 0 741 D. R. Garris 1988 "Effects of diabetes on uterine condition, decidualization, vascularization, and corpus luteum function in the pseudopregnant rat" Endocrinology 122 2 665-672 "The effects of alloxan-induced diabetes on uterine decidualization and the associated changes in uterine blood flow (UBF) and corpus luteum activity were evaluated in rats between days 4-9 of pseudopregnancy (day 0 = ovulation). Rats were made diabetic (D) with a 40 mg/kg injection (iv) of alloxan on day 1 of pseudopregnancy. Saline-treated rats served as controls (C). Uterine weights were depressed in D rats between days 6-7 of pseudopregnancy in association with elevated blood glucose levels (greater than 300 mg/dl) relative to control values. UBF rates were also depressed in D rats between days 6-7 of pseudopregnancy compared with control values. Insulin replacement therapy (6 IU bovine/day) effectively normalized both uterine weight and UBF in diabetic rats. Decidual tissue (DT) growth was impaired in D rats between days 7 and 9 of pseudopregnancy (DT induction on day 4 of pseudopregnancy) compared with controls. Tissue blood flow rates were severely depressed throughout pseudopregnancy in D rats, but insulin treatment normalized both uterine parameters to control levels. Serum progesterone levels were lower in D rats than in controls between days 7 and 9 of pseudopregnancy. Daily insulin treatment normalized luteal function to control levels. The depressed DT weights in D rats were mimicked by the experimental reduction of DT blood flow in control rats. These results indicate that the uterine atrophy and poor endometrial decidualization that characterized the D rat are accompanied by impaired UBF and luteal activity. These findings suggest that the D-associated depression in female reproductive performance is related to the lack of proper hormone support of tissue vascular dynamics" http://www.ncbi.nlm.nih.gov/pubmed/3276500 0 742 W. Jahn 1969 "[N6-(naphthyl-(1))-methyladenosine, an adenosine derivative with prolonged coronary effect]" Arzneimittelforschung. 19 5 701-704 http://www.ncbi.nlm.nih.gov/pubmed/5819777 0 743 "A. I. Nikolaev, M. N. Nazarmukhamedova and M. I. Rozgon" 1973 [Restoration of immunogenesis by a complex cobalt (Co-30) compound during streptomycin therapy] Zh.Mikrobiol.Epidemiol.Immunobiol. 50 10 69-72 http://www.ncbi.nlm.nih.gov/pubmed/4799122 0 744 "P. Schwandt, R. Lindlbauer and M. Knedel" 1969 "[On the action of ouabain-, nicotini acid- and potassium-free incubation media on the ACTH stimulated lipolysis in isolated fat cells]" Clin.Chim.Acta 24 2 267-274 http://www.ncbi.nlm.nih.gov/pubmed/4306860 0 745 S. Kubota and T. Kitajima 2008 A model for synaptic development regulated by NMDA receptor subunit expression J.Comput.Neurosci. 24 1 Jan-20 "Activation of NMDA receptors (NMDARs) is highly involved in the potentiation and depression of synaptic transmission. NMDARs comprise NR1 and NR2B subunits in the neonatal forebrain, while the expression of NR2A subunit is increased over time, leading to shortening of NMDAR-mediated synaptic currents. It has been suggested that the developmental switch in the NMDAR subunit composition regulates synaptic plasticity, but its physiological role remains unclear. In this study, we examine the effects of the NMDAR subunit switch on the spike-timing-dependent plasticity and the synaptic weight dynamics and demonstrate that the subunit switch contributes to inducing two consecutive processes-the potentiation of weak synapses and the induction of the competition between them-at an adequately rapid rate. Regulation of NMDAR subunit expression can be considered as a mechanism that promotes rapid and stable growth of immature synapses" http://www.ncbi.nlm.nih.gov/pubmed/18202921 0 746 C. E. Inturrisi 1969 Thallium-induced dephosphorylation of a phosphorylated intermediate of the (sodium plus thallium-activated) ATPase Biochim.Biophys.Acta 178 3 630-633 http://www.ncbi.nlm.nih.gov/pubmed/4239444 0 747 S. I. Pashchenko and A. E. Pashchenko 1969 [Functional reorganization of the thyroid gland in experimental tuberculosis and its antibacterial therapy] Biull.Eksp.Biol.Med. 68 11 30-33 http://www.ncbi.nlm.nih.gov/pubmed/5397936 0 748 "R. O. Peluffo, N. T. de Gomez Dumm, M. J. de Alaniz and R. R. Brenner" 1971 Effect of protein and insulin on linoleic acid desaturation of normal and diabetic rats J.Nutr. 101 8 1075-1083 http://www.ncbi.nlm.nih.gov/pubmed/5565094 0 749 M.-H. Han and A. K. Friedman 2012 Virogenetic and optogenetic mechanisms to define potential therapeutic targets in psychiatric disorders "Neuropharmacology.62 (1) ()(pp 89-100), 2012.Date of Publication: January 2012." 1 89-100 "A continuously increasing body of knowledge shows that the brain is an extremely complex neural network and single neurons possess their own complicated interactive signaling pathways. Such complexity of the nervous system makes it increasingly difficult to investigate the functions of specific neural components such as genes, proteins, transcription factors, neurons and nuclei in the brain. Technically, it has been even more of a significant challenge to identify the molecular and cellular adaptations that are both sufficient and necessary to underlie behavioral functions in health and disease states. Defining such neural adaptations is a critical step to identify the potential therapeutic targets within the complex neural network that are beneficial to treat psychiatric disorders. Recently, the new development and extensive application of in vivo viral-mediated gene transfer (virogenetics) and optical manipulation of specific neurons or selective neural circuits in freely-moving animals (optogenetics) make it feasible, through loss- and gain-of-function approaches, to reliably define sufficient and necessary neuroadaptations in the behavioral models of psychiatric disorders, including drug addiction, depression, anxiety and bipolar disorders. In this article, we focus on recent studies that successfully employ these advanced virogenetic and optogenetic techniques as a powerful tool to identify potential targets in the brain, and to provide highly useful information in the development of novel therapeutic strategies for psychiatric disorders. This article is part of a Special Issue entitled 'Anxiety and Depression'. © 2011 Elsevier Ltd. All rights reserved" DO - http://dx.doi.org/10.1016/j.neuropharm.2011.09.009 0 750 "C. Fromm, J. Haase and E. Wolf" 1977 Depression of the recurrent inhibition of extensor motoneurons by the action of group II afferents Brain Res. 120 3 459-468 "The influence of varying the muscular afferent fiber input on both the normal firing rate (Fn) and the amount of recurrent inhibition (Fn-Fi) induced by a constant ventral root stimulation was investigated on tonic extensor motoneurons recorded from ventral root filaments in decerebrate cats. The afferent input was varied by graded electrical stimulation of the gastrocnemius nerves and by vibrating the triceps surae muscle (100 mum amplitude). When the input consisted solely of impulses in Ia afferents, as was the case during vibration, the mean recurrent inhibition Fn-Fi was 2.3 times greater than during nerve tetanization at 1.8 times threshold of group I (TI). This strength generally excited all group I and some low-threshold group II afferents. Between 1.8 TI and 8 TI, Fn-Fi decreased by some 50%. The average Fn increased slightly and motoneurons with a phasic discharge pattern were recruited when the stimulus strength was raised so as to excite group II afferents; these cells were never recruited during vibration and nerve tetanization at 1.8 TI. The results indicate the possibility of a disinhibitory action of secondary muscle spindle afferents on extensor motoneurons by reducing the recurrent inhibition" http://www.ncbi.nlm.nih.gov/pubmed/832135 0 751 T. L. Sills and P. J. Fletcher 1997 Fluoxetine attenuates morphine-induced locomotion and blocks morphine-sensitization Eur.J.Pharmacol. 337 02-Mar 161-164 "Repeated morphine treatments result in sensitization, an increase in the efficacy of morphine to stimulate locomotor activity. study examined the effects of increasing serotonin (5-hydroxytryptamine, 5-HT) transmission on morphine-sensitization. For five days rats were administered saline or 5.0 mg/kg fluoxetine prior to treatment with saline or 5.0 mg/kg morphine. Twenty-one days later, rats were tested for their locomotor response to 2.0 mg/kg morphine. Fluoxetine treatment attenuated the locomotor activating effect of acute morphine treatments and blocked the sensitized response to the morphine challenge. These results indicate that increased 5-HT transmission attenuates the locomotor stimulating effects of morphine and prevents the development of morphine-sensitization" http://www.ncbi.nlm.nih.gov/pubmed/9430410 0 752 "S. Mori, W. H. Miller and T. Tomita" 1976 Microelectrode study of spreading depression (SD) in frog retina--general observations of field potential associated with SD Jpn.J.Physiol 26 2 203-217 "Using microelectrodes, the field potential change associated with SD (SDP) was recorded from frog retinas conditioned with Cl-free Ringer's. In such retinas, SDP was induced by light or chemical agents such as glutamate, aspartate and K+. The chemicals, when applied iontophoretically, produced a local graded response which eventually triggered SDP. A potential similar to the local response to chemicals was often discerned on the rising phase of SDPs produced by light or occurring spontaneously. The SDP was maximal across an innermost retinal layer 50 mum or less in thickness with the intraretinal polarity predominantly negative, indicating that the major sink of SDP is in the inner plexiform layer. The influence of SDP on the receptor potential was relatively small, but the other components completely disappeared at the beginning of SDP, recovering gradually thereafter. Concomitantly, a strong depolarization occurred in the ganglion cells. Stimulation of the optic nerve could induce SDP, but nerve impulse activity is not important for SDP because tetrodotoxin was unable to prevent SDP due to light or chemical agents" http://www.ncbi.nlm.nih.gov/pubmed/1085830 0 753 "B. Lindborg, J. G. Johansson and R. Dahlbom" 1974 "Cyclizing compounds. IV. Tertiary N-(2-(3,4,5-trimethoxybenzoyloxy)ethyl)-N-haloalkylamines with hemicholinium-like activity" Acta Pharm.Suec. 11 4 401-409 http://www.ncbi.nlm.nih.gov/pubmed/4412690 0 754 B. Zadrozna and W. Buczko 1976 Influence of fibrinogen degradation products (FD) on the central action of acetylcholine "Polish Journal of Pharmacology and Pharmacy.28 (6) ()(pp 679-684), 1976.Date of Publication: 1976." 6 679-684 "Depressive behavioral effects of acetylcholine (10mug ivtr) and physostigmine (0.3mg/kg ip), and prolongation of the duration of electrogenic seizures produced by the drugs were prevented by intraperitoneal or intraventricular administration of FDP (0.5 mg/kg or 5mug resp.). The peptides did not affect the brain acetylcholine level and did not influence the inhibitory effect of physostigmine on AChE activity" 1 755 "M. E. Breuer, L. Groenink, R. S. Oosting, H. G. Westenberg and B. Olivier" 2007 Long-term behavioral changes after cessation of chronic antidepressant treatment in olfactory bulbectomized rats Biol.Psychiatry 61 8 990-995 "BACKGROUND: Olfactory bulbectomy (OBX) in rats causes several behavioral and neurochemical central nervous system changes, reminiscent of symptoms of human depression. Moreover, depression-like behavior after OBX can be reversed with antidepressant drugs. However, the lasting effects of these antidepressant drugs on behavior after cessation of treatment have never been studied. METHODS: Male rats received OBX or sham surgery. After recovery, animals received 14 consecutive daily doses of imipramine (20 mg/kg), escitalopram (5 and 10 mg/kg), or vehicle. Animals were tested in an open field after acute, sub-chronic, and chronic injections, as well as 1, 2, 6, and 10 weeks after cessation of treatment. RESULTS: The OBX-induced hyperactivity was normalized after sub-chronic administration of imipramine and escitalopram. Two weeks after treatment, activity of OBX animals was comparable to sham-treated animals, but after 6 weeks, OBX animals treated with both doses of escitalopram had returned to pre-treatment hyperactivity levels. The OBX animals treated with the high imipramine dose (20 mg/kg) retained activity levels comparable to sham-treated animals until 10 weeks after cessation of treatment. CONCLUSIONS: Chronic but not acute administration of imipramine and escitalopram normalizes OBX-induced hyperactivity. This effect continues for up to 10 weeks after cessation of treatment in a dose dependant manner" http://www.ncbi.nlm.nih.gov/pubmed/17141743 1 756 "L. R. Schwarz, M. Schwenk, E. Pfaff and H. Greim" 1977 Cholestatic steroid hormones inhibit taurocholate uptake into isolated rat hepatocytes Biochem.Pharmacol. 26 24 2433-2437 http://www.ncbi.nlm.nih.gov/pubmed/597331 0 757 "G. Patki, N. Solanki, F. Atrooz, A. Ansari, F. Allam, B. Jannise, J. Maturi and S. Salim" 2014 Novel mechanistic insights into treadmill exercise based rescue of social defeat-induced anxiety-like behavior and memory impairment in rats Physiol Behav. 130 135-144 "Social defeat (SD) induced stress causes physiological and behavioral deficits in rodents, including depression and anxiety-like behaviors, as well as memory impairment. Anxiolytic and mood elevating effects of physical exercise are also known. However, rescue effect of physical exercise in social defeat-induced anxiety, depression or memory impairment has not been addressed. The role of epigenetic mechanisms that potentially contribute to these rescue or protective effects is also not known. The present study investigated the effect of moderate treadmill exercise on anxiety-like behavior and memory function in rats subjected to SD using a modified version of the resident-intruder model for social stress (defeat). Changes in histone acetylation and histone-modifying enzymes were examined in hippocampus, amygdala and frontal cortex which are considered critical for anxiety, depression and cognition. Sprague Dawley rats were randomly assigned in four groups; control, exercised, social defeat, social defeat and exercise. At the end of the SD or control exposure lasting 30 min daily for 7 days, one group of SD rats was subjected to treadmill exercise for 2 weeks, whereas the other SD group was handled without exercise. Anxiety-like behavior tests and radial arm water maze test suggested that moderate treadmill exercise rescued social defeat induced anxiety-like behavior and memory impairment. Moreover, exercise normalized SD-induced increase in oxidative stress, most likely by adjusting antioxidant response. Our data suggests involvement of epigenetic mechanisms including histone acetylation of H3 and modulation of methyl-CpG-binding in the hippocampus that might contribute to the rescue effects of exercise in SD-induced behavioral deficits in rats" http://www.ncbi.nlm.nih.gov/pubmed/24732411 0 758 "T. Sano, J. C. Drummond, P. M. Patel, M. R. Grafe, J. C. Watson and D. J. Cole" 1992 A comparison of the cerebral protective effects of isoflurane and mild hypothermia in a model of incomplete forebrain ischemia in the rat Anesthesiology 76 2 221-228 "The present study was undertaken to examine the cerebral protective properties attributed to isoflurane and at the same time to compare its protective effects with those of mild hypothermia (temperature reduction by 3 degrees C). Twenty-one fasted Wistar-Kyoto rats were assigned to one of three groups (n = 7); 1.3 MAC (end-tidal) isoflurane-normothermia (pericranial temperature 38.0 degrees C), 1.3 MAC halothane-normothermia, and 1.3 MAC halothane-hypothermia (pericranial temperature 35.0 degrees C during ischemia). In each animal the trachea was intubated and the lungs were mechanically ventilated. Each animal was subjected to temporary incomplete forebrain ischemia induced by 10 min of bilateral carotid artery occlusion with simultaneous hypotension (mean arterial pressure 35 mmHg) induced by trimetaphan and blood withdrawal. After a 3-day survival period, perfusion-fixation was performed, and two blinded observers assessed histopathologic injury according to a four-point scale (0 = no damage; 1 = less than 10% of neurons damaged; 2 = 10-50% damaged; and 3 = greater than 50% damaged). The assessment was performed at two points in the rostrocaudal axis chosen to permit evaluation of regions with varying levels of ischemic damage. In the rostral sections, in the isoflurane- and halothane-normothermia groups, moderate to severe injury was observed in striatum, cerebral cortex, hippocampus (CA1 and CA3 areas), and reticular nucleus of the thalamus (e.g., the median scores for the CA1 area were 3 in both the halothane-hypothermia and the isoflurane-normothermia groups), and there were no differences between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)" http://www.ncbi.nlm.nih.gov/pubmed/1736699 0 759 "V. Singh, Amarpal, P. Kinjavdekar, H. P. Aithal and K. Pratap" 2005 Medetomidine with ketamine and bupivacaine for epidural analgesia in buffaloes Vet.Res.Commun. 29 1 Jan-18 "The efficacy of ketamine and bupivacaine in enhancing the epidural analgesia induced by medetomidine was evaluated in 10 buffalo calves utilized repeatedly after a gap of 10 days so that each drug combination was tested in 4 randomly selected animals. In group A, medetomidine (15 microg/kg), in group B ketamine (2.0 mg/kg), in group C bupivacaine (0.125 mg/kg), in group D medetomidine and ketamine (15 microg/kg and 2.0 mg/kg), and in group E medetomidine and bupivacaine (15 microg/kg and 0.125 mg/kg) was administered epidurally. Onset of analgesia was significantly earlier in animals of groups B and D compared to the animals of groups A, C and E. Medetomidine alone or in combination with ketamine/bupivacaine produced complete analgesia of the tail, perineum, inguinal region and upper parts of hind limbs. Ketamine produced a very short duration of complete analgesia at the tail and perineum. Bupivacaine alone produced only mild to moderate analgesia. Both ketamine and bupivacaine prolonged the duration of analgesia. Motor incoordination was mild to moderate in animals of all the groups, but animals remained standing throughout the period of observation. Animals of groups A, D and E showed mild to moderate sedation during the observation period. Ruminal movements decreased nonsignificantly in animals of groups A and E. Mild salivation was observed in animals of all the groups except group C. Significant decrease in heart rate (HR) was recorded after epidural administration of medetomidine or bupivacaine; however, ketamine caused short duration of tachycardia. The administration of ketamine with medetomidine caused lesser decrease in HR compared to medetomidine alone or in combination with bupivacaine. Significant fall in respiratory rate (RR) was recorded after epidural administration of medetomidine or bupivacaine alone, but an increase in RR was recorded after ketamine administration. The fall in RR was less pronounced in animals in which medetomidine was used with ketamine compared to the animals in which medetomidine was used alone or in combination with bupivacaine. Mean arterial pressure (MAP) decreased and central venous pressure (CVP) increased significantly after epidural administration of medetomidine in combination with ketamine or bupivacaine. The ECG changes included tall T wave, QS pattern, RS pattern and ST elevation and heart blocks at different intervals, which were more frequent and pronounced in animals given bupivacaine with medetomidine. It can be concluded that epidural administration of medetomidine can produce complete analgesia of the tail, perineum, inguinal region and upper hind limbs in buffaloes. However, significant depression of cardiovascular parameters was recorded. Administration of ketamine along with medetomidine resulted in significantly early onset and slightly longer duration of analgesia with lesser cardiopulmonary side-effects compared to medetomidine alone or medetomidine with bupivacaine. Addition of ketamine to medetomidine thus seems to be useful for producing epidural analgesia; however, addition of bupivacaine failed to provide any advantage over medetomidine alone" http://www.ncbi.nlm.nih.gov/pubmed/15727287 0 760 "G. Tilloca, M. A. Meloni, L. Sciola and P. Pippia" 1991 [Cell adhesion in neoplastic cells and syngeneic fibroblasts of the rat: effect of progesterone and estradiol] Boll.Soc.Ital.Biol.Sper. 67 12 1031-1037 "Recent advances in the study on the importance of steroid receptors in the treatment of hormone-responsive tumors established the relationship between plasma membrane and the first steps of the cellular response to the endocrine stimulus. We have therefore found interesting to study the influence of estrogen and progesterone on cell adhesion of neoplastic (SGS/3A) and normal syngeneic (FG) cells. We demonstrated the presence of a nuclear estrogenic and a cytosolic progestin receptor in the SGS/3A cells. In syngeneic fibroblasts both receptors are absent. Cell adhesion kinetics obtained determining the percent of single labeled cells with 3H-leucine adhering to confluent monolayer (cell-cell adhesion) showed that the physiological concentrations of estradiol and progesterone induce an inhibition of cell-substratum adhesion (25-30%) in neoplastic cells, but do not influence cell-cell adhesion. In FG cells the two hormones cause an increase of cell-substratum adhesion (35-40%), but do not influence cell-cell adhesion. Results suggest that FG cells, although lacking cytoplasmic or nuclear receptors for estradiol and progesterone, probably have other steroid-receptive molecules involved in adhesive processes on their cell-surface" http://www.ncbi.nlm.nih.gov/pubmed/1840794 0 761 "E. Binder, K. Malki, J. L. Paya-Cano, C. Fernandes, K. J. Aitchison, A. A. Mathe, F. Sluyter and L. C. Schalkwyk" 2011 Antidepressants and the resilience to early-life stress in inbred mouse strains Pharmacogenet.Genomics 21 12 779-789 "RATIONALE: Selecting an effective treatment for patients with major depressive disorder is a perpetual problem for psychiatrists. It is of particular interest to explore the interaction between genetic predisposition and environmental factors. OBJECTIVES: Mouse inbred strains vary in baseline performance in depression-related behaviour tests, which were originally validated as tests of antidepressant response. Therefore, we investigated interactions between environmental stress, genotype, and drug response in a multifactorial behaviour study. METHOD: Our study design included four inbred mouse strains (129S1/SvlmJ, C57LB/6J, DBA/2J and FVB/NJ) of both sexes, two subjected to environmental manipulations (maternal separation and unpredictable chronic mild stress) and two representative of treatment with antidepressants (escitalopram and nortryptiline vs. vehicle). The mice treated with antidepressants were further divided into those administered acute (1 day) and subchronic (14 days) regimes, giving 144 experimental groups in all, each with at least seven animals. All animals were tested using the Porsolt forced-swim test (FST) and the hole-board test. RESULTS: Despite a 24-h maternal separation (MS) or a 14-day unpredictable chronic mild stress protocol, most animals seemed to be resilient to the stress induced. One compelling finding is the long-lasting, strain-specific effect of MS resulting in an increased depression-like behaviour in the Porsolt FST and elevated anxiety-related behaviour in the hole-board test seen in 129S1/SvImJ mice. Nortriptyline was effective in reversing the effect of MS in the FST in 129S1/SvlmJ male mice. CONCLUSION: A single 24-h maternal separation of pups from their mother on postnatal day 9 is a sufficient insult to result in a depression-like phenotype in adult 129S1/SvImJ mice but not in C57LB/6 J, DBA/2 J, and FVB/NJ mice" http://www.ncbi.nlm.nih.gov/pubmed/22016050 1 762 "T. E. Rizzi, M. V. Reichard, L. A. Cohn, A. J. Birkenheuer, J. D. Taylor and J. H. Meinkoth" 2015 "Prevalence of Cytauxzoon felis infection in healthy cats from enzootic areas in Arkansas, Missouri, and Oklahoma" Parasit.Vectors. 8 13 "BACKGROUND: Infection with Cytauxzoon felis in domestic cats can cause fever, lethargy, depression, inappetence, icterus, and often death. With a high mortality rate, cytauxzoonosis was historically considered a fatal disease. Within the last 15 years, cats with or without treatment have been recognized as chronically infected survivors of C. felis infection. Our objective was to determine the prevalence of C. felis in healthy domestic cats from Arkansas, Missouri, and Oklahoma. METHODS: Infection with C. felis was determined using DNA extracted from anticoagulated whole blood and PCR amplification using C. felis-specific primers. Chi-square, Fisher's exact tests, and odds ratios were used to compare proportions of cats infected with C. felis. RESULTS: Blood samples were collected from 902 healthy domestic cats between October 2008 and April 2012. DNA from Cytauxzoon felis was detected in 56 of 902 (6.2%; 95% confidence interval, 4.7-7.9) samples. The highest prevalence of C. felis infection (15.5%; 10.3-21.7) was observed in cats from Arkansas, followed by cats from Missouri (12.9%; 6.1-24.0), and cats from Oklahoma (3.4%; 2.2-5.1). Cats sampled in Arkansas and Missouri were 5.1 and 4.2, respectively, times more likely to be chronically infected with C. felis than cats from Oklahoma. CONCLUSIONS: Infection with C. felis is common in domestic cats through Arkansas, Missouri, and Oklahoma. The high prevalence of C. felis reported herein suggests that infected domestic cats are likely reservoirs of infection for naive felines. The high prevalence of C. felis substantiates the importance for the use of approved acaricides on cats to prevent cytauxzoonosis" http://www.ncbi.nlm.nih.gov/pubmed/25566776 0 763 M. C. Gwee and L. S. Cheah 1993 Ranitidine inhibits adrenergic but not nonadrenergic noncholinergic transmission in the rat isolated anococcygeus muscle Arch.Int.Pharmacodyn.Ther. 321 92-102 "The effects of ranitidine on adrenergic and nonadrenergic noncholinergic transmission in the rat isolated anococcygeus muscle and on the contractile responses of the muscle to noradrenaline, potassium chloride, 5-hydroxytryptamine and carbachol were investigated. Ranitidine (2-8 mM) produced a concentration-dependent and readily reversible inhibition of motor (excitatory) responses of the anococcygeus muscle evoked via field stimulation (20-30 V, 10 Hz x 10 sec, 1 msec pulse width, every 2 min), whereas the contractile response of the anococcygeus muscle to exogenous noradrenaline (3 microM) was potentiated by 57 +/- 3.7%; the contractile response to potassium chloride (50 mM) was only slightly decreased, whereas the responses to carbachol (3 microM) or 5-hydroxytryptamine (30 microM) were completely inhibited by ranitidine (8 mM). When the tone of the muscle was raised by noradrenaline (3 microM) after complete inhibition of the motor responses by ranitidine (8 mM), field stimulation produced relaxant (inhibitory) responses which were inhibited by tetrodotoxin (2 microM) or NG-nitro-L-arginine methylester (50 microM). Similar results were obtained with guanethidine (0.5-3 microM) on adrenergic and non-adrenergic noncholinergic transmission. The results clearly show that ranitidine can selectively inhibit adrenergic transmission in the anococcygeus muscle with consequent unmasking of nonadrenergic noncholinergic transmission; ranitidine can also produce a super-sensitivity-type response of the muscle to exogenous noradrenaline but not to potassium chloride, carbachol or 5-hydroxytryptamine. Thus, the inhibition of adrenergic transmission by ranitidine in the rat isolated anococcygeus muscle closely resembles the action of guanethidine on adrenergic transmission" http://www.ncbi.nlm.nih.gov/pubmed/8391790 0 764 "M. Romanowicz, S. Ehlers, D. Walker, P. Decker, J. Rundell, G. Shinozaki, M. Litzow, W. Hogan, D. Mrazek and J. L. Black" 2012 Testing a diathesis-stress model: potential genetic risk factors for development of distress in context of acute leukemia diagnosis and transplant "Psychosomatics.53 (5) ()(pp 456-462), 2012.Date of Publication: 2012 Sep-Oct." 5 456-462 "Brain-derived neurotrophic factor (BDNF) is a nerve growth factor that has antidepressant-like effects in animals and may be implicated in the etiology of mood-related phenotypes, specifically in the context of stressful life events. We hypothesized that this single-nucleotide polymorphism will predict the development of psychological distress among patients diagnosed with acute leukemia and preparing for hematopoietic stem cell transplant (HSCT). We also explored the relationship of other genetic factors to psychological distress, including 5HTTLPR and STin2, FKBP5, and the CRHR1 TAT haplotype. In a retrospective cohort design, 107 adult acute leukemia survivors preparing for HSCT at a major medical center completed a pre-HSCT psychological evaluation and volunteered to donate blood to the HSCT Cell and Serum Research Repository for future research studies. There was evidence of a potential association between BDNF (Val66Met) and psychological distress. More specifically, rs6265 was related to both personal mental health history (P = 0.09, 0.06 adjusted) and diagnosis of depression/adjustment disorder at time of pre-transplant evaluation (P = 0.11, 0.09 adjusted). Other genetic factors were unrelated to distress. The BDNF Val66Met polymorphism may contribute to development of depressive symptomatology in patients undergoing stressful life events, such as diagnosis of acute leukemia and preparation for HSCT. The SNPs in BDNF might be applicable in identifying patients at risk for developing psychological distress and depression in the context of coping with stressful medical conditions. Polymorphism in other genes (FKBP5, CRHR1, and 5HTT) did not show any significant relationships. Replication studies are needed with larger samples of people undergoing similar significant life stressors. Copyright © 2012 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved" 0 765 "J. Mujkosova, O. Ulicna, I. Waczulikova, J. Vlkovicova, O. Vancova, M. Ferko, S. Polak and A. Ziegelhoffer" 2010 Mitochondrial function in heart and kidney of spontaneously hypertensive rats: influence of captopril treatment Gen.Physiol Biophys. 29 2 203-207 "Effect of captopril treatment on capability of heart and kidney mitochondria to produce ATP was investigated in spontaneously hypertensive rats (SHR). Heart mitochondria from SHR responded to hypertension with tendency to compensate the elevated energy demands of cardiac cells by moderate increase in mitochondrial Mg2+-ATPase activity, membrane fluidity (MF) and in majority of functional parameters of the mitochondria (p>0.05). Significant increase exhibited only the oxygen consumption (QO2; p<0.01-0.001) and oxidative phosphorylation rate (OPR; p<0.003) with glutamate+malate (GLUT+MAL) as substrates. Lowering the blood pressure (p<0.02) captopril also eliminated the above compensatory response and impaired the oxidative ATP production by decreasing OPR (p<0.001). Kidney mitochondria of SHR experienced serious disarrangement in parameters of oxidative ATP production: increase in Mg2+-ATPase activity (p<0.05) but, also scattered QO2 values (p<0.03-0.01) leading to decrease in OPR and the ADP:O (p<0.05-0.01) values with both GLUT+MAL and succinate as substrates. Captopril treatment does not alleviated but even worsened the above alterations. Mg2+-ATPase became also decreased and the depression of ADP:O became aggravated (p<0.0001)" http://www.ncbi.nlm.nih.gov/pubmed/20577032 0 766 "Z. Peterfi, G. M. Urban, O. I. Papp, B. Nemeth, H. Monyer, G. Szabo, F. Erdelyi, K. Mackie, T. F. Freund, N. Hajos and I. Katona" 2012 Endocannabinoid-mediated long-term depression of afferent excitatory synapses in hippocampal pyramidal cells and GABAergic interneurons J.Neurosci. 32 41 14448-14463 "Although endocannabinoids have emerged as essential retrograde messengers in several forms of synaptic plasticity, it remains controversial whether they mediate long-term depression (LTD) of glutamatergic synapses onto excitatory and inhibitory neurons in the hippocampus. Here, we show that parvalbumin- and somatostatin/metabotropic glutamate receptor 1(a) (mGlu(1a))-positive GABAergic interneurons express diacylglycerol lipase-alpha (DGL-alpha), a synthesizing enzyme of the endocannabinoid 2-arachidonoylglycerol (2-AG), albeit at lower levels than principal cells. Moreover, this lipase accumulates postsynaptically around afferent excitatory synapses in all three cell types. To address the role of retrograde 2-AG signaling in LTD, we investigated two forms: (1) produced by postsynaptic spiking paired with subsequent presynaptic stimulation or (2) induced by group I mGlu activation by (S)-3,5-dihydroxyphenylglycine (DHPG). Neither form of LTD was evoked in the presence of the mGlu(5) antagonist MPEP [2-methyl-6-(phenylethynyl)-pyridine], the DGL inhibitor THL [N-formyl-l-leucine (1S)-1-[[(2S,3S)-3-hexyl-4-oxo-2-oxetanyl]methyl]dodecyl ester], or the intracellularly applied Ca(2+) chelator BAPTA in CA1 pyramidal cells, fast-spiking interneurons (representing parvalbumin-containing cells) and interneurons projecting to stratum lacunosum-moleculare (representing somatostatin/mGlu(1a)-expressing interneurons). Both forms of LTD were completely absent in CB(1) cannabinoid receptor knock-out mice, whereas pharmacological blockade of CB(1) led to inconsistent results. Notably, in accordance with their lower DGL-alpha level, a higher stimulation frequency or higher DHPG concentration was required for LTD induction in interneurons compared with pyramidal cells. These findings demonstrate that hippocampal principal cells and interneurons produce endocannabinoids to mediate LTD in a qualitatively similar, but quantitatively different manner. The shifted induction threshold implies that endocannabinoid-LTD contributes to cortical information processing during distinct network activity patterns in a cell type-specific manner" http://www.ncbi.nlm.nih.gov/pubmed/23055515 0 767 S. Y. Kawaguchi and T. Sakaba 2015 Control of inhibitory synaptic outputs by low excitability of axon terminals revealed by direct recording Neuron 85 6 1273-1288 "An axon is thought to faithfully conduct action potentials to its terminals. However, many features of the axon and axon terminals, especially at inhibitory synapses, remain unknown. By directly recording from the axon and terminal of a cultured cerebellar Purkinje cell (PC), we demonstrate that low membrane excitability of axon terminals shapes synaptic output. Simultaneous measurements of presynaptic capacitance and evoked IPSCs revealed PC axon terminals contained large readily releasable synaptic vesicles that exhibited a low release probability. Nevertheless, IPSCs evoked by stimulating a PC soma underwent frequency-dependent depression. Direct axonal recordings showed that high-frequency action potentials were faithfully conducted over axonal bifurcations but were attenuated around terminals. Sparse Na(+) channels relative to enriched voltage-gated K(+) channels in terminals caused short-term depression of IPSCs by reducing Ca(2+) influx. Together with confirmation in slice recordings, our findings reveal a presynaptic mechanism that shapes short-term synaptic depression without depleting releasable vesicles" http://www.ncbi.nlm.nih.gov/pubmed/25728570 0 768 R. B. Philp and J. P. Lemieux 1969 Interactions of dipyridamole and adenosine on platelet aggregation Nature 221 5186 1162-1164 http://www.ncbi.nlm.nih.gov/pubmed/4975285 0 769 E. B. Issa and X. Wang 2008 Sensory responses during sleep in primate primary and secondary auditory cortex J.Neurosci. 28 53 14467-14480 "Most sensory stimuli do not reach conscious perception during sleep. It has been thought that the thalamus prevents the relay of sensory information to cortex during sleep, but the consequences for cortical responses to sensory signals in this physiological state remain unclear. We recorded from two auditory cortical areas downstream of the thalamus in naturally sleeping marmoset monkeys. Single neurons in primary auditory cortex either increased or decreased their responses during sleep compared with wakefulness. In lateral belt, a secondary auditory cortical area, the response modulation was also bidirectional and showed no clear systematic depressive effect of sleep. When averaged across neurons, sound-evoked activity in these two auditory cortical areas was surprisingly well preserved during sleep. Neural responses to acoustic stimulation were present during both slow-wave and rapid-eye movement sleep, were repeatedly observed over multiple sleep cycles, and demonstrated similar discharge patterns to the responses recorded during wakefulness in the same neuron. Our results suggest that the thalamus is not as effective a gate for the flow of sensory information as previously thought. At the cortical stage, a novel pattern of activation/deactivation appears across neurons. Because the neural signal reaches as far as secondary auditory cortex, this leaves open the possibility of altered sensory processing of auditory information during sleep" http://www.ncbi.nlm.nih.gov/pubmed/19118181 0 770 "R. E. Nicholls, X. L. Zhang, C. P. Bailey, B. R. Conklin, E. R. Kandel and P. K. Stanton" 2006 mGluR2 acts through inhibitory Galpha subunits to regulate transmission and long-term plasticity at hippocampal mossy fiber-CA3 synapses Proc.Natl.Acad.Sci.U.S.A 103 16 6380-6385 "Presynaptic inhibitory G protein-coupled receptors play a critical role in regulating transmission at a number of synapses in the central and peripheral nervous system. We generated transgenic mice that express a constitutively active form of an inhibitory Galpha subunit to examine the molecular mechanisms underlying the actions of one such receptor, metabotropic glutamate receptor (mGluR) 2, at mossy fiber-CA3 synapses in the hippocampus. mGluR2 participates in at least three types of mossy fiber synaptic plasticity, (i) transient suppression of synaptic transmission, (ii) long-term depression (LTD), and (iii) inhibition of long-term potentiation (LTP), and we find that inhibitory Galpha signaling is sufficient to account for the actions of mGluR2 in each. The fact that constitutively active Galphai2 occludes the transient suppression of synaptic transmission by mGluR2, while enhancing LTD, suggests further that these two forms of plasticity are expressed via different mechanisms. In addition, the LTP deficit observed in constitutively active Galphai2-expressing mice suggests that mGluR2 activation may serve as a metaplastic switch to permit the induction of LTD by inhibiting LTP" http://www.ncbi.nlm.nih.gov/pubmed/16606834 0 771 "R. Fallach, A. Shainberg, O. Avlas, M. Fainblut, Y. Chepurko, E. Porat and E. Hochhauser" 2010 Cardiomyocyte Toll-like receptor 4 is involved in heart dysfunction following septic shock or myocardial ischemia J.Mol.Cell Cardiol. 48 6 1236-1244 "Toll-like receptors are expressed in immune cells and cardiac muscle. We examined whether the cardiac Toll-like receptor 4 (TLR4) is involved in the acute myocardial dysfunction caused by septic shock and myocardial ischemia (MI). We used wild type mice (WT), TLR4 deficient (TLR4-ko) mice and chimeras that underwent myeloablative bone marrow transplantation to dissociate between TLR4 expression in the heart (TLR4-ko/WT) and the immunohematopoietic system (WT/TLR4-ko). Mice were injected with lipopolysaccharide (LPS) (septic shock model) or subjected to coronary artery ligation (MI model) and tested in vivo and ex vivo, for function, histopathology proinflammatory cytokine and TLR4 expression. WT mice challenged with LPS or MI displayed reduced cardiac function, increased myocardial levels of IL-1 beta and TNF-alpha and upregulation of mRNA encoding TLR4 prior to myocardial leukocyte infiltration. TLR4 deficient mice sustained significantly smaller infarctions as compared to control mice at comparable areas at risk. The cardiac function of TLR4-ko mice was not affected by LPS and demonstrated reduced suppression by MI compared to WT. Chimeras deficient in myocardial TLR4 were resistant to suppression induced by LPS and the heart function was less depressed, compared to the TLR4-ko, following MI in the acute phase (4h). In contrast, hearts of chimeras deficient in immunohematopoietic TLR4 expression were suppressed both by LPS and MI, exhibiting increased myocardial cytokine levels, similar to WT mice. We concluded that cardiac function of TLR4-ko mice and chimeric mice expressing TLR4 in the immunohematopoietic system, but not in the heart, revealed resistance to LPS and reduced cardiac depression following MI, suggesting that TLR4 expressed by the cardiomyocytes themselves plays a key role in this acute phenomenon" http://www.ncbi.nlm.nih.gov/pubmed/20211628 0 772 "E. S. Nordoy, O. C. Ingebretsen and A. S. Blix" 1990 Depressed metabolism and low protein catabolism in fasting grey seal pups Acta Physiol Scand. 139 2 361-369 "Grey seal pups (Halichoerus grypus) were collected at the time of weaning (mid-October) and fasted for 52 days at thermoneutrality in separate cages. Body weight decreased exponentially, while metabolic rate dropped 45% from an average of 2.95 +/- 0.15 (SEM) W kg-1 at day 2 of fasting to a stable level of 1.62 +/- 0.06 (SEM) W kg-1 from day 10 to day 47 of fasting. Respiratory quotient was low, indicating extensive catabolism of triglycerides, while plasma cortisol was fairly stable at 110 +/- 8 (SEM) nmol l-1 throughout the fasting period. Daily urinary output decreased from 236 +/- 20 (SEM) ml day-1 at day 2 to a stable value of 87 +/- 6 (SEM) ml day-1 between days 8 and 50 of fasting. The urine was analysed for urea, uric acid, creatinine, ammonia, total nitrogen and osmolality. Urea was always the principal excretory end-product, amounting to between 70 and 80% of the total excreted nitrogen. The urine was moderately concentrated (range 770-1300 mosmol kg-1). Total excreted urinary nitrogen decreased by 68% from 3.7 +/- 0.7 (SEM) g day-1 to 1.2 +/- 0.4 (SEM) g day-1 between days 2 and 50. The urinary nitrogen was used to calculate the daily amount of protein being oxidized and its energy content was compared with the measured basal metabolic rate of individual animals. Approximately 6% of the energy expended by grey seal pups during the post-weaning fast is derived from oxidation of protein. It is concluded that a rapid depression of basal metabolic rate and extensive blubber catabolism enable grey seal pups to endure prolonged periods of fasting without any apparent signs of discomfort or stress" http://www.ncbi.nlm.nih.gov/pubmed/2368622 0 773 "D. Dhawan, A. Singh, B. Singh, H. K. Bandhu, B. Chand and N. Singh" 1999 Effect of lithium augmentation on the trace elemental profile in diabetic rats Biometals 12 4 375-381 "Energy dispersive X-ray fluorescence technique was employed to study the interactions among various elements, viz.: K, Zn, Br, Fe, Cu, Br & Rb in 4 groups of rats viz. control-GI, diabetic-GII (diabetes induced by i.p. administration of alloxan monohydrate at a dose level of 150 mg/kg b.w; single injection), lithium treated-GIII (lithium administered as Li2 Co3 at a dose level of 1.1 g of Li2 Co3/kg animal diet; free access; serum lithium levels--0.5-1.2 mEq/L) and lithium + diabetic rats-GIV. The different treatments continued for a total duration of 1 month. The K contents were found to be significantly lowered in all the treatment groups which was maximum (28%) in lithium treated diabetic rats. Depression in the levels of Rb was noticed in lithium treated and lithium treated diabetic (G-III and G-IV) groups. However, the levels (Rb) remained unaltered in diabetic (G-II) group. Interestingly, a significant decline was observed in Fe levels in G-III following lithium administration but the levels remained unchanged in G-IV with lithium administration to diabetic rats. On the other hand, lithium treatment to normal (G-III) and diabetic (G-IV) rats indicated statistically significant elevation in the levels of Cu and Br. However, diabetic (G-II) rats did not indicate any elevation in the levels of these two elements. Interestingly, the concentrations of Zn were found to be significantly elevated in all the treatment groups, which was maximum (37%) in G-III (lithium) group. A comparison of various elements from lithium treated diabetic group G-IV with the corresponding elements from the diabetic group G-II, implied a significant depression in K and Rb levels and a significant elevation in the levels of Br" http://www.ncbi.nlm.nih.gov/pubmed/10816739 0 774 "G. J. Boer, M. G. Feenstra, B. H. Erdtsieck-Ernste, J. A. Gorter and M. Mirmiran" 1990 Lasting effects of early noradrenergic receptor occupation on brain noradrenaline turnover and on beta-receptors Dev.Pharmacol.Ther. 15 03-Apr 224-233 "Neuroactive substances reaching the developing brain can affect the formation of the functionality of nervous circuitry. To explain this so-called functional neuroteratology it has been proposed that neurotransmission has persistently been altered. Pharmacological interference with the developing central noradrenergic system in the rat by means of drugs like clonidine, yohimbine and propranolol, indeed revealed lasting changes in the turnover of noradrenaline in several brain areas, but no changes were found in beta-receptor density. It is assumed that either alpha-receptor density is affected or that signal transduction is altered, since electrophysiologically a persistent supersensitivity was found for the noradrenaline-evoked depression of glutamate-evoked firing in e.g. CA1 pyramidal cells of the hippocampus. Elucidation of the underlying neurochemical mechanisms of such lasting effects of perinatal exposure to noradrenergic drugs aims at establishing the role of noradrenaline in development, but also to provide physicians with the possibility to better assess the advantages and disadvantages of drugs to be prescribed during reproduction and, hence, to make the best choice of treatment" http://www.ncbi.nlm.nih.gov/pubmed/1966021 0 775 "L. M. Carini, C. A. Murgatroyd and B. C. Nephew" 2013 Using chronic social stress to model postpartum depression in lactating rodents J.Vis.Exp. 76 e50324 "Exposure to chronic stress is a reliable predictor of depressive disorders, and social stress is a common ethologically relevant stressor in both animals and humans. However, many animal models of depression were developed in males and are not applicable or effective in studies of postpartum females. Recent studies have reported significant effects of chronic social stress during lactation, an ethologically relevant and effective stressor, on maternal behavior, growth, and behavioral neuroendocrinology. This manuscript will describe this chronic social stress paradigm using repeated exposure of a lactating dam to a novel male intruder, and the assessment of the behavioral, physiological, and neuroendocrine effects of this model. Chronic social stress (CSS) is a valuable model for studying the effects of stress on the behavior and physiology of the dam as well as her offspring and future generations. The exposure of pups to CSS can also be used as an early life stress that has long term effects on behavior, physiology, and neuroendocrinology" http://www.ncbi.nlm.nih.gov/pubmed/23792810 1 776 "R. D. White, W. C. Daughtrey and M. S. Wells" 1995 Health effects of inhaled tertiary amyl methyl ether and ethyl tertiary butyl ether Toxicol.Lett. 82-83 719-724 "Government specifications on the oxygen content of motor gasoline sold in certain areas of the USA have resulted in commercialization of the oxygenate fuel additives tertiary amyl methyl ether (TAME) and ethyl tertiary butyl ether (ETBE). TAME and ETBE were evaluated in 4-week rat inhalation studies sponsored by Amoco Corporation. Target vapor concentrations were 0, 500, 2000, or 4000 ppm for 6 h per day, 5 days per week, for 4 weeks. TAME exposure at 4000 ppm resulted in 25% mortality, apparently as a consequence of severe CNS depression. Body weight gain was decreased in the TAME high dose male rats. In contrast, no ETBE exposed animals died during the study and no changes in body weight gain were observed. Significant effects on functional observational battery (FOB) parameters were only found in the TAME high and mid-dose groups immediately after exposure. All affected FOB parameters were normal by the next day. Both TAME and ETBE exposures significantly increased relative liver weights in the high and mid-dose groups. However, no treatment-related histopathologic findings were noted for either compound. Clinical chemistry and hematology findings were absent with ETBE exposure and minimal with TAME exposure. The results indicate that 500 ppm was a NOAEL for both compounds in these studies" http://www.ncbi.nlm.nih.gov/pubmed/8597132 0 777 "S. K. Batta, F. Piva and L. Martini" 1973 "Effect of prostaglandins E1, E2, and F2alpha on gonadotrophin-induced ovulation in immature female rats" Adv.Biosci. 9 723-730 http://www.ncbi.nlm.nih.gov/pubmed/4805884 0 778 "F. Keshavarzy, C. Bonnet, G. Behzadi and R. Cespuglio" 2015 Expression patterns of c-Fos early gene and phosphorylated ERK in the rat brain following 1-h immobilization stress: concomitant changes induced in association with stress-related sleep rebound Brain Struct.Funct. 220 3 1793-1804 "An immobilization stress (IS) of 1 h applied at the beginning of the dark phase is followed by a sleep rebound. During the restraint, serotonin released by the dorsal raphe nucleus within the arcuate area stimulates the availability of corticotropin-like intermediate lobe peptide (CLIP or ACTH18-39). Three hours after the restraint, CLIP, through its hypnogenic properties, contributes to the sleep rebound that follows the IS. Here, we immunohistochemically evaluated protein expression of the immediate early gene, c-Fos and phosphorylated extracellular signal-regulated kinase (p-ERK) in hypothalamic (preoptic area [POA], paraventricular nucleus [PVN], arcuate nucleus [ARC]) and brain stem (dorsal raphe [DR], locus coeruleus [LC]) nuclei involved in the acute response to stress and the subsequent stress-related sleep rebound (recovery period). Immediately after the 1-h restraint, c-Fos and p-ERK expression increased in all structures studied, particularly in PVN and LC. Three hours later, the number of p-ERK- and c-Fos-positive neurons was reduced in PVN and LC (p < 0.001) as well as in DR (p < 0.01) compared to control animals. In contrast, both c-Fos and p-ERK expression in POA neurons (p < 0.01) and c-Fos expression in ARC neurons (p < 0.001) were increased 3 h after the IS. The marked activation observed in PVN and LC nucleus immediately after the IS confirms that these structures are clearly reactive to stress. However, the high activity observed in POA and ARC neurons during the recovery period, not described to date, highlights the particular part played by these structures in the stress-related sleep rebound. An unbalance in the above processes may contribute to pathological outcomes, such as anxiety and depression" http://www.ncbi.nlm.nih.gov/pubmed/24567082 0 779 I. Bakhvala 1970 [Homosynaptic depression and presynaptic inhibition of the N-I component of the dorsal surface potential in the spinal cord of rats with extracerebral neoplasms] Fiziol.Zh. 16 6 825-828 http://www.ncbi.nlm.nih.gov/pubmed/4328745 0 780 "S. Fanous, E. F. Terwilliger, R. P. Hammer, Jr. and E. M. Nikulina" 2011 "Viral depletion of VTA BDNF in rats modulates social behavior, consequences of intermittent social defeat stress, and long-term weight regulation" Neurosci.Lett. 502 3 192-196 "Mesolimbic brain-derived neurotrophic factor (BDNF) is implicated in sustained behavioral changes following chronic social stress, and its depletion may reduce susceptibility to such behavioral alterations. Enhanced mesolimbic BDNF is proposed as pro-depressive and anhedonic, while depleting ventral tegmetal area (VTA) BDNF increases weight by enhancing hedonic eating. Here, we questioned whether depletion of VTA BDNF would alleviate social defeat stress-induced deficits in weight regulation, or affect social behavior in the presence or absence of social stress. Male Sprague-Dawley rats received bilateral intra-VTA infusions of adeno-associated virus (AAV) vectors containing shRNA against BDNF or a control virus. Three weeks later, rats underwent 4 episodes of social defeat stress involving exposure to an aggressive Long-Evans resident rat, or control handling every third day. Depleted VTA BDNF conferred resistance to the deficient weight regulation normally observed during intermittent social defeat stress, and enhanced long-term weight gain regardless of stress history. In addition, social approach and avoidance behavior towards a novel social target were measured 7 weeks after stress. Social defeat stress chronically reduced social behavior, whereas depletion of VTA BDNF chronically increased social behavior. Our results reveal that depletion of VTA BDNF alleviates some consequences of intermittent social defeat stress, enhances social behavior, and may contribute to weight gain. These data implicate VTA BDNF in protracted behavioral responses to stress, social stimuli, and weight regulation" http://www.ncbi.nlm.nih.gov/pubmed/21839142 1 781 P. E. Stokes 1995 The potential role of excessive cortisol induced by HPA hyperfunction in the pathogenesis of depression "European Neuropsychopharmacology.5 (SUPPL.) ()(pp 77-82), 1995.Date of Publication: 1995." Suppl 77-82 "Prolonged hypothalamic-pituitary-adrenocortical (HPA) axis overactivity occurs at all levels of this axis during stress in normals and some depressed patients. This can induce enlargement of the pituitary and adrenals. Various reports showed that cortisol can affect mood and behavior, and disrupt memory and recall. The integrity of the hippocampus is essential for memory function and, via the high density of its cortisol receptors, cortisol induced inhibitory feedback to the HPA axis. Animal data suggest that over time aging and stress can permanently downregulate hippocampal cell receptors, produce chronic hippocampal inflammation (astroglial), and kill cells. Gushing's syndrome patients (high cortisol) show diminished hippocampal size and verbal recall inversely related to cortisol levels. All the above is consistent with the 'cascade hypothesis' of cortisol induced hippocampal damage with resultant diminished inhibition to HPA hyperactivity in a circular manner. High cortisol is associated with altered neurotransmitter function, e.g., diminished brain serotonin synthesis, low CSF 5HIAA, and increased noradrenergic activity" DO - http://dx.doi.org/10.1016/0924-977X%2895%2900039-R 0 782 "F. Elvinger, P. J. Hansen, H. H. Head and R. P. Natzke" 1991 Actions of bovine somatotropin on polymorphonuclear leukocytes and lymphocytes in cattle J.Dairy Sci. 74 7 2145-2152 "Objectives were to determine 1) in vitro effects of bST on function of polymorphonuclear leukocytes and lymphocytes and 2) in vivo effects of bST on leukocyte function of heifers fed to maintain medium or high growth rates. When administered in vitro, bST did not affect function of polymorphonuclear leukocytes. [Methyl-3H]thymidine incorporation by resting lymphocytes was stimulated by 1000 ng/ml bST. When given in vitro, bST did not further enhance [methyl-3H]thymidine uptake by mitogen-stimulated lymphocytes cultured at 38.5 degrees C but reduced the depression of mitogen-stimulated proliferation caused by incubating cells at 42 degrees C. When bST was administered in vivo, phagocytosis and killing of Escherichia coli by polymorphonuclear leukocytes from bST-treated heifers were not different from cells of control heifers. As measured by [methyl-3H]thymidine uptake after stimulation with phytohemagglutinin, lymphocytes from bST-treated heifers responded similarly to those of control heifers when incubated at 38.5 degrees C, but the depression in [methyl-3H]thymidine uptake due to culture at 42 degrees C was less for lymphocytes obtained from bST-treated heifers. In conclusion, bST had little effect on function of polymorphonuclear leukocytes but could promote proliferation of lymphocytes in vitro and protect cells from effects of elevated temperature" http://www.ncbi.nlm.nih.gov/pubmed/1894810 0 783 "D. J. Ruktanonchai, R. S. El-Mallakh, R. Li and R. S. Levy" 1998 Persistent hyperactivity following a single intracerebroventricular dose of ouabain Physiol Behav. 63 3 403-406 "Intracerebroventricular (i.c.v.) administration of ouabain has been shown to alter motor activity in the rat. It has been purported that this may model the behavioral abnormalities of human manic-depressive (bipolar) illness. Since manic-depression is a recurrent condition, we elected to investigate the effects of the multiple administration of i.c.v. ouabain. Male Sprague-Dawley rats were allowed to acclimate to the animal facility for 7-10 days after which time i.c.v. cannulae were placed. Animals received two i.c.v. injections of either ouabain (10[-3] M) or artificial cerebrospinal fluid (aCSF) 9 days apart, so that 6 rats received aCSF-aCSF, 6 received ouabain-aCSF, and 6 received ouabain-ouabain. Behavioral activity was evaluated in an open field (86 x 86 cm subdivided into sixteen 21.5 x 21.5-cm squares) for 20 min at baseline and immediately following each i.c.v. injection. After the last behavioral test, the animals were killed, and the brains were rapidly harvested and dissected over ice. Specific ouabain binding and sodium pump activity were determined. A single dose of ouabain produced a marked increase (297.0%, p = 0.002) in open field activity compared to both baseline behavior and to aCSF injected animals. The effects of ouabain appeared to last for 9 days. A second i.c.v. injection of either ouabain (136.5 +/- 60.4 SEM) or aCSF (108.0%, p < 0.01) had no effect on the activity level which was intermediate between the initial ouabain hyperactivity and the baseline level. Nine days after ouabain administration, hippocampal ouabain binding was increased relative to the control group (5477 +/- 485.7 vs. 3579 +/- 518.6, p < 0.05) and sodium pump activity was relatively lower (2293.8 +/- 265.5 vs. 3174.2 +/- 410.5, p < 0.05)" http://www.ncbi.nlm.nih.gov/pubmed/9469734 0 784 E. Paul 1968 "[Histochemical, electron microscopic and quantitative studies of glycogen storage in the choroid plexus of Rana temporaria L]" Z.Zellforsch.Mikrosk.Anat. 88 4 511-536 http://www.ncbi.nlm.nih.gov/pubmed/5722599 0 785 "R. M. O' Connor, M. M. Pusceddu, T. G. Dinan and J. F. Cryan" 2013 "Impact of early-life stress, on group III mGlu receptor levels in the rat hippocampus: effects of ketamine, electroconvulsive shock therapy and fluoxetine treatment" Neuropharmacology 66 236-241 "The glutamatergic system is increasingly being viewed as a promising target for the development of novel treatments for depression. The group III metabotropic glutamate (mGlu) receptors (mGlu(4, 7) and (8) receptors) in particular are beginning to show promise in this respect. It remains unclear how antidepressant medications modulate mGlu receptors. In this study we investigated the effects of three antidepressant treatments (fluoxetine, ketamine and electroconvulsive shock therapy (ECT)). Ketamine is an NMDA receptor antagonist which possess a rapid antidepressant therapeutic profile and moreover is effective in cases of treatment-resistant depression. Furthermore, ECT is also a therapeutic strategy possessing increased efficacy compared to conventional monoamine based therapies. The effect these two highly efficacious treatments have on hippocampal group III mGlu receptors remains completely unexplored. To redress this deficit we investigated the effects these treatments and the prototypical selective serotonin reuptake inhibitor (SSRI) fluoxetine would have on hippocampal group III mGlu receptor mRNA levels in naive Sprague-Dawley rats and rats which had undergone early-life stress in the form of the maternal separation (MS) procedure. We found MS significantly reduced mGlu(4) receptor expression and fluoxetine reversed this MS induced change. ECT and ketamine treatment significantly reduced mGlu(4) receptor expression in non-separated (NS) animals while having no effect in MS animals. Fluoxetine and ECT significantly increased mGlu(7) receptor expression in NS animals. This work demonstrates changes to mGlu(4) receptor expression may be a lasting molecular change which occurs due to early-life stress. Taken together our data shows there are selective changes to group III mGlu receptors under basal and early-life stress conditions. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'" http://www.ncbi.nlm.nih.gov/pubmed/22609536 1 786 M. E. Trulson and B. L. Jacobs 1979 "Effects of 5-methoxy-N,N-dimethyltryptamine on behavior and raphe unit activity in freely moving cats" Eur.J.Pharmacol. 54 01-Feb 43-50 "5-methoxy-N,N-dimethyltryptamine (5-MeODMT) produced a dose-dependent decrease in the discharge rate of serotonin-containing neurons in the dorsal raphe nucleus of freely moving cats. This ranged from a 15% decrease at 10 microgran/kg, i.m., to a virtual complete depression of activity at 250 microgram/kg. 5-MeODMT's effects on raphe units occurred with a very short latency (3-5 min) and its duration of action was dose-dependent and limited to an hour or less. The degree of depression of raphe unit activity was directly related to the frequency of occurrence of a number of hallucinogen-specific cat behaviors such as limb flick and abortive groom. There was also a close temporal correlation between the depression of raphe unit activity and the occurrence of these behaviors. These data indicate that the effects of 5-MeODMT may be primarily dependent on its actions upon brain serotonin neurons" http://www.ncbi.nlm.nih.gov/pubmed/283930 0 787 A. J. Milnerwood and L. A. Raymond 2007 Corticostriatal synaptic function in mouse models of Huntington's disease: early effects of huntingtin repeat length and protein load J.Physiol 585 Pt 3 817-831 "Huntington's disease (HD) is an autosomal dominant, late onset, neurodegenerative disease characterized by motor deficits and dementia that is caused by expansion of a CAG repeat in the HD gene. Clinical manifestations result from selective neuronal degeneration of predominantly GABAergic striatal medium-sized spiny neurons (MSNs). A growing number of studies demonstrate that personality, mood and cognitive disturbances are some of the earliest signs of HD and may reflect synaptic dysfunction prior to neuronal loss. Previous studies in striatal MSNs demonstrated early alterations in NMDA-type glutamate receptor currents in several HD mouse models, as well as evidence for presynaptic dysfunction prior to disease manifestations in the R6/2 HD fragment mouse model. We have compared corticostriatal synaptic function in full-length, human HD gene-carrying YAC transgenic mice expressing a non-pathogenic CAG repeat (YAC18; control) with three increasingly severe variants of pathogenic HD gene-expressing mice (YAC72 and two different lines of YAC128), at ages that precede any detectable disease phenotype. We report presynaptic dysfunction and a propensity towards synaptic depression in YAC72 and YAC128 compared to YAC18 mice, and, in the most severe model, we also observed altered AMPA receptor function. When normalized to evoked AMPAR currents, postsynaptic NMDAR currents are augmented in all three pathogenic HD YAC variants. These findings demonstrate multiple perturbations to corticostriatal synaptic function in HD mice, furthering our understanding of the early effects of the HD mutation that may contribute to cognitive dysfunction, mood disorders and later development of more serious dysfunction. Furthermore, this study provides a set of neurophysiological sequelae against which to test and compare other mouse models and potential therapies in HD" http://www.ncbi.nlm.nih.gov/pubmed/17947312 0 788 "O. Miyamoto, T. Nakamura, S. Yamagami, T. Negi, M. Tokuda, H. Matsui and T. Itano" 2000 Depression of long term potentiation in gerbil hippocampus following postischemic hypothermia Brain Res. 873 1 168-172 "To investigate the mechanism of chronic cell death following postischemic hypothermia, the change of N-methyl-D-aspartate receptor (NMDAR) were examined by immunohistochemistry of NMDAR1 and long-term potentiation (LTP) in the CA1 subfield of the gerbil hippocampus. At 1 week following postischemic hypothermia (32 degrees Cx4 h), all CA1 neurons survived; however, immunoreactivity of NMDAR1 increased in neuronal perikarya whereas decreased in dendrites in the CA1 neurons. The abnormality was still observed in remaining CA1 neurons at 1 month after hypothermia. LTP was also significantly depressed at 1 week after hypothermia. These results suggest that some abnormalities in the glutamate receptor may be caused by ischemia; such abnormality would persist in spite of hypothermia treatment, resulting in the depression of LTP" http://www.ncbi.nlm.nih.gov/pubmed/10915827 0 789 "M. Lee, Y. H. Ryu, W. G. Cho, Y. W. Kang, S. J. Lee, T. J. Jeon, C. H. Lyoo, C. H. Kim, D. G. Kim, K. Lee, T. H. Choi and J. Y. Choi" 2015 Relationship between dopamine deficit and the expression of depressive behavior resulted from alteration of serotonin system Synapse 69 9 453-460 "Depression frequently accompanies in Parkinson's disease (PD). Previous research suggested that dopamine (DA) and serotonin systems are closely linked with depression in PD. However, comprehensive studies about the relationship between these two neurotransmitter systems are limited. Therefore, the purpose of this study is to evaluate the effect of dopaminergic destruction on the serotonin system. The interconnection between motor and depression was also examined. Two PET scans were performed in the 6-hydroxydopamine (6-OHDA) lesioned and sham operated rats: [(18) F]FP-CIT for DA transporters and [(18) F]Mefway for serotonin 1A (5-HT(1A)) receptors. Here, 6-OHDA is a neurotoxin for dopaminergic neurons. Behavioral tests were used to evaluate the severity of symptoms: rotational number for motor impairment and immobility time, acquired from the forced swim test for depression. Region-of-interests were drawn in the striatum and cerebellum for the DA system and hippocampus and cerebellum for the 5-HT system. The cerebellum was chosen as a reference region. Nondisplaceable binding potential in the striatum and hippocampus were compared between 6-OHDA and sham groups. As a result, the degree of DA depletion was negatively correlated with rotational behavior (R(2) = 0.79, P = 0.003). In 6-OHDA lesioned rats, binding values for 5-HT(1A) receptors was 22% lower than the sham operated group. This decrement of 5-HT(1A) receptor binding was also correlated with the severity of depression (R(2) = 0.81, P = 0.006). Taken together, this research demonstrated that the destruction of dopaminergic system causes the reduction of the serotonergic system resulting in the expression of depressive behavior. The degree of dopaminergic dysfunction was positively correlated with the impairment of the serotonin system. Severity of motor symptoms was also closely related to depressive behavior" http://www.ncbi.nlm.nih.gov/pubmed/26089169 1 790 "M. Nashed, E. Seidlitz and G. Singh" 2015 A novel pre-clinical model of cancer-induced depression "Biological Psychiatry.Conference: 70th Annual Scientific Convention and Meeting of the Society of Biological Psychiatry, SOBP 2015 Toronto, ON Canada.Conference Start: 20150514 Conference End: 20150516.Conference Publication: (var.pagings).77 (9 Suppl" var.pagings 54S "Background: Nearly 42% of cancer inpatients develop depression, compared with 8-12% of the general population. In addition to the psychosocial impact of a cancer diagnosis, biological mechanisms may be involved, with evidence suggesting that depression symptoms precede cancer diagnosis. This study aims to establish the first pre-clinical model of cancer-induced depression (CID). Methods: 51 BALB/c mice were randomized to 4 groups. The positive control (PC; n=12) and reversal (n=12) mice received 35ug/ mL of oral corticosterone for 21 days to induce depressive behaviours. Reversal mice received 150ug/mL of fluoxetine (FLX) for an additional 21 days. Cancer mice (n=15) received subcutaneous injections of 4T1 mammary carcinoma cells. Negative control (NC; n=12) mice received sham injections. The sucrose preference test (SPT) was used to test for anhedonia, and the forced swim test (FST) was used to test for behavioural despair. Data was analyzed using one-way ANOVA with Tukey's correction for multiple comparisons. Results: PC mice had reduced sucrose preference on the SPT and increased immobility time on the FST compared to control (SPT: 58.5+/-3.3% vs. 70.2+/-2.1%, p<0.05; FST: 233.8+/-23.1s vs. 191.2+/-31.5s, p<0.01). Reversal mice had intermediate sucrose preference (64.5+/-3.2%, n.s.) and decreased immobility compared to PC (190.4+/-42.7s vs. 233.8+/-23.1s, p<0.01). Cancer mice had decreased sucrose preference and increased immobility compared to NC (SPT: 60.4+/-3.35% vs. 70.2+/-2.1%, p<0.05; FST: 227.7+/-30.7s vs. 191.2+/-31.5s, p<0.01). Conclusions: Detection of depressive behaviours in the PC group, and reversal of these behaviours by FLX establish the validity of the SPT and FST. Using these tests, the proposed CID model demonstrated depressive behaviours. This model opens new avenues of investigation into CID mechanisms and novel drug targets" 0 791 K. D. Peters and R. I. Wood 2005 "Androgen dependence in hamsters: overdose, tolerance, and potential opioidergic mechanisms" Neuroscience 130 4 971-981 "Anabolic steroids are drugs of abuse. However, the potential for steroid reward and addiction remains largely unexplored. This study used i.c.v. testosterone self-administration and controlled infusions of testosterone or vehicle in hamsters to explore central mechanisms of androgen overdose. Forty-two hamsters used nose-pokes to self-administer 1 microg/microl testosterone i.c.v. 4 h/day in an operant chamber. During 1-56 days of androgen self-administration, 10 (24%) hamsters died. Deaths correlated with peak daily intake of testosterone. Of the hamsters that self-administered a peak intake of <20 microg/day, there was 100% survival (10/10). Survival decreased to 86% (19/22) when daily testosterone intake peaked at 20-60 microg/day. Only 30% (three of 10) survived when daily testosterone intake exceeded 60 microg/day. Deaths are not due to volume or vehicle because i.c.v. infusions of 80 mul vehicle had no effect. Testosterone overdose resembles opiate intoxication. When male hamsters received infusions of 40 microg testosterone, locomotion (25.1+/-18.8 grid-crossings/10 min), respiration (72.7+/-5.4 breaths/min) and body temperature (33.5+/-0.4 degrees C) were significantly reduced, compared with males receiving vehicle infusions (186.1+/-8.1 crossings/10 min, 117.6+/-1.0 breaths/min, 35.9+/-0.1 degrees C, P<0.05). However, males developed tolerance to continued daily testosterone infusion. After 15 days, locomotion (170.2+/-6.3 crossings), respiration (118.4+/-1.3 breaths/min), and body temperature (35.3+/-0.3 degrees C) in testosterone-infused males were equivalent to that in vehicle controls (P>0.05). The depressive effects of testosterone infusion are blocked by the opioid antagonist, naltrexone. With naltrexone pre-treatment (10 mg/kg s.c.), locomotion (183.7+/-1.8 crossings/10 min), respiration (116.9+/-0.3 breaths/min), and body temperature (36.1+/-0.4 degrees C) during testosterone infusion were equivalent to vehicle controls. Likewise, naltrexone prevents the reinforcing effects of i.c.v. testosterone self-administration. These results indicate that testosterone at high doses causes central autonomic depression, which may be a factor in deaths during self-administration. As well, the depressive effects of large quantities of testosterone may be mediated, at least in part, by an opioidergic mechanism" http://www.ncbi.nlm.nih.gov/pubmed/15652994 0 792 R. M. Lopez and D. B. Murcia 2008 First description of malignant retrobulbar and intracranial teratoma in a lesser kestrel (Falco naumanni) Avian Pathol. 37 4 413-414 "Teratomas are defined as germ cell origin neoplasms that can be rarely found in either humans or animals. Their most common localization is the gonads, although extragonadal localization has also been observed. In avian medicine, there is scarce literature about the occurrence of teratomas and their clinical implications, and this is mainly in wildlife birds . For this reason, we report the first description of a teratoma with both retrobulbar and intracranial locations in a 10-day-old chick of a lesser kestrel (Falco naumanni) born in captivity. The raptor was treated in a centre of wildlife rehabilitation because of the presence of left periocular swelling and exopthalmos. The bird worsened rapidly with signs of vestibular syndrome, ataxia and depression, and euthanasia was practised for humanitarian reasons. Histological examination characterized both masses as malignant teratomas based on the presence of tissues of the three germ cell layers and the presence of both anaplastic foci and immature tissues" http://www.ncbi.nlm.nih.gov/pubmed/18622858 0 793 "M. Orsetti, P. L. Canonico, A. Dellarole, L. Colella, B. F. Di and P. Ghi" 2007 Quetiapine prevents anhedonia induced by acute or chronic stress Neuropsychopharmacology 32 8 1783-1790 "The role of atypical antipsychotics as add-on treatments and as primary mood stabilizers in different phases of bipolar disorder is an important current research area. Although in bipolar patients the main therapeutic indication of quetiapine (QTP) is the management of acute mania, several observations suggest that this agent may exert antidepressant as well as antimanic effects. However, in our knowledge, there are no preclinical studies supporting this hypothesis. Thus, the main goal of the present work was to evaluate the putative antidepressant effect of QTP (0.4, 2.0, or 10 mg/kg/day), in comparison to amitriptyline (AMI) (2 or 5 mg/kg/day), in rats exposed to acute or chronic stress. The administration of QTP, 2 mg/kg/day, prevents the onset of anhedonia in rats exposed to a 6-week chronic mild stress (CMS) protocol. The effect of QTP has a slow onset, beginning at week 5, and causes a complete recovery from anhedonia. In this respect, the effect of QTP is similar to that obtained after chronic administration of AMI 2 or 5 mg/kg/day. Our findings also indicate that a 6-week administration of QTP, 2 or 10 mg/kg/day, has protective effects against the onset of anhedonia caused by the exposure to an acute subthreshold stressful event in rats that have previously experienced the CMS procedure. The results suggest that QTP is able to prevent both the transient mood depression caused by acute stress and the long-lasting anhedonic state induced by exposure, over a period of weeks, to a variety of unpredictable mild stressors" http://www.ncbi.nlm.nih.gov/pubmed/17213846 1 794 "S. Kasinathan, S. L. Basu and V. Sriramulu" 1977 Effect of steroids on the adenohypophyseal gonadotrophes & its relation to spermatogenesis in Rana hexadactyla lesson Indian J.Exp.Biol. 15 9 703-707 http://www.ncbi.nlm.nih.gov/pubmed/611087 0 795 "L. K. Malendowicz, B. Lesniewska, B. Baranowska, M. Nowak and M. Majchrzak" 1991 Effect of bombesin on the structure and function of the rat adrenal cortex Res.Exp.Med.(Berl) 191 2 121-128 "Intact and dexamethasone-treated adult female Wistar rats were infused (Alzet osmotic minipumps) with bombesin (0.75 micrograms/rat per day) for 7 days. Bombesin depressed body weight and capacity of adrenal homogenate to secrete corticosterone; the latter effect was reflected in intact rats by a drop in serum corticosterone level. Bombesin had no effect on pituitary and serum adrenocorticotropic hormone (ACTH) concentration and serum aldosterone level. In intact animals, infusion of bombesin resulted in lowering of the number of parenchymal cells in adrenal cortex connected with the hypertrophy of glomerulosa and fasciculata cells. Moreover, bombesin lowered basal corticosterone secretion by isolated rat adrenocortical cells; however, neuropeptide applied did not change the response of isolated cells to ACTH stimulation. The data obtained clearly demonstrate inhibitory effect of bombesin on basal corticosterone secretion by the rat adrenal cortex" http://www.ncbi.nlm.nih.gov/pubmed/1650017 0 796 D. Lagunoff and H. Wan 1979 Inhibition of histamine release from rat mast cells by cytochalasin A and other sulfhydryl reagents Biochem.Pharmacol. 28 11 1765-1769 http://www.ncbi.nlm.nih.gov/pubmed/89848 0 797 "H. W. Yang, Y. W. Lin, C. D. Yen and M. Y. Min" 2002 Change in bi-directional plasticity at CA1 synapses in hippocampal slices taken from 6-hydroxydopamine-treated rats: the role of endogenous norepinephrine Eur.J.Neurosci. 16 6 1117-1128 "The object of the present study is to investigate the role of endogenous adrenergic innervation in regulating bi-directional synaptic plasticity in rat hippocampal CA1 synapses. The endogenous adrenergic system was eliminated by giving subcutaneous injection of 6-hydroxydopamine (6-OHDA) to rats immediately after birth, and the animals were killed for experiments at postnatal ages of 25-35 days. In hippocampal slices taken from 6-OHDA-treated animals, theta-burst stimulation at 100 Hz failed to induce long-term potentiation (LTP) at CA1 synapses. However, the induction of long-term depression (LTD) by prolonged low frequency stimulation at 1 Hz was unaffected in slices from 6-OHDA-treated animals. Bath application of norepinephrine (NE) restored LTP to control levels and blocked LTD. This effect was mimicked by beta- but not alpha-adrenergic receptor agonists, i.e. by isoproterenol but not phenylephrine. The activators of adenylyl cyclase and protein kinase A (PKA), i.e. forskolin and 8-bromoadenosine-3', 5'-cyclic monophosphate, respectively, restored LTP in slices from 6-OHDA-treated animals. In addition, application of the D1/D5 receptor agonist, dihydrexidine, also restored LTP in slices from 6-OHDA-treated animals. These results suggest that physiologically the recruitment of catecholamine innervation may be important for induction of LTP at hippocampal CA1 synapses during tetanic stimulation, while it may not be essential for LTD induction by prolonged 1 Hz stimulation. The released NE and dopamine exert their role in modulating synaptic plasticity via activation of beta-adrenergic and D1/D5 receptors, respectively, which in turn increase the levels of cytoplasm adenosine-3',5'-cyclic monophosphate and PKA" http://www.ncbi.nlm.nih.gov/pubmed/12383241 0 798 T. Doi and N. Sawa 1980 Antagonistic effects of psycholeptic drugs on stress-induced analgesia Arch.Int.Pharmacodyn.Ther. 247 2 264-274 "Stress-induced analgesia was significantly antagonized by naloxone and was dose-dependently reduced by diazepam, chlordiazepoxide, flurazepam, medazepam, nitrazepam, estazolam, phenobarbital, chlorpromazine, levomepromazine, haloperidol and propranolol. In contrast to psycholeptics, morphine substantially increased in threshold of nociceptive response in the post-stress session. Centrally acting muscle relaxants, tolperisone and carosiprodol had no substantial anti-stress effects. These results suggest that the stress-induced analgesia is probably mediated through endogenous opioids in the central nervous system. The approach used in our study provides a simple method for assessing the anti-stress action of psycholeptics" http://www.ncbi.nlm.nih.gov/pubmed/6108747 0 799 "P. R. Pennington, Z. Wei, L. Rui, J. A. Doig, B. Graham, K. Kuski, G. G. Gabriel and D. D. Mousseau" 2011 Alzheimer disease-related presenilin-1 variants exert distinct effects on monoamine oxidase-A activity in vitro J.Neural Transm.(Vienna.) 118 7 987-995 "Monoamine oxidase-A (MAO-A) has been associated with both depression and Alzheimer disease (AD). Recently, carriers of AD-related presenilin-1 (PS-1) alleles have been found to be at higher risk for developing clinical depression. We chose to examine whether PS-1 could influence MAO-A function in vitro. Overexpression of selected AD-related PS-1 variants (wildtype, Y115H, DeltaEx9 and M146V) in mouse hippocampal HT-22 cells affects MAO-A catalytic activity in a variant-specific manner. The ability of the PS-1 substrate-competitor DAPT to induce MAO-A activity in cells expressing either PS-1 wildtype or PS-1(M146V) suggests the potential for a direct influence of PS-1 on MAO-A function. In support of this, we were able to co-immunoprecipitate MAO-A with FLAG-tagged PS-1 wildtype and M146V proteins. This potential for a direct protein-protein interaction between PS-1 and MAO-A is not specific for HT-22 cells as we were also able to co-immunoprecipitate MAO-A with FLAG-PS-1 variants in N2a mouse neuroblastoma cells and in HEK293 human embryonic kidney cells. Finally, we demonstrate that the two PS-1 variants reported to be associated with an increased incidence of clinical depression [e.g., A431E and L235V] both induce MAO-A activity in HT-22 cells. A direct influence of PS-1 variants on MAO-A function could provide an explanation for the changes in monoaminergic tone observed in several neurodegenerative processes including AD. The ability to induce MAO-A catalytic activity with a PS-1/gamma-secretase inhibitor should also be considered when designing secretase inhibitor-based therapeutics" http://www.ncbi.nlm.nih.gov/pubmed/21373759 0 800 "V. Babapour, R. Boivin, J. Bost, B. Coquet, J. Liautaud, J. Pla and R. Plan" 1974 [Histamine-liberation effect of hypotensive compounds present in various human serum albumins. Relation with blood group substances] Therapie 29 3 459-473 http://www.ncbi.nlm.nih.gov/pubmed/4140581 0 801 "C. Devaux, R. Lande and E. Porcher" 2014 Pollination ecology and inbreeding depression control individual flowering phenologies and mixed mating Evolution 68 11 3051-3065 "We analyze evolution of individual flowering phenologies by combining an ecological model of pollinator behavior with a genetic model of inbreeding depression for plant viability. The flowering phenology of a plant genotype determines its expected daily floral display which, together with pollinator behavior, governs the population rate of geitonogamous selfing (fertilization among flowers on the same plant). Pollinators select plant phenologies in two ways: they are more likely to visit plants displaying more flowers per day, and they influence geitonogamous selfing and consequent inbreeding depression via their abundance, foraging behavior, and pollen carry-over among flowers on a plant. Our model predicts two types of equilibria at stable intermediate selfing rates for a wide range of pollinator behaviors and pollen transfer parameters. Edge equilibria occur at maximal or minimal selfing rates and are constrained by pollinators. Internal equilibria occur between edge equilibria and are determined by a trade-off between pollinator attraction to large floral displays and avoidance of inbreeding depression due to selfing. We conclude that unavoidable geitonogamous selfing generated by pollinator behavior can contribute to the common occurrence of stable mixed mating in plants" http://www.ncbi.nlm.nih.gov/pubmed/25130655 0 802 "L. Trabace, M. Zotti, M. G. Morgese, P. Tucci, M. Colaianna, S. Schiavone, P. Avato and V. Cuomo" 2011 Estrous cycle affects the neurochemical and neurobehavioral profile of carvacrol-treated female rats Toxicol.Appl.Pharmacol. 255 2 169-175 "Carvacrol is the major constituent of essential oils from aromatic plants. It showed antimicrobial, anticancer and antioxidant properties. Although it was approved for food use and included in the chemical flavorings list, no indication on its safety has been estimated. Since the use of plant extracts is relatively high among women, aim of this study was to evaluate carvacrol effects on female physiology and endocrine profiles by using female rats in proestrus and diestrus phases. Serotonin and metabolite tissue content in prefrontal cortex and nucleus accumbens, after carvacrol administration (0.15 and 0.45g/kg p.o.), was measured. Drug effects in behavioral tests for alterations in motor activity, depression, anxiety-related behaviors and endocrine alterations were also investigated. While in proestrus carvacrol reduced serotonin and metabolite levels in both brain areas, no effects were observed in diestrus phase. Only in proestrus phase, carvacrol induced a depressive-like behavior in forced swimming test, without accompanying changes in ambulation. The improvement of performance in FST after subchronic treatment with fluoxetine (20mg/kg) suggested a specific involvement of serotonergic system. No differences were found across the groups with regard to self-grooming behavior. Moreover, in proestrus phase, carvacrol reduced only estradiol levels without binding hypothalamic estradiol receptors. Our study showed an estrous-stage specific effect of carvacrol on depressive behaviors and endocrine parameters, involving serotonergic system. Given the wide carvacrol use not only as feed additive, but also as cosmetic essence and herbal remedy, our results suggest that an accurate investigation on the effects of its chronic exposure is warranted" http://www.ncbi.nlm.nih.gov/pubmed/21723308 1 803 "N. J. Drouliscos, B. J. Macris and R. Kokke" 1976 Growth of Fusarium moniliforme on carob aqueous extract and nutritional evaluation of its biomass Appl.Environ.Microbiol. 31 5 691-694 "Fusarium moniliforme was cultured semicontinuously on a carob medium in a 14-liter fermentor (8.5-liter working volume). The growth medium provided 2.4% carob sugar, 0.72% NH4H2PO4, and 0.03% MgSO4-7H2O. The biomass harvest was 8.8 g/liter per day. Ninety percent of the sugars were consumed, and the pH dropped from 5.9 to about 3.7. The crude protein (N X 6.25) of the spray-dried mycelium was 380 g/kg, 300 g/kg for the true protein (Lowry), and 4.8 g/kg for the (Folin-Denis) tannic acid. The mycelium was evaluated nutritionally with the weanling rat as experimental animal. The protein efficiency ratio and net protein utilization values for the unsupplemented mycelium were 1.15 and 0.42, respectively, and for the mycelium supplemented with DL-methionine (5 g/kg) they were 2.31 and 0.72, respectively. No growth depression was observed in the experimental rats, and on dissection of the carcasses the internal organs were found to be normal" http://www.ncbi.nlm.nih.gov/pubmed/5952 0 804 K. Knudsen and J. Abrahamsson 1994 "Effects of epinephrine, norepinephrine, magnesium sulfate, and milrinone on survival and the occurrence of arrhythmias in amitriptyline poisoning in the rat" Crit Care Med. 22 11 1851-1855 "OBJECTIVES: Cardiac depression is the main adverse effect of severe tricyclic antidepressant poisoning. The aim of this study was to compare the effects of several inotropic drugs on survival and the occurrence of arrhythmias in the treatment of amitriptyline poisoning. DESIGN: Nonrandomized, controlled intervention trial. SETTING: University laboratory. SUBJECTS: Eighty-six male Wistar rats anesthetized with pentobarbital and mechanically ventilated. INTERVENTIONS: Rats subjected to a 60-min continuous infusion of amitriptyline (1.25 mg/kg/min) were treated with a continuous infusion of either epinephrine, norepinephrine, milrinone, magnesium, epinephrine + magnesium, or norepinephrine + magnesium. MEASUREMENTS AND MAIN RESULTS: Without treatment, all animals exhibited arrhythmias on the electrocardiogram within 20 mins. All treatment drugs delayed the onset of arrhythmias, but significant differences were only observed after administration of epinephrine, epinephrine + magnesium sulfate, and norepinephrine + magnesium sulfate. All the inotropic drugs markedly increased survival. Sodium concentrations were unaffected by all treatments. In control animals, potassium concentrations increased during amitriptyline infusion. Norepinephrine treatment had no effect on potassium concentrations, whereas all other treatments resulted in decreased potassium concentrations. CONCLUSIONS: All inotropic drugs used in the study increased survival in tricyclic antidepressant poisoning in rats without increasing the risk of arrhythmias. Furthermore, epinephrine and norepinephrine + magnesium sulfate were effective in preventing arrhythmias, possibly due to improved hemodynamic performance or potassium homeostasis" http://www.ncbi.nlm.nih.gov/pubmed/7956291 0 805 "X. Ren, Y. Dwivedi, A. C. Mondal and G. N. Pandey" 2011 Cyclic-AMP response element binding protein (CREB) in the neutrophils of depressed patients "Psychiatry Research.185 (1-2) ()(pp 108-112), 2011.Date of Publication: 30 Jan 2011." 01-Feb 108-112 "Cyclic-AMP response element binding (CREB) protein regulates the expression of many genes involved in the pathophysiology of depression. Increased CREB levels were found in the brain of antidepressant-treated rats and decreased protein and mRNA expression of CREB was reported in the postmortem brain of depressed suicide victims. We determined CREB protein expression, using Western blot technique, and CRE-DNA binding, using gel shift assay, in neutrophils obtained from 22 drug-free patients with major depressive disorder (MDD) and 23 normal control subjects. Diagnosis of patients was based on Diagnostic and Statistical Manual of Mental Disorders DSM-IV criteria; severity of illness was rated by Hamilton Depression Rating Scale (HDRS). We found that the CRE-DNA binding activity and CREB protein expression were significantly decreased in the neutrophils of drug-free MDD patients compared with normal control subjects. Our findings suggest that CREB may play an important role in the pathophysiology of depression and that it may be an important target for the therapeutic action of antidepressant drugs. Neutrophil CREB levels may also serve as a useful biomarker for patients with MDD. © 2010 Elsevier Ltd" DO - http://dx.doi.org/10.1016/j.psychres.2010.04.013 0 806 U. Ponnappan and L. S. Soderberg 2001 Inflammatory macrophage nuclear factor-kappaB and proteasome activity are inhibited following exposure to inhaled isobutyl nitrite J.Leukoc.Biol. 69 4 639-644 "A history of abuse of nitrite inhalants has been correlated with HIV seropositivity and Kaposi's sarcoma. A series of 14 daily, 45-min exposures of mice to 900-ppm isobutyl nitrite in an inhalation chamber reduced the number of peritoneal exudate macrophages (PEM) by 35% and the number of resident peritoneal macrophages (RPM) by 18%. Although the tumoricidal activity of RPM was not affected by the inhalant, the cytotoxicity of PEM was reduced by 26%. The induction of nitric oxide (NO) and the inducible NO synthase (iNOS) protein in PEM were inhibited by the inhalant to a similar extent. Inhibition of NF-kappaB activation in PEM from mice exposed to the inhalant corresponded to reduced degradation of the NF-kappaB inhibitor, IkappaB alpha. Proteasome-associated, enzymatic activity was compromised in PEM from inhalant-exposed mice, suggesting that inhaled isobutyl nitrite compromised macrophage, tumoricidal activity by inhibiting proteasomal degradation of the NF-kappaB inhibitor, IkappaB alpha" http://www.ncbi.nlm.nih.gov/pubmed/11310851 0 807 "M. Margalith, E. Margalith, T. Nasialski and N. Goldblum" 1970 Induction of simian virus 40 antigen in BSC1 transformed cells J.Virol. 5 3 305-308 "Heating to 45 C induced in virus-free clones of simian virus 40 (SV40) transformed BSC(1) cells the synthesis of SV40 viral antigen, as evidenced by immunofluorescence. Up to 3.8% of the cells exhibited viral antigen 72 hr after heating to 45 C for 30 min. Depletion of arginine from the medium of the heated cells enhanced and increased the percentage of cells synthesizing viral antigen to 11%. Cytosine arabinoside completely inhibited the induction of the viral antigen. No infectious virus was recovered from the cells in which synthesis of viral antigen was induced. However, small amounts of infectious SV40 virus were rescued from the BSC(1) transformed cells by fusion with rabbit kidney cells or by treatment with mitomycin C" http://www.ncbi.nlm.nih.gov/pubmed/4314551 0 808 L. F. Mal'tseva 1968 [Effect of serotonin antagonists and monoamine oxidase inhibitors on the antineoplastic effect of serotonin] Farmakol.Toksikol. 31 6 735-738 http://www.ncbi.nlm.nih.gov/pubmed/5713590 0 809 "A. Tsafriri, Y. Koch and H. R. Lindner" 1973 Ovulation rate and serum LH levels in rats treated with indomethacin or prostaglandin E2 Prostaglandins 3 4 461-467 http://www.ncbi.nlm.nih.gov/pubmed/4738126 0 810 "M. J. Armstrong, P. Gaunt, G. P. Aithal, D. Barton, D. Hull, R. Parker, J. M. Hazlehurst, K. Guo, G. Abouda, M. A. Aldersley, D. Stocken, S. C. Gough, J. W. Tomlinson, R. M. Brown, S. G. Hubscher and P. N. Newsome" 2016 "Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): A multicentre, double-blind, randomised, placebo-controlled phase 2 study" "The Lancet.387 (10019) ()(pp 679-690), 2016.Date of Publication: 13 Feb 2016." 10019 679-690 "Summary Background Glucagon-like peptide-1 (GLP-1) analogues reduce hepatic steatosis, concentrations of liver enzymes, and insulin resistance in murine models of fatty liver disease. These analogues are licensed for type 2 diabetes, but their efficacy in patients with non-alcoholic steatohepatitis is unknown. We assessed the safety and efficacy of the long-acting GLP-1 analogue, liraglutide, in patients with non-alcoholic steatohepatitis. Methods This multicentre, double-blinded, randomised, placebo-controlled phase 2 trial was conducted in four UK medical centres to assess subcutaneous injections of liraglutide (1.8 mg daily) compared with placebo for patients who are overweight and show clinical evidence of non-alcoholic steatohepatitis. Patients were randomly assigned (1:1) using a computer-generated, centrally administered procedure, stratified by trial centre and diabetes status. The trial was designed using A'Hern's single-group method, which required eight (38%) of 21 successes in the liraglutide group for the effect of liraglutide to be considered clinically significant. Patients, investigators, clinical trial site staff, and pathologists were masked to treatment assignment throughout the study. The primary outcome measure was resolution of definite non-alcoholic steatohepatitis with no worsening in fibrosis from baseline to end of treatment (48 weeks), as assessed centrally by two independent pathologists. Analysis was done by intention-to-treat analysis, which included all patients who underwent end-of-treatment biopsy. The trial was registered with ClinicalTrials.gov, number NCT01237119. Findings Between Aug 1, 2010, and May 31, 2013, 26 patients were randomly assigned to receive liraglutide and 26 to placebo. Nine (39%) of 23 patients who received liraglutide and underwent end-of-treatment liver biopsy had resolution of definite non-alcoholic steatohepatitis compared with two (9%) of 22 such patients in the placebo group (relative risk 4.3 [95% CI 1.0-17.7]; p=0.019). Two (9%) of 23 patients in the liraglutide group versus eight (36%) of 22 patients in the placebo group had progression of fibrosis (0.2 [0.1-1.0]; p=0.04). Most adverse events were grade 1 (mild) to grade 2 (moderate) in severity, transient, and similar in the two treatment groups for all organ classes and symptoms, with the exception of gastrointestinal disorders in 21 (81%) of 23 patients in the liraglutide group and 17 (65%) of 22 patients in the placebo group, which included diarrhoea (ten [38%] patients in the liraglutide group vs five [19%] in the placebo group), constipation (seven [27%] vs none), and loss of appetite (eight [31%] vs two [8%]). Interpretation Liraglutide was safe, well tolerated, and led to histological resolution of non-alcoholic steatohepatitis, warranting extensive, longer-term studies. Funding Wellcome Trust, National Institute of Health Research, and Novo Nordisk" DO - http://dx.doi.org/10.1016/S0140-6736%2815%2900803-X 0 811 "K. Sahin, M. Onderci, N. Sahin, M. F. Gursu and O. Kucuk" 2003 Dietary vitamin C and folic acid supplementation ameliorates the detrimental effects of heat stress in Japanese quail J.Nutr. 133 6 1882-1886 "We evaluated the effects of vitamin C (L-ascorbic acid) and folic acid supplementation on performance, carcass characteristics and concentrations of the oxidative stress markers [malondialdehyde (MDA), homocysteine], adrenocorticotropic hormone (ACTH), vitamins C, E, A, B-12 and folic acid, and mineral status in broiler Japanese quail (Coturnix coturnix japonica) exposed to high ambient temperature (34 degrees C, 8 h/d, 0900-1700 h). The birds (n = 150; 10-d-old) kept at 34 degrees C were fed a basal diet (HS group) or the basal diet supplemented with 250 mg of L-ascorbic acid/kg of diet (Vit C group), 1 mg of folic acid/kg of diet (FA group) or both (Vit C + FA group), whereas birds kept at 22 degrees C were fed the basal diet (TN group). Supplementing heat-stressed quail with vitamin C and folic acid improved performance compared to the HS group. Effects generally were greatest in quail supplemented with both. Although supplementation did not consistently restore concentrations to those of the TN group, it increased serum concentrations of the vitamins under study. Furthermore, serum and tissue MDA, homocysteine and ACTH concentrations were lower in the supplemented groups than in the heat-stressed controls. Retention of N, ash, Ca, P, Zn, Fe, Cu and Cr were highest in the Vit C + FA group and lowest in the HS group (P < 0.05). The results of the study indicate that vitamin C and folic acid supplementation attenuates the decline in performance and antioxidant status caused by heat stress. Such supplementation may offer protection against heat stress-related depression in performance of Japanese quail" http://www.ncbi.nlm.nih.gov/pubmed/12771333 0 812 F. Chang 1970 [Study on gastric secretory function by a combined stimulatory and inhibitory method] Zasshi Tokyo Ika Daigaku 28 5 727-747 http://www.ncbi.nlm.nih.gov/pubmed/5535744 0 813 "M. Honda, M. Tanabe and H. Ono" 2006 Spinal cord injury-specific depression of monosynaptic spinal reflex transmission by l-5-hydroxytryptophan results from loss of the 5-HT uptake system and not 5-HT receptor supersensitivity Exp.Neurol. 202 1 258-261 "We studied changes in the spinal segmental reflex and serotonergic (5-HT) responses in rats after spinal cord injury (SCI) produced by the weight-dropping method at the T8 level. The spinal monosynaptic reflex amplitude (MSR) was recorded from the L5 ventral root following stimulation of the ipsilateral L5 dorsal root. The 5-HT precursor l-5-hydroxytryptophan (L-5-HTP) depressed MSR in the spinal cord injured rats but not in normal rats. We investigated whether the SCI-specific depression of MSR by L-5-HTP was attributable to postsynaptic supersensitivity of 5-HT receptors or presynaptic loss of the 5-HT uptake system. Sumatriptan, a selective 5-HT(1B/1D) receptor agonist that is not taken up by 5-HT transporters, depressed the MSR similarly in both SCI and normal rats, suggesting that SCI resulted in the loss of 5-HT terminals and not postsynaptic supersensitivity of 5-HT receptors" http://www.ncbi.nlm.nih.gov/pubmed/16806182 0 814 J. T. TenBroeck 1968 Effect of nucleosides and nucleoside bases on the development of pre-implantation mouse embryos in vitro J.Reprod.Fertil. 17 3 571-573 http://www.ncbi.nlm.nih.gov/pubmed/5752109 0 815 S. J. Hopkins 1991 Sertraline hydrochloride "Drugs of Today.27 (4) ()(pp 235-237), 1991.Date of Publication: 1991." 4 235-237 1 816 A. Ruiz and J. Durand 2000 Blocking the trigeminal EPSP in rat abducens motoneurons in vivo with the AMPA antagonists NBQX and GYKI 53655 Brain Res.Bull. 52 2 99-107 "In pentobarbitone-anaesthetized rats, the effects of two AMPA receptor antagonists, the competitive antagonist 2, 3-dihydroxy-6-nitro-7-sulfamoyl-benzo-(F)-quinoxaline (NBQX) and the non-competitive 2,3-benzodiazepine GYKI 53655, were compared on excitatory synaptic transmission of trigeminal origin in intracellularly-recorded abducens motoneurons. The effects of both antagonists were also investigated on the alpha-amino-3-hydroxy-5-methyl isoxazole-4-propionic acid (AMPA)-, kainate-, and N-methyl-D-aspartate (NMDA)-induced depression of extracellular antidromic field potentials in the abducens motor nucleus. Microiontophoretic application (< or =100 nA) or intravenous injection of NBQX (< or =5 mg/kg) affected both" http://www.ncbi.nlm.nih.gov/pubmed/10808079 0 817 "L. C. Schenberg, J. C. de Aguiar, H. C. Salgado and F. G. Graeff" 1981 Depressant action of chlordiazepoxide on cardiovascular and respiratory changes induced by aversive electrical stimulation of the brain Braz.J.Med.Biol.Res. 14 1 69-72 "1. Electrical stimulation of the dorsal periaqueductal gray matter (DPAG), an aversive area of the rat brain, increased the mean blood pressure of awake rats as well as of animals anesthetized with urethane. 2. In the anesthetized rats, increases in heart rate and in breath rate were also induced by DPAG stimulation. 3. Chlordiazepoxide, a benzodiazepine, decreased the blood pressure rise caused by aversive stimulation of the brain in the awake rat. 4. Chlordiazepoxide elicited the same effect in urethane-anesthetized rats. In addition, the hyperpnea induced by electrical stimulation of the dorsal periaqueductal gray matter was also decreased by the drug. 5. The pressor response to intravenous noradrenaline was not affected by chlordiazepoxide. 6. These results suggest that benzodiazepines attenuate the neurovegetative changes accompanying emotion by depressing brain systems that integrate emotional behavior" http://www.ncbi.nlm.nih.gov/pubmed/7306724 0 818 P. J. Birch and M. Fillenz 1985 Stimulation of noradrenaline synthesis by the calcium ionophore A23187 and its modulation by presynaptic receptors Neurosci.Lett. 62 2 187-192 "Noradrenaline (NA) synthesis in rat hippocampal synaptosomes is increased by calcium ionophore, A23187, in the presence of calcium. Activation of presynaptic muscarinic, gamma-aminobutyric acidB (GABAB) and alpha 2-adrenergic receptors causes inhibition of the ionophore-stimulated synthesis. The results suggest that different mechanisms mediate the depression by presynaptic receptors of NA release and NA synthesis" http://www.ncbi.nlm.nih.gov/pubmed/3003624 0 819 "D. M. Iascone, S. Padidam, M. S. Pyfer, X. Zhang, L. Zhao and J. Chin" 2013 Impairments in neurogenesis are not tightly linked to depressive behavior in a transgenic mouse model of Alzheimer's disease PLoS.One. 8 11 e79651 "Alzheimer's disease (AD), the most common cause of dementia, is also associated with depression. Although the precise mechanisms that lead to depression in AD are unknown, the impairments in adult hippocampal neurogenesis observed in AD may play a role. Adult-born neurons play a critical role in regulating both cognition and mood, and reduced hippocampal neurogenesis is associated with depression in other neurological disorders. To assess the relationship between Alzheimer's disease, neurogenesis, and depression, we studied human amyloid precursor protein (hAPP) transgenic mice, a well-characterized model of AD. We report that reductions in hippocampal neurogenesis are evident early in disease progression in hAPP mice, but a mild depressive phenotype manifests only in later stages of disease. We found that hAPP mice exhibited a reduction in BrdU-positive cells in the subgranular zone of the dentate gyrus in the hippocampus, as well as a reduction in doublecortin-expressing cells, relative to nontransgenic controls at 5-7 months of age. These alterations in neurogenesis appeared to worsen with age, as the magnitude of reduction in doublecortin-expressing cells was greater in hAPP mice at 13-15 months of age. Only 13-15 month old hAPP mice exhibited depressive behavior in the tail suspension test. However, mice at both age groups exhibited deficits in spatial memory, which was observed in the Morris water maze test for hippocampus-dependent memory. These findings indicate that neurogenesis impairments are accompanied by cognitive deficits, but are not tightly linked to depressive behavior in hAPP mice" http://www.ncbi.nlm.nih.gov/pubmed/24244537 1 820 "J. P. Welsh, H. Yamaguchi, X. H. Zeng, M. Kojo, Y. Nakada, A. Takagi, M. Sugimori and R. R. Llinas" 2005 Normal motor learning during pharmacological prevention of Purkinje cell long-term depression Proc.Natl.Acad.Sci.U.S.A 102 47 17166-17171 "Systemic delivery of (1R-1-benzo thiophen-5-yl-2[2-diethylamino)-ethoxy] ethanol hydrochloride (T-588) prevented long-term depression (LTD) of the parallel fiber (PF)-Purkinje cell (PC) synapse induced by conjunctive climbing fiber and PF stimulation in vivo. However, similar concentrations of T-588 in the brains of behaving mice and rats affected neither motor learning in the rotorod test nor the learning of motor timing during classical conditioning of the eyeblink reflex. Rats given doses of T-588 that prevented PF-PC LTD were as proficient as controls in learning to adapt the timing of their conditioned eyeblink response to a 150- or 350-ms change in the timing of the paradigm. The experiment indicates that PF-PC LTD under control of the climbing fibers is not required for general motor adaptation or the learning of response timing in two common models of motor learning for which the cerebellum has been implicated. Alternative mechanisms for motor timing and possible functions for LTD in protection from excitotoxicity are discussed" http://www.ncbi.nlm.nih.gov/pubmed/16278298 0 821 C. V. Oddis and M. S. Finkel 1995 Cytokine-stimulated nitric oxide production inhibits mitochondrial activity in cardiac myocytes Biochem.Biophys.Res.Commun. 213 3 1002-1009 "We have previously proposed that cytokine-stimulated nitric oxide (NO) production is responsible for reversible myocardial depression in sepsis, trauma and ischemia. NO previously has been found to inhibit mitochondrial activity in other cell types. Accordingly, we sought to determine if cytokine-stimulated NO production inhibited cardiac myocyte mitochondrial activity. Treatment of neonatal rat cardiac myocytes with interleukin-beta (IL-1) resulted in the expression of mRNA for inducible NO synthase (iNOS) and stained positively for iNOS protein by immunohistochemistry. No iNOS staining was detected in untreated cells. IL-1 treatment resulted in significant nitrite levels vs control over 48 hrs (4.2 +/- 0.7 vs 0.3 +/- 0.2 nmol/1.25 x 10(5) cells, respectively) (n = 12) that was inhibited by 1mM NMA (0.3 +/- 0.2 nmoles; p < .01; n = 12). Mitochondrial activity was assessed by the MTT colorimetric assay using (3-4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and OD 570-630. Mitochondrial activity was significantly inhibited by IL-1 vs control cells (0.436 +/- 0.01 vs 0.608 +/- 0.03) and reversed by 1mM NMA (0.549 +/- 0.03) or removal of IL-1 (0.662 +/- 0.02) (p < .01; n = 12 for each). These data strongly suggest that cytokine-stimulated NO production by cardiac myocytes results in reversible inhibition of mitochondrial activity" http://www.ncbi.nlm.nih.gov/pubmed/7654217 0 822 D. G. McDevitt 1973 Symptomatology of chronic brucellosis Br.J.Ind.Med. 30 4 385-389 http://www.ncbi.nlm.nih.gov/pubmed/4270991 0 823 G. W. SCHEPERS 1961 The capacity of aluminum to prevent prothrombin depression by quartz. An experimental study on guinea pigs Toxicol.Appl.Pharmacol. 3 188-201 http://www.ncbi.nlm.nih.gov/pubmed/13747491 0 824 "W. C. Wallen, H. Rabin, R. H. Neubauer and J. L. Cicmanec" 1975 Depression in lymphocyte response to general mitogens by owl monkeys infected with Herpesvirus saimiri J.Natl.Cancer Inst. 54 3 679-685 "The effect of Herpesvirus saimiri (HVS) infection on the response of owl monkey lymphocytes to general mitogens was examined during the development of neoplastic disease. The reactivity of the lymphocytes was then correlated with the clinical condition of the infected monkeys and the content of virus rescued from the peripheral blood lymphocytes (PBL). Eight monkeys developed lymphoma which, in six monkeys, was accompanied by lymphocytic leukemia. All animals that died of HVS-induced neoplasia consistently showed a lack of mitogenic response to phytohemagglutinin and concanavalin A. The response to pokeweed mitogen, while always reduced, was generally less markedly affected than the response to the other two mitogens. Lymphocytes from five of the leukemic animals demonstrated an elevated level of spontaneous DNA synthesis in culture late in the disease. This increased spontaneous DNA synthesis tended to correlate with the rescue of HVS from the PBL as demonstrated by the infective center assay. Although mitogenic hyporesponsiveness corresponded with HVS rescue from PBL in six of nine monkeys, the impairment of normal lymphocyte responsiveness sometimes preceded virus recovery" http://www.ncbi.nlm.nih.gov/pubmed/164565 0 825 "E. N. Lazareva, L. A. Kovaleva, V. K. Vasil'ev and P. S. Braginskaia" 1969 "[N,N'-dibenzylethylenediamine salt of alpha-aminobenzylpenicillin (ampicillin) with prolonged effect]" Antibiotiki. 14 9 813-817 http://www.ncbi.nlm.nih.gov/pubmed/4982963 0 826 "F. Clenet, M. Hascoet, G. Fillion, H. Galons and M. Bourin" 2004 "Anxiolytic profile of HG1, a 5-HT-moduline antagonist, in three mouse models of anxiety" Eur.Neuropsychopharmacol. 14 6 449-456 "HG1 is a new 5-HT-moduline antagonist which is itself an endogenous tetrapeptide specifically acting as an antagonist of 5-HT(1B) auto- and heteroreceptors. Blockade of endogenous 5-HT-moduline might provoke anxiolysis, so it could be a new therapeutic target in anxiety disorders. The aim of our study was to examine the effects of HG1 in three mouse models of anxiety: the four plates test (FPT), the black and white (B&W) model and the elevated plus maze (EPM). Male Swiss mice were intraperitoneally and acutely administered HG1 at the doses of 8, 16, 32 and 64 mg/kg. In these three tests, HG1 exhibited an anxiolytic profile similar to that of diazepam, the referential benzodiazepine compound, without affecting locomotor activity. In the three models used, HG1 was as efficient as benzodiazepine and may consequently exert its anxiolytic effects via the GABA-ergic system. We cannot exclude that it might also act through 5-HT receptors and rather have the profile of a selective serotonin reuptake inhibitor" http://www.ncbi.nlm.nih.gov/pubmed/15589384 0 827 "A. Barral, E. A. Petersen, D. L. Sacks and F. A. Neva" 1983 Late metastatic Leishmaniasis in the mouse. A model for mucocutaneous disease Am.J.Trop.Med.Hyg. 32 2 277-285 "BALB/c, C57B1/6 and (BALB/c x C57B1/6)F1 mice all proved susceptible to infection by a strain of Leishmania isolated from a Central Brazilian with espundia. The course of disease differed markedly between BALB/c and C57B1/6 mice. BALB/c mice suffered from a rapidly progressive and widely metastatic, but non-ulcerative, disease resembling diffuse cutaneous leishmaniasis. In contrast, C57B1/6 mice initially contained parasite multiplication effectively and appeared clinically cured. However, the parasite could persistently be cultured up to about 1 year post-infection. At that time, the parasite load in the infected footpad increased and a patent disease developed characterized by distinctive ulcerative metastases with destruction of soft-tissue in the nasal region similar to the one observed in espundia. Development of disease in both strains of mice was associated with depression of cell-mediated immunity as monitored by delayed-type hypersensitivity in vivo and lymphocyte transformation in vitro. Thus, our study suggests that diffuse cutaneous leishmaniasis and espundia can be caused by the same strain of parasite, and that the particular clinical expression in the individual mouse is determined by the host response" http://www.ncbi.nlm.nih.gov/pubmed/6837839 0 828 "G. E. Seidel, Jr." 2009 ASAS Centennial Paper: Future research in physiology and endocrinology J.Anim Sci. 87 1 384-389 "Over the next quarter century in North America, the following eventualities are likely for physiology and endocrinology research with agricultural animals. 1) Total funding adjusted for inflation will change little but will come less from public sources, and most of that will be in the context of human health. Much of the privately funded research will be herd specific and remain proprietary. 2) The numbers of MS, PhD, and postdoctoral students probably will decrease, but research in the context of credentialing will remain important. 3) Resources such as expanded databases in genomics and proteomics, and remarkable new tools such as small inhibitory RNA will continue to become available, likely at a faster rate than in the previous 25 yr. 4) The huge amounts of data from production agriculture will make agricultural animals ideal models for some kinds of basic research, such as studying fetal programming, resulting in synergy with more applied research. Most of these experimental animals will be in private production herds and flocks, even when work is publicly funded. 5) The trend toward more interdisciplinary research will continue, especially considering interactions among reproduction, health, nutrition, selective breeding, management factors, and societal concerns; reductionist research probing deeper into cellular and molecular mechanisms will remain important, as will whole-animal approaches. 6) Agricultural animals are a product of evolution plus selective breeding. Insights drawn from the former will aid progress in the latter. One focus of research in physiology and endocrinology will be understanding heterosis, inbreeding depression, and epigenetic effects as it becomes possible to manipulate and identify the allelic structure of individual animals. 7) Additional insightful concepts will evolve that will simplify thinking in some respects, such as the maternal to embryonic shift in transcribed RNA in early embryos; however, animal biology will turn out to be even more complex than most of us currently imagine" http://www.ncbi.nlm.nih.gov/pubmed/18765843 0 829 "K. H. Tachiki, A. Takagi, T. Tateishi, A. Kido, K. Nishiwaki, E. Nakamura, H. Nagayama and R. Takahashi" 1978 Animal model of depression. III. Mechanism of action of tetrabenazine Biol.Psychiatry 13 4 429-443 "A study was undertaken to gain an understanding of the biochemical mechanism whereby tetrabenazine (TBZ) produces a sedative effect on the locomotor activity of rats. Rats injected with L-5-hydroxytryptophan (L-5-HTP, 30 mg/kg), the immediate precursor of 5-hydroxytryptamine (5-HT), showed the characteristic bison appearance, pitosis, and catalepsy normally observed after injecting TBZ (30 mg/kg). The treatment of rats with low doses of L-5-HTP (9 mg/kg) plus TBZ (2 mg/kg) significantly decreased locomotor activity, whereas low doses of either one of these drugs given alone had no significant effect on locomotor activity. The level of 5-hydroxyindoleacetic acid (5-HIAA) was elevated in the brain of rats sacrificed 3 hr after treatment with low doses of either L-5-HTP or TBZ alone. Treatment of rats with p-chlorophenylalanine to inhibit the synthesis of 5-HT had an inhibitory effect on the duration of sedation following an injection of TBZ (30 mg/kg). The results of the biochemical and pharmacological studies as reflected by changes in locomotor activity were interpreted to indicate that the sedative action of TBZ was due to an excess of functional 5-HT" http://www.ncbi.nlm.nih.gov/pubmed/150867 0 830 "C. Ganguly, S. De and S. Das" 2000 Prevention of carcinogen-induced mouse skin papilloma by whole fruit aqueous extract of Momordica charantia Eur.J.Cancer Prev. 9 4 283-288 "The anticarcinogenic effect of aqueous extract of fruit of Momordica charantia (bitter gourd), which is widely used as a vegetable in India, was studied in a two-step skin carcinogenesis model in mice. The possible mode of action was also investigated. Oral administration of the fruit extract was found to have an adverse effect on the general health and lifespan of the animals when used at a high concentration. But when this dose was reduced by half, the test extract afforded protection from the development of skin tumour and increased life expectancy. Carcinogen-induced lipid peroxidation in liver and DNA damage in lymphocytes were found to be reduced following treatment with Momordica. The fruit extract was found to significantly activate the liver enzymes glutathione-S-transferase, glutathione peroxidase and catalase (P < 0.001), which showed a depression following exposure to the carcinogen. The results suggest a preventive role of water-soluble constituents of M. charantia fruit during carcinogenesis, which is mediated possibly by their modulatory effect on enzymes of the biotransformation and detoxification system of the host" http://www.ncbi.nlm.nih.gov/pubmed/10958332 0 831 "H. Ujike, M. Kishimoto, Y. Okahisa, M. Kodama, M. Takaki, T. Inada, N. Uchimura, M. Yamada, N. Iwata, M. Iyo, I. Sora and N. Ozaki" 2011 Association Between 5HT1b Receptor Gene and Methamphetamine Dependence Curr.Neuropharmacol. 9 1 163-168 "Several lines of evidence implicate serotonergic dysfunction in diverse psychiatric disorders including anxiety, depression, and drug abuse. Mice with a knock-out of the 5HT1b receptor gene (HTR1B) displayed increased locomotor response to cocaine and elevated motivation to self-administer cocaine and alcohol. Previous genetic studies showed significant associations of HTR1B with alcohol dependence and substance abuse, but were followed by inconsistent results. We examined a case-control genetic association study of HTR1B with methamphetamine-dependence patients in a Japanese population. The subjects were 231 patients with methamphetamine dependence, 214 of whom had a co-morbidity of methamphetamine psychosis, and 248 age- and sex-matched healthy controls. The three single nucleotide polymorphisms (SNPs), rs130058 (A-165T), rs1228814 (A-700C) and rs1228814 (A+1180G) of HTR1B were genotyped. There was no significant difference in allelic and genotypic distributions of the SNPs between methamphetamine dependence and the control. Genetic associations of HTR1B were tested with several clinical phenotypes of methamphetamine dependence and/or psychosis, such as age at first abuse, duration of latency from the first abuse to onset of psychosis, prognosis of psychosis after therapy, and complication of spontaneous relapse of psychotic state. There was, however, no asscocation between any SNP and the clinical phenotypes. Haplotype analyses showed the three SNPs examined were within linkage disequilibrium, which implied that the three SNPs covered the whole HTR1B, and distribution of estimated haplotype frequency was not different between the groups. The present findings may indicate that HTR1B does not play a major role in individual susceptibility to methamphetamine dependence or development of methamphetamine-induced psychosis" http://www.ncbi.nlm.nih.gov/pubmed/21886584 0 832 J. Kraicer and J. V. Milligan 1970 Suppression of ACTH release from adenophypophysis by corticosterone: an in vitro study Endocrinology 87 2 371-376 http://www.ncbi.nlm.nih.gov/pubmed/4316573 0 833 H. Ogawa and S. Tadokoro 1972 "[Behavioral and pharmacological studies on doxepin, a tricyclic agent. 3. Comparison of actions of doxepin and diazepam on approach-withdrawal and approach-avoidance conflict schedules]" Nihon Yakurigaku Zasshi 68 5 560-571 http://www.ncbi.nlm.nih.gov/pubmed/4674708 1 834 K. Chergui 2011 Dopamine induces a GluN2A-dependent form of long-term depression of NMDA synaptic responses in the nucleus accumbens Neuropharmacology 60 6 975-981 "Natural rewards and addictive drugs are believed to exert their reinforcing actions by influencing synaptic plasticity in reward-related brain regions such as the nucleus accumbens (NAc). Long-lasting changes in the efficacy of excitatory synaptic transmission in the NAc are critically dependent on efficient interactions between the dopaminergic and the glutamatergic neurotransmitter systems. Potential targets to the actions of dopamine and of addictive drugs include the GluN2 subunits that compose the N-Methyl-D-Aspartate (NMDA) type of glutamate receptors. However, the ability of dopamine to induce synaptic plasticity by modulating specific subunits of the NMDA receptor has not been examined. The present study shows that in the mouse NAc, dopamine produces a long-lasting depression of NMDA responses which occludes long-term depression (LTD) induced by high frequency stimulation (HFS) of glutamatergic fibers. LTD induced by dopamine or by HFS does not involve a change in the subunit composition of NMDA receptors. Although GluN2B contributes to synaptic responses in the NAc and is affected by dopamine, this subunit might not be a direct target to the actions of dopamine. The results, however, identify a critical role for GluN2A in dopamine-induced and HFS-induced synaptic plasticity. This study suggests a possible mechanism of action for dopamine in the regulation of reward-related behaviors" http://www.ncbi.nlm.nih.gov/pubmed/21295045 0 835 "Z.-H. Gao, L.-N. Xiao, S.-X. Deng, J.-H. Zhang, H.-C. Li, W. Huang and Z.-S. Li" 2012 Investigation and research of fatigue due to military operation in the recruits during training period "Medical Journal of Chinese People's Liberation Army.37 (1) ()(pp 11-13), 2012.Date of Publication: 2012." 1 Nov-13 "Objective To investigate the relationship between the occurrence of fatigue as a result of military operation and sleep quality of recruits during period of training. Methods The Modified Fatigue Rating Scale (MFIS) and Pittsburgh Sleep Quality Index (PSQI) were used to conduct the survey of over 500 recruits undergoing basic military training. The aim of the survey was to analyze the relationship between their sleep quality and the occurrence of military fatigue. Results The mean fatigue score of the 500 recruits was 23.55. The physical fatigue score was 12.52, which was obviously higher than that of mental fatigue, which was 11.02 (P<0.05). MFIS-13 (always feeling muscle weakness), MFIS-21 (more frequent or longer rest necessary), and MFIS- 10 (difficult to keep physical strength for a long period) ranked highest in the 21 items of the MFIS, and all of them indicated physical fatigue. Among the recruits, mild symptoms of fatigue accounted for 51% (255/500), which was the highest percentage. The incidence of moderate fatigue was 4.6% (23/500), and no severe fatigue was reported. Among the participants, the Pittsburgh Sleep Quality Index was higher than 7 in 190 recruits (38%) and it was reflected as prolonged sleep latency and poor quality of sleep. A positive correlation between score of sheep quality and fatigue scores (P<0.05) was found. Conclusions Poor sleep quality of the recruits may be one of causes of fatigue occurrence, and the aggravation of fatigue can affect sleep quality. Therefore, the management and regulation of sleep quality of the recruits should be emphasized in order to reduce military fatigue" 0 836 "J. P. Bonjour, H. Fleisch and U. Trechsel" 1977 "Calcium absorption in diphosphonate-treated rats: effect of parathyroid function, dietary calcium and phosphorus" J.Physiol 264 1 125-139 "1. The role of parathyroid hormone (PTH) and 1, 25-dihydroxy-cholecalciferol (1,25-(OH)2D3) in modulation of intestinal Ca absorption was studied in rats, using disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP), which is known to reduce 1,25-(OH)2D3 formation. 2. EHDP decreased intestinal Ca absorption. This effect could be abolished by small amounts of 1,25-(OH)2D3, whereas even large doses of PTH were ineffective. EHDP also decreased Ca absorption in thyroparathyroidectomized (TPTX) rats. Therefore the effect of EHDP on 1,25-(OH)2D3 production is unlikely to be mediated through PTH. 3. The correction by PTH of the decreased Ca absorption in TPTX rats was inhibited by EHDP. Since EHDP inhibits formation of 1,25-(OH)2D3 the effect of PTH on Ca absorption is likely to be mediated through this vitamin D3 metabolite. 4. In normal rats both a low Ca and a low P diet stimulated Ca absorption. In EHDP-treated intact rats low Ca still stimulated Ca absorption, whereas the effect of low P abolished. This indicates that low Ca and low P diets affect Ca absorption through different mechanisms. 5. Intestinal adaptation to a low Ca diet was still observed in EHDP-treated TPTX rats. Thus, in the rat, intestinal adaptation to low Ca diet can occur without PTH" http://www.ncbi.nlm.nih.gov/pubmed/402471 0 837 "S. G. Willoughby, R. M. Hopps and N. W. Johnson" 1986 Changes in the rate of epithelial proliferation of rat oral mucosa in response to acute inflammation induced by turpentine Arch.Oral Biol. 31 3 193-199 "Inflammatory lesions were produced in the buccal mucosa by a subepithelial injection of turpentine; animals were killed 24 h later, 1 h after an intravenous injection of tritiated thymidine ( [3H]-Tdr). Control rats were given [3H]-Tdr but no turpentine. Lesions comprised a turpentine pool surrounded by a dense layer of inflammatory cells, beyond which the tissues were more diffusely inflamed. The labelling index (L.I.) for mitotic activity in overlying epithelium was determined in a region (C) close to the layer of dense infiltration and in a region (D) more distant. The L.I. in region D was over four times greater than in region C, and nearly four times greater than that of the contralateral, uninjected cheek. The L.I. in the uninjected cheek was significantly lower than that in controls, which may indicate a systemic depression of proliferative activity in the experimental animals, probably due to stress. Thus mild inflammatory injury stimulates epithelial proliferation, whereas more severe inflammation depresses it, perhaps due to more extensive progenitor-cell damage" http://www.ncbi.nlm.nih.gov/pubmed/3459408 0 838 "T. M. Hillhouse, Z. Shankland, K. S. Matazel, A. A. Keiser and A. J. Prus" 2014 The quetiapine active metabolite N-desalkylquetiapine and the neurotensin NTS(1) receptor agonist PD149163 exhibit antidepressant-like effects on operant responding in male rats Exp.Clin.Psychopharmacol. 22 6 548-556 "Major depressive disorder is the most common mood disorder in the United States and European Union; however, the limitations of clinically available antidepressant drugs have led researchers to pursue novel pharmacological treatments. Clinical studies have reported that monotherapy with the atypical antipsychotic drug quetiapine produces a rapid reduction in depressive symptoms that is apparent after 1 week of treatment, and it is possible that the active metabolite N-desalkylquetiapine, which structurally resembles an antidepressant drug, produces antidepressant effects. Neuropharmacological evaluations of the neurotensin NTS1 receptor agonist PD149163 suggest antidepressant efficacy, but the effects of a NTS(1) receptor agonist in an antidepressant animal model have yet to be reported. The present study examined the antidepressant-like effects of N-desalkylquetiapine, PD14916, quetiapine, the tricyclic antidepressant drug imipramine, the atypical antipsychotic drug risperidone, and the typical antipsychotic drug raclopride on responding in male Sprague-Dawley rats trained on a differential-reinforcement-of-low-rate 72-s operant schedule, a procedure used for screening antidepressant drugs. Quetiapine, PD149163, risperidone, and imipramine exhibited antidepressant-like effects by increasing the number of reinforcers earned, decreasing the number of responses emitted, and shifting the interresponse time (IRT) distributions to the right. N-Desalkylquetiapine produced a partial antidepressant-like effect by decreasing the number of responses emitted and producing a rightward shift in the IRT distributions, but it did not significantly alter the number of reinforcers earned. Raclopride decreased reinforcers and responses. These data suggest that N-desalkylquetiapine likely contributes to quetiapine's antidepressant efficacy and identify NTS(1) receptor activation as a potential novel pharmacologic strategy for antidepressant drugs" http://www.ncbi.nlm.nih.gov/pubmed/25285844 1 839 J. Heuser and R. Miledi 1971 Effects of lanthanum ions on function and structure of frog neuromuscular junctions Proc.R.Soc.Lond B Biol.Sci. 179 1056 247-260 http://www.ncbi.nlm.nih.gov/pubmed/4400214 0 840 "P. W. Burnet, A. Mead, S. L. Eastwood, K. Lacey, P. J. Harrison and T. Sharp" 1995 Repeated ECS differentially affects rat brain 5-HT1A and 5-HT2A receptor expression Neuroreport 6 6 901-904 "We investigated the effect of electroconvulsive shock (ECS), administered five times over 10 days, on 5-HT1A and 5-HT2A receptor mRNA and binding site densities in the rat brain using in situ hybridization histochemistry and quantitative autoradiography. ECS treatment increased 5-HT1A receptor mRNA abundance and binding site densities in the dentate gyrus, but decreased these parameters in the CA3c layer of the hippocampus. No changes in 5-HT1A receptor mRNA and binding sites occurred in other hippocampal subfields, neocortex or raphe nuclei. Repeated ECS was also found to increase 5-HT2A receptor binding site densities in the neocortex and this was accompanied by a non-significant increase in cortical 5-HT2A receptor mRNA abundance. Our study demonstrates that in the rat, repeated ECS produces anatomically and molecularly discrete effects on 5-HT1A and 5-HT2A receptor gene expression. These changes may be relevant to the therapeutic effect of repeated ECS in depression" http://www.ncbi.nlm.nih.gov/pubmed/7612879 0 841 "J. Mendlewicz, P. Kriwin, P. Oswald, D. Souery, S. Alboni and N. Brunello" 2006 Shortened onset of action of antidepressants in major depression using acetylsalicylic acid augmentation: A pilot open-label study "International Clinical Psychopharmacology.21 (4) ()(pp 227-231), 2006.Date of Publication: July 2006." 4 227-231 "Based on our preclinical data showing a potential accelerating effect of acetylsalicylic acid (ASA) in combination with fluoxetine in an animal model of depression, we examined the effect of ASA augmentation therapy on selective reuptake inhibitors (SSRI) in major depressed non-responder patients. Twenty-four non-responder patients having received at least 4 weeks of an adequate SSRI treatment were included in a pilot open-label study. Participants were treated openly during 4 weeks with 160 mg/day ASA in addition to their current antidepressant treatment. The combination SSRI-ASA was associated with a response rate of 52.4%. Remission was achieved in 43% of the total sample and 82% of the responder sample. In the responder group, a significant improvement was observed within week 1 (mean Hamilton Depression Rating Scale-21 items at day 0 = 29.3 +/- 4.5, at day 7 = 14.0 +/- 4.1; P < 0.0001) and remained sustained until day 28. Despite limitations due to the open nature of this study, our preliminary results confirm our preclinical findings and are in favour of an accelerating effect of ASA in combination with SSRIs in the treatment of major depression. Potential physiological and biochemical mechanisms may involve an anti-inflammatory and/or neurotrophic effect. © 2006 Lippincott Williams & Wilkins" DO - http://dx.doi.org/10.1097/00004850-200607000-00005 0 842 "L. G. Muller, L. Salles, H. A. Lins, P. R. Feijo, E. Cassel, R. Vargas, G. L. von Poser, F. Noel, L. E. Quintas and S. M. Rates" 2015 Effects of diene valepotriates from Valeriana glechomifolia on Na+/K+-ATPase activity in the cortex and hippocampus of mice Planta Med. 81 3 200-207 "Diene valepotriates obtained from Valeriana glechomifolia present antidepressant-like activity, mediated by dopaminergic and noradrenergic neurotransmissions. Also, previous studies have shown inhibitory activity of diene valepotriates towards Na(+)/K(+)-ATPase from the rat brain in vitro. Nevertheless, in vivo studies regarding the action of diene valepotriates on this enzyme are still lacking. Considering that Na(+)/K(+)-ATPase cerebral activity is involved in depressive disorders, the aim of this study was to investigate the effects of acute (5 mg/kg, p. o.) and repeated (5 mg/kg, p. o., once a day for three days) diene valepotriate administration on Na(+)/K(+)-ATPase activity in the cortex and hippocampus of mice submitted or not submitted to the forced swimming test. In addition, the protein expression of Na(+)/K(+)-ATPase alpha1, alpha2, and alpha3 isoforms in the cortex of mice repeatedly treated with diene valepotriates (and submitted or not submitted to the forced swimming test) was investigated. Diene valepotriates significantly decreased mice immobility time in the forced swimming test when compared to the control group. Only the animals repeatedly treated with diene valepotriates presented increased Na(+)/K(+)-ATPase activity in the cerebral cortex, and the exposure to the forced swimming test counteracted the effects of the diene valepotriates. No alterations in the hippocampal Na(+)/K(+)-ATPase activity were observed. Repeated diene valepotriate administration increased the cortical content of the alpha2 isoform, but the alpha3 isoform protein expression was augmented only in mice repeatedly treated with diene valepotriates and forced to swim. Mice treated with the vehicle and submitted to the forced swimming test also presented an increase in the content of the alpha2 isoform, but no alterations in Na(+)/K(+)-ATPase activity. These results suggest that cortical Na(+)/K(+)-ATPase may represent a molecular target of the diene valepotriates in vivo and long-term regulatory mechanisms are involved in this effect. Also, the forced swimming test per se influences the protein expression of Na(+)/K(+)-ATPase isoforms and counteracts the effects of the diene valepotriates on cortical Na(+)/K(+)-ATPase" http://www.ncbi.nlm.nih.gov/pubmed/25615276 1 843 "S. D. Stoev, V. Koynarsky and P. G. Mantle" 2002 Clinicomorphological studies in chicks fed ochratoxin A while simultaneously developing coccidiosis Vet.Res.Commun. 26 3 189-204 "The progression of coccidiosis and the resultant mortality were followed in chicks fed a OTA-contaminated diet. More complex and rapid progress of coccidiosis occurred in OTA-treated chicks than in chicks fed a OTA-free diet. The concentration of total protein in the serum was significantly decreased in the chicks in the OTA-treated group, whereas this was significantly increased in chicks infected with Eimeria tenella, irrespective of additional treatment with OTA. The serum glucose concentration was significantly increased in all the chicks exposed to OTA and/or suffering from coccidiosis, as was serum retention of uric acid in all groups, most notably in those consuming OTA. OTA induced degenerative changes in, and an increase in the weight of the kidneys, liver, heart and ventriculum; there was depletion of lymphoid tissue and a decrease in the lymphoid organs' weight and body weight. Coccidiosis induced only a slight growth depression and a slight increase in the relative weight of the kidneys and liver. The intensity of the clinical signs, the impairment of kidney function, macroscopic and histopathological changes, deviations in the weight of some organs and general depression in growth were greater when chicks infected with E. tenella were also given OTA" http://www.ncbi.nlm.nih.gov/pubmed/12090291 0 844 "J. Descotes, R. Tedone and J. C. Evreux" 1985 Different effects of psychotropic drugs on delayed hypersensitivity responses in mice J.Neuroimmunol. 9 01-Feb 81-85 "The influence of certain psychotropic drugs on the delayed-type hypersensitivity (DTH) response to sheep red blood cells in BALB/c mice was studied. The effects on the overall response and the induction and elicitation phases were evaluated, using two alternative dosage schedules for each agent. It was found that diazepam had no effect on the DTH reaction but the administration of imipramine, haloperidol, chlorpromazine or meprobramate all resulted in depression of the response, impairing both the induction or elicitation phases. The results indicate that psychotropic drugs may produce in vivo depression of cell-mediated immunity by different mechanisms" http://www.ncbi.nlm.nih.gov/pubmed/4008639 0 845 "N. A. Sokolova, V. G. Krasil'nikova and I. P. Ashmarin" 1990 "[The atropine-like action, not removed by naloxone, of the opioid dermorphin on the inotropic effects of acetylcholine]" Nauchnye.Doki.Vyss.Shkoly.Biol.Nauki 10 80-85 "Opioid dermorphin induced a negative inotropic effect on the isolated perfused by Straube frog's heart, this effect was blocked by naloxone. On the background of dermorphin negative inotropic effect acetylcholine inhibited the ventricular contractile activity to the same degree as in the control experiments before dermorphin injection. But after the combined infusion of naloxone and dermorphin removed the opioid inotropic effect, the negative inotropic effect of acetylcholine became significantly weaker than in the control. It has been concluded that there are opiate receptors in the frog's ventricular myocardium, their activation leads to the negative inotropic effect. Dermorphin may act like atropine on the inotropic effects of acetylcholine, this action doesn't depend on the opiate receptors activation" http://www.ncbi.nlm.nih.gov/pubmed/2275946 0 846 "M. B. Parent, S. Master, S. Kashlub and G. B. Baker" 2002 Effects of the antidepressant/antipanic drug phenelzine and its putative metabolite phenylethylidenehydrazine on extracellular gamma-aminobutyric acid levels in the striatum Biochem.Pharmacol. 63 1 57-64 "Phenelzine (PLZ) is a non-selective monoamine oxidase inhibitor (MAOI) commonly used to treat depression and panic disorder. As expected, PLZ increases brain levels of dopamine, norepinephrine, and serotonin. Interestingly, PLZ also elevates brain levels of gamma-aminobutyric acid (GABA), and previous studies have suggested that these increases may also contribute to the anxiolytic effects of PLZ. Using in vivo microdialysis in conscious, freely moving rats, combined with high performance liquid chromatography, the present experiments determined that PLZ (15 or 30 mg/kg, free base weight) increases extracellular levels of GABA in the caudate-putamen and nucleus accumbens. The results also indicated that phenylethylidenehydrazine (PEH; 29.6 mg/kg, free base weight), a putative intermediate metabolite of PLZ that is not an MAOI, also significantly increases extracellular GABA levels in the caudate-putamen. These findings provide further evidence that GABA may play an important role in the actions of PLZ and suggest that PEH should be pursued further as a GABAergic drug in its own right" http://www.ncbi.nlm.nih.gov/pubmed/11754874 1 847 "S. Jimenez-Fernandez, M. Gurpegui, F. Diaz-Atienza, L. Perez-Costillas, M. Gerstenberg and C. U. Correll" 2015 Oxidative stress and antioxidant parameters in patients with major depressive disorder compared to healthy controls before and after antidepressant treatment: Results from a meta-analysis "Journal of Clinical Psychiatry.76 (12) ()(pp 1658-1667), 2015.Date of Publication: December 2015." 12 1658-1667 "Objective: To investigate the role of oxidative stress and antioxidants in depression. Data Sources: We searched the literature without language restrictions through MEDLINE/PubMed, Cochrane Library, Fisterra, and Galenicom from database inception until December 31, 2013, supplemented by a hand search of relevant articles. Search terms included (1) oxidative stress, antioxidant*, nitrosative stress, nitrative stress, nitro-oxidative stress, free radical*, and names of individual oxidative stress markers/ antioxidants and (2) depression and related disorders and antidepressant. Study Selection: Included were studies in patients with depression comparing antioxidant or oxidative stress markers with those in healthy controls before and after antidepressant treatment. Data Extraction: Two authors independently extracted the data for antioxidant or oxidative stress markers. Standardized mean differences (SMDs) +/-95% confidence intervals (CIs) for results from > 3 studies were calculated. Data Synthesis: Altogether, 29 studies (N = 3,961; patients with depression = 2,477, healthy controls = 1,484) reported on the oxidative stress marker malondialdehyde (MDA) and total nitrites, the antioxidants uric acid and zinc, or the antioxidant-enhancing enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX). When patients with depression were compared with healthy controls, depression was associated with higher oxidative stress MDA levels (8 studies; n = 916; SMD = 1.34; 95% CI, 0.57 to 2.11; P < .001), lower antioxidant uric acid (4 studies; n = 512; SMD = -0.64; 95% CI, -1.22 to -0.06; P = .030) and zinc levels (13 studies; n = 2,002; SMD = -0.66; 95% CI, -0.98 to -0.34; P < .0001), and higher antioxidant-enhancing enzyme SOD levels (11 studies; n = 902; SMD = 0.62; 95% CI, 0.07 to 1.17; P = .028), while differences in total nitrites and CAT and GPX were nonsignificant. Antidepressant treatment, which significantly reduced Hamilton Depression Rating Scale scores (24.6 +/- 0.7 to 16.2 +/- 1.6; SMD = 2.65; 95% CI, 1.13 to 4.15; P = .00065), reduced MDA (4 studies; n = 194; SMD = -1.45; 95% CI, -2.43 to -0.47; P = .004) and increased uric acid (3 studies; n = 212; SMD = 0.76; 95% CI, 0.03 to 1.49; P = .040) and zinc levels (3 studies; n = 65; SMD = 1.22; 95% CI, 0.40 to 2.04, P = .004), without differences in MDA (P = .60), uric acid (P = .10), and zinc (P = .163) levels compared to healthy controls. Conclusions: Results suggest that oxidative stress plays a role in depression and that antidepressant activity may be mediated via improving oxidative stress/antioxidant function" DO - http://dx.doi.org/10.4088/JCP.14r09179 0 848 "T. Monclair, O. Mathisen and F. Kiil" 1980 Renal bicarbonate reabsorption during bicarbonate loading Kidney Int. 17 5 577-585 "To examine bicarbonate reabsorption at different GFR's, we varied the renal perfusion pressure in anesthetized dogs after inhibiting autoregulation by expanding extracellular volume and infusing ethacrynic acid. At a plasma bicarbonate concentration (PHCO3) of 28 +/- 1 mM, bicarbonate reabsorption varied in proportion to GFR (glomerulotubular balance). When PHCO3 was raised to 52 +/- 2 mM at constant PCO2 and hematocrit, bicarbonate reabsorption was reduced at all levels of filtered load. When plotted against GFR, different results were obtained dependent on the GFR level examined. At the control GFR,. bicarbonate loading reduced bicarbonate reabsorption by 30 +/- 5%. At a GFR level about 50% below the control GFR, bicarbonate loading increased reabsorption by about one third because the inhibitory effect of raising PHCO3 and extracellular pH was not sufficient to counteract the stimulatory effect of a higher filtered load. At intermediate levels of GFR, a rise in PHCO3 did not alter bicarbonate reabsorption. The finding that acetazolamide (30 mg/kg of body wt) at high PHCO3 failed to reduce bicarbonate reabsorption supports the hypothesis that the depressive effect of high extracellular pH on bicarbonate reabsorption may be attributed to reduced net tubular hydrogen ion secretion" http://www.ncbi.nlm.nih.gov/pubmed/7401459 0 849 A. Locker and P. Weish 1970 The radioprotective effects of psychotropic drugs Experientia 26 7 771 http://www.ncbi.nlm.nih.gov/pubmed/5431151 0 850 "K. Parameshwaran, M. A. Buabeid, S. S. Karuppagounder, S. Uthayathas, K. Thiruchelvam, B. Shonesy, A. Dityatev, M. C. Escobar, M. Dhanasekaran and V. Suppiramaniam" 2012 Developmental nicotine exposure induced alterations in behavior and glutamate receptor function in hippocampus Cell Mol.Life Sci. 69 5 829-841 "In the developing brain, nicotinic acetylcholine receptors (nAChRs) are involved in cell survival, targeting, formation of neural and sensory circuits, and development and maturation of other neurotransmitter systems. This regulatory role is disrupted when the developing brain is exposed to nicotine, which occurs with tobacco use during pregnancy. Prenatal nicotine exposure has been shown to be a strong risk factor for memory deficits and other behavioral aberrations in the offspring. The molecular mechanisms underlying these neurobehavioral outcomes are not clearly elucidated. We used a rodent model to assess behavioral, neurophysiological, and neurochemical consequences of prenatal nicotine exposure in rat offspring with specific emphasis on the hippocampal glutamatergic system. Pregnant dams were infused with nicotine (6 mg/kg/day) subcutaneously from the third day of pregnancy until birth. Results indicate that prenatal nicotine exposure leads to increased anxiety and depressive-like effects and impaired spatial memory. Synaptic plasticity in the form of long-term potentiation (LTP), basal synaptic transmission, and AMPA receptor-mediated synaptic currents were reduced. The deficit in synaptic plasticity was paralleled by declines in protein levels of vesicular glutamate transporter 1 (VGLUT1), synaptophysin, AMPA receptor subunit GluR1, phospho(Ser845) GluR1, and postsynaptic density 95 (PSD-95). These results suggest that prenatal nicotine exposure by maternal smoking could result in alterations in the glutamatergic system in the hippocampus contributing to the abnormal neurobehavioral outcomes" http://www.ncbi.nlm.nih.gov/pubmed/22033836 1 851 "F. M. Amat, P. Celada, A. A. Jensen, N. Plath, K. F. Herrik and F. Artigas" 2016 Ketamine inhibits the activity of thalamic neurons in anesthetized rats "European Neuropsychopharmacology.Conference: ECNP Workshop for Junior Scientists in Europe 2016 Nice France.Conference Start: 20160317 Conference End: 20160320.Conference Publication: (var.pagings).26 ()(pp S31-S32), 2016.Date of Publication: March 2" var.pagings S31-S32 "Background: Numerous lines of evidence suggest that the N-metyl-D-aspartate receptors (NMDA-R) are important for several of the functional domains affected in mood disorders. Clinical and preclinical studies have shown that sub-anesthetic doses of ketamine, a noncompetitive antagonist of NMDA-R, produce immediate and persistent antidepressant effects in treatment-resistant depressed patients and antidepressant-like effects in animal models [1,2]. The mechanism(s) underlying the therapeutic effects are poorly understood. Nevertheless, it has been proposed that antagonism of NMDA-R give rise to changes in cortical and thalamic excitability suggesting that thalamocortical activity plays an important role in the pathophysiology and treatment of major depression. Recent studies showed that phencyclidine (PCP), another non-competitive antagonist of NMDA-R, activates thalamo-cortical networks through the blockade of NMDA-R in GABAergic neurons of the reticular nucleus of the thalamus (RtN) [3,4]. This effect disinhibits excitatory inputs from the mediodorsal (MD) and centromedial (CM) nuclei of the thalamus, which are reciprocally connected with the prefrontal cortex (PFC), thereby increasing excitatory inputs onto this and other cortical areas [4,5] Thus, investigating the actions of NMDA-R antagonists on thalamo-cortico-thalamic and intracortical connectivity will increase our understanding of both the pathological processes involved in depression and the mechanisms underlying the antidepressant effects of NMDA-R antagonists. In the present study, we investigated the actions of ketamine on the activity of thalamic neurons. Methods: Single unit and local field potentials were recorded in the MD/CM and RtN of the thalamus (RtN) of chloral hydrate anesthetized male Wistar rats using glass electrodes. The effects of ketamine (0.25, 0.5, 1, 2, 5 mg/kg i.v.) on the firing properties and oscillations of these neuronal populations were assessed. Each treatment was recorded for 5 min, of which the last 2-min periods were normalized to a stable 5 min baseline. Power of the oscillatory activity and the firing rate were compared between treatments. The electrode placement was inspected at the end of the experiments. Results: Ketamine (1, 2, 5 mg/kg, i.v.) significantly inhibited firing activity of MD/CM neurons (to 65, 65, 73% of the baseline at the doses of 1, 2, 5 mg/kg, respectively) and evoked an increase in delta oscillations and a decrease in gamma oscillations. Likewise, ketamine significantly reduced the firing activity of RtN neurons (to 61, 66, 39% of the baseline at the doses of 1, 2, 5 mg/kg, respectively) and decreased delta oscillations. Ketamine (0.25 and 0.5 mg/kg, i.v.) did not affect MD/CM activity significantly. Conclusion: Ketamine reduces the activity of RtN neurons, which provides tonic feed-forward inhibition to the rest of the thalamic nuclei. However, unlike PCP, this effect is not translated into a disinhibition of the activity of CM/MD neurons. On the contrary, ketamine further attenuated the discharge of excitatory CM/MD neurons projecting to PFC. In future experiments, the reason(s) for this difference will be investigated, as will the net effect of ketamine on the activity of PFC neurons. Overall, the present and further data will help to understand the effect of ketamine on thalamo-cortical networks" DO - http://dx.doi.org/10.1016/S0924-977X%2816%2970036-8 0 852 "E. Fino, V. Paille, J. M. Deniau and L. Venance" 2009 Asymmetric spike-timing dependent plasticity of striatal nitric oxide-synthase interneurons Neuroscience 160 4 744-754 "Corticostriatal projections constitute the major inputs to basal ganglia, an ensemble of sub-cortical nuclei involved in the learning of cognitive-motor sequences in response to environmental stimuli. Besides striatal output neurons (medium-sized spiny neurons, MSNs) in charge of the detection of cortical activity, three main classes of interneurons (GABAergic, cholinergic and nitric oxide (NO)-synthase interneurons) tightly regulate the corticostriatal information transfer. Despite the crucial role of NO on neuronal signaling and synaptic plasticity, little is known about corticostriatal synaptic transmission and plasticity at the level of striatal neuronal nitric oxide synthase (nNOS) interneurons. Using a corticostriatal rat brain slice preserving the connections between the somatosensory cortex and the striatal cells, we have explored the synaptic transmission between the cerebral cortex and striatal nNOS interneurons and their capability to develop activity-dependent long-term plasticity based on the quasi-coincident cortical and striatal activities (spike-timing dependent plasticity, STDP). We have observed that cortical pyramidal cells activate monosynaptically and very efficiently the striatal nNOS interneurons. In addition, nNOS interneurons are able to develop strong bidirectional long-term plasticity, following STDP protocols. Indeed, the strength of cortically-evoked response at nNOS interneurons varied as a function of time interval between pre- and postsynaptic activations (Deltat=t(post)-t(pre)). For Deltat<0, excitatory post-synaptic currents (EPSCs) were depressed, peaking at a delay of -25 ms. For Deltat>0, EPSCs depressed for 00 and long-term potentiation (LTP) induced by ""late"" Deltat>0" http://www.ncbi.nlm.nih.gov/pubmed/19303912 0 853 "F. R. Edwards, G. D. Hirst and E. M. Silinsky" 1976 Interaction between inhibitory and excitatory synaptic potentials at a peripheral neurone J.Physiol 259 3 647-663 "1. The interaction between inhibitory and excitatory synaptic potentials in neurones lying in the submucous plexus of guinea-pig ileum has been examined. 2. It was found that during an inhibitory conductance change, electrotonic potentials were more depressed in amplitude than were excitatory synaptic potentials. 3. It is suggested that inhibitory conductance changes may have only a slight effect on the impedance seen by excitatory synaptic currents as much of the excitatory synaptic current flow is likely to be capacitive. 4. A part of the depression of excitatory synaptic potential amplitude was not associated with changes in electrical properties of neurones and it is suggested that inhibitory transmitter may reduce the release of excitatory transmitter" http://www.ncbi.nlm.nih.gov/pubmed/182966 0 854 "L. Zhao, S. Zheng, G. Su, X. Lu, J. Yang, Z. Xiong and C. Wu" 2015 In vivo study on the neurotransmitters and their metabolites change in depressive disorder rat plasma by ultra high performance liquid chromatography coupled to tandem mass spectrometry J.Chromatogr.B Analyt.Technol.Biomed.Life Sci. 988 59-65 "A sensitive and versatile, ultra-high performance, liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method coupled to pre-column derivatization for the simultaneous determination of 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), dopamine (DA), norepinephrine (NE), homovanillic acid (HVA), gamma-aminobutyric acid (GABA) and glutamic acid (Glu) was developed and validated in rat plasma. The analytes were dansylated under strong alkaline conditions after protein precipitation extraction, which were analyzed on a BEH C18 column using a gradient elution. The lower limit of quantification (LLOQ) values for 5-HT, 5-HIAA, DA, NE, HVA, GABA and Glu were 1.00, 1.00, 0.991, 0.992, 1.02, 1000, and 5030 pmol/mL, respectively. Good linearity was obtained (r > 0.99) and the intra- and inter-day precisions of the method (relative standard deviation, RSD%) were lower than 12%. The method was novel, sensitive and specific which can provide an alternative method for the quantification of neurotransmitters and their metabolites in plasma samples" http://www.ncbi.nlm.nih.gov/pubmed/25746753 0 855 "N. Yamada, H. Araki and H. Yoshimura" 2011 Identification of antidepressant-like ingredients in ginseng root (Panax ginseng C.A. Meyer) using a menopausal depressive-like state in female mice: Participation of 5-HT2A receptors "Psychopharmacology.216 (4) ()(pp 589-599), 2011.Date of Publication: August 2011." 4 589-599 "Rationale: After reports of adverse effects with hormone replacement therapy, such as reproductive and breast cancer and coronary heart disease, much attention has been given to the development of new remedies to alleviate menopausal depression in women, but methods for their preclinical evaluation have not been clarified. We previously developed a procedure to predict the drug effect on the menopausal depressive-like state in female mice. Objectives: We attempted to identify psychoactive components from ginseng root, one of the earliest known materials for menopausal disorder, and to clarify the possible mechanism involved. Methods: As an index of a depressive-like state, we used the prolongation of immobility time induced by an ovariectomy during the forced swimming test. Chronic treatment with the candidate substance began the day after ovariectomy and continued for 14 days. To examine whether the 5-HT 2A receptor antagonist ritanserin antagonized the antidepressant-like effect of ginsenoside Rb1, ritanserin was given as pretreatment 15 min before the daily administration of ginsenoside Rb1 and the antagonistic effect was compared with ginsenoside Rb1 alone. Results: Ginsenoside Rb1 and compound K were active ingredients that dose-dependently prevented the prolongation of immobility time induced by ovariectomy. Co-administration of ritanserin, a 5-HT2A-receptor antagonist, antagonized the effect of ginsenoside Rb1. Conclusions: We suggest that ginsenoside Rb1 and its metabolite, compound K, are antidepressant-like components of the ginseng root, and that 5-HT2A receptors may play an important role in mediating the antidepressant-like effect of ginsenoside Rb1. © 2011 Springer-Verlag" DO - http://dx.doi.org/10.1007/s00213-011-2252-1 1 856 "N. Pipatpiboon, W. Pratchayasakul, N. Chattipakorn and S. C. Chattipakorn" 2012 PPARgamma agonist improves neuronal insulin receptor function in hippocampus and brain mitochondria function in rats with insulin resistance induced by long term high-fat diets Endocrinology 153 1 329-338 "We previously demonstrated that a high-fat diet (HFD) consumption can cause not only peripheral insulin resistance, but also neuronal insulin resistance. Moreover, the consumption of an HFD has been shown to cause mitochondrial dysfunction in both the skeletal muscle and liver. Rosiglitazone, a peroxizome proliferator-activated receptor-gamma ligand, is a drug used to treat type 2 diabetes mellitus. Recent studies suggested that rosiglitazone can improve learning and memory in both human and animal models. However, the effects of rosiglitazone on neuronal insulin resistance and brain mitochondria after the HFD consumption have not yet been investigated. Therefore, we tested the hypothesis that rosiglitazone improves neuronal insulin resistance caused by a HFD via attenuating the dysfunction of neuronal insulin receptors and brain mitochondria. Rosiglitazone (5 mg/kg . d) was given for 14 d to rats that were fed with either a HFD or normal diet for 12 wk. After the 14(th) week, all animals were euthanized, and their brains were removed and examined for insulin-induced long-term depression, neuronal insulin signaling, and brain mitochondrial function. We found that rosiglitazone significantly improved peripheral insulin resistance and insulin-induced long-term depression and increased neuronal Akt/PKB-ser phosphorylation in response to insulin. Furthermore, rosiglitazone prevented brain mitochondrial conformational changes and attenuated brain mitochondrial swelling, brain mitochondrial membrane potential changes, and brain mitochondrial ROS production. Our data suggest that neuronal insulin resistance and the impairment of brain mitochondria caused by a 12-wk HFD consumption can be reversed by rosiglitazone" http://www.ncbi.nlm.nih.gov/pubmed/22109891 0 857 "G. Caletti, F. B. Almeida, G. Agnes, M. S. Nin, H. M. Barros and R. Gomez" 2015 Antidepressant dose of taurine increases mRNA expression of GABAA receptor alpha2 subunit and BDNF in the hippocampus of diabetic rats Behav.Brain Res. 283 Nov-15 "Diabetes mellitus is a metabolic disorder associated with higher risk for depression. Diabetic rats present depressive-like behaviors and taurine, one of the most abundant free amino acids in the brain, reverses this depressive behaviors. Because taurine is a GABAA agonist modulator, we hypothesize that its antidepressant effect results from the interaction on this system by changing alpha2 GABAA receptor subunit expression, beside changes on BDNF mRNA, and memory in diabetic rats. Streptozotocin-diabetic and non-diabetic Wistar rats were daily injected with 100mg/kg of taurine or saline, intraperitoneally, for 30 days. At the end of the experiment, rats were exposed to the novel object recognition memory. Later they were euthanized, the brains were weighed, and the hippocampus was dissected for alpha2 GABAA subunit and BDNF mRNA expression. Real-time quantitative PCR (qPCR) showed that diabetic rats presented lower alpha2 GABAA subunit and BDNF mRNA expression than non-diabetic rats and taurine increased both parameters in these sick rats. Taurine also reversed the lower brain weight and improved the short-term memory in diabetic rats. Thus, the taurine antidepressant effect may be explained by interference with the GABA system, in line to its neuroprotective effect showed here by preventing brain weight loss and improving memory in diabetic rats" http://www.ncbi.nlm.nih.gov/pubmed/25612506 1 858 "K. S. Hsu, W. M. Fu and S. Y. Lin-Shiau" 1993 "Blockade by 2,2',2''-tripyridine of the nicotinic acetylcholine receptor channels in embryonic Xenopus muscle cells" Br.J.Pharmacol. 110 1 163-168 "1. The effects of 2,2',2''-tripyridine on the nicotinic acetylcholine (ACh) receptor channels were studied in the cultured myocytes of 1-day-old Xenopus embryos. 2. 2,2',2''-Tripyridine depressed the amplitude of iontophoretic ACh-induced current at a low frequency of 0.7 Hz stimulation and it not only decreased the initial responses but also enhanced the run-down of ACh-induced current at higher frequency stimulation of 7 Hz and 30 Hz. 3. Single ACh channel recordings showed that 2,2',2''-tripyridine decreased the channel conductance, the opening frequency and mean open time of both types of low- and high-conductance channels. 4. These results suggest that the blocking actions of 2,2',2''-tripyridine on ACh receptor channels in the skeletal muscle may contribute to the depression of the nerve-evoked contraction of the mouse diaphragm as reported previously" http://www.ncbi.nlm.nih.gov/pubmed/7693275 0 859 K. Rabl and W. B. Thoreson 2002 Calcium-dependent inactivation and depletion of synaptic cleft calcium ions combine to regulate rod calcium currents under physiological conditions Eur.J.Neurosci. 16 11 2070-2077 "L-type Ca2+ currents (I(Ca)) in rod photoreceptors exhibit Ca2+-dependent inactivation. Perforated-patch whole-cell recordings were obtained from isolated rods of the tiger salamander using 1.8 mm Ca2+ in the bathing medium to determine the extent of Ca2+-dependent inactivation of I(Ca) with physiological [Ca2+] and endogenous buffering. I(Ca) was measured with voltage ramps applied before and after 5-s steps to -40, -30, -20, or -10 mV. Long depolarizing steps in isolated rods produced inactivation of I(Ca) ranging from 15% at -40 mV to > 80% at -10 mV. Because, in addition to Ca2+-dependent inactivation, depletion of synaptic cleft Ca2+ accompanying activation of I(Ca) can reduce presynaptic I(Ca) at calycal synapses, we investigated whether a similar mechanism worked at the invaginating rod synapse. Rods from retinal slices with intact synapses were compared with isolated rods in which synaptic cleft depletion is absent. I(Ca) was more strongly depressed by depolarization of rods in retinal slices, with ICa reduced by 47% following voltage steps to -40 mV. The depression of currents by depolarization was also greater for rods from retinal slices than isolated rods when Ca2+ was replaced with Ba2+ to reduce Ca2+-dependent inactivation. The stronger depolarization-evoked inhibition of I(Ca) in retinal slices compared to isolated rods probably reflects depletion of synaptic cleft Ca2+ arising from sustained Ca2+ influx. Inactivation of I(Ca) exhibited slow onset and recovery. These findings suggest that Ca2+-dependent inactivation and depletion of synaptic cleft Ca2+ may combine to regulate I(Ca) in response to light-evoked changes in rod membrane potential" http://www.ncbi.nlm.nih.gov/pubmed/12473074 0 860 "R. M. Vickery, S. H. Morris and L. J. Bindman" 1997 Metabotropic glutamate receptors are involved in long-term potentiation in isolated slices of rat medial frontal cortex J.Neurophysiol. 78 6 3039-3046 "The prelimbic region of medial frontal cortex in the rat receives a direct input from the hippocampus and this functional connection is essential for aspects of spatial memory. Activity-dependent changes in the effectiveness of synaptic transmission in the medial frontal cortex, namely long-term potentiation (LTP) and long-term depression (LTD) can persist for tens of minutes or hours and may be the basis of learning and memory storage. Glutamatergic activation of ionotropic receptors is required to induce both LTP and LTD. We now present evidence of the involvement of metabotropic glutamate receptors in LTP in isolated slices of frontal cortex. Repetitive bursts of stimulation at theta frequencies (TBS) were applied to layer II, and monosynaptic EPSPs were monitored in layer V neurons of the prelimbic area. TBS was found to be more effective at inducing LTP than tetanic stimulation at 100 Hz and produced LTP that lasted >30 min in 8 out of 14 neurons. Tetanic stimulation at 100 Hz in the presence of the N-methyl--aspartate (NMDA)-antagonist 2-amino-5-phosphonopentanoate (AP5) was reported to be a reliable method of inducing LTD in prelimbic cortex (). However we found that this protocol did not facilitate the induction of LTD. The role of metabotropic glutamate receptors (mGluR) in LTP was assessed by using the selective, broad-spectrum antagonist (R, S)-alpha-methyl-4- carboxyphenylglycine (MCPG). This drug significantly reduced the incidence of LTP after TBS to only 1 of 14 neurons (P < 0.02, chi2 test). The pooled responses to TBS in MCPG showed significantly reduced potentiation [(P < 0.02, analysis of variance (ANOVA)]. The broad-spectrum mGluR agonist (1S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) and the selective group I agonist S-3 hydroxyphenylglycine(S-3HPG) both produced membrane depolarization, an increase in number of spikes evoked by depolarizing current pulses, and a reduction in the afterhyperpolarization. Similar effects were produced by these agonists even when synaptic transmission was blocked by use of the gamma-aminobutyric acid-B (GABAB) receptor agonist, 200 microM baclofen, which suggests that group I mGluRs are present on layer V neurons. We conclude that mGluRs participate in the production of LTP in prelimbic cortex, and that this excitatory effect could be mediated by the postsynaptic group I mGluRs" http://www.ncbi.nlm.nih.gov/pubmed/9405523 0 861 "M. Reite, R. Short, C. Seiler and J. D. Pauley" 1981 "Attachment, loss, and depression" J.Child Psychol.Psychiatry 22 2 141-169 http://www.ncbi.nlm.nih.gov/pubmed/7196919 1 862 "A. W. Bruijnzeel, E. Small, T. M. Pasek and H. Yamada" 2010 Corticotropin-releasing factor mediates the dysphoria-like state associated with alcohol withdrawal in rats Behav.Brain Res. 210 2 288-291 This study investigated the role of CRF in the dysphoria-like state associated with alcohol withdrawal in rats. The intracranial self-stimulation procedure was used to assess brain reward thresholds. Cessation of chronic alcohol administration led to an elevation in brain reward thresholds in the alcohol dependent rats. The CRF receptor antagonist D-Phe CRF((12-41)) dose-dependently prevented the elevations in brain reward thresholds associated with alcohol withdrawal. This indicates that the dysphoria associated with alcohol withdrawal is at least partly mediated by the activation of central CRF receptors http://www.ncbi.nlm.nih.gov/pubmed/20193713 1 863 "S. Lee-Son, B. E. Waud and D. R. Waud" 1975 A comparison of the potencies of a series of barbiturates at the neuromuscular junction and on the central nervous system J.Pharmacol.Exp.Ther. 195 2 251-256 "The ability of a series of barbiturates to depress the depolarizing action of carbachol at the end-plate of guinea-pig lumbrical muscle was studied. The compounds studied were: amorbarbital, aprobarbital, barbital, barbituric acid, butabarbital, butalbital, dimethylbutylethyl barbituric acid, hexobarbital, mephobarbitak, secobarbital, thiamylal, and thiopental. The depressant activity was sensitive to small changes in structure of the compounds strongly suggesting that a specific receptor site was involved in the interaction of the drug with the tissue. The observed relative potencies on the motor end-plate were compared with their anesthetic potencies assayed on tadpoles. The two potencies went hand-in-hand for all the compounds studied, including the convulsant member of the series" http://www.ncbi.nlm.nih.gov/pubmed/1185595 0 864 "N. H. Jensen, R. M. Rodriguiz, M. G. Caron, W. C. Wetsel, R. B. Rothman and B. L. Roth" 2008 "N-Desalkylquetiapine, a potent norepinephrine reuptake inhibitor and partial 5-HT1A agonist, as a putative mediator of quetiapine's antidepressant activity" "Neuropsychopharmacology.33 (10) ()(pp 2303-2312), 2008.Date of Publication: September 2008." 10 2303-2312 "Quetiapine is an atypical antipsychotic drug that is also US FDA approved for treating bipolar depression, albeit by an unknown mechanism. To discover the potential mechanism for this apparently unique action, we screened quetiapine, its metabolite N-Desalkylquetiapine, and dibenzo[b,f][1,4]thiazepine-11(10-H)- one (DBTO) against a large panel of G-protein-coupled receptors, ion channels, and neurotransmitter transporters. DBTO was inactive at all tested molecular targets. N-Desalkylquetiapine had a high affinity (3.4 nM) for the histamine H1 receptor and moderate affinities (10-100 nM) for the norepinephrine reuptake transporter (NET), the serotonin 5-HT1A, 5-HT1E, 5-HT2A, 5-HT2B, 5-HT7 receptors, the alpha1B-adrenergic receptor, and the M1, M3, and M5 muscarinic receptors. The compound had low affinities (100-1000 nM) for the 5-HT1D, 5-HT2C, 5-HT 3, 5-HT5, 5-HT6, alpha1A, alpha2A, alpha2B, alpha2C, H2, M2, M4, and dopamine D1, D2, D 3, and D4 receptors. N-Desalkylquetiapine potently inhibited human NE transporter with a Ki of 12 nM, about 100-fold more potent than quetiapine itself. N-Desalkylquetiapine was also 10-fold more potent and more efficacious than quetiapine at the 5-HT1A receptor. N-Desalkylquetiapine was an antagonist at 5-HT2A, 5-HT2B, 5-HT2C, alpha1A, alpha1D, alpha2A, alpha2C, H1, M1, M 3, and M5 receptors. In the mouse tail suspension test, N-Desalkylquetiapine displayed potent antidepressant-like activity in VMAT2 heterozygous mice at doses as low as 0.1 mg/kg. These data strongly suggest that the antidepressant activity of quetiapine is mediated, at least in part, by its metabolite N-Desalkylquetiapine through NET inhibition and partial 5-HT 1A agonism. Possible contributions of this metabolite to the side effects of quetiapine are discussed. © 2008 Nature Publishing Group All rights reserved" DO - http://dx.doi.org/10.1038/sj.npp.1301646 0 865 "B. P. Griffith, J. T. Lavallee, J. Booss and G. D. Hsiung" 1984 Asynchronous depression of responses to T- and B-cell mitogens during acute infection with cytomegalovirus in the guinea pig Cell Immunol. 87 2 727-733 "The nonspecific functional capacity of spleen cells, taken from female guinea pigs with primary acute cytomegalovirus (CMV) infection, was assessed using lipopolysaccharide (LPS), a B-cell mitogen, and concanavalin A (Con A), a T-cell mitogen. Proliferative responses to the two mitogens were found to be significantly depressed in animals inoculated with CMV as compared to control animals. The defect in Con A responsiveness occurred earlier during the course of the infection than the defect in LPS responses. Although responses to the mitogens were depressed at the time of peak virus activity in the spleen, the possibility of lytic destruction of the spleen cells by the virus during in vitro culture was excluded. In addition, the depression in Con A responsiveness was noted with a wide range of Con A concentrations, and preculture studies failed to result in enhanced reactivity of the cells from infected animals. We conclude that reductions of both B- and T-cell functions, which differ in their timing during the course of acute CMV infection, occur concurrently with an enhanced viral specific immune response in guinea pigs acutely infected with CMV" http://www.ncbi.nlm.nih.gov/pubmed/6088091 0 866 "S. Bonoron-Adele, P. Besse, L. Tariosse and H. Bricaud" 1980 Effects of the calcium antagonistic compound nifedipine alone and combined with nitrites on the mechanical performance and the relaxation of hypoxic and reoxygenated myocardium Eur.Heart J. 1 Suppl B 23-30 http://www.ncbi.nlm.nih.gov/pubmed/6814914 0 867 H. W. Kosterlitz and F. M. Leslie 1977 Inhibition of [3H]-naloxone binding by opiate agonists [proceedings] Br.J.Pharmacol. 59 3 478P http://www.ncbi.nlm.nih.gov/pubmed/843716 0 868 "S. L. Cruz, P. Soberanes-Chavez, N. Paez-Martinez and C. Lopez-Rubalcava" 2009 Toluene has antidepressant-like actions in two animal models used for the screening of antidepressant drugs "Psychopharmacology.204 (2) ()(pp 279-286), 2009.Date of Publication: June 2009." 2 279-286 "Rationale: Many abused solvents share a profile of effects with classical antidepressants. For example, toluene, which is a representative and widely abused solvent, has been reported to increase both serotonin and noradrenaline levels in several brain areas after an acute exposure and to act as a noncompetitive antagonist of the glutamatergic N-methyl-d-aspartic acid (NMDA) receptor subtype. Therefore, it is possible that toluene could possess antidepressant-like actions. Objective: To provide an initial screening of toluene's antidepressant-like actions in the forced swimming test (FST) and the tail suspension test (TST) in mice and to analyze its possible mechanism of action. Materials and methods: Two series of experiments were performed. In the first one, male animals were exposed to toluene (0, 500, 1,000, 2,000, or 4,000 ppm) in a static exposure chamber for 30 min, and immediately after, evaluated for antidepressant-like effects. The results were compared with those obtained from mice treated with the serotonergic antidepressant clomipramine (CMI), the noradrenergic antidepressant desipramine (DMI), and the glutamatergic antidepressants, ketamine and MK-801. In the second part, we analyzed the effect of a combined administration of a subeffective concentration of toluene with a suboptimal dose of the various antidepressants acting at different neurotransmitter systems. Results: Toluene produced a concentration-dependent antidepressant-like action in the FST and TST and facilitated both MK-801 and ketamine antidepressant-like effects, but not those of DMI or CMI. Conclusions: Toluene has antidepressant-like effects that are synergized with NMDA receptor antagonists. © 2009 Springer-Verlag" DO - http://dx.doi.org/10.1007/s00213-009-1462-2 1 869 "S. D. Silberstein, D. G. Johnson, I. Hanbauer, F. E. Bloom and I. J. Kopin" 1972 Axonal sprouts and ( 3 H)norepinephrine uptake by superior cervical ganglia in organ culture Proc.Natl.Acad.Sci.U.S.A 69 6 1450-1455 "Superior cervical ganglia from adult rats maintained in organ culture show a progressive increase in the rate of uptake of [(3)H]norepinephrine. The enhanced uptake of norepinephrine is a consequence of the development of axonal sprouts. Formation of axonal sprouts, which appear to have many of the properties of sympathetic nerve endings, is inhibited by colchicine and vinblastine, presumably because of the interaction of these drugs with neurotubular protein" http://www.ncbi.nlm.nih.gov/pubmed/4504357 0 870 "D. V. Singh, J. Meites, L. Halmi, K. H. Kortright and M. J. Brennan" 1972 Effect of ergocornine on transplanted mammary tumor growth and pituitary prolactin level in BALB/c mice J.Natl.Cancer Inst. 48 6 1727-1731 http://www.ncbi.nlm.nih.gov/pubmed/5056256 0 871 "S. Bhatt, R. Mahesh, A. Jindal and T. Devadoss" 2014 "Neuropharmacological effect of novel 5-HT3 receptor antagonist, N-n-propyl-3-ethoxyquinoxaline-2-carboxamide (6n) on chronic unpredictable mild stress-induced molecular and cellular response: Behavioural and biochemical evidences" Pharmacol.Rep. 66 5 804-810 "BACKGROUND: Chronic unpredictable stressors can produce a situation similar to human depression and such animal models can be used for the preclinical evaluation of antidepressants. The 5-HT3 receptor antagonists modulate serotonergic pathways and show antidepressant-like effect in various animal models of depression. METHODS: In this study, a novel and potential 5-HT3 receptor antagonist N-n-propyl-3-ethoxyquinoxaline-2-carboxamide (6n) with good Log P (2.52) value and pA2 (7.6) values, synthesized in our laboratory was explore to study the effects on CUMS-induced behavioural and biochemical alterations in mice. Mice were subjected to different stress paradigms daily for a period of 28 days to induce depressive-like behaviour. RESULTS: CUMS caused depression-like behaviour in mice, as indicated by the significant decrease in sucrose consumption and increase in immobility time in the forced swim test (FST) while there was no significant effect on spontaneous locomotor activity (SLA) observed. In addition it was found that lipid peroxide and nitrite levels were significantly increased, whereas glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels were decreased in brain tissue of CUMS-treated mice. Compound 6n (1 and 2mg/kg, po, 21 days) and fluoxetine treatment (20mg/kg, po, 21 days) significantly altered the CUMS-induced behavioural (increased immobility period, reduced sucrose preference) and biochemical (increased lipid peroxidation, increased brain nitrite; decreased GSH, SOD and CAT levels) parameters while there was no significant effect of observed on SLA. CONCLUSION: Compound 6n produced antidepressant-like effects in behavioural despair paradigm in chronically stressed mice by restoring antioxidant enzyme activity up to significant level" http://www.ncbi.nlm.nih.gov/pubmed/25149984 1 872 T. J. Campbell 1983 Importance of physico-chemical properties in determining the kinetics of the effects of Class I antiarrhythmic drugs on maximum rate of depolarization in guinea-pig ventricle Br.J.Pharmacol. 80 1 33-40 "The effects of Class I antiarrhythmic drugs on the maximum rate of depolarization (Vmax) of guinea-pig ventricular action potentials were studied by standard microelectrode techniques. The ability of seven different drugs to depress Vmax in unstimulated tissue ('resting block') was found to correlate poorly with the lipophilicity (log P) of the compounds and only a little better with their molecular weights. Depression of Vmax in stimulated tissue was studied for 11 drugs and found, in all cases, to increase with stimulation frequency ('rate-dependent block'). The rapidity of onset of rate-dependent block (at approximately equipotent concentrations) varied markedly between drugs. It correlated well with molecular weight (r = 0.83; P less than 0.01). The time constant of recovery from rate-dependent block (tau re) also correlated very well with molecular weight (r = 0.94; P less than 0.001) for the seven drugs thus studied. A simplified model for the interaction of Class I drugs with the fast sodium channel is proposed in which the drugs all act as 'inactivation enhancers' (as suggested by other workers) but in which their molecular weight plays a central role in determining the kinetics of this interaction" http://www.ncbi.nlm.nih.gov/pubmed/6652373 0 873 U. Tarachand and J. Eapen 1977 Effect of ethanol on placenta & liver of mice Indian J.Exp.Biol. 15 4 274-276 http://www.ncbi.nlm.nih.gov/pubmed/562316 0 874 "J. Halme, J. Uitto, K. I. Kivirikko and L. Saxen" 1972 Effect of triiodothyronine in the metabolism of collagen in cultured embryonic bones Endocrinology 90 6 1476-1482 http://www.ncbi.nlm.nih.gov/pubmed/4336436 0 875 "B. Ballantyne, W. M. Snellings and J. C. Norris" 2006 "Respiratory peripheral chemosensory irritation, acute and repeated exposure toxicity studies with aerosols of triethylene glycol" J.Appl.Toxicol. 26 5 387-396 "The potential for adverse effects from exposure to respirable aerosols of triethylene glycol (TEG: CAS Number 112-27-6) was investigated by a peripheral chemosensory irritation study, and by acute and repeated exposure toxicity studies. The sensory irritation study, conducted with male Swiss Webster mice, showed an exposure concentration-related depression of breathing rate that allowed the calculation of an RD50 of 5140 mg m(-3). In an acute study male and female Sprague Dawley rats were exposed whole body to aerosols of TEG up to 6730 mg m(-3) for 4 h. No mortalities occurred at this high concentration, but unexplained mortality occurred in female rats at 5230 mg m(-3) at 2-3 days postexposure. Two repeats of the 5230 mg m(-3) exposure did not cause mortality. Signs at 6730 and 5230 mg m(-3) were limited to those of irritancy. For a 9 day repeated exposure study rats were exposed whole body to 0, 494, 2011 and 4824 mg m(-3) TEG aerosols for 6 h day(-1). Mortalities occurred at 4824 mg m(-3) between exposure days 2 and 5. Nonspecific indications of toxicity at 2011 mg m(-3) were signs of irritation, decreased body weight and increased food and water consumption; evidence of hepatic dysfunction was indicated by increased serum alkaline phosphatase and alanine aminotransferase activities, but liver histology was normal. Fluid imbalance was suggested by increases in water consumption, blood urea nitrogen, relative kidney weight and urine volume, with decreased urine osmolality, pH and N-acetyl-beta-D-glucosaminidase activity. At 494 mg m(-3) there were minimal signs of irritation, increased water consumption and slightly increased alkaline phosphatase; histology of the kidney was normal. Thus, in this 9 day repeated aerosol whole body exposure study a No-Observed-Effect-Level (NOEL) could not be established. Since preening of the fur at these high aerosol concentrations exposures might have led to a confounding factor from the resultant oral intake, another 9 day repeated aerosol study was conducted, but by nose-only exposure of rats for 6 h day(-1) to TEG aerosol concentrations of 0, 102, 517 and 1036 mg m(-3). In this study there were no clinical signs, no effects on food and water consumption, and no biochemical or histological evidence of hepatorenal dysfunction. By the end of the exposure period, male and female rats of the 1036 mg m(-3) group had body weights lower than those of the controls, but not with statistical significance. Since there were no statistically significant effects on any monitors, 1036 mg m(-3) is considered to be a threshold for toxicity by nose-only exposure to TEG aerosol. The findings indicate that exposure to a respirable aerosol is not acutely harmful, but may cause sensory irritant effects. Repeated exposure to high concentrations of TEG aerosols may be harmful, particularly if there are contributions from additional routes of exposure" http://www.ncbi.nlm.nih.gov/pubmed/16909429 0 876 "M. J. Giglio, R. C. Santoro and C. E. Bozzini" 1984 Suppressive effect of acetylsalicylic acid on erythropoietin-responsive cells in mice Acta Physiol Pharmacol.Latinoam. 34 3 229-234 "The time-response curve for RBC-59Fe uptake following i.p. injections of 3 doses of 5 mg of acetylsalicylic acid (ASA) at 4 hour interval into normal, nonpolycythemic mice, shows a maximal depression (35% of normal) at 3 days after ASA with return to almost normal values by 7 days. The effect is dose-related, showing a plateau with doses of ASA above 5 mg/4 hr. The shape of the time-response curve indicates that the more mature cells in the erythron are not affected by ASA and that the major effect of the drug must be on earlier erythroid cells. Administration of ASA prior to administration of erythropoietin (Epo) into post-hypoxic polycythemic mice depresses the incorporation of 59Fe into erythrocytes. The depression of radioiron uptake is similar when ASA is given prior to or simultaneously with Epo. When ASA is given 24 hr after injection of Epo, suppression is less marked. These results suggest a suppressive effect of the drug on the erythropoietin-responsive cells (ERC)" http://www.ncbi.nlm.nih.gov/pubmed/6241781 0 877 "G. David, M. E. Selzer and Y. Yaari" 1986 Activity-dependent depression of nerve action potential by phenytoin Neurosci.Lett. 66 2 163-168 "The action of the anticonvulsant drug phenytoin was investigated on the responsiveness of isolated amphibian and human nerves to repetitive stimulation. At low frequencies of stimulation (0.5-25 Hz) the drug (at a concentration of 0.1 mM) had no notable effect on the compound nerve action potential. By contrast, at higher rates of stimulation (50-300 Hz), it produced a progressive decrease in amplitude and integral of the compound action potential. This effect was positively correlated with the frequency of nerve activation and was markedly enhanced by elevating the extracellular K+ concentration. Thus, phenytoin induces a use- and frequency-dependent depression of axon conduction, which may contribute to its preferential suppression of the spread of high-frequency seizure discharge in the brain" http://www.ncbi.nlm.nih.gov/pubmed/3725182 0 878 "C. A. Karle, E. Zitron, W. Zhang, S. Kathofer, W. Schoels and J. Kiehn" 2002 "Rapid component I(Kr) of the guinea-pig cardiac delayed rectifier K(+) current is inhibited by beta(1)-adrenoreceptor activation, via cAMP/protein kinase A-dependent pathways" Cardiovasc.Res. 53 2 355-362 "OBJECTIVE: The antiarrhythmic potential of betablockers contributes to their beneficial effects in the treatment of cardiac diseases, although the molecular basis of their class II antiarrhythmic action has not been clarified yet. METHODS: To investigate a putative functional link between beta-adrenoreceptors and the fast component of cardiac delayed rectifier K(+) channels (I(Kr)), whole-cell patch-clamp experiments were performed with isolated guinea-pig ventricular myocytes. Tail currents of I(Kr) were measured at -40 mV after short (200 ms) test pulses to +40 mV. RESULTS: After application of the unspecific beta-receptor agonist isoproterenol (10 microM) for 12 min, the I(Kr) tail current was decreased by 72%, with an IC(50) of 1.4 microM. The specific beta(1)-blocker CGP207120A (10 microM) significantly attenuated the isoproterenol effect (net 24% decrease). The specific beta(1)-agonist xamoterol (10 microM), could mimic the isoproterenol effect (58% decrease). Modulators of beta(2)- or beta(3)-adrenoreceptors were far less effective. When isoproterenol or xamoterol were combined with KT5720 (2.5 microM), a specific inhibitor of protein kinase A (PKA), their effects were drastically reduced, indicating that PKA presumably mediates the beta(1)-adrenergic inhibition of I(Kr). Tail current reductions by cAMP, forskolin, PKA catalytic subunit and a combination of PKA holoenzyme and cAMP support an involvement of PKA in the regulation of I(Kr). CONCLUSIONS: The functional link between I(Kr) and the beta(1)-adrenergic receptor involving PKA may play an important role in arrhythmogenesis and contribute to the antiarrhythmic action of clinically used beta(1)-blockers" http://www.ncbi.nlm.nih.gov/pubmed/11827686 0 879 "A. Keller, E. Miyashita and H. Asanuma" 1991 Minimal stimulus parameters and the effects of hyperpolarization on the induction of long-term potentiation in the cat motor cortex Exp.Brain Res. 87 2 295-302 "The aim of the research program of which the present work is a part is to understand the neural mechanisms involved in motor learning and memory. One of the mechanisms postulated to be involved in this process is the induction of long-term potentiation (LTP) in the motor cortex. LTP can be induced in motor cortical neurons by tetanic stimulation of their afferents from the somatosensory cortex. In the present study, the effects of different stimulating parameters on the induction of LTP were examined, using in-vivo, intracellular recordings from anesthetized cats. The expression of LTP was documented by measuring the amplitude and rise-time of excitatory postsynaptic potentials (EPSPs) before and after tetanic stimulation. The minimal tetanic stimulation capable of systematically inducing LTP was found to consist of a train of stimuli at 50 Hz, 5 s. Shorter trains of stimulation produced only a short-lasting, transient potentiation. In different cells, identical stimulation parameters resulted in different degrees of potentiation of synaptic responses. Following all the stimulation trains examined, EPSP amplitudes were transiently depressed before reaching potentiated levels. The duration of this depression was directly correlated with the duration and the frequency of the tetanic stimulation. In all the cells in which LTP was induced, the variability in the amplitudes of potentiated EPSP was significantly greater than that of control EPSP amplitudes. Hyperpolarization of the postsynaptic cell, during the delivery of the tetanic stimulation, inhibited the induction of LTP. These phenomena are discussed in relation to the postulated mechanisms of LTP induction in the cortex" http://www.ncbi.nlm.nih.gov/pubmed/1769383 0 880 "K. Lauderdale, T. Murphy, T. Tung, D. Davila, D. K. Binder and T. A. Fiacco" 2015 Osmotic Edema Rapidly Increases Neuronal Excitability Through Activation of NMDA Receptor-Dependent Slow Inward Currents in Juvenile and Adult Hippocampus ASN.Neuro. 7 5 "Cellular edema (cell swelling) is a principal component of numerous brain disorders including ischemia, cortical spreading depression, hyponatremia, and epilepsy. Cellular edema increases seizure-like activity in vitro and in vivo, largely through nonsynaptic mechanisms attributable to reduction of the extracellular space. However, the types of excitability changes occurring in individual neurons during the acute phase of cell volume increase remain unclear. Using whole-cell patch clamp techniques, we report that one of the first effects of osmotic edema on excitability of CA1 pyramidal cells is the generation of slow inward currents (SICs), which initiate after approximately 1 min. Frequency of SICs increased as osmolarity decreased in a dose-dependent manner. Imaging of real-time volume changes in astrocytes revealed that neuronal SICs occurred while astrocytes were still in the process of swelling. SICs evoked by cell swelling were mainly nonsynaptic in origin and NMDA receptor-dependent. To better understand the relationship between SICs and changes in neuronal excitability, recordings were performed in increasingly physiological conditions. In the absence of any added pharmacological reagents or imposed voltage clamp, osmotic edema induced excitatory postsynaptic potentials and burst firing over the same timecourse as SICs. Like SICs, action potentials were blocked by NMDAR antagonists. Effects were more pronounced in adult (8-20 weeks old) compared with juvenile (P15-P21) mice. Together, our results indicate that cell swelling triggered by reduced osmolarity rapidly increases neuronal excitability through activation of NMDA receptors. Our findings have important implications for understanding nonsynaptic mechanisms of epilepsy in relation to cell swelling and reduction of the extracellular space" http://www.ncbi.nlm.nih.gov/pubmed/26489684 0 881 "S. V. Pande, A. W. Siddiqui and A. Gattereau" 1971 Inhibition of long-chain fatty acid activation by -bromopalmitate and phytanate Biochim.Biophys.Acta 248 2 156-166 http://www.ncbi.nlm.nih.gov/pubmed/5130448 0 882 "H. J. Lubbesmeyer, D. J. Dehring, J. L. Theissen, D. Fleming, L. Traber, D. N. Herndon and D. L. Traber" 1990 Hydroxyethyl starch pretreatment in bacteremic sheep J.Trauma 30 10 1246-1251 "Live bacteria were infused in a chronic ovine lung lymph model to determine if a preceding infusion of the colloid, hydroxyethyl starch (HES), exaggerated the cardiopulmonary dysfunction or impaired removal of bacteria by macrophages in the pulmonary circulation. HES was infused (3 mL/kg/hr; n = 6) from 24 to 12 hr before the bacteria and decreased plasma protein content and increased pulmonary lymph to plasma protein concentration because of its oncotic properties. Ringer's lactate (2 mL/kg/hr) was given after stopping HES and also to the control group (n = 6). Infusion of live Ps. aeruginosa (2.5 x 10(8) Ps./min for approximately 30 min) induced equivalent pulmonary hypertension, increased pulmonary microvascular permeability, and cardiovascular depression in the two groups. The removal of bacteria in the lungs was not affected, indicating that this measurement of the function of the mononuclear phagocytic system was not impaired by the preceding HES" http://www.ncbi.nlm.nih.gov/pubmed/1698991 0 883 "M. P. Coba, L. M. Valor, M. V. Kopanitsa, N. O. Afinowi and S. G. Grant" 2008 Kinase networks integrate profiles of N-methyl-D-aspartate receptor-mediated gene expression in hippocampus J.Biol.Chem. 283 49 34101-34107 "The postsynaptic N-methyl-d-aspartate (NMDA) receptor activates multiple kinases and changes the phosphorylation of many postsynaptic proteins organized in signaling networks. Because the NMDA receptor is known to regulate gene expression, it is important to examine whether networks of kinases control signaling to gene expression. We examined the requirement of multiple kinases and NMDA receptor-interacting proteins for gene expression in mouse hippocampal slices. Protocols that induce long-term depression (LTD) and long-term potentiation (LTP) activated common kinases and overlapping gene expression profiles. Combinations of kinases were required for induction of each gene. Distinct combinations of kinases were required to up-regulate Arc, Npas4, Egr2, and Egr4 following either LTP or LTD protocols. Consistent with the combinatorial data, a mouse mutant model of the human cognition disease gene SAP102, which couples ERK kinase to the NMDA receptor, showed deregulated expression of specific genes. These data support a network model of postsynaptic integration where kinase signaling networks are recruited by differential synaptic activity and control both local synaptic events and activity-dependent gene expression" http://www.ncbi.nlm.nih.gov/pubmed/18815127 0 884 T. V. Widenius 1987 Ethanol-induced inhibition of testosterone biosynthesis in vitro: lack of acetaldehyde effect Alcohol Alcohol 22 1 17-22 "Acute ethanol intake has been shown to decrease plasma testosterone levels in rodents and man. This is mainly due to inhibition of testosterone synthesis, but there is still some controversy about the mechanisms responsible for the inhibition. These mechanisms were studied in the present experiments with isolated rat Leydig cells. Leydig cells were incubated for two hours in sealed plastic vials with various concentrations of ethanol (0.3-40 mM) or acetaldehyde (5-40 microM). Very low ethanol concentrations (2.5 mM) reduced testosterone production significantly, whereas even 40 microM acetaldehyde added repeatedly to the incubation medium had no effect on testosterone levels. An inhibitor of alcohol dehydrogenase, 4-methylpyrazole, abolished the ethanol-induced inhibition of testosterone synthesis. A suggested mechanism for the inhibition is an elevated free [NADH]/[NAD+] ratio in Leydig cells caused by the metabolism of ethanol" http://www.ncbi.nlm.nih.gov/pubmed/3593480 0 885 "T. Arunrut, H. Alejandre, M. Chen, J. Cha and A. Russo-Neustadt" 2009 "Differential behavioral and neurochemical effects of exercise, reboxetine and citalopram with the forced swim test" "Life Sciences.84 (17-18) ()(pp 584-589), 2009.Date of Publication: 24 Apr 2009." 17-18 584-589 "Aims: In this study, we investigated whether short-term exercise, known to promote hippocampal brain-derived neurotrophic factor (BDNF) expression, would also enhance activity in the Porsolt forced swim test (FST), a model for assessing antidepressant efficacy. We also wished to determine whether exercise combined with antidepressants would be more effective at modifying behavior in the FST than either intervention alone. In parallel with this, we also expected that these interventions would preserve post-stress levels of BDNF, and that antidepressants designed to selectively enhance noradrenergic or serotonergic neurotransmission (reboxetine or citalopram, respectively) would have differential effects on behavior and BDNF expression. Main methods: Male Sprague-Dawley rats were treated with exercise (voluntary wheel running), reboxetine, citalopram, or the combination of exercise and each antidepressant, for 1 week. At the end of this period, a subset of animals from each treatment group underwent the FST. Post-stress levels of hippocampal BDNF mRNA were then quantified via in situ hybridization. Key findings: Our results indicate that while both exercise and antidepressant treatment preserved post-stress levels of hippocampal BDNF mRNA, each intervention led to a unique behavioral profile in the FST. We found that antidepressant treatment increased swimming time in the FST, but that exercise decreased swimming time. While the combination of reboxetine-plus-exercise led to an increase in climbing and diving, citalopram-plus-exercise reduced these behaviors. Significance: It is possible that active behaviors during the FST, though specific to antidepressant medications, may not reflect increased hippocampal BDNF expression or other survival- associated benefits. © 2009 Elsevier Inc. All rights reserved" DO - http://dx.doi.org/10.1016/j.lfs.2009.02.005 1 886 "J. Luo, X. Li and Z. Lin" 2010 [Effect of combined use of rehmannia and rhodiola on hemopoietic function in mice with bone marrow depression] Zhongguo Zhong.Xi.Yi.Jie.He.Za Zhi. 30 11 1190-1192 "OBJECTIVE To explore the effect of combined use of rehmannia (RM) and rhodiola (RD) on peripheral leukopenia and bone marrow hematopoietic function suppression induced by cyclophosphamide (CTX) in mice. METHODS: ICR mice were established into bone marrow inhibition models by intraperitoneal injection of CTX, and were administered with RM, RD or its extract (RDE), singly or in mixture, via gastrogavage for 10 days. The changes of peripheral hemogram, bone marrow nucleated cell proliferation, CFU-GM colony formation, GM-CSF and erythropoietin (EPO) secretion were observed. RESULTS: Compared with the un-treated model mice, the peripheral white blood cell count was significantly higher in model mice treated with RDE and RM mixture; the bone marrow nucleated cells count, CFU-GM formation, and GM-CSF production were significant higher in model mice treated with RD and RM mixture, showing statistical significance (P < 0.01); while EPO production in the RD and RM mixture treated group was slightly elevated, but the difference showed no statistical significance. CONCLUSION: RD and RM mixture could regulate hematopoietic system by promoting the production of bone marrow cells and colonies, as well as enhancing the synthesis of related cytokines, such as GM-CSF, so as to increase the amount of peripheral white blood cells and restore the hematopoietic function of organism" http://www.ncbi.nlm.nih.gov/pubmed/21275174 0 887 J. Bieri and T. J. Kawecki 2003 Genetic architecture of differences between populations of cowpea weevil (Callosobruchus maculatus) evolved in the same environment Evolution 57 2 274-287 "We investigated the genetic architecture underlying differentiation in fitness-related traits between two pairs of populations of the seed beetle Callosobruchus maculatus (Coleoptera: Bruchidae). These populations had geographically distant (> 2000 km) origins but evolved in a uniform laboratory environment for 120 generations. For each pair of populations (Nigeria x Yemen and Cameroon x Uganda) we estimated the means of five fitness-related characters and a measure of fitness (net reproductive rate R0) in each of the parental populations and 12 types of hybrids (two F1 and two F2 lines and eight backcrosses). Models containing up to nine composite genetic parameters were fitted to the means of the 14 lines. The patterns of line means for all traits in the Nigeria x Yemen cross and for four traits (larval survival, developmental rate, female body weight, and fecundity) in the Cameroon x Uganda cross were best explained by models including additive, dominance, and maternal effects, but excluding epistasis. We did not find any evidence for outbreeding depression for any trait. An epistatic component of divergence was detected for egg hatching success and R0 in the Cameroon x Uganda cross, but its sign was opposite to that expected under outbreeding depression, that is, additive x additive epistasis had a positive effect on the performance of F2 hybrids. All traits except fecundity showed a pattern of heterosis. A large difference of egg-hatching success between the two reciprocal F1 lines in that cross was best explained as fertilization incompatibility between Cameroon females and sperm carrying Uganda genes. The results suggest that these populations have not converged to the same life-history phenotype and genetic architecture, despite 120 generations of uniform natural selection. However, the absence of outbreeding depression implies that they did not evolve toward different adaptive peaks" http://www.ncbi.nlm.nih.gov/pubmed/12683524 0 888 "M. Tardy, B. Rolland, J. Bardakjian and P. Gonnard" 1978 Action of beta-(4-chlorophenyl-GABA) on uptake and metabolism of GABA in different subcellular fractions of rat brain Experientia 34 9 1137-1138 http://www.ncbi.nlm.nih.gov/pubmed/720504 0 889 "A. K. Emanuelov, A. Shainberg, Y. Chepurko, D. Kaplan, A. Sagie, E. Porat, M. Arad and E. Hochhauser" 2010 Adenosine A3 receptor-mediated cardioprotection against doxorubicin-induced mitochondrial damage Biochem.Pharmacol. 79 2 180-187 "Cardiotoxicity associated with doxorubicin (DOX) treatment limits the therapeutic efficiency of this drug against cancer. 2-Chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide (Cl-IB-MECA), a selective agonist of A(3) adenosine receptor (A(3)R), reduces DOX toxicity in newborn rat cultured cardiomyocytes. The study's aim was to determine whether the protection demonstrated by Cl-IB-MECA attenuates cardiac depression in vivo. In addition, we wished to examine whether this protective pathway affects the sarcoplasmic reticulum (SR) calcium uptake and release, as well as intramitochondrial Ca(2+) accumulation induced by DOX. Rats were injected every alternate day (6 times) with (1) saline, (2) 2.5mg/kg i.p. DOX, (3) 33 microg/kg i.v. Cl-IB-MECA, (4) DOX+Cl-IB-MECA. Left ventricular functions were assessed by invasive (pressure) and non-invasive (echocardiography) techniques at the end of the injection period and 4 weeks later. Cytosolic and intramitochondrial calcium levels were measured with indo-1 and rhod-2 probes. SR Ca(2+) content was determined by exposing cultured rat cardiomyocytes to caffeine. Echocardiography data demonstrate left ventricular wall thinning (23%), an increase in the end systolic dimension (170%) and decreased fractional shortening (35+/-5% vs. 54+/-5%, p<0.01) in DOX-treated animals, compared to the control group. DOX increased Ca(2+) levels in the cytosol and in mitochondria by diminishing the SR Ca(2+) uptake. Pretreatment with Cl-IB-MECA attenuated left ventricular dysfunction, improved SR calcium storage capacity and prevented mitochondrial Ca(2+) overload. We conclude that the adenosine A(3) receptor agonist is effective in vivo against DOX cardiotoxicity via the restoration of Ca(2+) homeostasis and prevention of mitochondrial damage that occurs as a result of Ca(2+) overload" http://www.ncbi.nlm.nih.gov/pubmed/19686702 0 890 S. Odend'hal and T. C. Poulter 1966 Pressure regulation in the middle ear cavity of sea lions: a possible mechanism Science 153 3737 768-769 The mucosa lining the cavity of the middle ear of sea lions contains a complex network of venous channels and sinuses. During dives the pressure within the middle ear may be equalized with that in the external auditory meatus either by the distention or depression of the mucosa due to the presence or absence of blood in the sinuses http://www.ncbi.nlm.nih.gov/pubmed/5940898 0 891 "B. Freigang, P. Seidel and M. Flach" 1968 [On the problem of carbon monoxide effect on the microphonics and sum of action potentials of the guinea pig cochlea] Arch.Klin.Exp.Ohren.Nasen.Kehlkopfheilkd. 190 1 24-35 http://www.ncbi.nlm.nih.gov/pubmed/5666704 0 892 "L. Koranyi, E. ENDROECZI and K. LISSAK" 1965 DISINHIBITION OF EXTINGUISHED CONDITIONED REFLEX UNDER SPREADING DEPRESSION Acta Physiol Acad.Sci.Hung. 27 353-357 http://www.ncbi.nlm.nih.gov/pubmed/14336633 0 893 N. Anast and K. K. Caldwell 2010 Development and characterization of a mouse model of posttraumatic stress disorder "Journal of Investigative Medicine.Conference: American Federation for Medical Research Western Regional Meeting, AFMR 2010 Carmel, CA United States.Conference Start: 20100127 Conference End: 20100130.Conference Publication: (var.pagings).58 (1) ()(pp" var.pagings 229 "Purpose of Study: The lifetime prevalence rate of Post Traumatic Stress Disorder (PTSD) is estimated to be 8-9%. Efforts to better understand the pathophysiologic changes underlying PTSD, and the mechanisms by which exposure to traumatic events produce these changes, may rely on the use of animal models. Methods Used: Using a predator-odor exposure design, we developed an animal model of PTSD using adolescent male mice that demonstrates both the anxiety and depressive symptoms of PTSD. Male mice at postnatal day 30-42 were divided into two groups. The treatment group was exposed to soiled female rat bedding for 10 minutes and the control group was exposed to clean unsoiled bedding for 10 minutes. The mice were all reexposed to clean unsioled bedding 14 days later. Characterization of the model included the effects of predator odor exposure on learned helplessness and open field/ novel object behaviors. Summary of Results: Odor-exposed mice demonstrated an overall increase in the mean escape latency and number of escape failures as compared to controls in the learned helplessness test. However, a bimodal distribution of the data was noted with one subset of animals displaying a reduction in escape latency and failures while the other subset displayed increases in these measurements. No differences between odor-exposed mice and control mice were demonstrated in open field and novel object testing. Conclusions: The predator-odor exposure model of PTSD used in this study fulfills the five criteria for evaluating animal models of PTSD. This mouse model should be a useful tool in testing hypotheses about the neural mechanisms underlying PTSD and future studies aimed at pharmacologic treatment of PTSD" DO - http://dx.doi.org/10.231/JIM.0b013e3181c87db3 0 894 T. Mrsic-Flogel and M. Hubener 2002 Visual cortex: suppression by depression? Curr.Biol. 12 16 R547-R549 "The response of a neuron in the visual cortex to an oriented light bar is strongly reduced by concurrent presentation of a stimulus with a different orientation. New data suggest this 'cross-orientation suppression' is caused, not by intracortical inhibition, but by rapid depression of thalamocortical synapses" http://www.ncbi.nlm.nih.gov/pubmed/12194833 0 895 J. Pauluhn 2006 "Acute nose-only exposure of rats to phosgene. Part I: concentration x time dependence of LC50s, nonlethal-threshold concentrations, and analysis of breathing patterns" Inhal.Toxicol. 18 6 423-435 "Groups of young adult Wistar rats were acutely exposed to phosgene gas using a directed-flow nose-only mode of exposure. The exposure durations used were 10, 30, 60, and 240 min and the corresponding C x t products bracketed a range from 1538 to 2854 mg/m3 x min. The postexposure period was 2 wk. Subgroups of rats were subjected to respiratory function measurements. With few exceptions, mortality occurred within 24 h after exposure. The median lethal concentration (LC50) and the estimated nonlethal threshold concentrations (LC01) for 10, 30, 60, and 240 min were 253.3 (105.3), 54.5 (29.2), 31.3 (21.1), and 8.6 (5.3) mg/m3, respectively. With regard to the fixed outcome Cn x t product, the exponent n was found to be approximately 0.9 for both the LC50 and the LC01. Due to an apparent rodent-specific transient depression in ventilation, results from 10-min exposures were excluded for the calculation of average C x t products. The average LCt50 (and confidence interval 95%) and LCt01 were 1741 (1547-1929) mg/m3 x min and 1075 mg/m3 x min, respectively, with a LCt50/LCt01 ratio of 1.6. Respiratory function measurements revealed an increased apnea time (AT), which is typical for lower respiratory tract irritants. This response was associated with transiently decreased respiratory minute volumes. Borderline, although distinct, changes in AT occurred at 1.2 x 30 mg/m3 x min and above, which did not show evidence of recovery during a 30-min postexposure period at 47.6 x 30 mg/m3 x min and above. In an ancillary study, one group of rats was exposed to 1008 mg/m3 x min (at 4.2 mg/m3 for 240 min; postexposure period 4 wk). Emphasis was on the time course of nonlethal endpoints (bronchoalveolar lavage, BAL) and histopathology of the lungs of rats sacrificed at the end of the 4-wk postexposure period. The climax of BAL protein was on the first postexposure day and exceeded approximately 70 times the control without causing mortality. The changes in BAL protein resolved within 2 wk. Histopathology did not show evidence of lung remodeling or progressive, potentially irreversible changes 4 wk postexposure. In summary, the analysis of the C x t dependent mortality revealed a steep C x t mortality relationship. The C x t product in the range of the nonlethal threshold concentration (1008 mg/m3 x min) caused pulmonary injury as indicated by markedly increased protein in BAL. Changes resolved almost entirely within the 4-wk postexposure period" http://www.ncbi.nlm.nih.gov/pubmed/16556582 0 896 T. Kasaba and Y. Kosaka 1989 [The effects of intravenous lidocaine on the activity of medullary respiratory neurons in cats] Masui 38 6 741-745 "The effects of intravenous lidocaine on the activity of medullary respiratory neuron were studied in urethane anesthetized cats. Using a tungsten microelectrode, spikes from medullary inspiratory neurons were recorded around nucleus ambiguous. Lidocaine was administered using a constant-rate infusion pump until electrographic seizures appeared. The effect of lidocaine on the activity of respiratory neurons showed two types. In one type, consisting of 7 units out of 10, a sequence of changes was observed: the initial stage was represented by increased duration of the burst and decreased frequency of neural discharge; the second stage by desynchronization with mechanical lung inflation; the third stage by continuous activity and the forth stage by decreased spike activity and electrographic seizures. Blood concentration of the lidocaine was 9.6 +/- 3.5 micrograms.ml-1 at the second stage, 15.3 +/- 4.4 micrograms.ml-1 at the third stage, 26.6 +/- 4.1 micrograms.ml-1 at the fourth stage. In another type, consisting of 3 units out of 10, following administration of lidocaine the number of spikes showed only a concentration related depression. Blood concentration of the lidocaine was 6.9 +/- 2.7 micrograms.ml-1 when the spikes disappeared. These results indicate that intravenous lidocaine influences the respiratory rhythm and produces the respiratory depression working in the central nervous system" http://www.ncbi.nlm.nih.gov/pubmed/2795839 0 897 F. R. Bell and D. E. Webber 1979 "Gastric emptying and secretion in the calf on duodenal infusion of tryptophan, tryptamine and 5-hydroxytryptamine" J.Physiol 291 413-423 "1. Gastric emptying, gastric acid and pepsinogen secretion were assessed simultaneously in the conscious calf using the test meal and duodenal perfusion technique (Bell & Mostaghni, 1975).2. When 60 mM-HCl was infused into the duodenum, gastric emptying was arrested but both acid and pepsinogen secretion continued at a low level. Duodenal infusion with isotonic NaHCO(3) caused rapid exponential emptying of the test meal and acid and pepsinogen output was more than doubled.3. Duodenal infusion of amino acids in isotonic NaHCO(3) did not affect the rapid emptying, except infusion with tryptophan, which caused a measureable degree of inhibition of emptying, with concomitant effects on acid and pepsinogen secretion4. Tryptamine and 5-hydroxytryptamine (5-HT) incorporated in low concentration into isotonic NaHCO(3) also produced depression of gastric emptying, acid and pepsinogen levels comparable to the response initiated by acid infusate. Tryptophan was effective only in non-physiological amounts while 5-HT and tryptamine were active in smaller doses.5. Our results suggest that the inhibition of gastric emptying following duodenal infusion of tryptophan noted by Stephens, Woolson & Cooke (1975) may be due to the duodenal synthesis of its biogenic amine derivatives tryptamine and 5-HT.6. The level of activity of the three gastric functions, emptying, acid secretion and pepsinogen secretion appears to be linked. A single stimulus, therefore, could evoke a duodenal receptor or receptors to mediate or suppress activity of the gastric smooth muscle and secretory cells through interrelated mechanisms. The effect of some duodenal infusates, however, produces some variability in response which suggests differential activation of different receptors with consequent variable motor activity on effector cells" http://www.ncbi.nlm.nih.gov/pubmed/480233 0 898 "C. M. Whipps, K. Boorom, L. E. Bermudez and M. L. Kent" 2010 Molecular characterization of Blastocystis species in Oregon identifies multiple subtypes "Parasitology Research.106 (4) ()(pp 827-832), 2010.Date of Publication: March 2010." 4 827-832 "The association of Blastocystis species infections with gastrointestinal symptoms in humans is clouded by the variable presentation of disease and multiple lineages of the parasite that can infect humans and other animals. It has long been suspected that certain subtypes of Blastocystis may be more or less pathogenic, be restricted to certain hosts, or have limits to their geographic distribution. In the state of Oregon, USA, Blastocystis spp. are the most commonly encountered parasites in fecal specimens submitted for diagnostic evaluation, yet the diversity of subtypes is unknown. In this study, fecal samples were collected from individuals experiencing symptoms associated with blastocystosis and analyzed by polymerase chain reaction for presence of the parasite and DNA sequenced for subtyping. Five of 19 individuals tested positive for the parasite, all of which were also positive by previous ova and parasitology examination. DNA sequencing of the small subunit ribosomal DNA and elongation factor 1 alpha gene followed by phylogenetic subtyping identified five unique subtypes, representing Blastocystis subtypes 1, 2, 3, 4, and 8. No symptoms were consistently associated with presence or absence of infection, although abdominal pain and fatigue were reported by all infected individuals. Multiple subtypes are indicative of multiple sources of infection, suggesting more extensive surveys are required to understand the transmission of this parasite. © Springer-Verlag 2010" DO - http://dx.doi.org/10.1007/s00436-010-1739-8 0 899 F. Altermatt and D. Ebert 2007 The genotype specific competitive ability does not correlate with infection in natural Daphnia magna populations PLoS.One. 2 12 e1280 "BACKGROUND: Different evolutionary hypotheses predict a correlation between the fitness of a genotype in the absence of infection and the likelihood to become infected. The cost of resistance hypothesis predicts that resistant genotypes pay a cost of being resistant and are less fit in the absence of parasites. The inbreeding-infection hypothesis predicts that the susceptible individuals are less fit due to inbreeding depression. METHODS AND RESULTS: Here we tested if a host's natural infection status was associated with its fitness. First, we experimentally confirmed that cured but formerly infected Daphnia magna are genetically more susceptible to reinfections with Octosporea bayeri than naturally uninfected D. magna. We then collected from each of 22 populations both uninfected and infected D. magna genotypes. All were treated against parasites and kept in their asexual phase. We estimated their relative fitness in an experiment against a tester genotype and in another experiment in direct competition. Consistently, we found no difference in competitive abilities between uninfected and cured but formerly infected genotypes. This was the case both in the presence as well as in the absence of sympatric parasites during the competition trials. CONCLUSIONS: Our data do not support the inbreeding-infection hypothesis. They also do not support a cost of resistance, however ignoring other parasite strains or parasite species. We suggest as a possible explanation for our results that resistance genes might segregate largely independently of other fitness associated genes in this system" http://www.ncbi.nlm.nih.gov/pubmed/18060074 0 900 "C. Yates, A. Charlesworth, S. R. Allen, N. B. Reese, R. D. Skinner and E. Garcia-Rill" 2008 The onset of hyperreflexia in the rat following complete spinal cord transection Spinal Cord. 46 12 798-803 "STUDY DESIGN: Hyperreflexia occurs after spinal cord injury (SCI) and can be assessed by measuring low frequency-dependent depression of the H-reflex. Previous studies showed the time course for the onset of hyperreflexia to occur between 6-28 days in the contusion model of SCI. OBJECTIVE: To determine the time course of the onset of hyperreflexia in the transection model of SCI and examine changes in Connexin-36 (Cx-36) protein levels in the lumbar enlargement of animals. SETTING: Spinal Cord Injury Mobilization Program of the Center for Translational Neuroscience, the research arm of the Jackson T. Stephens Neuroscience Institute, Little Rock, AR, USA. METHODS: Adult female rats underwent transection at T10 level. Low frequency-dependent depression of the H-reflex was tested at 7, 14 and 30 days post-transection. Lumbar enlargement tissue was harvested following reflex testing and western blots were performed after immunoprecipitation to compare Cx-36 protein levels. RESULTS: Significant decreases in low frequency-dependent depression of the H-reflex were observed in animals tested 14 and 30 days post-transection compared with control animals, but it was not different from control animals at 7 days. Significant decreases in Cx-36 protein levels were observed in animals 7 days post-transection compared with controls. CONCLUSION: Rats transition to a state of hyperreflexia between 7 and 14 days post-transection. Cx-36 protein levels decreased at 7 days post-transection and gradually returned to control levels by 30 days post-transection. These data suggest there may be a relationship between changes in neuronal gap junction protein levels and the delayed onset of hyperreflexia" http://www.ncbi.nlm.nih.gov/pubmed/18542097 0 901 J. Bures and V. P. Neverov 1979 Reversed postoptokinetic nystagmus: a model of plasticity in the vestibuloocular system Acta Neurobiol.Exp.(Wars.) 39 6 477-490 "A simple manifestation of the memorial processes is the so called reversed postoptokinetic nystagmus (RPN), a trace phenomenon elicited in the rabbit by prolonged (60 min) optokinetic (OK) stimulation. Electrophysiological analysis of RPN indicated that the underlying neural trace is weakened, but not suppressed by spreading depression in the cerebral cortex or superior colliculus. An asymmetry of RPN is brought about by unilateral 6-OHDA lesion on substantia nigra. Electroconvulsive shock applied immediately after a period of OK stimulation blocks the subsequent RPN without interfering with OKN. About 70 percent of neurons in the vestibular complex changed their activity during OKN and RPK. The changes consisted in most cases of an excitation accompanying OKN and inhibition during RPN. The OKN-RPN related reacti6ns were also abundant in flocculus but significant activity changes during RPN were less frequent in this structure. Units in midbrain reticular formation reacted both during OKN and RPN in a similar fashion as the vestibular ones. On the other hand units in the cerebellar deep nuclei and brachium conjunctivum were only weakly influenced by OKN and/or RPN. It is suggested that the neural trace of RPN develops in the vestibular complex and vestibulocerebellum as a part of the process compensating the effect of continued optokinetic stimulation. Flocculus participates in input processing of the optokinetic stimulation whereas reticular formation mediates signal transmission to oculomotor and higher integrating centers. The trace, revealed by sudden cessation of the eliciting stimulus in absence of visual reference signals is probably the neural substrate of the so called motion habituation and visual hallucinations. As other compensatory phenomena in the motor system, RPN has features of instrumental (it improves the organisms control of environment) and classical (it is automatically established and involuntarily emitted) conditioning" http://www.ncbi.nlm.nih.gov/pubmed/547705 0 902 "C. J. Yang, S. Y. Mao, L. M. Long and W. Y. Zhu" 2012 "Effect of disodium fumarate on microbial abundance, ruminal fermentation and methane emission in goats under different forage: concentrate ratios" Animal. 6 11 1788-1794 "This study investigated the effects of disodium fumarate (DF) on methane emission, ruminal fermentation and microbial abundance in goats under different forage (F) : concentrate (C) ratios and fed according to maintenance requirements. Four ruminally fistulated, castrated male goats were used in a 4 x 4 Latin square design with a 2 x 2 factorial arrangement of treatments and the main factors being the F : C ratios (41 : 59 or 58 : 42) and DF supplementation (0 or 10 g/day). DF reduced methane production (P < 0.05) on average by 11.9%, irrespective of the F : C ratio. The concentrations of total volatile fatty acids, acetate and propionate were greater in the rumen of goats supplemented with DF (P < 0.05), whereas the abundance of methanogens was lower (P < 0.05). In high-forage diets, the abundance of Selenomonas ruminantium, a fumarate-reducing bacterium, was greater in the rumen of goats supplemented with DF. The abundance of fungi, protozoa, Ruminococus flavefaciens and Fibrobacter succinogenes were not affected by the addition of DF. Variable F : C ratios affected the abundance of methanogens, fungi and R. flavefaciens (P < 0.05), but did not affect methane emission. The result implied that DF had a beneficial effect on the in vivo rumen fermentation of the goats fed diets with different F : C ratios and that this effect were not a direct action on anaerobic fungi, protozoa and fibrolytic bacteria, the generally recognized fiber-degrading and hydrogen-producing microorganisms, but due to the stimulation of fumarate-reducing bacteria and the depression of methanogens" http://www.ncbi.nlm.nih.gov/pubmed/22717128 0 903 "W. C. Edwards, D. L. Whitenack, J. W. Alexander and M. A. Solangi" 1989 Selenium toxicosis in three California sea lions (Zalophus californianus) Vet.Hum.Toxicol. 31 6 568-570 "Selenium poisoning occurs worldwide in nearly all domestic animals. Acute selenium poisoning is associated with feeding high levels or injecting excessive amounts of selenium and is usually fatal. The acute poisoning may cause gastrointestinal disturbance, muscle weakness, depression of the central nervous system, prostration and death (1-2). Chronic selenium poisoning in cattle, sheep and horses may result from the consumption of seleniferous plants over an extended period of time. Chronic selenium results in ataxia, incoordination, partial blindness, paralysis, loss of hair or wool, abnormal hoof growth and possibly abnormal changes in behavior (1). There is little information regarding the clinical signs and pathology of selenium toxicosis in marine mammals. Likewise, there is little information regarding normal tissue levels or toxicologically significant levels of selenium in these species. The results of these investigations in sea lions, based on clinical signs, pathologic findings and tissue levels of selenium, suggest subacute or chronic selenium poisoning was most likely from dietary fish high in selenium" http://www.ncbi.nlm.nih.gov/pubmed/2617840 0 904 "A. M. Henken, E. A. Graat, H. W. Ploeger and T. E. Carpenter" 1994 Description of a model to simulate effects of Eimeria acervulina infection on broiler production Parasitology 108 ( Pt 5) 513-518 "A simulation model for effects of Eimeria acervulina infection on technical and economic characteristics in broiler production is presented. The model describes development over time of the growth depression, feed intake reduction, and decrease in feed efficiency associated with infection. The model also shows a phase of compensatory growth during which earlier negative effects are counterbalanced, at least partly. Major assumptions made were: infection with E. acervulina occurs in each flock; production is affected in each flock; compensatory growth takes place because immunity develops and cell regeneration occurs. The results show that the pattern of development of the production characteristics during a flock cycle depends on the initial contamination level. Both a high and low initial contamination level results in a lower average daily gain, a worse feed to gain ratio, and a reduced net revenue compared to an intermediate contamination level" http://www.ncbi.nlm.nih.gov/pubmed/8052506 0 905 "S. Chengfeng, L. Wei, W. Xinxing, W. Lei, Z. Rui and Q. Lingjia" 2014 "Hyperhomocysteinemia is a result, rather than a cause, of depression under chronic stress" PLoS.One. 9 10 e106625 "BACKGROUND: Although the accumulation of homocysteine (Hcy) has been implicated in the pathogenesis of depression, whether Hcy is directly involved and acts as the primary cause of depressive symptoms remains unclear. The present study was designed to clarify whether increased Hcy plays an important role in stress-induced depression. RESULTS: We employed the chronic unpredictable mild stress model (CUMS) of depression for 8 weeks to observe changes in the plasma Hcy level in the development of depression. The results showed that Wistar rats exposed to a series of mild, unpredictable stressors for 4 weeks displayed depression-like symptoms such as anhedonia (decreased sucrose preferences) and a decreased 5-Hydroxy Tryptophan (5-HT) concentration in the hippocampus. At the end of 8 weeks, the plasma Hcy level increased in the CUMS rats. The anti-depressant sertraline could decrease the plasma Hcy level and improve the depression-like symptoms in the CUMS rats. RhBHMT, an Hcy metabolic enzyme, could decrease the plasma Hcy level significantly, although it could not improve the depressive symptoms in the CUMS rats. CONCLUSIONS: The results obtained from the experiments did not support the hypothesis that the increased Hcy concentration mediated the provocation of depression in CUMS rats, and the findings suggested that the increased Hcy concentration in the plasma might be the result of stress-induced depression" http://www.ncbi.nlm.nih.gov/pubmed/25286230 1 906 "D. M. Spillane, T. W. Rosahl, T. C. Sudhof and R. C. Malenka" 1995 Long-term potentiation in mice lacking synapsins Neuropharmacology 34 11 1573-1579 "Synapsin I and synapsin II are widely expressed synaptic vesicle phosphoproteins that have been proposed to play an important role in synaptic transmission and synaptic plasticity. To gain further insight into the functional significance of the phosphorylation sites on the synapsins, we have examined a number of synaptic processes thought to be mediated by protein kinases in knockout mice lacking both forms of synapsin (Rosahl et al., 1995). Long-term potentiation (LTP) at both the mossy fiber (MF)-CA3 pyramidal cell synapse and the Schaffer collateral-CA1 pyramidal cell synapse appears normal in hippocampal slices prepared from mice lacking synapsins. Moreover, the effects on synaptic transmission of forskolin at MF synapses and H-7 at synapses on CA1 cells are also normal in the mutant mice. These results indicate that the synapsins are not necessary for: (1) the induction or expression of two different forms of LTP in the hippocampus, (2) the enhancement in transmitter release elicited by activation of the cAMP-dependent protein kinase (PKA) and (3) the depression of synaptic transmission caused by H-7. Although disappointing, these results are important in that they exclude the most abundant family of synaptic phosphoproteins as an essential component of long-term synaptic plasticity" http://www.ncbi.nlm.nih.gov/pubmed/8606805 0 907 "R. A. Finch, C. L. Parker and S. T. Walton" 1978 The lack of an inhibitory effect of hyaluronate on chondrogenesis in chick limb-bud mesoderm cells grown in culture Cell Differ. 7 5 283-293 "The effect of hyaluronate on chondrogenesis in cultures of chick limb-bud mesoderm cells, derived from stage 20--21, 23--24 and 26 embryos grown at different cell densities and in 3 different culture media, was studied. The results show that hyaluronate at a concentration of 500 microgram/ml, does not consistently produce an inhibition of chondrogenesis in cultures of stage 20--21, 23--24 or 26 limb-bud mesoderm cells in contrast to what has been reported by Toole et al. (1972). It was demonstrated that under optimal conditions, stage 26 cells grown in the absence of hyaluronate do not form as many cartilage colonies in culture as do cells from stage 20--21 or 23--24 embryos. It was determined that culture medium composed of Eagle's MEM supplemented with 7% horse serum, 3% fetal calf serum and 5% 10-day chick embryo extract supported chondrogenesis significantly better than Ham's F-12 supplemented with 10% fetal calf serum. Our results suggest that the inhibition of chondrogenesis by hyaluronate reported earlier is most likely due to the sub-optimal conditions of growth medium, cell density and embryonic stage than to the hyaluronate treatment" http://www.ncbi.nlm.nih.gov/pubmed/699055 0 908 S. A. Ferguson and K. J. Berry 2010 Chronic oral treatment with isotretinoin alters measures of activity but not anxiety in male and female rats Neurotoxicol.Teratol. 32 5 573-578 "Use of the anti-acne drug, Accutane (ACC) (isotretinoin, 13-cis-retinoic acid), has been associated with neuropsychiatric events ranging from depression in animal models to depression and suicide ideation in humans. Our studies, however, have consistently indicated few effects on measures of depression in male and female rats. Still, the comorbidity of depression and anxiety suggests that anxiety assessments in ACC-treated rats could be informative. Such assessments must be balanced with measures of activity since drug-induced activity alterations may impact the expression of anxiety-like behaviors. Here, Sprague-Dawley rats (n=15/sex/dose) were gavaged daily with 0 (soy oil), 7.5, or 30 mg/kg/day ACC beginning on postnatal day (PND) 59. Blood ACC levels similar to humans taking recommended ACC doses are produced by 7.5mg/kg/day. Short-term activity was assessed in open fields prior to ACC treatment (PND 51) and again at PNDs 129 and 164 and in a complex environment at PNDs 66 and PND 184. Long-term residential activity was measured in running wheels (PNDs 85-92) and figure 8 mazes (PNDs 99-106). Anxiety-like behavior was assessed via elevated plus maze (EPM) activity on PND 98 and in a black/white apparatus on PND 125. The typical sex differences in most behaviors were exhibited (i.e., increased EPM open arm entries and overall activity in most measures in females); however, there were no significant effects of ACC treatment on open field activity, complex environment activity, residential running wheel activity, or EPM activity. Residential figure 8 maze activity indicated that male and female rats treated with 30 mg/kg/day were less active on all nights (p<0.05) and females treated with 7.5 or 30 mg/kg/day were less active than same-sex controls on most days (p<0.05). Similarly, rats of both sexes treated with 30 mg/kg/day were significantly less active in the black/white apparatus (p<0.05), entering the darkened area less frequently (p<0.05), although duration in the darkened area did not differ. These data indicate that at blood levels typically achieved by humans (i.e., the 7.5 mg/kg group), there are no significant anxiogenic effects associated with ACC treatment. At higher ACC levels, there are mild effects on activity but these appear to be apparatus- and/or age-specific" http://www.ncbi.nlm.nih.gov/pubmed/20381607 0 909 H. Laborit and B. Weber 1967 [Effect of D actinomycin on the spontaneous activity of the isolated ileum and atrium of rabbits and on the activity of various pharmacologic agents] Agressologie 8 2 137-142 http://www.ncbi.nlm.nih.gov/pubmed/5602121 0 910 W. A. Mutch and A. R. Gardner-Medwin 1987 The influence of hypocarbia on the resolution of transient increases in brain extracellular potassium Anesthesiology 66 3 350-355 "The effect of acute hypocarbia on baseline extracellular K+ concentration [( K+]e) and its effect on the ability of the cerebral microenvironment to recover from transient increases in [K+]e has been assessed in rats. Spreading depression of cortical activity was used to present a reproducible K+ load to the extracellular space. Baseline [K+]e and the half-time for resolution of the [K+]e changes seen with spreading depression waves were measured for the hypocarbic and normocarbic states by means of double-barrelled K+ microelectrodes placed approximately 400 micron below the cortical surface. Three spreading depression waves were initiated in each animal for the two CO2 states. In group 1 (n = 10), the rats were initially normocarbic (PaCO2 41.6 +/- 3.0 mmHg; mean +/- SD), then hypocarbic (PaCO2 19.0 +/- 2.5 mmHg) for the second series of measurements. The baseline [K+]e was significantly higher in the normocarbic state 3.4 +/- 0.4 versus 3.0 +/- 0.4 mM l-1, P less than 0.01 (paired t test). During normocarbia, the K+ load (delta[K+]e) presented to the extracellular space following spreading depression was 49.4 +/- 7.5 mM l-1, n = 10 (peak [K+]e - baseline [K+]e). The half-time for resolution of the presented [K+]e load was 24.3 +/- 6.1 s. Following hypocarbia of 1.4 +/- 0.6 h, there was no change in delta[K+]e (49.0 +/- 6.0 mM l-1) but resolution t1/2 had increased to 35.8 +/- 11.2 s, P less than 0.01 paired t test.(ABSTRACT TRUNCATED AT 250 WORDS)" http://www.ncbi.nlm.nih.gov/pubmed/3103487 0 911 "W. Fan, J. Ster and U. Gerber" 2010 Activation conditions for the induction of metabotropic glutamate receptor-dependent long-term depression in hippocampal CA1 pyramidal cells J.Neurosci. 30 4 1471-1475 "Two forms of homosynaptic long-term depression (LTD) are distinguished in hippocampal CA1 pyramidal cells, one which is NMDA receptor dependent and the other metabotropic glutamate receptor (mGluR) dependent. Although the molecular processes involved in mGluR-LTD are well characterized, the conditions of circuit activation required for its induction remain unclear. We show that mGluR-LTD cannot be induced in synaptically coupled CA3-CA1 pyramidal cell pairs. Experiments to address the underlying mechanisms indicate that, even when glutamate transporters are blocked, one presynaptic cell releases insufficient glutamate to evoke an mGluR-mediated current in a connected CA1 cell. These findings imply that extrasynaptic diffusion is not a limiting factor and are consistent with a sparse distribution of functional mGluRs in the dendritic tree of pyramidal cells. Thus, the discharge of multiple Schaffer collaterals to a targeted cell is necessary for mGluR-LTD. Our experiments indicate that approximately eight CA3 inputs to a CA1 pyramidal cell must be activated to induce mGluR-LTD" http://www.ncbi.nlm.nih.gov/pubmed/20107074 0 912 "N. Z. Kara, S. Flaisher-Grinberg and H. Einat" 2015 Partial effects of the AMPAkine CX717 in a strain specific battery of tests for manic-like behavior in black Swiss mice Pharmacol.Rep. 67 5 928-933 "BACKGROUND: AMPA receptors are highly expressed throughout the central nervous system and are suggested to be involved in mood regulation. Studies found changes in glutamate, its metabolites and receptors in patients with bipolar disorder (BPD) or major depression (MD) and in animal models of stress. Additional data suggest that the glutamatergic system and AMPA receptors specifically, have an important role in modulating the therapeutic effects of mood stabilizers. Further research on the role of AMPA receptors in mood regulation can be done using AMPAkines, positive modulators of AMPA receptors. AMPAkines have been studied for cognitive enhancement in neurodegenerative disorders and some were also examined in preclinical studies of mood disorders. In that context, the present study was designed to test the effects of the AMPAkine CX717 in a strain specific battery of tests for mania-like behaviors. METHODS: Black Swiss male mice were sub-chronically treated with 5 different doses of CX717 or vehicle and tested in a battery of behavioral tests including spontaneous activity, sweet solution preference, resident-intruder, forced swim and amphetamine-induced hyperactivity. RESULTS: Data show that CX717 doses of 30mg/kg and above, but not lower, reduce activity levels. Moreover, 45mg/kg and above reduce interactions in the resident-intruder test and ameliorate amphetamine-induced hyperactivity. CONCLUSIONS: The results therefore show a partial effect of CX717 on manic-like behavior, somewhat similar to previously demonstrated effects of atypical antipsychotic drugs in this strain. It is therefore suggested that further work related to AMPAkines in the treatment of affective disorders might be warranted" http://www.ncbi.nlm.nih.gov/pubmed/26398387 0 913 "J. Bures, O. Buresova, T. Weiss and E. Fifkova" 1963 Excitability changes in non-specific thalamic nuclei during cortical spreading depression in the rat Electroencephalogr.Clin.Neurophysiol. 15 73-83 http://www.ncbi.nlm.nih.gov/pubmed/14016940 0 914 "C. E. Almado, B. H. Machado and R. M. Leao" 2012 Chronic intermittent hypoxia depresses afferent neurotransmission in NTS neurons by a reduction in the number of active synapses J.Neurosci. 32 47 16736-16746 "Long-term synaptic plasticity has been recently described in brainstem areas associated to visceral afferent sensory integration. Chronic intermittent hypoxia (CIH), an animal model for studying obstructive sleep apnea in humans, depresses the afferent neurotransmission in nucleus tractus solitarii (NTS) neurons, which affect respiratory and autonomic regulation. Here we identified the synaptic mechanisms of CIH-induced depression of the afferent neurotransmission in NTS neurons in juvenile rats. We verified that CIH reduced the amplitude of both NMDA and non-NMDA glutamatergic excitatory currents (eEPSCs) evoked by tractus solitarii stimulation (TS-eEPSC) of second-order neurons in the NTS. No changes were observed in release probability, evidenced by absence of any CIH-elicited effects on short-term depression and failures in EPSCs evoked in low calcium. CIH also produced no changes in TS-eEPSC quantal size, since the amplitudes of both low calcium-evoked EPSCs and asynchronous TS-eEPSCs (evoked in the presence of Sr(2+)) were unchanged. Using single TS afferent fiber stimulation in slices from control and CIH rats we clearly show that CIH reduced the quantal content of the TS-eEPSCs without affecting the quantal size or release probability, suggesting a reduction in the number of active synapses as the mechanism of CIH induced TS-eEPSC depression. In accordance with this concept, the input-output relationship of stimulus intensity and TS-eEPSC amplitude shows an early saturation in CIH animals. These findings open new perspectives for a better understanding of the mechanisms underlying the synaptic plasticity in the brainstem sensory neurons under challenges such as those produced by CIH in experimental and pathological conditions" http://www.ncbi.nlm.nih.gov/pubmed/23175827 0 915 "D. Arandjelovic, P. Misic, M. Petrovic, S. Serafimovic and V. Todorovic" 2009 Mental consequences resulting from torture "European Psychiatry.Conference: 17th European Psychiatric Association, EPA Congress Lisbon Portugal.Conference Start: 20090124 Conference End: 20090128.Conference Publication: (var.pagings).24 ()(pp S837), 2009.Date of Publication: 2009." var.pagings S837 "Torture is considered as physical or mental harassment, torment, causing pain, injuries and humiliation of an innocent person occurring during the shorter or longer period of time. Is human emotional behavior based on primary biological mechanism that human inherited not only from close animal predecessors, but also significantly more distant kinds on evolutionary ladder? Results of researches indicate that aggressiveness is stable pattern of behavior in children and young people. Aggressive behavior of humans decreases over the years, although certain types of personalities preserve stability of aggressive behavior. Psychological profile of torturer includes diagnostical category of antisocial personality disorder. Mental consequences resulting from torture are depression, psychosomatic reactions, aggression, state of anxiety. The contribution of victimology is significant, particularly from aspect of ""selecting"" psychopathological reaction. It is also important whether the torturer is known to be victims or it is a stranger. It is understandable that consequences are much more severe with people who had unfortunate to be tortured by known person. The most common psychopathological reactions are: 1. Fear lived during the torture. 2. Depressive reaction. 3. Aggression - which may not be demonstrated in adequate manner, may be shifted to other people, which may create interpersonal disputes, before all for the victim and represents one of physical consequences resulting from torture. Torture prevention is problem of individuals, community and society as whole. Degradation of authorities in one society leads to moral erosion, and on its part, to torture on all functioning levels" 0 916 M. Takase 1977 [Effects of acetazolamide and epinephrine on aqueous flow rate in rhesus monkey (author's transl)] Nippon Ganka Gakkai Zasshi 81 3 235-240 http://www.ncbi.nlm.nih.gov/pubmed/404859 0 917 "H. M. Yun, S. Kim, H. J. Kim, E. Kostenis, J. I. Kim, J. Y. Seong, J. H. Baik and H. Rhim" 2007 The novel cellular mechanism of human 5-HT6 receptor through an interaction with Fyn J.Biol.Chem. 282 8 5496-5505 "The human 5-HT(6) receptor (5-HT(6)R) is one of the latest cloned receptors among the known 5-HT receptors. Its abundant distribution in the limbic region, which participates in the control of mood and emotion and is involved in nervous system diseases such as depression and Alzheimer disease, has caused it to generate much interest. However, the cellular mechanisms of 5-HT(6)R are poorly understood. In the present study we found, using a yeast two-hybrid assay, that the carboxyl-terminal region of 5-HT(6)R interacts with the Fyn-tyrosine kinase. We also determined using a glutathione S-transferase pulldown assay that this interaction was mediated through the SH3 domain of Fyn and confirmed this by co-immunoprecipitation assays in two different transfected cell lines as well as in adult rat brains. Immunocyto(histo)chemistry also showed prominent co-localization between 5-HT(6)R and Fyn in transfected cells and a similar distribution between 5-HT(6)R and Fyn in the rat brain. Based on this interaction, we further examined the modulation of 5-HT(6)R by Fyn and vice versa. In addition, we demonstrated that the activation of 5-HT(6)R activated the extracellular signal-regulated kinase1/2 via an Fyn-dependent pathway. These findings suggest that Fyn may play an important role in 5-HT(6)R- mediated signaling pathways in the central nervous system" http://www.ncbi.nlm.nih.gov/pubmed/17189269 0 918 "G. H. Seol, J. Ziburkus, S. Huang, L. Song, I. T. Kim, K. Takamiya, R. L. Huganir, H. K. Lee and A. Kirkwood" 2007 Neuromodulators control the polarity of spike-timing-dependent synaptic plasticity Neuron 55 6 919-929 "Near coincidental pre- and postsynaptic action potentials induce associative long-term potentiation (LTP) or long-term depression (LTD), depending on the order of their timing. Here, we show that in visual cortex the rules of this spike-timing-dependent plasticity are not rigid, but shaped by neuromodulator receptors coupled to adenylyl cyclase (AC) and phospholipase C (PLC) signaling cascades. Activation of the AC and PLC cascades results in phosphorylation of postsynaptic glutamate receptors at sites that serve as specific ""tags"" for LTP and LTD. As a consequence, the outcome (i.e., whether LTP or LTD) of a given pattern of pre- and postsynaptic firing depends not only on the order of the timing, but also on the relative activation of neuromodulator receptors coupled to AC and PLC. These findings indicate that cholinergic and adrenergic neuromodulation associated with the behavioral state of the animal can control the gating and the polarity of cortical plasticity" http://www.ncbi.nlm.nih.gov/pubmed/17880895 0 919 "K. Kucharz, R. Sondergaard, I, A. Bach, K. Stromgaard and M. Lauritzen" 2016 PSD-95 uncoupling from NMDA receptors by Tat-N-dimer ameliorates neuronal depolarisation in cortical spreading depression J.Cereb.Blood Flow Metab "Cortical spreading depression is associated with activation of NMDA receptors, which interact with the postsynaptic density protein 95 (PSD-95) that binds to nitric oxide synthase (nNOS). Here, we tested whether inhibition of the nNOS/PSD-95/NMDA receptor complex formation by anti-ischemic compound, UCCB01-144 (Tat-N-dimer) ameliorates the persistent effects of cortical spreading depression on cortical function. Using in vivo two-photon microscopy in somatosensory cortex in mice, we show that fluorescently labelled Tat-N-dimer readily crosses blood-brain barrier and accumulates in nerve cells during the first hour after i.v. injection. The Tat-N-dimer suppressed stimulation-evoked synaptic activity by 2-20%, while cortical blood flow and cerebral oxygen metabolic (CMRO2) responses were preserved. During cortical spreading depression, the Tat-N-dimer reduced the average amplitude of the negative shift in direct current potential by 33% (4.1 mV). Furthermore, the compound diminished the average depression of spontaneous electrocorticographic activity by 11% during first 40 min of post-cortical spreading depression recovery, but did not mitigate the suppressing effect of cortical spreading depression on cortical blood flow and CMRO2 We suggest that uncoupling of PSD-95 from NMDA receptors reduces overall neuronal excitability and the amplitude of the spreading depolarisation wave. These findings may be of interest for understanding the neuroprotective effects of the nNOS/PSD-95 uncoupling in stroke" http://www.ncbi.nlm.nih.gov/pubmed/27107027 0 920 "T. L. Tieman, D. J. Steel, Y. Gor, J. Kehoe, J. H. Schwartz and S. J. Feinmark" 2001 A pertussis toxin-sensitive 8-lipoxygenase pathway is activated by a nicotinic acetylcholine receptor in aplysia neurons J.Neurophysiol. 85 5 2150-2158 "Acetylcholine (ACh) activates two types of chloride conductances in Aplysia neurons that can be distinguished by their kinetics and pharmacology. One is a rapidly desensitizing current that is blocked by alpha-conotoxin-ImI and the other is a sustained current that is insensitive to the toxin. These currents are differentially expressed in Aplysia neurons. We report here that neurons that respond to ACh with a sustained chloride conductance also generate 8-lipoxygenase metabolites. The sustained chloride conductance and the activation of 8-lipoxygenase have similar pharmacological profiles. Both are stimulated by suberyldicholine and nicotine, and both are inhibited by alpha-bungarotoxin. Like the sustained chloride conductance, the activation of 8-lipoxygenase is not blocked by alpha-conotoxin-ImI. In spite of the similarities between the metabolic and electrophysiological responses, the generation of 8-lipoxygenase metabolites does not appear to depend on the ion current since an influx of chloride ions is neither necessary nor sufficient for the formation of the lipid metabolites. In addition, the application of pertussis toxin blocked the ACh-activated release of arachidonic acid and the subsequent production of 8-lipoxygenase metabolites, yet the ACh-induced activation of the chloride conductance is not dependent on a G protein. Our results are consistent with the idea that the nicotinic ACh receptor that activates the sustained chloride conductance can, independent of the chloride ion influx, initiate lipid messenger synthesis" http://www.ncbi.nlm.nih.gov/pubmed/11353029 0 921 "A. Kizu, A. Kusaba, M. Nakamura, S. Kato and K. Sawada" 1976 "Effect of 4-hydroxypyrazolo[3,4-d]pyrimidine (allopurinol) administration of growth of Ehrlich tumor cells" Gan 67 6 903-907 "Effect of the administration of 4-hydroxypyrazolo([3,4-d]pyrimidine (allopurinol) on the growth of Ehrlich ascites tumor cells was investigated in an in vivo system. Oral administration of allopurinol (0.1% in diet) suppressed the growth of both ascites and solid types of the tumor after the implantation of Ehrlich tumor cells in mice. The inhibitory action depended on the dose but was lost repidly when the administration was interrupted. Possible mechanisms involved in the inhibitory effect of allopurinol on tumor growth were briefly discussed" http://www.ncbi.nlm.nih.gov/pubmed/1021510 0 922 "J. C. Dong, J. Ni and Z. H. Gong" 2004 [Experimental study on prevention and treatment of bronchial asthma by compound Chinese herbal monomer recipe] Zhongguo Zhong.Xi.Yi.Jie.He.Za Zhi. 24 8 717-721 "OBJECTIVE: To observe the effect of compound Chinese herbal monomer (CHM) recipe, consisted of ligustrazin (3.75 mg/kg x d), baicalin (7.5 mg/kg x d) and ginkgolide (2 mg/kg x d), on airway atopic inflammation and hyper-responsiveness in asthma. METHODS: Model guinea pigs of asthma were randomly divided into three groups, the model group, the CHM group and the cromlyn sodium (CS) group, they were treated by atomizing inhalation with normal saline, CHM and CS respectively. The eosinophil count and eosinophil cation protein (ECP) in blood and bronchial alveolar lavage fluid (BALF), and total cell count in BALF were measured and compared. And the effect of treatment on the airway hyperresponsiveness and pathology among groups were compared. RESULTS: CHM showed significant inhibition on blood eosinophil count and BALF and total cell count in BALF, showing significant difference (P < 0.05 or P < 0.01) as compared with those in the model group. The level of ECP was not different in the various groups. Airway responsiveness determination showed that CHM has significant inhibitory action on it. And the pathology of airway inflammation in the CHM group was significantly milder than that in the model group. CONCLUSION: The compound inhalation liquid consisted of ligustrazin, baicalin and ginkgolide, has the anti-asthmatic airway atopic inflammation and depression on airway hyper-responsiveness, suggesting that components of compound CHM recipe could inhibit the multiple pathogenetic asthmatic inflammation from different angles and on multiple targets, so as to cure asthma effectively" http://www.ncbi.nlm.nih.gov/pubmed/15366597 0 923 S. F. Phillips and P. F. Schmalz 1970 Bicarbonate secretion by the rat colon: effect of intraluminal chloride and acetazolamide Proc.Soc.Exp.Biol.Med. 135 1 116-122 http://www.ncbi.nlm.nih.gov/pubmed/4990912 0 924 "L. P. Renaud, J. B. Martin and P. Brazeau" 1975 "Depressant action of TRH, LH-RH and somatostatin on activity of central neurones" Nature 255 5505 233-235 http://www.ncbi.nlm.nih.gov/pubmed/806808 0 925 I. Bobkov and I. S. Morozov 1982 [Correction of psychodepressive effects of benzodiazepine tranquilizers by administration of psychostimulants] Biull.Eksp.Biol.Med. 94 10 48-51 http://www.ncbi.nlm.nih.gov/pubmed/6129008 1 926 "D. Wang, J. Bai, F. Sun and D. Yang" 2010 Chemical constituents and antidepressant activity of the new species Hypericum enshiense occurring in China Phytomedicine. 17 6 410-413 "Hypericum enshiense L. H. Wu et F. S. Wang is a new species of Hypericum occurring in China, which was first identified and denominated by our laboratory. No research has been reported on the antidepressant activity and chemical constituents of this new species. In this study, the qualitative and quantitative analyses of the chemical constituents in the hydroalcoholic extract of this species were performed using HPLC/DAD/ESI-MS online method. Hypericin, pseudohypericin and some flavonoids were identified or tentatively identified. Furthermore, H. enshiense had a high content of hypericins than H. perforatum. In addition, the antidepressant activity of the hydroalcoholic extract of the species was investigated using forced swimming test (FST) and tail suspension test (TST). The extract significantly shortened the immobility time in FST and TST, while did not alter the locomoter activity of mice. These results suggested for the first time that the hydroalcoholic extract of H. enshiense might possess potential antidepressant-like activity in the animal behavioral models, and this species might act as a new potential resource for developing antidepressants to treat depressive disorders" http://www.ncbi.nlm.nih.gov/pubmed/19699627 1 927 "M. C. Hellion-Ibarrola, D. A. Ibarrola, Y. Montalbetti, M. L. Kennedy, O. Heinichen, M. Campuzano, E. A. Ferro, N. Alvarenga, J. Tortoriello, T. C. de Lima and S. Mora" 2008 The antidepressant-like effects of Aloysia polystachya (Griseb.) Moldenke (Verbenaceae) in mice Phytomedicine. 15 06-Jul 478-483 "The aim of the present work is to evaluate the putative antidepressant-like effects of a hydro-ethanolic extract (CEAp) and their fractions from the aerial parts of Aloysia polystachya (Griseb.) Moldenke (Verbenaceae) on the performance of male mice in the forced swimming test (FST). A single dose (100.0mg/kgp.o.) of CEAp, in male mice provoked a significant reduction of the immobility time (p<0.01). Such effect was also observed with short-term treatment (7 days) with single doses of 1.0 (p<0.01), 10.0 (p<0.05) and 100.0 (p<0.05)mg/kg/day of CEAp. Additionally, in a different set of experiments, repeated administration in a 24-h period (24, 18 and 1h before swimming test) with doses of 1.0 (p<0.05) and 10.0 (p<0.05)mg/kg p.o., of CEAp and 10.0mg/kgp.o., (p<0.05) of ethyl acetate fraction, provoked significant reduction of the immobility time of male mice in the FST. Moreover, it was noted important differences in the onset of the antidepressant-like effect in the FST, depending on the modality of treatment with CEAp (acute, short-term or repeated). Both, efficacy and potency were higher when repeated administration of CEAp was used, and surprisingly the dose of 10mg/kg (24, 18 and 1h before swimming test) was more effective than imipramine. In the same way, the short term administration (7 days) improved significantly efficacy and potency of the CEAp in comparison to a single dose treatment. The ethyl acetate fraction submitted to TLC demonstrated that main and minor components are phenolics and terpenes, respectively. In addition, this fraction gives a negative Shinoda's test for flavonoids. These results indicate an antidepressant-like profile of action for the hydro-ethanolic extract and the component(s) of the ethyl acetate fraction obtained from A. polystachya, which deserve further investigation" http://www.ncbi.nlm.nih.gov/pubmed/18222666 1 928 A. Sietnieks and B. J. Meyerson 1980 Enhancement by progesterone of lysergic acid diethylamide inhibition of the copulatory response in the female rat Eur.J.Pharmacol. 63 1 57-64 "Copulatory behavior in the ovariectomized rat, the lordosis response (L.R.) was induced by either estrogen alone or estrogen followed by progesterone. L.R. has been shown to be inhibited dose-dependently by lysergic acid diethylamide (LSD). The effects of various hormone treatments on the LSD-induced inhibition were tested in the present study. Progesterone but not estrogen was found to significantly enhance the LSD effect in a dose-dependent manner. In contrast, the effect of LSD on spontaneous behaviors in an exploratory situation was not influenced by progesterone treatment. This phenomenon of increased L.R. inhibitor effect by LSD was probably not due to a steroid-induced change in LSD metabolism. The data show instead that progesterone specifically influences monoaminergic mechanisms, which are related to the action of LSD. This has important implications for the possibility that progesterone induces the L.R. by acting on monoaminergic mechanisms" http://www.ncbi.nlm.nih.gov/pubmed/7379849 0 929 C. Macek 1982 Of mind and morbidity: can stress and grief depress immunity? JAMA 248 4 405-407 http://www.ncbi.nlm.nih.gov/pubmed/7087134 0 930 "S. Aonuma, T. Hama, N. Tamaki and H. Okumura" 1969 "Orotate as a beta-alanine donor for anserine and carnosine biosynthesis, and effects of actinomycin D and azauracil on their pathway" J.Biochem. 66 2 123-132 http://www.ncbi.nlm.nih.gov/pubmed/5394595 0 931 "C. Nocjar, B. L. Roth and E. A. Pehek" 2002 Localization of 5-HT(2A) receptors on dopamine cells in subnuclei of the midbrain A10 cell group Neuroscience 111 1 163-176 "Considerable evidence suggests that a dysfunction of the dopamine and serotonin (5-hydroxytryptamine or 5-HT) neurotransmitter systems contributes to a diverse range of pathological conditions including schizophrenia, depression and drug abuse. Recent electrophysiological and behavioral studies suggest that 5-HT modulates dopaminergic neurons in the ventral tegmental area via activation of 5-HT(2A) receptors. It is currently unknown if 5-HT(2A) receptors mediate their actions on dopaminergic neurons in the ventral tegmental area via direct or indirect mechanisms. This study investigated whether 5-HT(2A) receptors were localized on dopamine cells within the A10 dopamine subnuclei of the rat, including the ventral tegmental area. We discovered that 5-HT(2A) receptor-like immunoreactivity colocalized with tyrosine hydroxylase, a marker for dopamine neurons, throughout the A10 dopamine cell population. Colocalization was most prominent in rostral and mid A10 regions, including the paranigral, parabrachial, and interfascicular subnuclei. Though more rare, non-dopaminergic neurons also expressed 5-HT(2A) receptor immunoreactivity in the ventral tegmental area. Additionally, although a dense population of 5-HT(2A) immunoreactive cells was observed in the rostral dorsal raphe nucleus, rarely were these cells immunoreactive for tyrosine hydroxylase. The linear raphe A10 dopamine subdivisions also displayed a low degree of 5-HT(2A) receptor and tyrosine hydroxylase colocalization. These findings provide an anatomical basis for the physiological modulation of dopamine neurons in the rostral ventral tegmental area either directly, by 5-HT(2A) receptors localized on dopamine cells, or indirectly, through a non-dopaminergic mechanism. Interestingly, 5-HT(2A) receptors were expressed on dopamine neurons in several A10 subnuclei that project to mesolimbic forebrain regions implicated in drug addiction, and recent evidence indicates that ventral tegmental area 5-HT(2A) receptor activation may modulate reward-related behavior in rodents. 5-HT(2A) receptors were also expressed on dopamine cells in A10 subnuclei that project to forebrain areas that have been implicated in schizophrenia, and atypical antipsychotic drugs have high affinities for 5-HT(2A) receptors. Thus, findings in this study could have important implications for understanding 5-HT and dopamine circuitry dysfunction in schizophrenia" http://www.ncbi.nlm.nih.gov/pubmed/11955720 0 932 K. Haddley 2013 Trastuzumab emtansine for the treatment of HER2-positive metastatic breast cancer "Drugs of Today.49 (11) ()(pp 701-715), 2013.Date of Publication: November 2013." 11 701-715 "Trastuzumab emtansine is an antibody-drug conjugate comprised of the receptor tyrosine-protein kinase erbB-2 (HER2) antibody trastuzumab, and a derivative of the cytostatic agent maytansinoid DM1, covalently linked by a thiol linker. The drug was developed in an attempt to overcome trastuzumab resistance in patients with HER2-positive breast carcinoma, but it is also of potential use in other HER2-positive cancers. The preclinical antitumor activity of trastuzumab emtansine was established in HER2-positive breast cancer cell lines and murine xenograft models. Preclinically, trastuzumab emtansine was efficacious in HER2-positive cells that were resistant to trastuzumab or lapatinib. Clinically, the drug is well tolerated in most patients, with a predictable pharmacokinetic profile and minimal systemic exposure to free cytotoxic DM1. Unlike with trastuzumab, cardiac toxicity has not been seen in patients receiving trastuzumab emtansine and less adverse events have been reported than with other chemotherapy regimens. Results from a number of phase II studies and early results from a phase III investigation (EMILIA) demonstrated response rates of 25-35% in patients with breast cancer who had previously received trastuzumab. Several phase II and III studies are under way investigating trastuzumab emtansine in combination with other regimens in patients with HER2-positive cancers. Copyright © 2013 Prous Science, S.A.U. or its licensors. All rights reserved" DO - http://dx.doi.org/10.1358/dot.2013.49.11.2020937 0 933 "S. H. Preskorn, T. A. Kent, R. K. Glotzbach, G. H. Irwin and J. V. Solnick" 1984 Cerebromicrocirculatory defects in animal model of depression Psychopharmacology (Berl) 84 2 196-199 "In the tetrabenazine (TBZ) model of depression, the cerebromicrocirculation was discovered to respond abnormally to metabolic demand as mimicked by the administration of CO2. Altered responsivity of cerebral blood flow and effective permeability of the blood--brain barrier to changes in PaCO2 were found. These physiologic defects coincided temporally with TBZ-induced depletion of central norepinephrine and dopamine and with the development of the behavioral effects of TBZ (the end points used to test the antidepressant potential of experimental drugs). Pretreatment with amitriptyline (a standard antidepressant and amine reuptake inhibitor) prevented the development of these TBZ-induced abnormalities in the cerebromicrocirculation, just as it prevented the behavioral effects" http://www.ncbi.nlm.nih.gov/pubmed/6438678 1 934 "E. B. Oliveira-Sales, M. A. Toward, R. R. Campos and J. F. Paton" 2014 Revealing the role of the autonomic nervous system in the development and maintenance of Goldblatt hypertension in rats Auton.Neurosci. 183 23-29 "Despite extensive use of the renovascular/Goldblatt model of hypertension-2K-1C, and the use of renal denervation to treat drug resistant hypertensive patients, autonomic mechanisms that underpin the maintenance of this hypertension are important yet remain unclear. Our aim was to analyse cardiovascular autonomic function by power spectral density analysis of both arterial pressure and pulse interval measured continuously by radio telemetry for 6weeks after renal artery clipping. Mean arterial pressure increased from 106+/-5 to 185+/-2mmHg during 5weeks post clipping when it stabilized. A tachycardia developed during the 4th week, which plateaued between weeks 5 and 6. The gain of the cardiac vagal baroreflex decreased immediately after clipping and continued to do so until the 5th week when it plateaued (from -2.4+/-0.09 to -0.8+/-0.04bpm/mmHg; P<0.05). A similar time course of changes in the high frequency power spectral density of the pulse interval was observed (decrease from 13.4+/-0.6 to 8.3+/-0.01ms(2); P<0.05). There was an increase in both the very low frequency and low frequency components of systolic blood pressure that occurred 3 and 4weeks after clipping, respectively. Thus, we show for the first time the temporal profile of autonomic mechanisms underpinning the initiation, development and maintenance of renovascular hypertension including: an immediate depression of cardiac baroreflex gain followed by a delayed cardiac sympathetic predominance; elevated sympathetic vasomotor drive occurring after the initiation of the hypertension but coinciding during its mid-development and maintenance" http://www.ncbi.nlm.nih.gov/pubmed/24560525 0 935 P. Ralph and I. Nakoinz 1980 Environmental and chemical dissociation of antibody-dependent phagocytosis from lysis mediated by macrophages: stimulation of lysis by sulfhydryl-blocking and esterase-inhibiting agents and depression by trypan blue and trypsin Cell Immunol. 50 1 94-105 http://www.ncbi.nlm.nih.gov/pubmed/7397785 0 936 "K. Yang, H. Furue, E. Kumamoto, Y. X. Dong and M. Yoshimura" 2003 Pre- and postsynaptic inhibition mediated by GABA(B) receptors in rat ventrolateral periaqueductal gray neurons Biochem.Biophys.Res.Commun. 302 2 233-237 "The present study examined the actions of a GABA(B)-receptor agonist, baclofen, on synaptic transmission in rat ventrolateral periaqueductal gray (PAG) neurons of brainstem slices by using whole-cell voltage-clamp recordings. Baclofen (10 microM) induced a slow outward current (peak amplitude: 30.1+/-3.1pA, n=13) at -70mV, which persisted in the presence of tetrodotoxin (0.5 microM) and was diminished in the presence of postsynaptic intracellular K(+)-channel blockers (Cs(+) and TEA) and GDP-beta-S, indicating a direct postsynaptic depression mediated by K(+) channels and G proteins. Baclofen (10 microM) also decreased the frequency of both glutamatergic spontaneous EPSC (by 36+/-7%, n=11) and GABAergic spontaneous IPSC (by 37+/-12%, n=6) without changes in their amplitudes, indicating its presynaptic inhibitions. Taken together, the activation of postsynaptic GABA(B) receptors inhibits ventrolateral PAG neurons directly. At the same time, activating presynaptic GABA(B) receptors on glutamatergic and GABAergic nerve terminals inhibits glutamate and GABA release, respectively. The overall effects might influence an output of ventrolateral PAG neurons that build up the descending pain control system to the spinal dorsal horn" http://www.ncbi.nlm.nih.gov/pubmed/12604336 0 937 B. Kawin and E. E. Winters 1970 "Effects of d-penicillamine and N-acetyl-d, l-penicillamine treatment on distribution of inorganic and chlormerodrin mercury in rats" J.Nucl.Biol.Med. 14 4 145-149 http://www.ncbi.nlm.nih.gov/pubmed/5521070 0 938 "Y. Kametani, S. Iwai and I. Kuraoka" 2014 An RNA synthesis inhibition assay for detecting toxic substances using click chemistry J.Toxicol.Sci. 39 2 293-299 "Biological risk assessment studies of chemical substances that induce DNA lesions have been primarily based on the action of DNA polymerases during replication. However, DNA lesions interfere not only with replication, but also with transcription. There is no simple method for the detection of the DNA lesion-induced inhibition of transcription. Here, we report an assay for estimating the toxicity of chemical substances by visualizing transcription in mammalian cells using nucleotide analog 5-ethynyluridine (EU) and its click chemistry reaction. Ultraviolet light and representative chemical substances (camptothecin, 4-nitroquinoline-1-oxide, mitomycin C, and cisplatin, but not etoposide) of DNA- damaging agents show toxicity, as indicated by RNA synthesis inhibition in response to DNA damage in HeLa cells. Using titanium dioxide, we observed RNA synthesis inhibition in response to the rutile form, but not the anatase form, indicating that rutile titanium dioxide is a toxic substance. Because this method is based on the transcriptional response to DNA lesions, we can use terminally differentiated neuron-like PC12 cells, the differentiation of which can be induced by nerve growth factors, for evaluating chemical substances. Ultraviolet light and some chemicals (camptothecin, 4-nitroquinoline-1-oxide, mitomycin C, and cisplatin, but not etoposide) inhibited RNA synthesis in non-differentiated PC12 cells. Conversely, camptothecin and cisplatin did not inhibit RNA synthesis in differentiated PC12 cells, but 4-nitroquinoline-1-oxide, mitomycin C, and etoposide did. And using titanium dioxide, we did not observed any RNA synthesis inhibition. These data suggest that this method might be used to estimate the potential risk of chemical substances in differentiated mammalian cells, which are the most common cell type found in the human body" http://www.ncbi.nlm.nih.gov/pubmed/24646711 0 939 "C. Larsen, M. Ehrich, C. Driscoll and W. B. Gross" 1985 Aflatoxin-antioxidant effects on growth of young chicks Poult.Sci. 64 12 2287-2291 "Butylated hydroxytoluene (BHT), an antioxidant, was provided to chicks at 8 X, 30 X and 80 X the normal concentrations in their feed beginning at 1 day of age and continuing for the next 6 weeks. The ability of these birds to resist the adverse effects of dietary aflatoxin (3000 ppb, beginning Day 8) was measured by weight gain and feed efficiency over the 6-week period of study. Birds on aflatoxin-contaminated feed did not gain weight as rapidly or as efficiently as birds on uncontaminated feed. Depression of growth caused by aflatoxin was significantly less in birds given BHT than in those fed the diet not containing antioxidant" http://www.ncbi.nlm.nih.gov/pubmed/4095064 0 940 "S. Wilhelm, U. Buhlmann, D. F. Tolin, S. A. Meunier, G. D. Pearlson, H. E. Reese, P. Cannistraro, M. A. Jenike and S. L. Rauch" 2008 Augmentation of behavior therapy with D-cycloserine for obsessive-compulsive disorder Am.J.Psychiatry 165 3 335-341 "OBJECTIVE: This study examined whether d-cycloserine, a partial agonist at the N-methyl-D-aspartate (NMDA) glutamatergic receptor, enhances the efficacy of behavior therapy for obsessive-compulsive disorder (OCD). METHOD: A randomized, double-blind, placebo-controlled trial investigating D-cycloserine versus placebo augmentation of behavior therapy was conducted in 23 OCD patients. Patients first underwent a diagnostic interview and pretreatment evaluation, followed by a psychoeducational/treatment planning session. Then they received 10 behavior therapy sessions. Treatment sessions were conducted twice per week. One hour before each of the behavior therapy sessions, the participants received either D-cycloserine, 100 mg, or a placebo. RESULTS: Relative to the placebo group, the D-cycloserine group's OCD symptoms were significantly more improved at mid-treatment, and the D-cycloserine group's depressive symptoms were significantly more improved at posttreatment. CONCLUSIONS: These data provide support for the use of D-cycloserine as an augmentation of behavior therapy for OCD and extend findings in animals and other human disorders suggesting that behavior therapy acts by way of long-term potentiation of glutamatergic pathways and that the effects of behavior therapy are potentiated by an NMDA agonist" http://www.ncbi.nlm.nih.gov/pubmed/18245177 0 941 "K.-Y. Xu, Z.-F. Li and J. Gao" 2014 Effect of Shu-yu capsule on liver-QI stagnation rat model of depressive disorder based on the analysis of gene expression microarray technique "Chinese Pharmacological Bulletin.30 (3) ()(pp 437-438), 2014.Date of Publication: March 2014." 3 437-438 DO - http://dx.doi.org/10.3969/j.issn.1001-1978.2014.03.031 1 942 "U. Koster, I. Nolte and M. C. Michel" 2016 Preclinical research strategies for newly approved drugs as reflected in early publication patterns "Naunyn-Schmiedeberg's Archives of Pharmacology.389 (2) ()(pp 187-199), 2016.Date of Publication: 01 Feb 2016." 2 187-199 "The present study aimed to explore early publication patterns (i.e. up to 1 year after obtaining regulatory approval) for newly registered drugs. From the website of the US Food and Drug Administration, all newly approved drugs for 6 calendar years between 1991 and 2011 were identified. Non-clinical original publications for these compounds were retrieved from PubMed and their abstracts analysed for type of study and reported data. This yielded 170 compounds for which 1954 original non-clinical publications were identified, i.e. a median/mean of 5/11.5 publications per compound; however, number of publications per compound varied widely (0-90) and this variation exhibited a non-Gaussian distribution. The earliest non-clinical publication typically was published less than 5 years before regulatory approval and more than 5 years after filing of the primary patent, but some compounds exhibited notable deviations from this pattern. Publications most often reported on efficacy related to the target indication and on potential future indications, with fewer studies addressing mechanisms of action, potency, selectivity, pharmacokinetics and toxic effects. For most compounds, data at the cellular and in vivo level were published, with fewer reports on effects on isolated tissues and even fewer at the molecular level. The preferred species for cellular studies was human, whereas for in vivo studies, it was rats and mice. In 75 % of cases, the lead author of the publication came from an academic institution, and most studies were published in classic pharmacology journals. We conclude that number, timing and scope of early non-clinical publications on newly approved drugs exhibit major variance. Factors potentially associated with such variance are explored in a companion paper" DO - http://dx.doi.org/10.1007/s00210-015-1187-1 0 943 F. O. Risinger and R. A. Oakes 1995 Nicotine-induced conditioned place preference and conditioned place aversion in mice Pharmacol.Biochem.Behav. 51 02-Mar 457-461 "The motivational effects of nicotine were examined in mice using an unbiased place conditioning design. Swiss-Webster mice received four 15-min parings of a tactile stimulus with different doses of nicotine (0.25-2.0 mg/kg, IP). A different tactile stimulus was paired with saline injections. During conditioning, nicotine produced locomotor depression at the 2.0-mg/kg dose, with the greatest reduction in activity occurring during the latter part of each nicotine conditioning session. After four trials, nicotine produced increases in locomotor activity during the initial part of the nicotine sessions at doses 0.5 mg/kg or above. Upon testing, nicotine-induced conditioned place preference was noted in mice receiving 0.5 mg/kg nicotine. Conditioned place aversion was noted in mice receiving 2.0 mg/kg nicotine whereas doses of 0.25 and 1.0 mg/kg produced no conditioning. These results indicate that nicotine has dose-dependent rewarding and aversive effects measured in an unbiased place conditioning paradigm using mice" http://www.ncbi.nlm.nih.gov/pubmed/7667368 0 944 "W. Adidharma, G. Leach and L. Yan" 2012 Orexinergic signaling mediates light-induced neuronal activation in the dorsal raphe nucleus Neuroscience 220 201-207 "Seasonal affective disorder (SAD), a major depressive disorder recurring in the fall and winter, is caused by the reduction of light in the environment, and its depressive symptoms can be alleviated by bright light therapy. Both circadian and monoaminergic systems have been implicated in the etiology of SAD. However, the underlying neural pathways through which light regulates mood are not well understood. The present study utilized a diurnal rodent model, Arvicanthis niloticus, to explore the neural pathways mediating the effects of light on brain regions involved in mood regulation. Animals kept in constant darkness received light exposure in early subjective day, the time when light therapy is usually applied. The time course of neural activity following light exposure was assessed using Fos protein as a marker in the following brain regions/cells: the suprachiasmatic nucleus (SCN), orexin neurons in the perifornical-lateral hypothalamic area (PF-LHA) and the dorsal raphe nucleus (DRN). A light-induced increase in Fos expression was observed in orexin neurons and the DRN, but not in the SCN. As the DRN is densely innervated by orexinergic inputs, the involvement of orexinergic signaling in mediating the effects of light on the DRN was tested in the second experiment. The animals were injected with the selective orexin receptor type 1 (OXR1) antagonist SB-334867 prior to the light exposure. The treatment of SB-334867 significantly inhibited the Fos induction in the DRN. The results collectively point to the role of orexin neurons in mediating the effects of light on the mood-regulating monoaminergic areas, suggesting an orexinergic pathway that underlies light-dependent mood fluctuation and the beneficial effects of light therapy" http://www.ncbi.nlm.nih.gov/pubmed/22710065 1 945 W. L. Perry 1968 Indolealkylamines and behavior. Introductory remarks Adv.Pharmacol. 6 Pt B 209-211 http://www.ncbi.nlm.nih.gov/pubmed/5658324 0 946 "E. Chartoff, A. Sawyer, A. Rachlin, D. Potter, A. Pliakas and W. A. Carlezon" 2012 Blockade of kappa opioid receptors attenuates the development of depressive-like behaviors induced by cocaine withdrawal in rats Neuropharmacology 62 1 167-176 "Drug dependence is characterized by dysregulation of brain reward systems and increased sensitivity to stress. Chronic exposure to drugs of abuse is associated with increased expression of the neuropeptide dynorphin, the endogenous ligand for kappa opioid receptors (KORs). Activation of KORs causes depressive- and aversive-like responses in rodents, raising the possibility that drug-induced upregulation of dynorphin plays a role independence-associated negative states. Here we used ""binge"" exposure to cocaine (3 daily intraperitoneal injections of 15 mg/kg for 14 days) to examine the development of dependence-like behavior in the intracranial self-stimulation (ICSS) test and the forced swim test (FST). When rats were tested 1 h before their first scheduled injection of each day-a period of drug withdrawal corresponding to 20 h after their last injection on the previous day-there were exposure-dependent increases in ICSS thresholds (a putative indicator of anhedonia) and decreases in latencies to immobility in the FST (a putative indicator of behavioral despair). Administration of the long-lasting KOR antagonist norBNI (20 mug, intracerebroventricular) before the beginning of the binge regimen attenuated the development of cocaine withdrawal-induced anhedonia in the ICSS test. In contrast, administration of norBNI in the midst of the binge regimen had no effect on expression of cocaine withdrawal-induced anhedonia in the ICSS test, although it did attenuate despair-like behavior in the FST. These data suggest that blockade of KORs before exposure to a stressor (in this case, cocaine withdrawal or forced swimming) can attenuate the development of stress-induced behavioral adaptations. This article is part of a Special Issue entitled 'Anxiety and Depression'" http://www.ncbi.nlm.nih.gov/pubmed/21736885 1 947 C. Gardey-Levassort and P. Lechat 1974 Dose-dependent potentiation or inhibition by Ro4-4602 of 5-HTP hyperthermia in rabbits J.Pharm.Pharmacol. 26 4 278-279 http://www.ncbi.nlm.nih.gov/pubmed/4151387 0 948 L. Velisek 1998 Extracellular acidosis and high levels of carbon dioxide suppress synaptic transmission and prevent the induction of long-term potentiation in the CA1 region of rat hippocampal slices Hippocampus 8 1 24-32 "Long-term potentiation (LTP) is a long-lasting increase in synaptic strength induced by high frequency stimulation. LTP may participate in learning and memory formation. In many synaptic systems, LTP is dependent on intact function of N-methyl-D-aspartate (NMDA) receptors. NMDA receptors may be inhibited in different conditions involving also extracellular acidosis. A decrease in the extracellular pH accompanies many pathological states such as ischemia, hypoxia, and the CNS injury. The study was designed to determine whether comparable extracellular acid-base imbalances are able to interfere with the LTP induction. Hippocampal slices from adult rats were stimulated with high frequency stimulation (1 x 100 Hz/1 s) at Schaffer collateral-commissural synaptic system in the environment with different pH (6.7-7.8) and the field responses were recorded in CA1. Acidosis was achieved by supplying excessive CO2 or by HCO3-decrease in standard bicarbonate-containing buffer or by a direct acidification of the buffer containing Na-HEPES. Invariably, all forms of acidification suppressed the efficacy of normal, low frequency synaptic transmission and prevented the induction of LTP in a reversible manner; i.e., after reperfusion of the slices at pH 7.3 and restimulation, there was a return of synaptic transmission back to baseline, and a significant amount of LTP occurred. In contrast, alkalization to pH 7.8, although enhancing synaptic transmission efficacy, did not further increase the LTP magnitude compared to control environment with pH 7.3. The results suggest that extracellular acidosis associated with several pathological conditions in the CNS may significantly diminish the LTP induction, and thus negatively affect all physiological processes that utilize LTP" http://www.ncbi.nlm.nih.gov/pubmed/9519884 0 949 J. Leo 2005 Methylphenidate-induced neuropathology in the developing rat brain: Implications for humans "Ethical Human Psychology and Psychiatry.7 (2) ()(pp 107-110), 2005.Date of Publication: Summer 2005." 2 107-110 0 950 "R. Klopfleisch, O. Werner, E. Mundt, T. Harder and J. P. Teifke" 2006 Neurotropism of highly pathogenic avian influenza virus A/chicken/Indonesia/2003 (H5N1) in experimentally infected pigeons (Columbia livia f. domestica) Vet.Pathol. 43 4 463-470 "This investigation assessed the susceptibility of experimentally infected pigeons to the highly pathogenic avian influenza virus (HPAIV) H5N1 that caused recent outbreaks of avian influenza in birds and humans in several countries of Asia. For this purpose 14 pigeons were infected ocularly and nasally with 10(8) EID50 and clinical signs were recorded and compared with five chickens infected simultaneously as positive controls. The chickens demonstrated anorexia, depression, and 100% mortality within 2 days postinoculation. Three of the pigeons died after a history of depression and severe neurological signs consisting of paresis to paralysis, mild enteric hemorrhage, resulting in a mortality of 21%. Gross lesions in these pigeons were mild and inconsistent. Occasionally subcutaneous hyperemia and hemorrhage and cerebral malacia were observed. Microscopic lesions and detection of viral antigen were confined to the central nervous system of these pigeons. In the cerebrum and to a minor extent in the brain stem a lymphohistiocytic meningoencephalitis with disseminated neuronal and glial cell necrosis, perivascular cuffing, glial nodules, and in one bird focally extensive liquefactive necrosis could be observed. The remaining nine pigeons showed neither clinical signs nor gross or histological lesions associated with avian influenza, although seroconversion against H5 indicated that they had been infected. These results confirm that pigeons are susceptible to HPAIV A/chicken/Indonesia/2003 (H5N1) and that the disease is associated with the neurotropism of this virus. Although sentinel chickens and most pigeons did not develop disease, further experiments have to elucidate whether or not Columbiformes are involved in transmission and spread of highly pathogenic avian influenza" http://www.ncbi.nlm.nih.gov/pubmed/16846988 0 951 "D. I. Lubman, A. Cheetham and M. Yucel" 2015 Cannabis and adolescent brain development "Pharmacology and Therapeutics.148 ()(pp 1-16), 2015.Date of Publication: April 2015." Jan-16 "Heavy cannabis use has been frequently associated with increased rates of mental illness and cognitive impairment, particularly amongst adolescent users. However, the neurobiological processes that underlie these associations are still not well understood. In this review, we discuss the findings of studies examining the acute and chronic effects of cannabis use on the brain, with a particular focus on the impact of commencing use during adolescence. Accumulating evidence from both animal and human studies suggests that regular heavy use during this period is associated with more severe and persistent negative outcomes than use during adulthood, suggesting that the adolescent brain may be particularly vulnerable to the effects of cannabis exposure. As the endocannabinoid system plays an important role in brain development, it is plausible that prolonged use during adolescence results in a disruption in the normative neuromaturational processes that occur during this period. We identify synaptic pruning and white matter development as two processes that may be adversely impacted by cannabis exposure during adolescence. Potentially, alterations in these processes may underlie the cognitive and emotional deficits that have been associated with regular use commencing during adolescence" DO - http://dx.doi.org/10.1016/j.pharmthera.2014.11.009 0 952 "G. Biala, K. Pekala, A. Boguszewska-Czubara, A. Michalak, M. Kruk-Slomka and B. Budzynska" 2016 Behavioral and Biochemical Interaction Between Nicotine and Chronic Unpredictable Mild Stress in Mice Mol.Neurobiol. "Nicotine, the main component of tobacco smoke, exerts influence on mood, and contributes to physical and psychological dependence. Taking into account frequent concomitance of nicotine abuse and stress, we aimed to research behavioral and biochemical effects associated with nicotine administration in combination with chronic unpredictable mild stress (CUMS). Mice were submitted to the procedure of CUMS for 4 weeks, 2 h per day. Our results revealed that CUMS-exposed animals exhibited behavioral alteration like anxiety disorders in the elevated plus maze (EPM) test, the disturbances in memory in the passive avoidance (PA) test and depressive effects in the forced swim test (FST). Moreover, nicotine (0.05-0.5 mg/kg), after an acute or subchronic administration decreased stress-induced depression- and anxiety-like effect as well as memory deficit. Administration of metyrapone (50 mg/kg), a glucocorticosteroid antagonist, alleviated the depressive effect induced by the CUMS. The biochemical experiments showed decreased values of the total antioxidant status (TAS), activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) with simultaneously increased in malondialdehyde (MDA) concentration in mice submitted to the CUMS. The same effects were observed after an acute and subchronic nicotine administration within all examined brain structures (i.e., hippocampus, cortex, and cerebellum) and in the whole brain in non-stressed and stressed mice confirming pro-oxidative effect of nicotine. Our study contributes to the understanding of behavioral and biochemical mechanisms involved in stress-induced disorders such as depression, anxiety and memory disturbances as well as dual nicotine-stress interactions on the basis of the development of nicotine dependence" http://www.ncbi.nlm.nih.gov/pubmed/26780460 1 953 "R. D. Le, L. Juvin, T. Boutin, F. Auclair and R. Dubuc" 2010 A neuronal substrate for a state-dependent modulation of sensory inputs in the brainstem Eur.J.Neurosci. 32 1 53-59 "Central networks modulate sensory transmission during motor behavior. Sensory inputs may thus have distinct impacts according to the state of activity of the central networks. Using an in-vitro isolated lamprey brainstem preparation, we investigated whether a brainstem locomotor center, the mesencephalic locomotor region (MLR), modulates sensory transmission. The synaptic responses of brainstem reticulospinal (RS) cells to electrical stimulation of the sensory trigeminal nerve were recorded before and after electrical stimulation of the MLR. The RS cell synaptic responses were significantly reduced by MLR stimulation and the reduction of the response increased with the stimulation intensity of the MLR. Bath perfusion of atropine prevented the depression of sensory transmission, indicating that muscarinic receptor activation is involved. Previous studies have shown that, upon stimulation of the MLR, behavioral activity switches from a resting state to an active-locomotor state. Therefore, our results suggest that a state-dependent modulation of sensory transmission to RS cells occurs in the behavioral context of locomotion and that muscarinic inputs from the MLR are involved" http://www.ncbi.nlm.nih.gov/pubmed/20576031 0 954 "P. F. Anderson, D. M. Jackson, G. B. Chesher and R. Malor" 1975 "Tolerance to the effect of delta9-tetrahydrocannabinol in mice on intestinal motility, temperature and locomotor activity" Psychopharmacologia. 43 1 31-36 "The onset and duration of tolerance to three effects of delta9-tetrahydrocannabinol (delta9-THC) given orally to mice were compared. The effects of delta9-THC studied were: hypothermia, the depression of intestinal motility and the effect on spontaneous locomotor activity. When mice were dosed and tested at 24 hrs intervals it was apparent that tolerance was complete to its hypothermic and locomotor depressant effects after the first doses and to depression of intestinal motility after the fourth dose. Duration of tolerance also differed so that the normal hypothermic response had returned after 12 dose-free days, but not after 5 drug-free days; the effect on locomotor activity had returned within 4 days; and apparent partial tolerance to the depressant effect of an acute challenging dose of delta9-THC on intestinal motility still existed after 19 dose-free days. It is apparent that the time of onset and the duration of tolerance to delta9-THC in mice showed a different pattern in the three parameters studied. It seems unlikely therefore that any one mechanism, such as metabolic tolerance, explains all the results observed and that several mechanisms should be explored to explain the phenomenon of tolerance to delta9-THC" http://www.ncbi.nlm.nih.gov/pubmed/1161992 0 955 "K. Takahama, T. Miyata and Y. Kase" 1977 "Pharmacology of N methyl 9, 10 ethanoanthracene 9(10H) methylamine hydrochloride (benzoctamine), a new psychotropic agent. Part 1. Effects on the central nervous system" "Folia Pharmacologica Japonica.73 (2) ()(pp 151-176), 1977.Date of Publication: 1977." 2 151-176 "Tranquilizing and other related actions of benzoctamine (Benz), N-methyl-9, 10-ethanoanthracene-9(10 H)-methylamine hydrochloride were studied in comparison with those of chlorpromazine (CPZ) and chlordiazepoxide (CDP). Toxic symptoms in mice and rats were due to CNS depression. This agent was 4.2 times (s.c.) and 6.1 times (i.p.) as toxic as CDP in mice, 3.8 times (i.p.) more toxic than CDP in rats; 1.9 times, equally and about half as toxic as CPZ, respectively. A potent muscle relaxant action was demonstrated in mice, and a decerebrate rigidity in cats was depressed with Benz. Tonic extension of mice induced by electroshock was suppressed but chemo-shock was not inhibited. Discriminative and non-discriminative conditioned avoidance responses were depressed in rats. Benz suppressed both fighting behavior in mice and hyperemotionality in rats due to olfactory bulb ablation or long-term isolation; the effects were 1/4 to 1/2 of those of CPZ; 4-5 times and 1/2 to 1 time as potent as those of CDP in suppressing effects on fighting behavior and hyperemotionality, respectively. Hyperactivity caused by amphetamine or morphine was reduced, but amphetamine hyperactivity was facilitated in small doses. Benz did not antagonize hypothermia nor ptosis caused by reserpine in rats and apomorphine-induced vomiting was not inhibited in dogs. In small doses, depressing EEG patterns appeared at the limbic system; in large doses, the depression extended to the neocortex and mid-brain reticular formation. EEG arousal response was also depressed. Generally speaking, the effects of Benz on EEG were similar to those of CDP in small doses and those of CPZ in large doses. Thus Benz is a new type of tranquilizer with a potent muscle-relaxant action, and cannot be categorized with major or minor tranquilizers" 0 956 M. A. Medina 1967 Inhibition of D-aspartate uptake in rat cerebral cortex slices by hydrazines. SAM-TR-67-115 Tech.Rep.SAM.-TR. 01-May http://www.ncbi.nlm.nih.gov/pubmed/5301196 0 957 "F. E. SOUTH, Jr. and S. F. COOK" 1954 "Argon, xenon, hydrogen, and the oxygen consumption and glycolysis of mouse tissue slices" J.Gen.Physiol 37 3 335-341 "The effects of xenon, argon, and hydrogen on the aerobic and anaerobic metabolism of mouse liver, brain, and sarcoma slices have been investigated. Xenon was found to alter the rates of metabolism of these tissues in a manner almost identical with helium. The gas increased the rate of oxygen consumption in all three tissues and significantly depressed that of anaerobic glycolysis in brain and liver. The depression of glycolysis in sarcoma was less pronounced and not highly significant. Although both the magnitude and statistical significance of the effects observed with argon were much smaller, there was a seeming adherence to the general pattern established by xenon and helium. Hydrogen while remaining essentially ineffective insofar as oxygen uptake was concerned, depressed glycolysis in both liver and brain slices but did not significantly affect sarcoma slices. The following points are stressed in the Discussion: (1) the magnitude and direction of effects exerted by helium, argon, xenon, hydrogen, and nitrogen do not conform with the relative values of molecular weight, density, and solubility of these gases; (2) the effect of these gases on tissue metabolism does not necessarily parallel that exerted upon the whole organism" http://www.ncbi.nlm.nih.gov/pubmed/13118104 0 958 "M. Z. Khan, J. Szarek, A. Koncicki and Krasnodebska-Dept" 1994 Oral administration of monensin and lead to broiler chicks: effects on haematological and biochemical parameters Acta Vet.Hung. 42 1 111-120 "Monensin and lead were administered separately or concurrently at different toxic doses to broiler chicks. Administration of lead alone did not result in a significant depression of haematological parameters. Administration of higher levels of monensin caused a reduction in haematocrit and an increase in blood serum levels of alanine aminotransferase, aspartate aminotransferase and cholesterol. Concurrent administration of monensin and lead caused a severe depression of haematological profiles which indicated the existence of an interaction between the two substances. It was concluded that concurrent administration of monensin and lead potentiated the toxic effects of each other" http://www.ncbi.nlm.nih.gov/pubmed/7810394 0 959 E. L. Golubeva and S. N. Khayutin 1968 Interrelationships between the cortex and subcortical brain structures in the reaction to hypoxia "Fiziol.Zh.Sechenov.54 (8) ()(pp 884-892), 1968.Date of Publication: 1968." 8 884-892 "In experiments on rabbits under urethane anesthesia, studies were made of the effect of a short term inhalation of hypoxic mixtures on the electrical activity of the cortex and the subcortical structures. Two types of reaction of the CNS to hypoxia were established. Inhalation of a gaseous mixture consisting of 7.57. O2 in nitrogen increases both the frequency and the amplitude of respiratory movements and evokes a regular rhythm of 4.7/sec (stress rhythm) in the reticular formation of the midbrain, hippocampus, nonspecific thalamic nuclei, the posterior hypothalamus as well as in the parietal, temporal and occipital parts of the cortex. Desynchronization of electrical oscillations or stress rhythm may be observed in the sensory motor zone. EEG changes in subcortical structures precede those in the cortex. Inhalation of a mixture of 5 O2 in nitrogen evokes slow, high amplitude polymorphous waves in the cortex and later on in the subcortical structures (depressive reaction). In spite of identical EEG manifestations, painful and hypoxic reactions of the CNS exhibit a different biological specificity" 0 960 "R. Hasumuma, K. Kawaguchi, S. Kikuchi, T. Sugiyama and Y. Kumazawa" 2007 Effects of isoflavones and soybeans fermented with Bacillus subtilis on lipopolysaccharide-induced production of tumor necrosis factor-alpha and fibrinolysis in vivo Immunopharmacol.Immunotoxicol. 29 2 323-333 "The effects of isoflavones and of a derivative of soybeans fermented with Bacillus subtilis, designated Nattoesse, on the lipopolysaccharide (LPS)-induced production of tumor necrosis factor-alpha (TNF-alpha) and fibrinolysis were investigated in vivo. The dietary supplement Nattoesse contains several isoflavones. Therefore, we examined the effects of individual isoflavones (daidzein, daidzin, genistein, and genistin) on the LPS-induced production of TNF-alpha. Intraperitoneal injections of daidzein, daidzin, and genistin (but not of genistein before a challenge with LPS) resulted in significant depression of serum levels of TNF-alpha in mice. Daidzein had the strongest activity in this assay. Oral administration of daidzein to mice also had a significant suppressive effect, as compared with that of the Citrus flavanone naringin. In galactosamine-sensitized mice, by contrast, the suppression of LPS-induced lethal shock by daidzein was very weak. Nattoesse did not inhibit the production of TNF-alpha nor did it prevent lethal shock. However, oral administration of Nattoesse to mice significantly suppressed LPS-induced increases in scores of the fibrin degradation product, and the effect was both dose- and time-dependent. Thus, it appears that Nattoesse has fibrinolytic activity during LPS-induced circulatory failure" http://www.ncbi.nlm.nih.gov/pubmed/17849275 0 961 "N. E. Klow, O. Hevroy, E. Mortensen, K. Dale and O. D. Mjos" 1990 Low osmolality contrast media and metabolic changes in the myocardium during free and reduced coronary flow in the dog Invest Radiol. 25 2 127-132 "The authors assessed whether intracoronary injection of low osmolality contrast media induces metabolic and electrocardiographic changes consistent with myocardial ischemia in anesthetized dogs. Ioxaglate and iohexol were injected into the left main coronary artery (eight dogs) and into a carotid-coronary artery shunt (eight dogs), during free coronary flow and during 50% flow reduction. Blood samples were obtained simultaneously from a femoral artery and from a small cardiac vein draining the contrast perfused area. Contrast media had no immediate or late effects on lactate balance during free or reduced flow. Early depression of the ST segment in epicardial ECG did not reflect ischemia. The authors conclude that the two low-osmolality contrast media, iohexol and ioxaglate, did not induce ischemic changes in the myocardium" http://www.ncbi.nlm.nih.gov/pubmed/2312248 0 962 "K. Deuchi, O. Kanauchi, Y. Imasato and E. Kobayashi" 1995 Effect of the viscosity or deacetylation degree of chitosan on fecal fat excreted from rats fed on a high-fat diet Biosci.Biotechnol.Biochem. 59 5 781-785 "Several chitosan preparations, either with a comparable degree of deacetylation but differing viscosity or with comparable viscosity but a differing degree of deacetylation, were examined for their effect on the fecal fat excreted from rats fed on a high-fat diet. As the viscosity or deacetylation degree of a chitosan preparation increased, the more its effect on the apparent fat digestibility by rats became conspicuous. A supplement of ascorbic acid to each chitosan diets resulted in a significant depression of fat digestion and absorption in the lumen. The chitosan intake caused a higher level of fat to be excreted in the feces of the corn oil-receiving rats than the lard-receiving ones, although the effect was strong with both diet groups" http://www.ncbi.nlm.nih.gov/pubmed/7787292 0 963 "P. Y. Pan, Q. Cai, L. Lin, P. H. Lu, S. Duan and Z. H. Sheng" 2005 SNAP-29-mediated modulation of synaptic transmission in cultured hippocampal neurons J.Biol.Chem. 280 27 25769-25779 "Identifying the molecules that regulate both the recycling of synaptic vesicles and the SNARE components required for fusion is critical for elucidating the molecular mechanisms underlying synaptic plasticity. SNAP-29 was initially isolated as a syntaxin-binding and ubiquitously expressed protein. Previous studies have suggested that SNAP-29 inhibits SNARE complex disassembly, thereby reducing synaptic transmission in cultured superior cervical ganglion neurons in an activity-dependent manner. However, the role of SNAP-29 in regulating synaptic vesicle recycling and short-term plasticity in the central nervous system remains unclear. In the present study, we examined the effect of SNAP-29 on synaptic transmission in cultured hippocampal neurons by dual patch clamp whole-cell recording, FM dye imaging, and immunocytochemistry. Our results demonstrated that exogenous expression of SNAP-29 in presynaptic neurons significantly decreased the efficiency of synaptic transmission after repetitive firing within a few minutes under low and moderate frequency stimulations (0.1 and 1 Hz). In contrast, SNAP-29 did not affect the density of synapses and basal synaptic transmission. Whereas neurotransmitter release was unaffected during intensive stimulation, recovery after synaptic depression was impaired by SNAP-29. Furthermore, knockdown of SNAP-29 expression in neurons by small interfering RNA increased the efficiency of synaptic transmission during repetitive firing. These findings suggest that SNAP-29 acts as a negative modulator for neurotransmitter release, probably by slowing recycling of the SNARE-based fusion machinery and synaptic vesicle turnover" http://www.ncbi.nlm.nih.gov/pubmed/15890653 0 964 "A. S. Saratikov, L. P. Alekseeva, V. P. Agarkova and M. I. Naidenova" 1978 [Effect of lithium chloride on the excitability of the subcortical structures of the rabbit brain] Farmakol.Toksikol. 41 3 261-263 "Lithium chloride microinjections in doses of 100 mkg/mkl into the brain structures of rabbits produce a depressive effect on the subcortical formations. The drug brings down the excitability of the hippocampus, caudate nucleus, mesencephalic reticular formations, thalamus and hypothalamus, raising the excitability of the amygdalae" http://www.ncbi.nlm.nih.gov/pubmed/658370 0 965 "N. N. Petrashevskaia, A. P. Malykhina, A. V. Sidorov and L. M. Lobanok" 1999 [The effect of stimulation of the adrenergic receptors on the frequency depression of the temporal parameters of the action potential in the right atrium of rats] Ross.Fiziol.Zh.Im I.M.Sechenova 85 4 554-560 "At a stimulation rate of 1 Hz, activation of alpha-adrenoreceptors prolonged the AP duration at 10%, 50%, and 90% repolarisation at 10(-7), 10(-6) M in the rat isolated right atria, but shortened it at a higher concentration of 10(-5) M. The frequency-induced depression of the AP duration became more evident in cardiomyocytes stimulated by 10(-7), 10(-6) M and less obvious at 10(-5) M of alpha-adrenoagonist. Activation of alpha-adrenoreceptors by isoprenalin shortened the AP duration and enhanced the stimulation-rate-dependent changes in the atrial AP configuration" http://www.ncbi.nlm.nih.gov/pubmed/10513390 0 966 "C. G. Jolivalt, M. Rodriguez, J. Wahren and N. A. Calcutt" 2015 Efficacy of a long-acting C-peptide analogue against peripheral neuropathy in streptozotocin-diabetic mice Diabetes Obes.Metab 17 8 781-788 "AIMS: To investigate the efficacy of a pegylated C-peptide (Peg-C-peptide) against indices of peripheral neuropathy in a mouse model of type 1 diabetes and to compare efficacy of this C-peptide analogue against that of the native molecule. METHODS: C57Bl/6 mice were injected with two consecutive doses of streptozotocin (STZ) to induce type 1 diabetes. Mice were treated twice daily with native C-peptide [0.4-1.3 mg/kg subcutaneously (s.c.)] or twice weekly with Peg-C-peptide (0.1-1.3 mg/kg s.c.) for 20 weeks. Motor and sensory nerve conduction velocities, thermal and tactile responses and rate dependent H-wave depression were assessed after 20 weeks of diabetes. Foot skin intraepidermal fibres and corneal nerves were counted, and sciatic nerve substance P and plasma C-peptide levels were also determined. RESULTS: After 5 months of STZ-induced diabetes, mice exhibited significant motor and sensory nerve conduction slowing, thermal hypoalgesia, tactile allodynia and attenuation of rate-dependent depression of the H reflex. These functional disorders were accompanied by nerve substance P depletion but not loss of small sensory fibres in the hind paw epidermis or the cornea. The efficacy of twice-daily treatment with native C-peptide in preventing these disorders was matched or exceeded by twice-weekly treatment with Peg-C-peptide. Both native and Peg-C-peptide also increased corneal nerve occupancy in the sub-basal nerve plexus of control rats. CONCLUSIONS: These data identify actions of C-peptide against novel and clinically pertinent aspects of diabetic neuropathy in mice and also establish Peg-C-peptide as a long-acting therapeutic method of potential clinical value" http://www.ncbi.nlm.nih.gov/pubmed/25904006 0 967 "J. G. Eales, J. M. McLeese, J. A. Holmes and J. H. Youson" 2000 "Changes in intestinal and hepatic thyroid hormone deiodination during spontaneous metamorphosis of the sea lamprey, Petromyzon marinus" J.Exp.Zool. 286 3 305-312 "We measured microsomal low-K(m) outer-ring deiodination (ORD) and inner-ring deiodination (IRD) activities for thyroxine (T(4)) and 3, 5,3'-triiodothyronine (T(3)) in intestine and liver in nonmetamorphosing (undersized) larvae, immediately premetamorphic larvae, animals in stages 1-7 of metamorphosis, and immediately postmetamorphic sea lampreys (Petromyzon marinus). For intestine: T(4)ORD activity was relatively low in nonmetamorphosing larvae, increased in premetamorphic individuals, was highest in stages 1 and 2 and was very low during stages 3-7; T(4)IRD activity was negligible until stage 3 but increased 4.7-fold through stages 3 to 7 such that T(4)IRD activity was 14 times T(4)ORD activity at stage 6; T(3)ORD activity was undetectable; T(3)IRD activity was not measured through stages 3-7 but correlated with T(4)IRD activity at other stages. For liver: deiodination was only measured up to stage 2 and in postmetamorphic animals; in contrast to intestine, T(4)ORD activity fell to low levels at stage 2 and was low during postmetamorphosis; T(4)IRD and T(3)IRD activities were very low and uninfluenced by developmental stage; T(3)ORD activity was undetectable. We conclude that (1) deiodination activity is usually much higher in intestine than in liver, (2) intestinal ORD and IRD activities change reciprocally so that ORD predominates in early metamorphosis but IRD predominates in mid and late metamorphosis, and (3) changes in intestinal deiodination may contribute to the characteristic depression of plasma T(4) and T(3) levels during spontaneous metamorphosis. J. Exp. Zool. 286:305-312, 2000" http://www.ncbi.nlm.nih.gov/pubmed/10653969 0 968 "C. Blake, K. D. R. Setchell, T. D. Lund and E. D. Lephart" 2010 Effect of soy diets and equol on female depressive behaviors and body weight in long-evans rats "FASEB Journal.Conference: Experimental Biology 2010, EB Anaheim, CA United States.Conference Start: 20100424 Conference End: 20100428.Conference Publication: (var.pagings).24 (no pagination), 2010.Date of Publication: April, 2010." var.pagings "In five different studies we examined the effect of soy-containing diets and equol injections on depression, serotonin levels, weight gain and white adipose tissue (WAT) deposition of female Long-Evans rats in various stages of life. In these experiments the rats were intact, ovariectomized or experienced natural ovarian failure (NOF). The results of all the experiments will be presented, but experiment 5 is covered here due to space limitations. From conception the female rats were exposed to either: a) a soy-rich (Phyto-600) or b) low-soy diet (Phyto-low). After approximately 290 days all the rats experienced NOF. At 330 days-old the animals were examined in the Porsolt forced swim test (PFST). One month later the animals were again tested in the PFST [after the animals fed the Phyto-low diet were injected with equol (@ 5 mg/kg/day) for one week]. At the first PFST, serotonin levels and mobility were decreased in the Phyto-low fed animals compared to the Phyto-600 animals. After the equol injections the differences in the measured parameters by treatment disappeared. Equol increased mobility in aged-female rats that had undergone NOF and increased serotonin levels comparable to Phyto-600 fed animals. In all the studies, animals fed a soy-rich diet decreased body weight and adipose tissue deposition vs. a low-soy diet" 0 969 K. D. Lafferty 2005 Look what the cat dragged in: Do parasites contribute to human cultural diversity? "Behavioural Processes.68 (3 SPEC.ISS.) ()(pp 279-282), 2005.Date of Publication: 31 Mar 2005." 3 Spec Iss 279-282 DO - http://dx.doi.org/10.1016/j.beproc.2004.08.019 0 970 "Z. Cui, R. Feng, S. Jacobs, Y. Duan, H. Wang, X. Cao and J. Z. Tsien" 2013 Increased NR2A:NR2B ratio compresses long-term depression range and constrains long-term memory Sci.Rep. 3 1036 "The NR2A:NR2B subunit ratio of the NMDA receptors is widely known to increase in the brain from postnatal development to sexual maturity and to aging, yet its impact on memory function remains speculative. We have generated forebrain-specific NR2A overexpression transgenic mice and show that these mice had normal basic behaviors and short-term memory, but exhibited broad long-term memory deficits as revealed by several behavioral paradigms. Surprisingly, increased NR2A expression did not affect 1-Hz-induced long-term depression (LTD) or 100 Hz-induced long-term potentiation (LTP) in the CA1 region of the hippocampus, but selectively abolished LTD responses in the 3-5 Hz frequency range. Our results demonstrate that the increased NR2A:NR2B ratio is a critical genetic factor in constraining long-term memory in the adult brain. We postulate that LTD-like process underlies post-learning information sculpting, a novel and essential consolidation step in transforming new information into long-term memory" http://www.ncbi.nlm.nih.gov/pubmed/23301157 0 971 "P. Calabresi, A. Pisani, N. B. Mercuri and G. Bernardi" 1993 Lithium treatment blocks long-term synaptic depression in the striatum Neuron 10 5 955-962 "We have studied the effect of acute and chronic lithium treatment on the activity of striatal neurons recorded from corticostriatal slices. Under control conditions, tetanic stimulation of glutamatergic corticostriatal terminals caused long-term depression (LTD) of excitatory synaptic potentials. Acute lithium treatment did not affect the peak of the induction phase, but it reduced the following phases of LTD. LTD was completely blocked in slices obtained from rats chronically injected with LiCl. Lithium treatment failed to affect the intrinsic membrane properties of striatal neurons and the presynaptic inhibitory effects of carbachol and t-ACPD. We suggest that the lithium-induced blockade of LTD may contribute to the therapeutic action of lithium salts in mania and depression" http://www.ncbi.nlm.nih.gov/pubmed/8494646 0 972 C. R. Hopkins 2010 ACS chemical neuroscience molecule spotlight on Valdoxen ACS Chem.Neurosci. 1 12 772-773 A new and novel non-SSRI potential treatment option for major depressive disorders is Valdoxen (agomelatine) which is currently in phase III clinical studies. Valdoxen is a norepinephrine disinhibitor (NNDI) and is also an antagonist of the 5-HT(2C) receptor http://www.ncbi.nlm.nih.gov/pubmed/22778814 0 973 K. Prasannan and P. A. Kurup 1973 Effect of long-term administration of tolbuamide & phenformin to normal rats on the metabolism of glycosaminoglycans L-glutamine: D-fructose-6-phosphate aminotransferase activity of the liver & aorta Indian J.Biochem.Biophys. 10 2 141-142 http://www.ncbi.nlm.nih.gov/pubmed/4779279 0 974 "C. E. Sortwell, F. Petty, G. Kramer and J. Sagen" 1994 In vivo release of catecholamines from xenogeneic chromaffin cell grafts with antidepressive activity Exp.Neurol. 130 1 01-Aug "Previous studies in our laboratory have demonstrated that allografts of adrenal medullary tissue and xenografts of isolated bovine chromaffin cells to the rat frontal cortex can increase antidepressive activity in two separate animal models. Biochemical and pharmacological evidence suggest that the most likely mechanism of these antidepressive effects is via local release of catecholamines into the surrounding cortical parenchyma. The aim of the present study was to directly characterize the antidepressive mechanism of chromaffin cell xenografts by utilizing in vivo microdialysis to measure extracellular catecholamine levels from bovine chromaffin cell and control implanted rat frontal cortex. Following transplantation, only bovine chromaffin cell grafted rats displayed significant increases in antidepressive activity, as assessed by the forced swimming test, compared to rats with grafts of bovine adrenal medullary fibroblasts or nontransplanted rats. In vivo microdialysis results revealed remarkably elevated levels of epinephrine (EPI) and norepinephrine (NE), but not dopamine, in dialysates from bovine chromaffin cell-transplanted frontal cortex. The most likely source of these enhanced EPI and NE levels is the grafted xenogeneic chromaffin cells. The results of this study directly demonstrate that xenografts of bovine chromaffin cells to the rat frontal cortex provide a releasable pool of catecholamines for antidepressive activity" http://www.ncbi.nlm.nih.gov/pubmed/7821384 0 975 "R. E. See, E. D. Levin and G. D. Ellison" 1988 Characteristics of oral movements in rats during and after chronic haloperidol and fluphenazine administration Psychopharmacology (Berl) 94 3 421-427 "Rats were chronically administered either haloperidol (HAL) or fluphenazine (FLU) via depot injections for 8 months, given these same drugs in their drinking water for the next 2 months, and then withdrawn from the drugs. Throughout the experiment the animals were tested repeatedly in an enclosed tube using a computerized device which measured computer-scored movelets (CSMs) and, in the latter half of the experiment, were also scored by a human observer in the tube, as well as in an open cage, for observed oral movements (OMs). In the tube, the animals in both neuroleptic-treated groups showed initial decreases in the number of CSMs and made sluggish CSMs; these effects were generally larger in the FLU animals. After 6 months of chronic neuroleptics, the HAL-treated animals showed increased oral movements, both as reported by the human observer and in CSMs of all amplitudes, and this effect increased upon drug withdrawal. FLU-treated animals showed a more persistent depression of both OMs and CSMs of large amplitudes. However, the behavior most characteristic of both neuroleptic-treated groups was the gradual development of increases in CSMs of the smallest amplitudes measurable. A different pattern was observed in the open cage test, where both neuroleptic groups showed significant increases in vacuous OMs during drug administration which rapidly became attenuated upon drug withdrawal. These results indicate a complex syndrome of oral activity in the drugged animals which changed over time. The measure of oral activity which most clearly showed the time-course for late-onset changes in oral activity was CSMs of the smallest amplitudes" http://www.ncbi.nlm.nih.gov/pubmed/3128820 0 976 "G. Muzio, B. Marengo, R. Salvo, A. Semeraro, R. A. Canuto and L. Tessitore" 1999 Liver cancer is induced by a subnecrogenic dose of DENA when associated with fasting/refeeding: role of glutathione-transferase and lipid peroxidation Free Radic.Biol.Med. 26 09-Oct 1314-1320 "In previous studies, we reported that fasting/refeeding has a role in sustaining the initiation of liver cancer by a subnecrogenic (noninitiating) dose of diethylnitrosamine (DENA). This research investigated whether the metabolic alterations imposed by fasting/refeeding provide an imbalance between the generation of carcinogenic molecules and the scavenger defense mechanisms in rat liver. Metabolism of DENA, levels of reduced glutathione (GSH) and GSH transferase (GST) activity, as well as basal and stimulated malondialdehyde (MDA) production, were examined. Rats fasted for 4 days showed a decrease in the liver levels of GSH, GST activity, monounsaturated fatty acids and % of labeled nuclei. After 1 day of refeeding, at which point DENA was administered, the levels of GSH recovered, GST activity remained below control values, basal and stimulated MDA production and content of total polyunsaturated fatty acids in liver phospholipids decreased. One day after DENA treatment, MDA production further decreased, although the % of labeled nuclei increased. No significant changes in the content of arachidonic acid, the main target of peroxidation, were observed at any time. The results indicated that the induction of the hepatocellular carcinoma was associated with a depression of GST activity and lipid peroxidation when rats were given 20 mg/kg of DENA after 1 day of refeeding after 4-day fasting" http://www.ncbi.nlm.nih.gov/pubmed/10381205 0 977 "H. Lee, M. Ohno, S. Ohta and T. Mikami" 2013 Regular moderate or intense exercise prevents depression-like behavior without change of hippocampal tryptophan content in chronically tryptophan-deficient and stressed mice PLoS.One. 8 7 e66996 "Regular exercise has an antidepressant effect in human subjects. Studies using animals have suggested that the antidepressant effect of exercise is attributable to an increase of brain 5-hydroxytryptamine (5-HT); however, the precise mechanism underlying the antidepressant action via exercise is unclear. In contrast, the effect of 5-HT on antidepressant activity has not been clarified, in part because the therapeutic response to antidepressant drugs has a time lag in spite of the rapid increase of brain 5-HT upon administration of these drugs. This study was designed to investigate the contribution of brain 5-HT to the antidepressant effect of exercise. Mice were fed a tryptophan-deficient diet and stressed using chronic unpredictable stress (CUS) for 4 weeks with or without the performance of either moderate or intense exercise on a treadmill 3 days per week. The findings demonstrated that the onset of depression-like behavior is attributable not to chronic reduction of 5-HT but to chronic stress. Regular exercise, whether moderate or intense, prevents depression-like behavior with an improvement of adult hippocampal cell proliferation and survival and without the recovery of 5-HT. Concomitantly, the mice that exercised showed increased hippocampal noradrenaline. Regular exercise prevents the impairment of not long-term memory but short-term memory in a 5-HT-reduced state. Together, these findings suggest that: (1) chronic reduction of brain 5-HT may not contribute to the onset of depression-like behavior; (2) regular exercise, whether moderate or intense, prevents the onset of chronic stress-induced depression-like behavior independent of brain 5-HT and dependent on brain adrenaline; and (3) regular exercise prevents chronic tryptophan reduction-induced impairment of not long-term but short-term memory" http://www.ncbi.nlm.nih.gov/pubmed/23861751 1 978 "Y. Kim, B. Morath, C. Hu, L. K. Byrne, S. L. Sutor, M. A. Frye and S. J. Tye" 2016 Antidepressant actions of lateral habenula deep brain stimulation differentially correlate with CaMKII/GSK3/AMPK signaling locally and in the infralimbic cortex Behav.Brain Res. 306 170-177 "High frequency deep brain stimulation (DBS) of the lateral habenula (LHb) reduces symptoms of depression in severely treatment-resistant individuals. Despite the observed therapeutic effects, the molecular underpinnings of DBS are poorly understood. This study investigated the efficacy of high frequency LHb DBS (130Hz; 200muA; 90mus) in an animal model of tricyclic antidepressant resistance. Further, we reported DBS mediated changes in Ca(2+)/calmodulin-dependent protein kinase (CaMKIIalpha/beta), glycogen synthase kinase 3 (GSK3alpha/beta) and AMP-activated protein kinase (AMPK) both locally and in the infralimbic cortex (IL). Protein expressions were then correlated to immobility time during the forced swim test (FST). Antidepressant actions were quantified via FST. Treatment groups comprised of animals treated with adrenocorticotropic hormone alone (ACTH; 100mug/day, 14days, n=7), ACTH with active DBS (n=7), sham DBS (n=8), surgery only (n=8) or control (n=8). Active DBS significantly reduced immobility in ACTH-treated animals (p<0.05). For this group, western blot results demonstrated phosphorylation status of LHb CaMKIIalpha/beta and GSK3alpha/beta significantly correlated to immobility time in the FST. Concurrently, we observed phosphorylation status of CaMKIIalpha/beta, GSK3alpha/beta, and AMPK in the IL to be negatively correlated with antidepressant actions of DBS. These findings suggest that activity dependent phosphorylation of CaMKIIalpha/beta, and GSK3alpha/beta in the LHb together with the downregulation of CaMKIIalpha/beta, GSK3alpha/beta, and AMPK in the IL, contribute to the antidepressant actions of DBS" http://www.ncbi.nlm.nih.gov/pubmed/26956153 1 979 "A. N. van den Pol, V. Cao and A. B. Belousov" 1996 Dopamine enhancement and depression of glutamate-regulated calcium and electrical activity in hypothalamic neurons J.Neurophysiol. 76 6 3934-3948 "1. The neurotransmitter dopamine is found throughout the hypothalamus both in cell bodies and in axons originating from intra- and extrahypothalamic sources. To study the mechanisms of action of dopamine on cultured rat hypothalamic neurons, particularly in relation to Ca2+ regulation, we used Ca2+ digital imaging with fura-2 and whole cell patch-clamp recording. We focused on the modulatory actions of dopamine on glutamate. 2. Dopamine administration had little or no independent effect on intracellular Ca2+. However, in the presence of tetrodotoxin to block action potentials and action-potential-dependent transmitter release, dopamine (10 microM for 2-3 min) caused an increase in glutamate-evoked Ca2+ rises in 22% of 64 neurons and depressed glutamate-evoked Ca2+ rises in an equal number of neurons. Shorter exposure to dopamine reduced the number of responding cells. 3. Dopamine application to neurons with an elevated Ca2+ due to synaptic release of glutamate (in the absence of tetrodotoxin) generally caused a decrease in Ca2+ levels (40% of 106 neurons), but sometimes increased cytosolic Ca2+ (10% of 106 neurons). That dopamine influenced cells differently in conditions of spontaneous activity compared with evoked activity may be due to dopamine effects on presynaptic receptors detected under conditions of ongoing synaptic release of glutamate. 4. Dopamine modulation of glutamate responses was detected at early stages of neuronal development (embryonic day 18 after 2 days in vitro) and also after 60 days in vitro. 5. The D1, D2, and D3 dopamine receptor agonists SKF38393, quinpirole, and 7-OH-DPAT (+/- 7 hydroxy-dipropylaminotetralin) caused a reduction in Ca2+ levels raised by endogenous glutamate release or evoked by exogenous glutamate application. 6. To block the actions of dopamine released by hypothalamic neurons, D1 and D2 dopamine receptor antagonists were used. As with dopamine, dopamine antagonists had no effect on intracellular Ca2+ during glutamate receptor blockade. In the absence of glutamate receptor block, the D1 antagonist SCH23390 (1 microM) reduced Ca2+ in responding cells; in contrast, the D2 antagonist eticlopride (1 microM) generated a delayed increase in Ca2+ levels. 7. Dopamine is known to activate second messengers through G proteins independent of changes in membrane potential or input resistance. Whole cell recording was used to demonstrate that, parallel to the modulation of Ca2+, dopamine exerted a dramatic change in glutamate-mediated electrical activity, generally depressing activity and hyperpolarizing the membrane potential (8 of 15 neurons). In a smaller number of neurons (5 of 15), dopamine enhanced glutamate-mediated excitatory activity. 8. Dopamine-evoked changes in membrane potential were in part mediated through modulation of glutamate actions. Dopamine depressed glutamate-evoked currents in a dose-dependent fashion, with Hill slopes in individual neurons ranging from 0.3 to 0.6. Dopamine could also evoke a direct hyperpolarizing action on hypothalamic neurons in the presence of tetrodotoxin or glutamate receptor blockers, at least in part by opening K+ channels. 9. Glutamate plays an important role as a primary excitatory transmitter within the hypothalamus. Our data support the hypothesis that a major mechanism of dopamine's influence on hypothalamic neurons involves the modulation of glutamate's excitatory action, mostly by inhibition. This is consistent with the hypothesis that modulation of glutamate activity may be an important mechanism of dopamine action throughout the nervous system" http://www.ncbi.nlm.nih.gov/pubmed/8985891 0 980 M. D. Gershon 2003 Plasticity in serotonin control mechanisms in the gut "Current Opinion in Pharmacology.3 (6) ()(pp 600-607), 2003.Date of Publication: December 2003." 6 600-607 "5-hydroxytryptamine (5-HT or serotonin) is a charged molecule and must be transported across biological membranes. Enzymes that catabolize 5-HT are all intracellular; therefore, 5-HT inactivation requires a high affinity transporter, known as serotonin transporter (SERT or 5-HTT). In the central and enteric nervous systems, SERT is located in serotonergic neurons; however, these neurons are not present in the gastrointestinal mucosa, where 5-HT initiates peristaltic and secretory reflexes. Instead, SERT is expressed by enterocytes. The severity of gastrointestinal effects caused by drugs that inhibit SERT, such as tricyclic antidepressants, selective serotonin reuptake inhibitors and cocaine, does not usually prevent their therapeutic or recreational use because backup transporters and alterations in receptor gene expression allow the gut to adapt, albeit imperfectly, to their toxicity" DO - http://dx.doi.org/10.1016/j.coph.2003.07.005 0 981 "F. Z. Meerson, V. P. Tverdokhlib and A. A. Nikonorov" 1988 [Prevention of atherogenic dislipoproteinemias and metabolic disorders in the liver in emotional-pain stress] Vopr.Med.Khim. 34 6 104-109 "Atherogenous dislipoproteinemia, involving a decrease in HDL cholesterol and 3-4-fold increase in the atherogeneity index was found to develop in rats after emotional-pain-dependent stress. Lipid peroxidation was activated in liver tissue of the animals, which was expressed as an increase in the MDA content, a decrease in SOD activity and as marked activation of fructose I-phosphate aldolase, an enzyme specific for liver tissue, in blood serum. The impairment of liver tissue caused an inhibition of 7 alpha-cholesterol hydroxylase--key enzyme of cholesterol hydroxylation into bile acids; the phenomenon may be of importance in development of dislipoproteinemias. Preadaptation of the animals to moderate hypoxia as well as administration of an antioxidant ionol prevented the activation of lipid peroxidation in liver tissue, liberation of fructose I-phosphate aldolase into blood, depression of 7 alpha-cholesterol hydroxylase and protected against the stress-dependent atherogenous dislipoproteinemia. Possible chemical and adaptational protection of liver, which is a very stress-sensitive tissue, is discussed" http://www.ncbi.nlm.nih.gov/pubmed/3238931 0 982 "Y. Tomita, M. Tomita, I. Schiszler, T. Amano, N. Tanahashi, M. Kobari, H. Takeda, M. Ohtomo and Y. Fukuuchi" 2002 Repetitive concentric wave-ring spread of oligemia/hyperemia in the sensorimotor cortex accompanying K(+)-induced spreading depression in rats and cats Neurosci.Lett. 322 3 157-160 "Vascular changes accompanying spreading depression (SD) remain controversial. We examined dynamic alterations of local cerebral blood volume (CBV) during SD by observing light transmission at an isosbestic point of hemoglobin (550 nm) in seven rats and five cats under alpha-chloralose/urethane anesthesia. The two species were used for comparison between the lissencephalic and gyrencephalic brains. We found that a concentrated K(+) solution microinjected into the sensorimotor cortex provoked CBV changes that appeared as a repetitive propagation of concentric wave-rings of ischemia followed by hyperemia expanding peripherally from the injection site at speeds of 1.9-3.2 mm/min. The dynamic CBV changes continued repeatedly every 1-5 min for more than 30 min in three rats, ceased within 30 min in three rats and remained at the site of K(+) injection in one rat. Similar repeated CBV changes occurred in two out of five cats" http://www.ncbi.nlm.nih.gov/pubmed/11897162 0 983 "C. Esteve, E. A. Tolner, R. Shyti, A. M. van den Maagdenberg and L. A. McDonnell" 2016 Mass spectrometry imaging of amino neurotransmitters: a comparison of derivatization methods and application in mouse brain tissue Metabolomics. 12 30 "The detection of small polar compounds such as amino neurotransmitters by MALDI mass spectrometry imaging has been hindered by low-detection sensitivity and background interferences. Recently, several of on-tissue chemical derivatization strategies have been independently reported that enable their detection. Here, we present a comparison between these methods, and demonstrate the visualization of the distributions of up to 23 amino metabolites in tissue. We applied this methodology to detect alterations of these compounds after inducing an experimental cortical spreading depression in mouse brain, which causes profound transient alterations in key neurotransmitters in one hemisphere and is relevant for migraine and various other neurological disorders" http://www.ncbi.nlm.nih.gov/pubmed/26793043 0 984 "K. Kikugawa, H. Suehiro and A. Aoki" 1977 Platelet aggregation inhibitors. VIII. 2-Thioadenine derivatives Chem.Pharm.Bull.(Tokyo) 25 7 1811-1821 http://www.ncbi.nlm.nih.gov/pubmed/908099 0 985 B. P. Curran and J. J. O'Connor 2003 The inhibition of long-term potentiation in the rat dentate gyrus by pro-inflammatory cytokines is attenuated in the presence of nicotine Neurosci.Lett. 344 2 103-106 "Nicotine has previously been shown to affect both long-term potentiation (LTP) and long-term depression and to reverse age-related impairments of LTP in the hippocampus. Levels of proinflammatory cytokines are known to be elevated with age and to inhibit LTP. In the present study we have investigated the effects of three pro-inflammatory cytokines on nicotine-enhanced LTP in the rat hippocampus in vitro. In the presence of nicotine the inhibitory effect of interleukin-1 beta, interleukin-18 and tumour necrosis factor-alpha on LTP was eliminated. Furthermore, significant depotentiation of established LTP could not be obtained in slices treated with nicotine. These experiments demonstrate that nicotine can reverse the inhibitory effects of pro-inflammatory cytokines on LTP" http://www.ncbi.nlm.nih.gov/pubmed/12782338 0 986 "C. Chrysohoou, G. Tsitsinakis, G. Siassos, T. Psaltopoulou, N. Galiatsatos, V. Metaxa, G. Lazaros, A. Miliou, E. Giakoumi, C. Mylonakis, M. Zaromytidou, E. Economou, G. Triantafyllou, C. Pitsavos and C. Stefanadis" 2011 Fish Consumption Moderates Depressive Symptomatology in Elderly Men and Women from the IKARIA Study Cardiol.Res.Pract. 2011 219578 "Background. The aim was to examine the association of depressive symptoms with fish eating habits, in elderly individuals. Methods. From June to October of 2009, we studied 330 men and 343 women, aged 65 to 100 years, permanent inhabitants of Ikaria Island. Among several characteristics, depression was assessed with the Geriatric Depression scale (GDS range 0-15), while dietary habits through a valid semiquantitative food frequency questionnaire. Results. Women had significantly higher values of the GDS compared to men (4.8 +/- 3.5 versus 3.3 +/- 3.1, P = .001). Participants in the upper tertile of depression scale ate less frequent fish and consumed higher quantities of alcohol, compared to those in the lowest tertile (all P < .05). Regarding fish consumption, 50% of the individuals reported consuming 1-2 times weekly, 32% 3 to 5 times weekly, 11% 2-3 times monthly, while the rest reported rare (4.5%) and everyday (1.2%) consumption. Logistic regression showed that increased fish consumption (>3 times/week versus never/rare) was inversely associated with the odds of having GDS greater the median value (i.e., 4) (odds ratio = 0.34, 95% CI: 0.19, 0.61), after controlling for several cofounders. Conclusion. Frequent fish consumption in elderly seems to moderate depression mood" http://www.ncbi.nlm.nih.gov/pubmed/21197433 0 987 "M. C. Maillard, O. Nikodijevic, K. F. LaNoue, D. Berkich, X. D. Ji, R. Bartus and K. A. Jacobson" 1994 "Adenosine receptor prodrugs: synthesis and biological activity of derivatives of potent, A1-selective agonists" J.Pharm.Sci. 83 1 46-53 "5'-Ester derivatives of the potent adenosine agonists N6-[4-[[[[4-[[[(2-acetylaminoethyl)amino]carbonyl]methyl] anilino]carbonyl]methyl]phenyl]adenosine (N-AcADAC; 1) and N6-cyclopentyladenosine (CPA; 2) were prepared as prodrugs. Both alkyl esters or carbonates (designed to enter the brain by virtue of increased lipophilicity) and 1,4-dihydro-1-methyl-3-[(pyridinylcarbonyl)oxy]esters designed to concentrate in the brain by virtue of a redox delivery system were synthesized. In the 5'-blocked form, the adenosine agonists displayed highly diminished affinity for rat brain A1-adenosine receptors in binding assays. The dihydropyridine prodrug 29 was active in an assay of locomotor depression in mice, in which adenosine agonists are highly depressant. The behavior depression was not reversible by peripheral administration of a non-central nervous system active adenosine antagonist. In an assay of the peripheral action of adenosine (i.e., the inhibition of lipolysis in rats), the parent compounds were highly potent and the dihydropyridine prodrug was much less potent" http://www.ncbi.nlm.nih.gov/pubmed/8138909 1 988 C. L. Guard and W. S. Schwark 1984 "Influence of yohimbine on xylazine-induced depression of central nervous, gastrointestinal and cardiovascular function in the calf" Cornell Vet. 74 4 312-321 "The antagonistic effect of yohimbine HCl (0.25 mg/kg IV), and alpha 2-adrenergic antagonist, on xylazine (0.05 mg/kg IV)-induced depression of central nervous and cardiovascular activity and rumen motility was studied in post-weaning calves. Yohimbine, administered 3 min post-xylazine, significantly decreased the duration of rumen amotility (38.3 +/- 4.2 min versus 14.0 +/- 2.2 min). Sedation, however, as monitored by the duration of fetlock knuckling in calves suspended in a body sling, was not shortened by yohimbine treatment. Yohimbine alone produced a significant tachycardia and led to a reduction of the duration of xylazine-induced bradycardia. Our data indicate that yohimbine produces a significant reversal of xylazine-induced rumen hypomotility at dosage levels that are without effect on sedation induced by this drug" http://www.ncbi.nlm.nih.gov/pubmed/6478835 0 989 "R. Castillo, I. Kissin and E. L. Bradley" 1986 Selective kappa opioid agonist for spinal analgesia without the risk of respiratory depression Anesth.Analg. 65 4 350-354 "The effects of the selective kappa agonist, U-50,488H, on the motor response to noxious mechanical stimulation when administered intrathecally, as well as on respiratory rate and PaCO2 when administered by intracerebroventricular injection, were compared with those of morphine in experiments on rats. The agonist U-50,488H caused a dose-dependent increase in the threshold to noxious stimulation but did not have a potential for depression of resting ventilation. The results suggest that selective kappa opioid agonists may be suitable for clinical spinal (epidural) analgesia without the associated risk of respiratory depression" http://www.ncbi.nlm.nih.gov/pubmed/3006552 0 990 "H. Nomaru, Y. N. Ohnishi, M. Hokama, N. Yutsudo and Y. Nakabeppu" 2011 Comprehensive analysis of gene expression profiles regulated by fosB gene in brain "Neuroscience Research.Conference: 34th Annual Meeting of the Japan Neuroscience Society, Neuroscience 2011 Yokohama Japan.Conference Start: 20110914 Conference End: 20110917.Conference Publication: (var.pagings).71 ()(pp e121), 2011.Date of Publicati" var.pagings e121 "fosB gene produces two transcripts, fosB and DELTAfosB mRNAs by alternative splicing, thus encoding multiple subunits of AP-1 (activator protein-1) transcription factors. DELTAFosB andDELTA2DELTAFosB proteins lack the C-terminal 101- amino-acid region of FosB protein encoded by the fosB mRNA. Because the region contains the motifs responsible for the interaction with TATA-box binding protein (TBP) and TFIID complex and also for the repression of c-fos and fosB promoters, it is likely that the fosB gene products, FosB, DELTAFosB and DELTA2DELTAFosB may differentially modulate the expression of various AP-1 targets. The basal expression of fosB is detected in throughout brain, especially cerebral cortex and hippocampus, and is highly inducible upon various brain stimuli. We recently found that fosB-knockout (KO) mice exhibit depressive behavior and epilepsy, while fosBd/d mutant mice expressing only theDELTAfosB mRNA exhibit increased locomotor activity. In the present study, we prepared primary neurons, astrocytes and microglia from wild-type cortex and hippocampus and compared the expression levels of fosB andDELTAfosB mRNAs. We found that expression levels of fosB and DELTAfosB mRNAs vary according to types of cells or brain regions, and especially those in cortical neurons are twenty times higher than those in hippocampal neurons. In addition, the ratio of fosB and DELTAfosB mRNAs also varies according to types of cells. We therefore expect that fosB gene products regulate gene expression in cell type-dependent manner. We then compared gene expression profiles in wild-type, fosB-KO and fosBd/d mutant microglia by microarray analysis. Eight genes exhibit significantly different expression levels more than 1.5 fold among the three samples, and 5 of them are likely to be regulated only by FosB. We also found that one gene among the eight genes is likely to be repressed and the other may be partly activated by DELTAFosB or DELTA2DELTAFosB" DO - http://dx.doi.org/10.1016/j.neures.2011.07.516 0 991 Y. Nakamura and T. Hirano 2016 Intracellular Ca(2+) thresholds for induction of excitatory long-term depression and inhibitory long-term potentiation in a cerebellar Purkinje neuron Biochem.Biophys.Res.Commun. 469 4 803-808 "Synaptic plasticity in the cerebellar cortex contributes to motor learning. In particular, long-term depression at excitatory parallel fiber - Purkinje neuron synapses has been intensively studied as a primary cellular mechanism for motor learning. Recent studies showed that synaptic plasticity other than long-term depression such as long-term potentiation at inhibitory interneuron - Purkinje neuron synapses called rebound potentiation is also involved in motor learning. It was suggested that long-term depression and rebound potentiation might synergistically support motor learning. Here, we have examined induction conditions of long-term depression and rebound potentiation in cultured rat Purkinje neurons, and found that both of them were induced simultaneously by certain patterns of depolarization of a Purkinje neuron. Further, we found that long-term depression was induced by shorter depolarizing pulses causing a smaller intracellular Ca(2+) increase than rebound potentiation. These results support an idea that long-term depression and rebound potentiation synergistically contribute to motor learning, and suggest that long-term depression may play a primary role in wider variety of motor learning paradigms than rebound potentiation" http://www.ncbi.nlm.nih.gov/pubmed/26707644 0 992 "C. Vanzella, P. Bianchetti, S. Sbaraini, S. I. Vanzin, M. I. Melecchi, E. B. Caramao and I. R. Siqueira" 2012 Antidepressant-like effects of methanol extract of Hibiscus tiliaceus flowers in mice BMC.Complement Altern.Med. 12 41 "BACKGROUND: Hibiscus tiliaceus L. (Malvaceae) is used in postpartum disorders. Our purpose was to examine the antidepressant, anxiolytic and sedative actions of the methanol extract of H. tiliaceus flowers using animal models. METHODS: Adult male Swiss albino mice were treated with saline, standard drugs or methanol extract of H. tiliaceus and then subjected to behavioral tests. The forced swimming and tail suspension tests were used as predictive animal models of antidepressant activity, where the time of immobility was considered. The animals were submitted to the elevated plus-maze and ketamine-induced sleeping time to assess anxiolytic and sedative activities, respectively. RESULTS: Methanol extract of H. tiliaceus significantly decreased the duration of immobility in both animal models of antidepressant activity, forced swimming and tail suspension tests. This extract did not potentiate the effect of ketamine-induced hypnosis, as determined by the time to onset and duration of sleeping time. CONCLUSION: Our results indicate an antidepressant-like profile of action for the extract of Hibiscus tiliaceus without sedative side effect" http://www.ncbi.nlm.nih.gov/pubmed/22494845 1 993 "S. A. Queen, M. J. Chen and D. M. Feeney" 1997 d-Amphetamine attenuates decreased cerebral glucose utilization after unilateral sensorimotor cortex contusion in rats Brain Res. 777 01-Feb 42-50 "Unilateral contusion injury to the sensorimotor cortex causes, among other symptoms, a transient contralateral hindlimb hemiparesis in rats. A single i.p. 2 mg/kg dose of d-amphetamine (d-AMPH) 24 h after injury accelerates spontaneous recovery from this particular deficit. The mechanism(s) of spontaneous and d-AMPH enhanced recovery are unknown but alleviation of a neuronal depression has been proposed. This quantitative CMRglu study was designed to determine effects of cortical contusion injury and d-AMPH on CMRglu in cortical and subcortical structures. At 2 days after injury, CMRglu was significantly reduced compared to sham-operated controls only in structures ipsilateral to contusion. Affected structures included the caudate putamen, medial geniculate nucleus, lateral geniculate nucleus and the parietal cortex immediately posterior to injury. By 6 days post-contusion, the hypometabolism partially reversed in all structures. A single low dose of d-AMPH significantly alleviated the post-traumatic CMRglu reduction at 2 days after injury. Importantly, while this alleviation was not significant for any single structure, the main effect of treatment was highly significant. d-AMPH increased CMRglu at 2 days post-injury by 18-33% compared to contused/saline-treated rats. These results suggest that alleviation of neuronal metabolic depression may contribute to spontaneous and d-AMPH enhanced recovery" http://www.ncbi.nlm.nih.gov/pubmed/9449411 0 994 "S. E. Adam, A. A. Al-Qarawi and E. A. Elhag" 2000 Effects of various levels of dietary Artemisia abyssinica leaves on rats Lab Anim 34 3 307-312 "Artemisia abyssinica leaves, a traditional medicine for the treatment of various disorders, were fed to male Wistar rats at 2% and 10% of the standard diet for 6 weeks. A 2% A. abyssinica leaf diet was not toxic to rats. Depression in growth, hepatopathy and nephropathy were observed in rats fed a diet containing 10% of A. abyssinica leaves. These findings were accompanied by leukopenia, anaemia and alterations of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) activities with changes in concentrations of total protein, albumin, cholesterol and urea" http://www.ncbi.nlm.nih.gov/pubmed/11037126 0 995 "W. Zada, S. Zeeshan, H. A. Bhatti, W. Mahmood, K. Rauf and G. Abbas" 2016 Cinnamomum cassia: an implication of serotonin reuptake inhibition in animal models of depression Nat.Prod.Res. 30 10 1212-1214 "The aim of the study was to explore the traditional use of Cinnamomum cassia against depression. The standardised methanolic extract of the bark of C. cassia was evaluated for antidepressant activity using various behavioural tests, i.e. tail suspension test (TST), forced swim test (FST) and locomotor activity test. The serotonergic and noradrenergic modulation was assessed using 5-hydroxytryptophan (5-HTP)-induced head twitches and yohimbine potentiation tests, respectively. The fluoxetine and phenelzine were used as positive controls in the study. The C. cassia extract significantly decreased the immobility time in TST (maximum effective dose tested was 50 mg/kg) while no effect was observed in FST and locomotor activity test. The extract significantly increased the 5-HTP-induced head twitches while yohimbine-induced lethality remained unaltered. The aforementioned results are similar to that caused by fluoxetine. The standardised methanolic extract of C. cassia demonstrated antidepressant activity that can be attributed to rise in serotonin levels" http://www.ncbi.nlm.nih.gov/pubmed/26134381 1 996 "T. Mazel, F. Richter, L. Vargova and E. Sykova" 2002 Changes in extracellular space volume and geometry induced by cortical spreading depression in immature and adult rats Physiol Res. 51 Suppl 1 S85-S93 "Changes in extracellular space (ECS) diffusion parameters, DC potentials and extracellular potassium concentration were studied during single and repeated cortical spreading depressions (SD) in 13-15 (P13-15), 21 (P21) and 90-day-old (adult) Wistar rats. The real-time iontophoretic method using tetramethylammonium (TMA+)-selective microelectrodes was employed to measure three ECS parameters in the somatosensory cortex: the ECS volume fraction alpha (alpha = ECS volume/total tissue volume), ECS tortuosity lambda (increase in diffusion path length) and the nonspecific TMA+ uptake k'. SD was elicited by needle prick. SD was significantly longer at P13-15 than at P21 and in adults. During SD, alpha in all age groups decreased from 0.21-0.23 to 0.05-0.09; lambda increased from 1.55-1.65 to 1.95-2.07. Ten minutes after SD, alpha (in adults) and lambda (all age groups) increased compared to controls. This increase persisted even 1 hour after SD. When SD was repeated at 1 hour intervals, both alpha and lambda showed a gradual cumulative increase with SD repetition. Our study also shows that cortical SD is, as early as P13, accompanied by severe ECS shrinkage and increased diffusion path length (tortuosity) with values similar to adults, followed by a long-lasting increase in ECS volume and tortuosity when compared to pre-SD values" http://www.ncbi.nlm.nih.gov/pubmed/12479789 0 997 G. Zimmerman and N. Fleischer 1970 Role of calcium ions in the release of ACTH from rat pituitary tissue in vitro Endocrinology 87 2 426-429 http://www.ncbi.nlm.nih.gov/pubmed/4316575 0 998 "U. Reuter, J. R. Weber, L. Gold, G. Arnold, T. Wolf, J. Dreier, U. Lindauer and U. Dirnagl" 1998 Perivascular nerves contribute to cortical spreading depression-associated hyperemia in rats Am.J.Physiol 274 6 Pt 2 H1979-H1987 "We investigated the contribution of perivascular nerves and neurotransmitters to cortical spreading depression (CSD)-associated hyperperfusion in the rat. Chronic transection of the nasociliary nerve (NCN, 2 wk before) decreased ipsilateral CSD-associated hyperperfusion by 23 +/- 13% (mean +/- SD; n = 5, P < 0.05), whereas acute transection of the NCN or sham surgery had no effect (n = 8). When the NCN and parasympathetic nerve fibers (PSN) were both chronically transected, CSD hyperperfusion was attenuated by 55 +/- 19% (n = 5, P < 0.05). Cerebrovascular reactivity to hypercapnia was not significantly affected. Brain topical superfusion of the muscarinic receptor antagonist atropine (10(-4) M) caused a reduction of CSD hyperperfusion by 41 +/- 13% (n = 5, P < 0.05). The competitive blockade of calcitonin gene-related peptide (CGRP) receptors by CGRP-(8-37) (5 x 10(-7) M) afforded a decrease by 49 +/- 19% (n = 5, P < 0.05), without affecting CO2 reactivity (n = 4). The combined application of both CGRP-(8-37) and atropine further attenuated CSD hyperperfusion (by 69 +/- 17%, n = 5, P < 0.05). After chronic NCN and PSN transection brain topical superfusion of CGRP-(8-37) (5 x 10(-7) M) reduced CSD hyperperfusion slightly by 9.5 +/- 5% (n = 3). Atropine (10(-4) M) afforded a decrease by 17 +/- 6% (n = 3). These reductions were not statistically significant. We conclude that CSD-associated hyperperfusion is mediated in part by a depolarization of trigeminal sensory and parasympathetic nerve fibers, resulting in a release of vasoactive trigeminal and parasympathetic neurotransmitters" http://www.ncbi.nlm.nih.gov/pubmed/9841481 0 999 "K. Krnjevic, E. Cherubini and Y. Ben-Ari" 1989 Anoxia on slow inward currents of immature hippocampal neurons J.Neurophysiol. 62 4 896-906 "1. The effects of brief anoxia (2-4 min) on membrane currents--especially the tetrodotoxin (TTX)-insensitive, Cd2+-sensitive slow inward currents, presumed to be Ca2+ currents--were studied by single-electrode voltage clamp in CA1 and CA3 neurons in submerged hippocampal slices from adult and newborn Wistar rats (PN1-13). 2. In mature neurons, anoxia had no effect on Q-type inward relaxations, but slowly activating C-type outward currents were depressed. The most striking change was the suppression of Ca inward currents (especially the slowly inactivating L-type, by greater than 95%). This effect of anoxia was not sensitive to the N-methyl-D-aspartate (NMDA) receptor blocker, D-aminophosphonovalerate. Anoxia also reversibly abolished the NMDA-evoked inward current. 3. In neurons from newborn animals (PN1-6), Q-type inward relaxations and postanoxic outward currents were very small or undetectable. The slow inward (Ca) currents were smaller than in mature cells, but they showed a clearer separation between low-threshold, fast-inactivating and high-threshold, slowly inactivating currents. Both types of current were more resistant to anoxia (mean depression of L-type was by only 53.3 +/- 5.6%, mean +/- SE). 4. In such immature neurons, the NMDA-evoked inward currents were also more resistant to anoxia. 5. By PN7-13, increasing maturation was reflected in 1) larger voltage-dependent inward currents, 2) increasingly evident Q-type relaxations and postanoxic outward currents, and 3) near-complete blockade of inward currents by anoxia (at PN11-13, mean depression of L-type currents was by 98.5 +/- 1.5%)" http://www.ncbi.nlm.nih.gov/pubmed/2553881 0 1000 "C. Pittenger, S. Fasano, D. Mazzocchi-Jones, S. B. Dunnett, E. R. Kandel and R. Brambilla" 2006 Impaired bidirectional synaptic plasticity and procedural memory formation in striatum-specific cAMP response element-binding protein-deficient mice J.Neurosci. 26 10 2808-2813 "The striatum has a well documented role in procedural learning and memory. However, the synaptic and molecular mechanisms of acquisition and storage of this form of memory remain poorly understood. We examined procedural memory and plasticity in transgenic mice reversibly expressing a dominant-negative cAMP response element-binding protein (CREB) mutant in the dorsal striatum. In these transgenic mice, corticostriatal long-term potentiation and depression are abolished, indicating that CREB function is essential for bidirectional long-term synaptic plasticity in this structure. Importantly, CREB-deficient animals show reversible alterations in several forms of striatum-dependent memory, including footshock avoidance learning and ""response"" learning in the cross maze. These findings implicate transcriptional regulation by CREB family transcription factors in striatum-dependent information processing and provide the first clear correlation between procedural learning and memory and synaptic plasticity at the corticostriatal synapse" http://www.ncbi.nlm.nih.gov/pubmed/16525060 0 1001 "J. Haller, S. R. Goldberg, K. G. Pelczer, M. Aliczki and L. V. Panlilio" 2013 The effects of anandamide signaling enhanced by the FAAH inhibitor URB597 on coping styles in rats Psychopharmacology (Berl) 230 3 353-362 "RATIONALE: Coping styles are fundamental characteristics of behavior that affect susceptibility to, and resilience during, mental and physical illness. Shifts from passive to active coping are considered therapeutic goals in many stress-related disorders, but the neural control of coping is poorly understood. Based on earlier findings, we hypothesized that coping styles are influenced by endocannabinoids. OBJECTIVES: Here, we tested whether FAAH inhibition by URB597 affects behaviors aimed at controlling a critical situation and the degree to which environmental stimuli influence behavior i.e., we studied the impact of URB597 on the two main attributes of coping styles. METHODS: Rats were tested in the tail-pinch test of coping and in the elevated plus-maze test that was performed under highly divergent conditions. RESULTS: Under the effects of URB597, rats focused their behavior more on the discomfort-inducing clamp in the tail-pinch test, i.e., they coped with the challenge more actively. In the elevated plus-maze, URB597-treated rats demonstrated an autonomous behavioral control by reducing both ""wariness"" induced by aversive conditions and ""carelessness"" resulting from favorable conditions. CONCLUSIONS: URB597 treatment-induced behavioral changes indicated a shift towards active coping with challenges. This behavioral change appears compatible with the previously suggested role of endocannabinoids in emotional homeostasis. Albeit further studies are required to characterize the role of endocannabinoids in coping, these findings suggest that the enhancement of endocannabinoid signaling may become a therapeutic option in emotional disorders characterized by passive coping (e.g., anxiety and depression) and in physical diseases where active coping is therapeutically desirable" http://www.ncbi.nlm.nih.gov/pubmed/23743650 0 1002 R. Engelhardt and H. Kalbfleisch 1973 [Effect of chronic application of aminorex-fumarate on the pulmonary circulation of the rat] Arzneimittelforschung. 23 8 1057-1061 http://www.ncbi.nlm.nih.gov/pubmed/4801026 0 1003 S. N. Kozhechkin 1989 [Does ethanol potentiate GABAergic inhibition?] Farmakol.Toksikol. 52 2 83-86 "The effect of systemically and microelectro-osmotically applied ethanol on sensitivity of sensorimotor cortical neurons of unanesthetized rabbit brain to microiontophoretically administered GABA and glycine was studied. No correlation was found between responses of single neurons to ethanol, GABA and glycine. The inhibitory responses to ethanol were summed with responses to GABA and glycine (additive interaction). Ethanol failed to potentiate GABA effect" http://www.ncbi.nlm.nih.gov/pubmed/2545469 0 1004 "C. Hess, H. Enichlmayr, D. Jandreski-Cvetkovic, D. Liebhart, I. Bilic and M. Hess" 2013 Riemerella anatipestifer outbreaks in commercial goose flocks and identification of isolates by MALDI-TOF mass spectrometry Avian Pathol. 42 2 151-156 "Several outbreaks of Riemerella anatipestifer in commercial geese occurred within a short time period. A serious disease was recognized in the affected birds, mainly characterized by depression and severe neurologic disturbances. The morbidity ranged from 20 to 30% and the mortality from 5 to 20%. Generally, the clinical signs started at the age of 8 to 10 days. Post-mortem examination revealed fibrinous pericarditis, perihepatitis and airsacculitis in all birds. Some of the birds also had synovitis of the tibio-tarsal joints and oedematous swelling of the subcutaneous tissues around these joints and metatarsus. Histology revealed a characteristic severe inflammation with heterophilic granulocytes in different organs. Bacteriological investigation was made from several organs and R. anatipestifer could be isolated from all birds investigated. The identification of these clinical isolates, done for the first time by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry, confirmed the aetiology. Sequence analysis showed 100% similarity between the clinical isolates, indicating a common source of infection" http://www.ncbi.nlm.nih.gov/pubmed/23581442 0 1005 "G. Caletti, D. B. Olguins, E. F. Pedrollo, H. M. Barros and R. Gomez" 2012 Antidepressant effect of taurine in diabetic rats Amino.Acids 43 4 1525-1533 "Clinical and preclinical studies have shown that diabetic individuals present more depressive behaviors than non-diabetic individuals. Taurine, one of the most abundant free amino acids in the central nervous system, modulates a variety of biological functions and acts as an agonist at GABAA receptors. Our objective was to assess the antidepressant effect of taurine in diabetic rats. Additionally, we studied the effect of taurine on weight gain, water and food intake, and blood glucose levels in diabetic and non-diabetic rats. Male Wistar rats were divided into control (CTR) and streptozotocin-induced diabetic (STZ) groups and were administered daily 0, 25, 50 or 100 mg/kg of taurine (n = 10 per subgroup) intraperitoneally. After 28 days of treatment, the animals were exposed to the forced swimming test, and their behaviors were recorded. Weight gain, water and food intake, and blood glucose levels were measured weekly. Our results showed that STZ rats had a higher immobility duration than CTR rats, and taurine decreased this depressive-like behavior in STZ rats at doses of 25 and 100 mg/kg. Both of these doses of taurine also decreased water intake and improved weight gain in STZ rats. All doses of taurine decreased the water intake in CTR rats. Taurine, at a dose of 100 mg/kg, decreased food intake and blood glucose levels in STZ rats. Because taurine is a GABA agonist and both amino acids are lower in the plasma of diabetic and depressive individuals, we hypothesize that taurine may represent a new adjuvant drug for the treatment of depression in diabetic individuals" http://www.ncbi.nlm.nih.gov/pubmed/22302366 1 1006 "Y. Zhao, H. Yang, K. B. Storey and M. Chen" 2014 Differential gene expression in the respiratory tree of the sea cucumber Apostichopus japonicus during aestivation Mar.Genomics 18 Pt B 173-183 "Sea cucumbers, Apostichopus japonicus, experience seasonally high water temperatures during the summer months and enter aestivation to survive. Aestivation is characterized by strong metabolic rate depression which is supported by a series of strategies including reorganizing metabolic processes, suppressing cell functions, enhancing cytoprotective mechanisms, and altered gene expression. The respiratory tree tissue of the sea cucumber is an excellent material for studying aestivation, undergoing obvious atrophy during aestivation. The present study analyzed the global gene expression profile of respiratory tree tissue of A. japonicus during aestivation by constructing and screening three libraries representing key stages of aestivation: non-aestivation (NA), deep-aestivation (DA), and arousal from aestivation (AA) using RNA-seq. A total of 1240, 1184 and 303 differentially expressed genes (DEGs) were identified following the criteria of |log2 ratio|>/=1 and FDR3)-beta-D-glucan (25 mg/kg, i.p., 48 h before paracetamol) for the macrophage stimulation or with gadolinium chloride (GdCl3, 7.5 mg/kg, i.v., 24 h before paracetamol) for the macrophage suppression has a protective effect manifested by normalization of the liver function test parameters and by a decrease in the degree of morphological changes in the liver cells. A relation between these positive effects and the TNF-alpha secretion by macrophages is discussed" http://www.ncbi.nlm.nih.gov/pubmed/12683084 0 1046 "B. Matuszczak, E. Pekala and C. E. Muller" 1998 "1-Substituted 4-[chloropyrazolyl][1,2,4]triazolo[4,3-a]quinoxalines: Synthesis and structure-activity relationships of a new class of benzodiazepine and adenosine receptor ligands" "Archiv der Pharmazie.331 (5) ()(pp 163-169), 1998.Date of Publication: 1998." 5 163-169 "Starting from 3-(3-chloro-1H-pyrazol-5-yl)-1H-quinoxalin-2-one (2) a series of substituted [1,2,4]triazolo[4,3-a]quinoxalines (3a-f) was prepared via a multistep reaction sequence. Affinities of the novel derivatives 3a-f for benzodiazepine as well as for adenosine A1- and A(2A)-receptors of rat brain were determined by radioligand binding assays. 1-Methyl-4-(3-chloro- 1H-pyrazol-5-yl) derivative 3a exhibited submicromolar affinity for the benzodiazepine binding site of GABA(A) receptors (K(i) = 340 nM) and was less potent at A1- (K(i) = 7.85 muM) and A(2A)-(K(i) = 1.43 muM) adenosine receptors (AR). Derivatives with larger substituents in the 1-position showed reduced binding to benzodiazepine and A(2A)-AR, but increased A1-AR affinity, the 2-thienylmethyl derivative 3f being the most potent and selective A1-AR ligand of the present series (K(i) = 200 nM)" DO - http://dx.doi.org/10.1002/%28SICI%291521-4184%28199805%29331:5%3C163::AID-ARDP163%3E3.0.CO 0 1047 "A. M. Galzin, D. Graham and S. Z. Langer" 1990 Serotonin transport systems and antidepressants "Psychiatrie et Psychobiologie.5 (3) ()(pp 201-207), 1990.Date of Publication: 1990." 3 201-207 "The sodium-dependent serotonin transport associated with plasmatic membranes of platelets or serotonin nerve terminals serves to inactivate the neurotransmitter and maintain low levels of transmitter in the synaptic cleft. It has been suggested that changes in serotonergic transmission could be linked to the pathophysiology of depression, and that modifications at the level of the serotonin transporter could exist during depressive episodes. A consistent decrease in the number of transporter sites has been reported in blood platelets from depressed patients, and similar results were also obtained in some regions of the post-mortem human brain. It is well established that tricyclic and nontricyclic serotonin uptake inhibitors are effective as antidepressant drugs, but a lag period of 2-3 wks is observed between the beginning of treatment and the clinical manifestation of therapeutic antidepressant effects. Therefore, studies on biochemical properties and molecular characterization of the serotonin transporter are of particular interest. Serotonin uptake can be selectively inhibited by citalopram, paroxetine, indalpine, fluoxetine and SL 81 0385. Moreover, this inhibition by paroxetine and SL 81 0385 has been shown to induce an increase in the electrically-evoked in vitro release of [3H]-5-HT from slices of the human frontal cortex. Radioligand binding studies with [3H]-imipramine, [3H]-paroxetine and [3H]-citalopram have been used in recent years to characterize the serotonin transporter. In dissociation kinetics experiments of [3H]-paroxetine binding to rat cerebral cortical membranes, exposure to citalopram, indalpine, fluoxetine, SL 81 0385, imipramine as well as serotonin itself produced monophasic dissociation curvers with t 1/2 values of dissociation similar to that obtained for paroxetine itself. Moreover, SL 81 0385, fluoxetine, imipramine and serotonin can protect [3H]-paroxetine binding against N-ethylmaleimide-induced inactivation. Combined, these results suggest that the substrate and the tricyclic and nontricyclic serotonin uptake inhibitors bind to the same (or at least overlapping) domains on the sodium-coupled serotonin transporter. The neuronal serotonin transporter has been solubilized from rat cerebral cortex membranes, and purified by affinity chromatography using an agarose gel to which a citalopram derivative had been covalently coupled. [3H]-paroxetine binding to a purified preparation gave a K(d) value of 0.71 nM and a value of B(max) greater than 1.962 pmoles/mg prot, corresponding to an enrichment of more than 3000-fold of [3H]-paroxetine binding activity compared to that of the parent membrane preparation. The binding of [3H]-paroxetine to this purified preparations was inhibited by citalopram, imipramine and serotonin with K(i) values of 19 nM, 80 nM and 3.5 nM, respectively, thereby confirming that an extensive purification of the sodium-coupled serotonin transporter had been achieved. This purification of the 5-HT carrier protein is the first step which should ultimately permit a detailed insight into the molecular mechanisms operating in this transport process" 1 1048 J. Acosta-Urquidi and R. Chase 1975 The effects of delta9-tetrahydrocannabinol on action potentials in the mollusc Aplysia Can.J.Physiol Pharmacol. 53 5 793-798 "The effects of delta9-tetrahydrocannabinol (delta9-THC) on action potentials were examined during intrasomatic recordings from the isolated buccal and parieto-visceral ganglia of Aplysia californica. When added to the saline solution bathing the preparation, the compound (in concentrations 10(-4) - 10(-5) M) caused a reduction in spike overshoot (15-20% of total amplitude) and increased the lability of responses to electrical stimulation. The somatic membrane appeared to be more affected than the axonal membrane. Diffusion barriers in the ganglion probably account for the high degree of variability in drug response, such that both of the characteristic changes were observed in only about 30% of the tests. This is the first report to describe effects of delta9-THC on invertebrate neurones. The results indicate that delta9-THC causes a depression in nerve cell excitability, and these data are consistent with reported effects of THC compounds in mammals" http://www.ncbi.nlm.nih.gov/pubmed/1201484 1 1049 "H. L. Gurtoo, J. H. Hipkens and S. D. Sharma" 1981 Role of glutathione in the metabolism-dependent toxicity and chemotherapy of cyclophosphamide Cancer Res. 41 9 Pt 1 3584-3591 "The role of glutathione in the biological effects of cyclophosphamide (CP) was evaluated by investigating the following: effect of CP on hepatic glutathione levels; relationship between hepatic glutathione depletion (repletion) and the binding of [chloroethyl-3H]CP and [4-14C]CP to hepatic macromolecules; effects of interaction between CP (or acrolein) and diethyl maleate (a classical glutathione depletor), and/or between CP and cysteine on the binding of labeled CP to hepatic macromolecules, on the induction of hematuria, on the content of hepatic cytochrome P-450, on weight gain in rats, on survival in mice, and on the chemotherapeutic efficacy of CP against Walker 256 carcinoma in rats. CP and acrolein produced dose-dependent depletion of hepatic glutathione in mice, whereas phosphoramide mustard was at least one order of magnitude less effective. Acrolein caused death in mice; CP became covalently bound to hepatic macromolecules, prevented weight gain in rats, and produced hematuria and depression of hepatic cytochrome P-450 in vivo. These effects of CP (or acrolein) were enhanced by diethyl maleate but partially blocked by cysteine. On the other hand, reduction in the volume of Walker 256 carcinoma in rats by CP was not antagonized by cysteine. All these investigations point to the following conclusions: (a) acrolein produced during the metabolism of CP binds to proteins and, by doing so may denature these proteins; and (b) acrolein in vivo preferentially reacts with glutathione, and sulfhydryl-containing compounds may protect against acrolein toxicity and at the same time not interfere with the chemotherapeutic activity of CP" http://www.ncbi.nlm.nih.gov/pubmed/7260917 0 1050 "M. Randic, M. C. Jiang and R. Cerne" 1993 Long-term potentiation and long-term depression of primary afferent neurotransmission in the rat spinal cord J.Neurosci. 13 12 5228-5241 "Synaptic transmission between dorsal root afferents and neurons in the superficial laminae of the spinal dorsal horn (laminae I-III) was examined by intracellular recording in a transverse slice preparation of rat spinal cord. Brief high-frequency electrical stimulation (300 pulses at 100 Hz) of primary afferent fibers produced a long-term potentiation (LTP) or a long-term depression (LTD) of fast (monosynaptic and polysynaptic) EPSPs in a high proportion of dorsal horn neurons. Both the AMPA and the NMDA receptor-mediated components of synaptic transmission at the primary afferent synapses with neurons in the dorsal horn can exhibit LTP and LTD of the synaptic responses. In normal and neonatally capsaicin-treated rats, the induction of LTP requires the activation of NMDA receptor-gated conductances. The induction of LTP or LTD, however, was not abolished in the presence of bicuculline, a GABAA receptor antagonist. The results demonstrate that distinct and long-lasting modulation in synaptic efficiency can be induced at primary afferent synapses with neurons in the superficial laminae of spinal dorsal horn by high-frequency stimulation of dorsal root afferents and that these changes may be physiologically relevant for transmission and integration of sensory information, including pain" http://www.ncbi.nlm.nih.gov/pubmed/8254370 0 1051 F. L. Yu and P. Feigelson 1969 Effects of cortisone and actinomycin-D upon pyrimidine nucleotide and RNA metabolism in rat liver Arch.Biochem.Biophys. 129 1 152-157 http://www.ncbi.nlm.nih.gov/pubmed/5762960 0 1052 S. DeMesquita and W. H. Haney 1986 Effect of chronic intracerebroventricular infusion of cholecystokinin on respiration and sleep Brain Res. 378 1 127-132 We investigated the effect of chronic intracerebroventricular infusion of the sulfated cholecystokinin octapeptide (CCK-8S) on sleep pattern and respiratory rate. The results indicate a depression of respiratory rate during Non-REM and REM sleep as well as an increase in the number of REM periods occurring per hour of Non-REM sleep. It is suggested that central release of CCK-8S is capable of modulating the automatic regulation of respiration during sleep and altering the normal sleep-waking pattern http://www.ncbi.nlm.nih.gov/pubmed/3742195 0 1053 "Z. Xiong, B. Jiang, P. F. Wu, J. Tian, L. L. Shi, J. Gu, Z. L. Hu, H. Fu, F. Wang and J. G. Chen" 2011 Antidepressant effects of a plant-derived flavonoid baicalein involving extracellular signal-regulated kinases cascade Biol.Pharm.Bull. 34 2 253-259 "Depression and related mood disorders are among the world's greatest public health problems. Previous studies have demonstrated that baicalein (Bai), one plant-derived active flavonoid, exhibits neuroprotection against ischemic brain injury and stimulates the levels of phosphorylation of extracellular signal-regulated kinase (pERK) and brain-derived neurotrophic factor (BDNF) expression in vivo. In this study, the antidepressant-like effects of baicalein was investigated using acute and chronic animal models of depression. The results showed that acute application of Bai at doses of 1, 2 and 4 mg/kg by intraperitoneal injection (i.p.) significantly reduced the immobility time in the forced swimming test (FST) and tail suspending test (TST) of mice. In addition, the chronic application of Bai by i.p. for 21 d also reduced the immobility time and improved locomotor activity in chronic unpredictable mild stress (CMS) model rats. Furthermore, it was shown that Bai reversed the reduction of extracellular ERKs phosphorylation and the level of BDNF expression in the hippocampus of CMS model rats. These results suggest that Bai produce an antidepressant-like effect and this effect is at least partly mediated by hippocampal ERK-mediated neurotrophic action" http://www.ncbi.nlm.nih.gov/pubmed/21415537 1 1054 A. Dhir and S. K. Kulkarni 2008 "Possible involvement of nitric oxide (NO) signaling pathway in the antidepressant-like effect of MK-801(dizocilpine), a NMDA receptor antagonist in mouse forced swim test" Indian J.Exp.Biol. 46 3 164-170 "L-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) is an important signaling pathway involved in depression. With this information, the present study aimed to study the involvement of this signaling pathway in the antidepressant-like action of MK-801 (dizocilpine; N-methyl-d-aspartate receptor antagonist) in the mouse forced-swim test. Total immobility period was recorded in mouse forced swim test for 6 min. MK-801 (5-25 microg/kg., ip) produced a U-shaped curve in reducing the immobility period. The antidepressant-like effect of MK-801 (10 microg/kg, ip) was prevented by pretreatment with L-arginine (750 mg/kg, ip) [substrate for nitric oxide synthase (NOS)]. Pretreatment of mice with 7-nitroindazole (7-NI) (25 mg/kg, ip) [a specific neuronal nitric oxide synthase inhibitor] produced potentiation of the action of subeffective dose of MK-801 (5 microg/kg, ip). In addition, treatment of mice with methylene blue (10 mg/kg, ip) [direct inhibitor of both nitric oxide synthase and soluble guanylate cyclase] potentiated the effect of MK-801 (5 microg/kg, ip) in the forced-swim test. Further, the reduction in the immobility period elicited by MK-801 (10 microg/kg, ip) was also inhibited by pretreatment with sildenafil (5 mg/kg, ip) [phosphodiesterase 5 inhibitor]. The various modulators used in the study and their combination did not produce any changes in locomotor activity per se and in combination with MK-801. MK-801 however, at higher doses (25 microg/kg, ip) produced hyperlocomotion. The results demonstrated the involvement of nitric oxide signaling pathway in the antidepressant-like effect of MK-801 in mouse forced-swim test" http://www.ncbi.nlm.nih.gov/pubmed/18432055 1 1055 N. Nagata and H. Rasmussen 1968 Parathyroid hormone and renal cell metabolism Biochemistry 7 10 3728-3733 http://www.ncbi.nlm.nih.gov/pubmed/4300707 0 1056 "S. Ferre, L. Gimenez-Llort, F. Artigas and E. Martinez" 1994 "Motor activation in short- and long-term reserpinized mice: role of N-methyl-D-aspartate, dopamine D1 and dopamine D2 receptors" Eur.J.Pharmacol. 255 01-Mar 203-213 "The effects of dopamine D1 and dopamine D2 receptor agonists and of subconvulsant doses of N-methyl-D-aspartate (NMDA) and the non-competitive NMDA receptor antagonist, dizocilpine (MK-801), alone and in combination, on the motor activity of short- and long-term reserpinized mice (mice pretreated with 5 mg/kg reserpine 4 h or 20 h before, respectively) were analyzed. With short-term reserpinization, the dopamine D2 receptor agonist, quinpirole (1.5 mg/kg), but not the dopamine D1 receptor agonist, SKF-38393 (15 mg/kg), increased motor activity. The effect of quinpirole in short-term reserpinized mice was potentiated by the simultaneous administration of SKF-38393 (15 mg/kg) and was counteracted by the previous administration of the dopamine D2 receptor antagonist, raclopride (1 mg/kg), or by the simultaneous administration of NMDA (25 mg/kg) or MK-801 (0.5 mg/kg). Neither NMDA (25-100 mg/kg) nor MK-801 (0.5-3 mg/kg) induced motor activation in short-term reserpinized mice. With long-term reserpinization, either quinpirole (1.5 mg/kg) or SKF-38393 (15 mg/kg) increased motor activity. The effect of quinpirole in long-term reserpinized mice was not potentiated by the concurrent administration of SKF-38393 (15 mg/kg), was inhibited by the simultaneous administration of MK-801 (0.5 mg/kg) and was not modified by NMDA (25 mg/kg). The effect of SKF-38393 (15 mg/kg) in long-term reserpinized mice was inhibited by the concomitant administration of MK-801 (0.5 mg/kg) and was slightly antagonized by NMDA (25 mg/kg). NMDA induced motor activation in long-term reserpinized mice at doses which were similar to those causing motor activation in non-reserpinized mice (75 and 100 mg/kg), while MK-801 induced motor activation at a dose which was associated with motor depression in non-reserpinized mice (2 mg/kg). The NMDA-induced motor activation in long-term reserpinized mice was counteracted by the previous administration of a low dose of MK-801 (0.5 mg/kg) and was still present when a stronger dopamine-depleting pretreatment was used. These results are interpreted on the basis of changes in sensitivity of the direct striatal efferent pathway after long-term reserpinization" http://www.ncbi.nlm.nih.gov/pubmed/7913043 0 1057 "D. H. Snow, J. A. Bogan, T. A. Douglas and H. Thompson" 1979 Phenylbutazone toxicity in ponies Vet.Rec. 105 2 26-30 "The oral administration of phenylbutazone at a dose rate of approximately 10 mg per kg per day for seven to 14 days resulted in the development of signs of toxicity in seven of eight ponies treated. Clinical signs included anorexia, depression and abdominal oedema. Blood biochemical determinations showed a decrease in total plasma protein and calcium concentrations with an increase in urea concentration. These changes were considered indicative of water retention. Three of the ponies died during treatment following the development of shock. Shock was considered to arise from the submucosal oedema of the large intestine observed on necropsy. Oral ulceration was also found in these animals. In two ponies intravenous administration of phenylbutazone (4.0 mg per kg) for seven days was studied. In one of these ponies a marked decrease in total plasma protein concentration occurred" http://www.ncbi.nlm.nih.gov/pubmed/555115 0 1058 "S. Matsuyama, A. Matsumoto, T. Enomoto and T. Nishizaki" 2000 Activation of nicotinic acetylcholine receptors induces long-term potentiation in vivo in the intact mouse dentate gyrus Eur.J.Neurosci. 12 10 3741-3747 "The present study was conducted to clarify the role of nicotinic ACh receptors (nAChRs) on long-term potentiation (LTP) in vivo in the intact mouse dentate gyrus using extracellular recording techniques. Intraperitoneal application of nicotine at a dose of 3.0 mg/kg but not 0.03 or 0.3 mg/kg produced a gradually developing, long-lasting increase for 120 min similar to tetanic LTP. Nicotine at a dose of 9. 0 mg/kg caused a temporary increase followed by depression. The long-lasting potentiation induced by nicotine at 3.0 mg/kg, which was named nicotinic long-term potentiation (LTPn), and tetanic LTP were significantly suppressed by pretreatment with mecamylamine (0.5 mg/kg i.p.), a nonselective nicotinic antagonist, but not affected by postapplication of mecamylamine. Interestingly, choline, a selective alpha7 nAChR agonist, at 3.0-90 mg/kg, induced the long-lasting potentiation similar to LTPn in a dose-dependent manner in vivo in the intact mouse dentate gyrus. The long-lasting potentiation induced by choline (30 mg/kg i.p.) was additionally increased by postapplication of nicotine (3.0 mg/kg i.p.) or tetanic stimulation. The present study revealed that systemic application of nicotine or choline induced the long-lasting potentiation in vivo in the intact mouse dentate gyrus, suggesting that alpha7 nAChRs may contribute to the induction of LTP by nicotine, and supporting in vivo animal studies that nicotine improves learning and memory performance" http://www.ncbi.nlm.nih.gov/pubmed/11029644 0 1059 "J. Y. Sun, X. S. Wu and L. G. Wu" 2002 Single and multiple vesicle fusion induce different rates of endocytosis at a central synapse Nature 417 6888 555-559 "During synaptic transmission, neurotransmitter-laden vesicles fuse with the presynaptic membrane and discharge their contents into the synaptic cleft. After fusion, the vesicular membrane is retrieved by endocytosis for reuse. This recycling mechanism ensures a constant supply of releasable vesicles at the nerve terminal. The kinetics of endocytosis have been measured mostly after intense or non-physiological stimulation. Here we use capacitance measurements to resolve the fusion and retrieval of single and multiple vesicles following mild physiological stimulation at a mammalian central synapse. The time constant of endocytosis after single vesicle fusion was 56 ms; after a single action potential or trains at < or = 2 Hz it was about 115 ms, but increased gradually to tens of seconds as the frequency and the number of action potentials increased. These results indicate that an increase in the rate of exocytosis at the active zone induces a decrease in the rate of endocytosis. Existing models, including inhibition of endocytosis by Ca(2+), could not account for these results our results suggest that an accumulation of unretrieved vesicles at the plasma membrane slows endocytosis. These findings may resolve the debate about the dependence of endocytosis kinetics on the stimulation frequency, and suggest a potential role of regulation of endocytosis in short-term synaptic depression" http://www.ncbi.nlm.nih.gov/pubmed/12037569 0 1060 J. BABINSKI 1950 [Cure of a case of melancholia after a provoked attack of voltaic vertigo] Ann.Med.Psychol.(Paris) 108 1 3 325-330 http://www.ncbi.nlm.nih.gov/pubmed/15425999 0 1061 "W. Malinka, M. Sieklucka-Dziuba, G. Rajtar, R. Rejdak, K. Rejdak and Z. Kleinrok" 2000 "Synthesis of some N-substituted 3,4-pyrroledicarboximides as potential CNS depressive agents" Pharmazie 55 1 Sep-16 "As a continuation of our work on N-[4-aryl(heteroaryl)piperazin-1-ylalkyl]-3,4-pyrro ledicarboximides, which were characterized by strong analgesic activity and CNS depressive action, several novel N-substituted 3,4-pyrroledicarboximides were prepared and eleven representatives were examined in a series of in vivo CNS tests. A few of these compounds displayed a similar profile of biological selectivity to that of 3,4-pyrroledicarboximides described previously; their structure-activity relationships are discussed" http://www.ncbi.nlm.nih.gov/pubmed/10683864 0 1062 Y. Akiba and J. Matsumoto 1976 Antithyroid activity of goitrin in chicks Poult.Sci. 55 2 716-719 "Antithyroid activity of orally administered goitrin was assessed by parallel-line assay in chicks using four indices. The relative potency of goitrin in chicks was estimated to be approximately 0.31 times the potency of PTU in causing enlargement of thyroid gland, 0.06 times in effect on depression in plasma thyroid hormone, and 0.08 times in inhibitory effects on biosynthesis of thyroid hormone in the gland. It might be concluded that thyroid hormone synthesis is not so much suppressed to the degree expected from the enlargement of thyroid gland when goitrin is administered orally to the chick" http://www.ncbi.nlm.nih.gov/pubmed/59353 0 1063 R. H. Haschke and B. R. Fink 1975 Lidocaine effects on brain mitochondrial metabolism in vitro Anesthesiology 42 6 737-740 "Both lidocaine and anoxia inhibit rapid axonal transport. In an attempt to elucidate the mechanism of this action of lidocaine, its effect on mitochondrial respiration was studies. The local anesthetic produces a dose-dependent inhibition of oxygen consumption (50 per cent inhibition at 8mM) by porcine brain mitochondria when glutamate, but not when succinate, serves as the substrate. This indicates electron transport is blocked at the NADH dehydrogenase level. Potent uncoupling of oxidative phosphorylation is observed with both substrates. All of the effects are readily reversible upon removal of the anesthetic. It is concluded that lidocaine apparently inhibits rapid axonal transport by depressing oxidative metabolism" http://www.ncbi.nlm.nih.gov/pubmed/1130742 0 1064 B. Gajkowska and J. W. Borowicz 1982 Ultrastructural study of the hypothalamo-neurohypophyseal system in rats after colchicine treatment Neuropatol.Pol. 20 03-Apr 317-328 http://www.ncbi.nlm.nih.gov/pubmed/6191249 0 1065 E. Friedman and S. Gershon 1974 Effect of delta8-THC on alcohol-induced sleeping time in the rat Psychopharmacologia. 39 3 193-198 http://www.ncbi.nlm.nih.gov/pubmed/4427987 0 1066 "J. Svejcar, J. Pekarek and J. Johanovsky" 1968 Studies on production of biologically active substances which inhibit cell migration in supernatants and extracts of hypersensitive lymphoid cells incubated with specific antigen in vitro Immunology 15 1 01-Nov http://www.ncbi.nlm.nih.gov/pubmed/5664398 0 1067 "J. J. Lehot, B. J. Leone and P. Foex" 1987 Calcium reverses global and regional myocardial dysfunction caused by the combination of verapamil and halothane Acta Anaesthesiol.Scand. 31 5 441-447 "In order to evaluate the effects of the combination of halothane and verapamil on left ventricular function and coronary blood flow (CBF), six sheep were anaesthetized with halothane (1.2% inspired) and given increasing cumulative doses of intravenous verapamil. Regional myocardial function was assessed by sonomicrometry in the areas supplied by the left anterior descending coronary artery (LAD) and the left circumflex coronary artery (LC). Changes in global haemodynamics, atrioventricular conduction, LV relaxation and systolic shortening after 0.32 mg X kg-1 intravenous verapamil indicated impaired left ventricular function. Significant myocardial dysfunction (post-systolic shortening) occurred in the LAD territory, accompanied by a 64% decrease (42 +/- 6 to 15 +/- 3, P less than 0.01) in coronary perfusion pressure (CPP). Coronary blood flow in the LC segment decreased 83% (102 +/- 15 to 17 +/- 13, P less than 0.01) as coronary reserve was exhausted with the decrease in CPP. Calcium chloride reversed the impairment of global and regional myocardial function observed with verapamil, improved the impaired left ventricular relaxation, but did not significantly alter atrioventricular conduction. Thus the combination halothane-verapamil can cause significant left ventricular depression and myocardial dysfunction, possibly by inducing subendocardial ischaemia or by direct pharmacologic effect. Calcium chloride reverses this regional myocardial dysfunction as well as the deleterious global haemodynamic changes caused by halothane-verapamil; however, the changes in atrioventricular conduction are not corrected by calcium" http://www.ncbi.nlm.nih.gov/pubmed/3630588 0 1068 L. C. York and M. C. van Rossum 2009 Recurrent networks with short term synaptic depression J.Comput.Neurosci. 27 3 607-620 "Cortical circuitry shows an abundance of recurrent connections. A widely used model that relies on recurrence is the ring attractor network, which has been used to describe phenomena as diverse as working memory, visual processing and head direction cells. Commonly, the synapses in these models are static. Here, we examine the behaviour of ring attractor networks when the recurrent connections are subject to short term synaptic depression, as observed in many brain regions. We find that in the presence of a uniform background current, the network activity can be in either of three states: a stationary attractor state, a uniform state, or a rotating attractor state. The rotation speed can be adjusted over a large range by changing the background current, opening the possibility to use the network as a variable frequency oscillator or pattern generator. Finally, using simulations we extend the network to two-dimensional fields and find a rich range of possible behaviours" http://www.ncbi.nlm.nih.gov/pubmed/19578989 0 1069 S. B. Ross and A. L. Renyi 1977 "Inhibition of the neuronal uptake of 5-hydroxytryptamine and noradrenaline in rat brain by (Z)- and (E)-3-(4-bromophenyl)-N,N-dimethyl-3-(3-pyridyl) allylamines and their secondary analogues" Neuropharmacology 16 1 57-63 http://www.ncbi.nlm.nih.gov/pubmed/834363 0 1070 "W. K. Ilias, C. H. Williams, R. T. Fulfer and S. E. Dozier" 1985 Diltiazem inhibits halothane-induced contractions in malignant hyperthermia-susceptible muscles in vitro Br.J.Anaesth. 57 10 994-996 "The ability of diltiazem to suppress halothane and halothane-caffeine induced contractures in malignant hyperthermia (MH) susceptible pig muscle, was tested in vitro. Muscle specimens were divided into two groups and tested with a modified halothane-caffeine contracture test. One group acted as the control; the other group was pretreated with diltiazem 20 mumol litre-1. The control muscles developed contractures attributable to halothane and halothane-caffeine, whereas the diltiazem-treated specimens did not. Increases in muscle twitch tension as a result of halothane or halothane-caffeine exposure occurred in treated and untreated specimens, but were significantly delayed in the presence of diltiazem. Muscle exhaustion observed after halothane and halothane-caffeine exposure in the control specimens did not occur in the diltiazem treated muscles" http://www.ncbi.nlm.nih.gov/pubmed/4041327 0 1071 "P. Willner, T. Montgomery and D. Bird" 1981 Behavioural changes during withdrawal from desmethylimipramine (DMI). II. Increased resistance to extinction Psychopharmacology (Berl) 75 1 60-64 "Rats withdrawn from chronic treatment with the tricyclic antidepressant desmethylimipramine (DMI) showed increased resistance to extinction in a runway and in continuously reinforced lever pressing. Changes were not seen in animals maintained on DMI. In acquisition, in the runway, there were no significant differences between groups; in the Skinner box, animals maintained on DMI performed worse than controls, but withdrawn animals recovered to control levels of performance. It is suggested that the effect on extinction may be mediated by a decrease in the efficacy of the dorsal noradrenaline bundle, which develops during chronic DMI treatment, but is masked by the presence of DMI. The implications of the conclusion for the "" revised catecholamine hypothesis of depression"" are discussed" http://www.ncbi.nlm.nih.gov/pubmed/6795662 1 1072 "R. L. Momparler, M. Y. Chu and G. A. Fischer" 1968 Studies on a new mechanism of resistance of L5178Y murine leukemia cells to cytosine arabinoside Biochim.Biophys.Acta 161 2 481-493 http://www.ncbi.nlm.nih.gov/pubmed/4174433 0 1073 "A. V. Kalueff, P. S. Gallagher and D. L. Murphy" 2006 Are serotonin transporter knockout mice 'depressed'?: hypoactivity but no anhedonia Neuroreport 17 12 1347-1351 "Although the serotonin transporter is a key target for antidepressants, its exact role in depression etiology remains unclear. While serotonin transporter knockout mice are a potential model to examine this problem, their depression profile is unclear in several 'despair' tests, and may be confounded by their hypoactivity phenotype (confirmed here by marble-burying and bedding tests). To assess depression in these mice, we evaluated wild-type, heterozygous, and serotonin transporter knockout C57BL/6 male mice on a well-validated, anhedonia-based depression paradigm, the sucrose preference test. Overall, all three genotypes showed similar sucrose preference, indicating an unaltered hedonic state. These results demonstrate that depression-like behavior (unlike hypoactivity) is not a baseline phenotypic feature of serotonin transporter knockout mice, suggesting anew that these mice do not represent a genetic model of depression" http://www.ncbi.nlm.nih.gov/pubmed/16951583 1 1074 "S. B. Chaudhuri, N. M. Roy, S. Sikdar, P. K. Mukherjee, P. C. Das and A. Chatterjee" 1977 Further chemical & pharmacological studies of some 4-N-substituted piperazine-I-carboxylic acid ethyl ester Indian J.Exp.Biol. 15 8 639-641 http://www.ncbi.nlm.nih.gov/pubmed/606669 0 1075 "D. J. Bonthius, J. L. Stringer, E. W. Lothman and O. Steward" 1994 Spreading depression and reverberatory seizures induce the upregulation of mRNA for glial fibrillary acidic protein Brain Res. 645 01-Feb 215-224 "The present study evaluates the relative roles of seizure activity and spreading depression in upregulating glial fibrillary acidic protein (GFAP) mRNA expression. Stimulating electrodes were placed bilaterally in the angular bundle, and recording electrodes were placed bilaterally in the dentate gyrus of adult rats. Intense electrographic seizures were induced by delivering stimulus trains through one stimulating electrode. In some cases, spreading depression accompanied the seizures, while in other cases, the seizures occurred in the absence of spreading depression. Animals were killed 24 h following the last stimulus train, and the forebrains were prepared for quantitative in situ hybridization. Seizure activity and spreading depression led to significant increases in GFAP mRNA levels in the hippocampal formation. Seizure activity alone (without spreading depression) induced a 4-fold increase in GFAP mRNA levels in the hilus and molecular layer of the dentate gyrus and in stratum lacunosum-moleculare of the hippocampus. When seizure activity was accompanied by spreading depression, there was a 10-fold increase in GFAP mRNA levels in these same regions. Regional differences within the hippocampal formation in glial cell response were evident. While GFAP mRNA levels in stratum lacunosum-moleculare of the hippocampus were upregulated by seizure activity and spreading depression, levels in hippocampal stratum radiatum of the hippocampus remained unchanged. The results suggest that abnormal neuronal activity can influence glial cell gene expression and that spreading depression is a stronger signal than seizure activity in upregulating GFAP mRNA levels" http://www.ncbi.nlm.nih.gov/pubmed/8062084 0 1076 C. Schmauss 2015 An HDAC-dependent epigenetic mechanism that enhances the efficacy of the antidepressant drug fluoxetine Sci.Rep. 5 8171 "Depression is a prevalent and debilitating psychiatric illnesses. However, currently prescribed antidepressant drugs are only efficacious in a limited group of patients. Studies on Balb/c mice suggested that histone deacetylase (HDAC) inhibition may enhance the efficacy of the widely-prescribed antidepressant drug fluoxetine. This study shows that reducing HDAC activity in fluoxetine-treated Balb/c mice leads to robust antidepressant and anxiolytic effects. While reducing the activity of class I HDACs 1 and 3 led to antidepressant effects, additional class II HDAC inhibition was necessary to exert anxiolytic effects. In fluoxetine-treated mice, HDAC inhibitors increased enrichment of acetylated histone H4 protein and RNA polymerase II at promotor 3 of the brain-derived neurotrophic factor (Bdnf) gene and increased Bdnf transcription from this promotor. Reducing Bdnf-stimulated tropomyosin kinase B receptor activation in fluoxetine-treated mice with low HDAC activity abolished the behavioral effects of fluoxetine, suggesting that the HDAC-triggered epigenetic stimulation of Bdnf expression is critical for therapeutic efficacy" http://www.ncbi.nlm.nih.gov/pubmed/25639887 1 1077 A. Rahkamo and H. Tuompo 1974 Effect of molybdenum on the developing rat tooth in tissue culture Proc.Finn.Dent.Soc. 70 4 141-146 http://www.ncbi.nlm.nih.gov/pubmed/4413073 0 1078 "L. Korbova, J. Kohout, J. Cizkova and A. Cihak" 1977 Inhibitory effect of cycloheximide on gastric secretion in rats Biochem.Pharmacol. 26 10 979-981 http://www.ncbi.nlm.nih.gov/pubmed/16607 0 1079 P. Hedqvist 1974 Prostaglandin action on noradrenaline release and mechanical responses in the stimulated guinea pig vas deferens Acta Physiol Scand. 90 1 86-93 http://www.ncbi.nlm.nih.gov/pubmed/4814547 0 1080 B. S. Seebach and L. M. Mendell 1996 Maturation in properties of motoneurons and their segmental input in the neonatal rat J.Neurophysiol. 76 6 3875-3885 "1. The isolated neonatal rat spinal chord preparation was used to investigate the development of segmental afferent input to lumbar motoneourons during the first nine postnatal days. Motoneurons, identified with the use of antidromic stimulation of the ventral roots, were characterized electrophysiologically, and their synaptic input in response to stimulation of the homologous dorsal root was studied. 2. Motoneurons in postnatal day (P) 1-3 preparations exhibited lower rheobase and lower input conductance than those impaled in spinal cords taken from animals at P7-9. This finding is consistent with the increase in motoneuron size known to occur during this time. 3. Monosynaptic excitatory postsynaptic potentials (EPSPs) evoked at low-frequency (0.1-Hz) stimulation in high-Ca2+ saline exhibited no change in mean amplitude between P1-3 and P7-9 despite an increase in input conductance of the motoneurons, suggesting that some aspect of these synapses underwent a compensatory change. Polysynaptic EPSPs were smaller in the older animals. 4. When bursts of stimuli were delivered at higher frequencies ranging from 10 to 167 Hz, the EPSPs exhibited substantial depression. The depression of monosynaptic EPSPs was significantly less at P7-9 than at P1-3. Changing the bathing solution from a high-Ca2+ saline to a low-Ca2+/high-Mg2+ saline reduced the amplitude of the monosynaptic EPSP and made it less susceptible to depression during high-frequency stimulation. Facilitation of the evoked response, which has been observed in the adult rat, was never seen under any of these conditions. 5. Although synapses on high-rheobase motoneurons exhibited less depression than those on low-rheobase motoneurons, as anticipated from previous results in adults, the EPSPs at synapses on high-rheobase motoneurons tended to be larger in amplitude, not smaller as expected. This suggests that the specialization among synapses on motoneurons that exists in adults has not yet developed by P7-9. Instead, EPSP amplitude may be greater in motoneurons that have been growing rapidly, such as the high-rheobase motoneurons found during these stages of development. 6. Evidence is presented that the growing diversity shown in modulation behavior at the Ia afferent motoneuron synapse during the first postnatal week is determined primarily by motoneuron characteristics. It is speculated that as motoneurons grow during the immediate postnatal period, the presynaptic terminal regions of axons terminating on them become specialized to render the synapse less susceptible to depression. This specialization may be myelination of the afferent terminals or may perhaps be related to the transmitter release process itself. The adult distribution of depression develops later, presumably as the components of the monosynaptic reflex mature" http://www.ncbi.nlm.nih.gov/pubmed/8985885 0 1081 "S. I. Deutsch, R. B. Rosse, K. D. Long, B. L. Gaskins, J. A. Burket and J. Mastropaolo" 2008 "Sodium butyrate, an epigenetic interventional strategy, attenuates a stress-induced alteration of MK-801's pharmacologic action" Eur.Neuropsychopharmacol. 18 8 565-568 "Twenty-four hours after mice are exposed to a single session of forced swimming in cold water, the ability of MK-801 (dizocilpine), a noncompetitive NMDA receptor antagonist, to antagonize electrically precipitated seizures is reduced. Conceivably, this reduction in MK-801's antiseizure efficacy reflects a stress-induced alteration in NMDA receptor-mediated neurotransmission due to changes in gene expression 24 h after a single stress. Recently, epigenetic interventional strategies impacting expression of genes whose regulation is controlled by the acetylation status of histone proteins in the nucleosome, an octomeric complex of histone proteins and promoter regions of double-stranded DNA, have been tested in preclinical models of various neuropsychiatric disorders, including Huntington disease and major depression. These strategies have been studied extensively in cancer biology. In the current investigation, the severity of the stress-induced reduction of MK-801's ability to raise the threshold voltage for the elicitation of tonic hindlimb extension was reduced when sodium butyrate (1.5 g/kg, ip) was administered around the time of stress. Prior research showed that this dose of sodium butyrate reliably increased the acetylation status of H3 and H4 histone proteins in the hippocampus and cerebral cortex of mice. Thus, the attenuation of the stress-induced reduction of MK-801's antiseizure efficacy may be due to the increased acetylation of histone proteins in the nucleosomal core and promotion of gene expression. These data encourage development of epigenetic strategies to prevent some of the deleterious consequences of stress" http://www.ncbi.nlm.nih.gov/pubmed/18164185 0 1082 "N. Rawal, L. Nuutinen, P. P. Raj, S. L. Lovering, A. H. Gobuty, J. Hargardine, L. Lehmkuhl, R. Herva and E. Abouleish" 1991 "Behavioral and histopathologic effects following intrathecal administration of butorphanol, sufentanil, and nalbuphine in sheep" Anesthesiology 75 6 1025-1034 "A large number of opioids and nonopioids have been administered epidurally and intrathecally in the hope of providing segmental analgesia without serious adverse effects. However, neurotoxicity data are generally unavailable for many of these drugs. The present study evaluated the behavioral, motor, electroencephalographic, and histopathologic changes following intrathecal injection of large and small doses of butorphanol, sufentanil, and nalbuphine in sheep. Thirty-two sheep (20-32 kg) were anesthetized and catheters placed intrathecally after hemilaminectomy. The large doses of butorphanol, sufentanil and nalbuphine were 0.375 mg/kg (4.4-5.2 ml), 7.5 micrograms/kg (3.6-4.8 ml) and 0.75 mg/kg (1.5-2.4 ml), and the small doses were 0.075 mg/kg (0.9-1.1 ml), 1.5 micrograms/kg (0.7-0.9 ml) and 0.15 mg/kg (0.38-0.5 ml), respectively. The opioids were administered intrathecally every 6 h for 3 days and the above-mentioned parameters studied. Five sheep received intrathecal saline (1.1 or 5.2 ml) and served as controls. Histopathologic changes were evaluated by a neuropathologist blinded to the study protocol. Irrespective of dose, intrathecal injection of butorphanol was associated with severe behavioral responses such as agitation, rigidity, vocalization, and restlessness, as well as prolonged or irreversible hindlimb paralysis. Electroencephalography showed increased cortical activity or seizure activity. One sheep died because of severe respiratory depression that did not respond to naloxone. Spinal cord histologic changes consisted of suppurative meningitis and myelitis as well as neuronal changes such as spongiosis and chromatolysis. Large doses of intrathecal sufentanil were associated with similar though somewhat less severe responses. The behavioral and motor changes following the small dose of intrathecal sufentanil were of mild to moderate nature. Following intrathecal nalbuphine, the above-mentioned changes were similar to those seen in control animals. We conclude that butorphanol in doses of 0.075 and 0.375 mg/kg intrathecally and sufentanil 7.5 micrograms/kg intrathecally are neurotoxic in sheep" http://www.ncbi.nlm.nih.gov/pubmed/1835823 0 1083 D. R. Ackerman and R. Gonzalez-Enders 1969 Metabolism of rabbit spermatozoa in homologous immune serum and oviductal fluid Biol.Reprod. 1 4 407-410 http://www.ncbi.nlm.nih.gov/pubmed/5406668 0 1084 "K. S. Kim, Y. M. Kang, Y. Kang, T. S. Park, H. Y. Park, Y. J. Kim, B. S. Han, C. H. Kim, C. H. Lee, P. A. Ardayfio, P. L. Han, B. H. Jung and K. S. Kim" 2014 Pitx3 deficient mice as a genetic animal model of co-morbid depressive disorder and parkinsonism Brain Res. 1552 72-81 "Approximately 40-50% of all patients with Parkinsons disease (PD) show symptoms and signs of depressive disorders, for which neither pathogenic understanding nor rational treatment are available. Using Pit3x-deficient mice, a model for selective nigrostriatal dopaminergic neurodegeneration, we tested depression-related behaviors and acute stress responses to better understand how a nigrostriatal dopaminergic deficit increases the prevalence of depressive disorders in PD patients. Pitx3-deficient mice showed decreased sucrose consumption and preference in the two-bottle free-choice test of anhedonia. Acute restraint stress increased c-Fos (known as a neuronal activity marker) expression levels in various brain regions, including the prefrontal cortex, striatum, nucleus accumbens, and paraventricular nucleus of the hypothalamus (PVN), in both Pitx3+/+ and -/- mice. However, the stress-induced increases in c-Fos levels in the cortex, dorsal striatum, and PVN were significantly greater in Pitx3-/- than +/+ mice, suggesting that signs of depressive disorders in parkinsonism are related to altered stress vulnerability. Based on these results, we propose that Pitx3-/- mice may serve as a useful genetic animal model for co-morbid depressive disorder and parkinsonism" http://www.ncbi.nlm.nih.gov/pubmed/24480473 1 1085 J. A. Jesberger and J. S. Richardson 1986 Differential effects of antidepressant drugs on [3H]dihydroalprenolol and [3H]imipramine ligand recognition sites in olfactory bulbectomized and sham-lesioned rats Gen.Pharmacol. 17 3 293-307 "In the olfactory bulbectomy rat model of major depression, the binding of [3H]imipramine is increased by 60% in the midbrain, reduced by 30% in the pons and by 20% in the hippocampus, and unchanged in the hypothalamus 6 weeks after the bulbectomy. Binding of [3H]dihydroalprenolol is unchanged in the midbrain but is increased by 30% in the pons and 15% in the hippocampus. The i.p. administration of the antidepressants amitriptyline, mianserin, tranylcypromine (all at a dose of 10 mg/kg) or iprindole (25 mg/kg) for 28 days followed by a 5-day drug washout period, alters brain part [3H]imipramine and [3H]dihydroalprenolol binding in a manner that is a function of the particular drug, brain part and lesion effect. Only in the hippocampus did the lesion increase beta-binding that was reduced by all four antidepressant drugs" http://www.ncbi.nlm.nih.gov/pubmed/3013716 1 1086 "C. M. Czarnecki, O. A. Evanson, M. D. Powers, D. A. Grahn and A. L. Good" 1981 Effect of furazolidone on plasma enzyme and protein levels in turkey poults Poult.Sci. 60 7 1537-1543 "Furazolidone (FZ) at a dose of 700 ppm was fed to turkey poults beginning at 2 weeks of age. In trial 1, plasma collected by venipuncture was assayed for glutamic oxalacetic transaminase (GOT), lactate dehydrogenase (LDH), and total protein at 19, 23, 26, and 30 days of age. Significant (P less than or equal to .05) differences were noted only in levels of plasma LDH, which were elevated in FZ-fed poults at all stages studied. In Trial 2, plasma collected by venipuncture was assayed for creatine phosphokinase (CPK), GOT, glutamic pyruvic transaminase (GPT), and LDH daily from 15 through 19 days of age and for protein at 19 days of age. Significant elevations (P less than or equal to .05) were noted in levels of plasma a) CPK at 15 days, b) GOT at 18 days, and c) LDH at 17 and 19 days. A significant (P less than or equal to .01) depression in plasma protein was observed at 19 days. Plasma GPT was either absent or present in very low concentrations. These data suggest that FZ exerts its primary effect on the myocardium. THe initial myocardial changes occur prior to their detection by known electrocardiographic (ECG) technics" http://www.ncbi.nlm.nih.gov/pubmed/7322976 0 1087 "S. J. Chen, C. L. Kao, Y. L. Chang, C. J. Yen, J. W. Shui, C. S. Chien, I. L. Chen, T. H. Tsai, H. H. Ku and S. H. Chiou" 2007 Antidepressant administration modulates neural stem cell survival and serotoninergic differentiation through bcl-2 Curr.Neurovasc.Res. 4 1 19-29 "The hippocampus has long been associated with learning, memory, and modulation of emotional responses. Previous studies demonstrated that stress-induced loss of hippocampal neurons may contribute to the pathogenesis of depression. The recent observations supported that antidepressant drugs increase the production of serotoninergic neurotransmitter and they play a critical role in the initiation of neurogenesis in the hippocampus. In order to explore the possible new mechanism of the treatment of depression, we cultured neural stem cells (NSCs) derived from the hippocampus of adult rats as an in vitro model to evaluate the capabilities of neuroprotection and neural differentiation in NSCs by fluoxetine (FL) treatment. Our results showed that 20 microM FL treatment can significantly increase the proliferation rate of NSCs (p<0.05), and up-regulate the mRNA and protein expressions of Bcl-2 in Day-7 FL-treated NSCs (p<0.01). Using Bcl-2 gene silencing with small interfering RNA, our data verified that FL can prevent Fas ligand-induced caspase-dependent apoptosis in NSCs through the activation of Bcl-2. The in vitro observation and immunofluorescent study further demonstrated that FL treatment can stimulate the neurite development and serotoninergic differentiation of NSCs through the activation of Bcl-2. Using microdialysis with high performance liquid chromatography- electrochemical detection, the functional release of serotonin in the differentiating NSCs with FL treatment was increased and simultaneously regulated by the Bcl-2 expressions. In sum, the study results indicate that antidepressant administration can increase NSCs survival, promote the neurite development, and facilitate NSCs differentiating into the functional serotoninergic neurons via the modulation of Bcl-2 expression" http://www.ncbi.nlm.nih.gov/pubmed/17311541 0 1088 "M. Woyke, H. Cwajda and J. Wojcicki" 1978 Platelet aggregation and adhesiveness as well as blood lipids level in dogs treated with di-(1-isoquinolinyl)-di-(pyridyl-2')-butane and carbocromen Pol.J.Pharmacol.Pharm. 30 1 77-81 "The effect of di-(1-isoquinolinyl)-di-(pyridyl-2')-butane (S-147) on platelet aggregation and adhesiveness as well as on blood lipids level (total lipids, triglycerides, total cholesterol) was tested in mongrel dogs, in comparison with carbocromen. The compounds administered iv (2 mg/kg/day) over 7 days inhibited ADP-induced aggregation, being without depressive influence on platelet adhesiveness. S-147 exhibited slightly stronger effect than carbocromen. The inhibition of platelet aggregation was accompanied by the decrease of serum lipids level" http://www.ncbi.nlm.nih.gov/pubmed/643741 0 1089 N. R. Kreisman and M. L. Smith 1993 Potassium-induced changes in excitability in the hippocampal CA1 region of immature and adult rats Brain Res.Dev.Brain Res. 76 1 67-73 "Orthodromic and spontaneous population spike activity was measured in vitro in the CA1 region of rat hippocampal slices to determine maturational differences in excitability and susceptibility to K(+)-induced seizures. Several indices of excitability in the CA1 region changed in a non-monotonic fashion during maturation, in response to step-wise increases in bath [K+]. Slices from rats 18-22 days old, showed a greater probability of both spontaneous epileptiform activity and episodes of seizure-like activity followed by spreading depression, and more prolonged durations of evoked seizure-like events. Elevation of [K+] in the bathing medium increased these indices in a similar manner in older rats but not to the same degree as in 18- to 22-day-old rats. However, the threshold level of bath [K+] resulting in evoked bursts of population spikes was lower in adult and 28- to 32-day-old rats than in 18- to 22-day-old rats, suggesting that excitability is not uniformly greater at any given age. In 10- to 15-day-old rats, elevation of bath [K+] either produced persistent blockade of population responses, or increased the amplitude of the initial population spike, without producing bursts. Basal levels of [K+] in the interstitium of the slices corresponded to the various levels of [K+] placed in the bathing medium and there were no differences among age groups. Therefore, differences in basal [K+]o cannot account for the maturational changes in excitability and seizure activity. The period from 18-22 days of age in the rat is a useful focal point for investigating mechanisms underlying maturational changes in propensity to develop seizures" http://www.ncbi.nlm.nih.gov/pubmed/8306432 0 1090 "A. Romano, D. Rubolini, M. Caprioli, G. Boncoraglio, R. Ambrosini and N. Saino" 2011 Sex-related effects of an immune challenge on growth and begging behavior of barn swallow nestlings PLoS.One. 6 7 e22805 "Parent-offspring conflicts lead the offspring to evolve reliable signals of individual quality, including parasite burden, which may allow parents to adaptively modulate investment in the progeny. Sex-related variation in offspring reproductive value, however, may entail differential investment in sons and daughters. Here, we experimentally manipulated offspring condition in the barn swallow (Hirundo rustica) by subjecting nestlings to an immune challenge (injection with bacterial lipopolysaccharide, LPS) that simulates a bacterial infection, and assessed the effects on growth, feather quality, expression of morphological (gape coloration) and behavioral (posture) begging displays involved in parent-offspring communication, as well as on food allocation by parents. Compared to sham-injected controls, LPS-treated chicks suffered a depression of body mass and a reduction of palate color saturation. In addition, LPS treatment resulted in lower feather quality, with an increase in the occurrence of fault bars on wing feathers. The color of beak flanges, feather growth and the intensity of postural begging were affected by LPS treatment only in females, suggesting that chicks of either sex are differently susceptible to the immune challenge. However, irrespective of the effects of LPS, parents equally allocated food among control and challenged offspring both under normal food provisioning and after a short period of food deprivation of the chicks. These results indicate that bacterial infection and the associated immune response entail different costs to offspring of either sex, but a decrease in nestling conditions does not affect parental care allocation, possibly because the barn swallow adopts a brood-survival strategy. Finally, we showed that physiological stress induced by pathogens impairs plumage quality, a previously neglected major negative impact of bacterial infection which could severely affect fitness, particularly among long-distance migratory birds" http://www.ncbi.nlm.nih.gov/pubmed/21818393 0 1091 "J. E. Chelly, E. S. Hysing, D. C. Hill, D. R. Abernethy, A. Dlewati, M. F. Doursout and R. G. Merin" 1987 Cardiovascular effects of and interaction between calcium blocking drugs and anesthetics in chronically instrumented dogs. V. Role of pharmacokinetics and the autonomic nervous system in the interactions between verapamil and inhalational anesthetics Anesthesiology 67 3 320-325 "To assess the role of both pharmacokinetics and the autonomic nervous system in the interaction between inhalational anesthetics and verapamil, dogs were chronically instrumented to measure heart rate, PR interval, dP/dt, cardiac output, and aortic blood pressure. In a first group of seven dogs, studied awake and during halothane (1.2%), enflurane (2.5%), and isoflurane anesthesia (1.6%), verapamil was infused for 30 min in doses calculated to obtain similar plasma concentrations (83 +/- 10, 82 +/- 6, 81 +/- 10, and 77 +/- 9 ng.ml-1, respectively). For the latter purpose, the infusion dose was 3 and 2 micrograms.kg-1.min-1 awake and during anesthesia, respectively, preceded by a loading dose of 200, 150, and 100 micrograms.kg-1, awake, during isoflurane, and halothane and enflurane, respectively. In awake dogs, verapamil induced an increase in heart rate (24 +/- 5 bpm) and PR interval (35 +/- 9 msec) and a decrease in mean arterial pressure (-5 +/- 2 mmHg) and dP/dt (-494 +/- 116 mmHg/s). Although plasma concentrations were similar in awake and in anesthetized dogs, the only statistically significant changes induced by verapamil were an increase in heart rate and a decrease in dP/dt during halothane and enflurane, while left atrial pressure increased only with enflurane. In a second group of six dogs, verapamil pharmacokinetics were determined in the presence and absence of a ganglionic blocking drug (chlorisondamine, 2 mg.kg-1 iv). Blockade of ganglionic transmission resulted in a decrease in both initial volume of distribution and total clearance of verapamil--changes similar to those previously reported with inhalational anesthetics.(ABSTRACT TRUNCATED AT 250 WORDS)" http://www.ncbi.nlm.nih.gov/pubmed/2888422 0 1092 "L. A. Jans, C. K. Lieben and A. Blokland" 2007 Influence of sex and estrous cycle on the effects of acute tryptophan depletion induced by a gelatin-based mixture in adult Wistar rats Neuroscience 147 2 304-317 "Women are more vulnerable to develop depression and anxiety disorders than men. This may be related to higher serotonergic vulnerability in women. Serotonergic vulnerability entails that differences between people in the regulation of serotonin (5-HT) determine the vulnerability of an individual to develop depression or other 5-HT-related disorders. The aim of the present experiment was to evaluate whether male and female Wistar rats differ in serotonergic vulnerability. Here, a stronger behavioral response to acute tryptophan (TRP) depletion was assumed to reflect serotonergic vulnerability. Twenty-four male and 48 female rats were repeatedly subjected to treatment with a gelatin-based protein-carbohydrate mixture, either with or without L-tryptophan. Female estrous cycle phase was determined by means of vaginal smears and the females were divided into two groups based on their estrous cycle phase: pro-estrus/estrus and met-estrus/di-estrus. Blood samples showed stronger TRP depletion in males than females. There was no effect of estrous cycle on plasma TRP concentrations. In contrast, treatment effects on some brain TRP concentrations were influenced by estrous cycle phase, females in pro-estrus/estrus showed the strongest response to TRP depletion. In the open field test and home cage emergence test, females in pro-estrus/estrus also showed the strongest behavioral response to acute TRP depletion. In general, females showed more activity than males in anxiety-related situations and this effect appeared to be enhanced by TRP depletion. In the social interaction test, passive body contact in males and females in pro-estrus/estrus was decreased after TRP depletion whereas it was increased in females in the met-estrus/di-estrus phase. Acute TRP depletion affected object recognition, but did not affect behavior in the forced swimming test and a reaction time task. It is concluded that sex and estrous cycle phase can influence the behavioral response to TRP depletion, and that females in pro-estrus/estrus show the strongest behavioral response to acute TRP depletion" http://www.ncbi.nlm.nih.gov/pubmed/17531394 1 1093 T. Kameyama and K. Sasaki 1970 [Comparison of hypotensive activities between synthetic bradykinin and bradykinin analogs in rats] Nihon Yakurigaku Zasshi 66 5 503-510 http://www.ncbi.nlm.nih.gov/pubmed/5529892 0 1094 "K. Nakamura, Y. Ikoma, K. Kimura, Y. Nakada, S. Kobayashi, M. Yamaguchi and H. Nakagawa" 1989 [Effects in animal models of depression of lisuride alone and upon coadministration with antidepressants] Nihon Yakurigaku Zasshi 94 1 81-89 "Effects of lisuride, a central dopamine and serotonin agonist of the ergot type, in animal models of depression were investigated in comparison with those of desipramine, mianserin and rolipram. Lisuride, like desipramine and mianserin, inhibited reserpine-induced hypothermia in mice (0.5-5.0 mg/kg, i.p.) and suppressed muricide in olfactory bulbectomized rats (ED50 = 0.16 mg/kg, i.p.) in a dose-dependent manner. The anti-muricidal effect was slightly enhanced by the repeated administration of 0.25 mg/kg lisuride. Lisuride (0.05-0.25 mg/kg, i.p.), like desipramine, dose-dependently reduced the duration of immobility in rats forced to swim, and this effect was antagonized by haloperidol. The reduction of immobility time was enhanced by the repeated administration of lisuride; at the same time, the ambulation in rats increased. Furthermore, the immobility-reducing effects of desipramine and rolipram were markedly enhanced by the co-administration of a low dose of lisuride (0.025 mg/kg, i.p.), which by itself had no effect on the immobility time. These results indicate that lisuride may be useful for the treatment of depression and indicate that a low dose of lisuride may enhance the clinical effectiveness of antidepressants such as desipramine" http://www.ncbi.nlm.nih.gov/pubmed/2792964 1 1095 "M. Mambrini, A. J. Roem, J. P. Carvedi, J. P. Lalles and S. J. Kaushik" 1999 "Effects of replacing fish meal with soy protein concentrate and of DL-methionine supplementation in high-energy, extruded diets on the growth and nutrient utilization of rainbow trout, Oncorhynchus mykiss" J.Anim Sci. 77 11 2990-2999 "Our objectives were to test the potential replacement of fish meal by soy protein concentrate (SPC) in high-energy, extruded diets fed to rainbow trout (Oncorhynchus mykiss) and to evaluate the efficiency of DL-methionine supplementation of soy-based diets. Groups of trout (initial BW 103 to 106 g) were fed to visual satiety with isonitrogenous (6.6% DM) high-energy (22.8 MJ/kg DM gross energy), extruded diets, in which fish meal was progressively replaced with SPC (0, 50, 75, and 100%). Three 100% SPC diets were formulated to be either unsupplemented or supplemented with DL-methionine, so that total methionine content was .8 or 1.0% of DM. The quality of the SPC source used was assessed by measuring the antitryptic and antigenic activities and the concentrations of the isoflavones daidzein and genistein. Apparent digestibility of the diets was determined using the indirect method. A growth trial was conducted over 90 d at a water temperature of 18 degrees C. In addition to body composition analysis, plasma amino acid concentrations, anti-soy protein antibodies in the serum, and isoflavone concentrations in the bile were measured. The SPC source tested exhibited low antitryptic and antigenic activities, but it contained high concentrations of isoflavones (1,990 and 5,903 ppm for daidzein and genistein, respectively). Protein digestibility was high (92%) and was unaffected either the proportion of SPC in the diet or by DL-methionine supplementation. This was also true for the availability of amino acids, except phenylalanine. Digestibility of lipid and energy was reduced by 19% when SPC totally replaced fish meal. Growth rate was reduced when more than 50% of the dietary protein was of soy origin (daily growth coefficient of 3.2 and 2.1% for the control and the unsupplemented 100% SPC diet, respectively). The effect on growth was mainly explained by a general decline in feed intake (13.7 and 12.0 g DM x kg BW(-1) x d(-1) for the control and the unsupplemented 100% SPC diet, respectively) and in lipid and, thus, in energy digestibility. The DL-methionine supplementation partially reversed the depressive effects of high dietary SPC incorporation (+13% growth), mainly by enhancing intake. The negative effect of SPC incorporation either may be due to the high isoflavone concentration or to an interaction between the soy protein component and the dietary lipids" http://www.ncbi.nlm.nih.gov/pubmed/10568469 0 1096 "O. A. Olsson, E. Swanberg, I. Svedinger and B. Waldeck" 1979 Effects of beta-adrenoceptor agonists on airway smooth muscle and on slow-contracting skeletal muscle: in vitro and in vivo results compared Acta Pharmacol.Toxicol.(Copenh) 44 4 272-276 Ten beta-adrenoceptor agonists were examined with respect to a) relaxation of pilocarpine-contracted trachea and depression of contractions of the soleus muscle of the guinea-pig in vitro and b) counteraction of histamine-induced bronchospasm and depression of contractions of the soleus muscle of the cat in vivo. There was a close correlation between the results obtained in vitro and results obtained on the corresponding tissues in vivo in spite of the different species used. A close correlation was also observed between effects on airway smooth muscle and on the soleus muscle contractions in vitro as well as in vivo for all compounds examined http://www.ncbi.nlm.nih.gov/pubmed/34976 0 1097 J. J. Ashley and G. Levy 1972 Inhibition of diphenylhydantoin elimination by its major metabolite Res.Commun.Chem.Pathol.Pharmacol. 4 2 297-306 http://www.ncbi.nlm.nih.gov/pubmed/5074529 0 1098 "T. Lafarga, P. O'Connor and M. Hayes" 2015 In silico methods to identify meat-derived prolyl endopeptidase inhibitors Food Chem. 175 337-343 "According to the World Health Organization (WHO), approximately 450 million people suffer from mental or neurological disorders and five of the ten leading causes of disability and premature death worldwide are psychiatric conditions. Social, biological and neurological sciences provided extensive understanding into the role of risk and protective factors in the development of mental disorders and poor mental health. Altered activity of a number of enzymes, such as prolyl endopeptidase (PEP, EC 3.4.21.26), has been linked to the prevention and treatment of a number of mental disorders, including anxiety, depression and Alzheimer's disease. The inhibition of PEP has potential for use in the prevention and in the treatment of mental disorders. The objective of this work was to identify PEP-inhibitory peptides from meat proteins using in silico methods. In this paper, five proteins commonly found in meat by-products were evaluated as a substrate for use in the generation of PEP inhibitory peptides. These include serum albumin, collagen and myosin. These proteins were cleaved in silico using BIOPEP and ExPASy PeptideCutter and the generated peptides were compared to known PEP-inhibiting peptides in the database of BIOPEP. A number of novel PEP inhibitory peptide sequences were identified in this study, including PPL, APPH, IPP and PPG with corresponding IC50 values of 2.86, 3.95, 4.02 and 2.70 mM, respectively. This work demonstrates the usefulness of in silico analysis for predicting the release of PEP-inhibiting peptides from meat proteins" http://www.ncbi.nlm.nih.gov/pubmed/25577089 0 1099 "T. Toda, K. Ishida, H. Kiyama, T. Yamashita and S. Lee" 2014 "Down-regulation of KCC2 expression and phosphorylation in motoneurons, and increases the number of in primary afferent projections to motoneurons in mice with post-stroke spasticity" PLoS.One. 9 12 e114328 "Spasticity obstructs motor function recovery post-stroke, and has been reported to occur in spinal cord injury and electrophysiological studies. The purpose of the present study was to assess spinal cord circuit spasticity in post-stroke mice. At 3, 7, 21, and 42 d after photothrombotic ischemic cortical injury in C57BL/6J mice, we observed decreased rate-dependent depression (RDD) of the Hoffmann reflex (H reflex) in the affected forelimb of mice compared with the limbs of sham mice and the non-affected forelimb. This finding suggests a hyper-excitable stretch reflex in the affected forelimb. We then performed immunohistochemical and western blot analyses to examine the expression of the potassium-chloride cotransporter 2 (KCC2) and phosphorylation of the KCC2 serine residue, 940 (S940), since this is the main chloride extruder that affects neuronal excitability. We also performed immunohistochemical analyses on the number of vesicular glutamate transporter 1 (vGluT1)-positive boutons to count the number of Ia afferent fibers that connect to motoneurons. Western bolts revealed that, compared with sham mice, experimental mice had significantly reduced KCC2 expression at 7 d post-stroke, and dephosphorylated S940 at 3 and 7 d post-stroke in motoneuron plasma membranes. We also observed a lower density of KCC2-positive areas in the plasma membrane of motoneurons at 3 and 7 d post-stroke. However, western blot and immunohistochemical analyses revealed that there were no differences between groups 21 and 42 d post-stroke, respectively. In addition, at 7 and 42 d post-stroke, experimental mice exhibited a significant increase in vGluT1 boutons compared with sham mice. Our findings suggest that both the down-regulation of KCC2 and increases in Ia afferent fibers are involved in post-stroke spasticity" http://www.ncbi.nlm.nih.gov/pubmed/25546454 0 1100 E. Brode 1968 [Percutaneous resorption of corticosteroids. II. Resorption of flucocinolone acetonide through normal rat skin and its influence] Arzneimittelforschung. 18 5 580-585 http://www.ncbi.nlm.nih.gov/pubmed/4303730 0 1101 J. S. Shields and K. M. Dhandapani 2014 Toll-like receptor 4 mediates post-traumatic changes to the circadian clock "Journal of Neurotrauma.Conference: 32nd Annual National Neurotrauma Symposium San Francisco, CA United States.Conference Start: 20140629 Conference End: 20140702.Conference Publication: (var.pagings).31 (12) ()(pp A96), 2014.Date of Publication: 15 J" var.pagings A96 "Traumatic brain injury (TBI) is a leading cause of death and disability. About 2% of the population currently lives with the long-term consequences of TBI. In particular, 46% of patients are diagnosed with depression in the 12 months following injury, making it the most commonly diagnosed neuropsychological illness after TBI. Despite the high comorbidity between TBI and depression, the relationship between them remains unclear. Circadian rhythms are disrupted in TBI patients and have been implicated in the pathology of depression. These rhythms are created by oscillating molecular patterns and are particularly susceptible to immune activation, such that occurs after TBI. Previous work from our lab shows that the innate immune receptor, Toll-like receptor 4 (TLR4) is activated after TBI and inhibition of TLR4 reduced neuroinflammation and secondary injury. We hypothesize that activation of TLR4 after TBI disrupts the molecular clock and contributes to depressive behavior. Using a mouse model of TBI, we found that gene expression patterns of multiple components of the molecular clock are decreased 72 hours after injury. This disruption is temporally correlated with increased depressive phenotype, as assessed by the open field test and tail suspension test. TLR4 knockout animals do not exhibit post-traumatic gene changes in molecular clock components and have an attenuated depressive phenotype. These data indicate that circadian changes after TBI are mediated at least in part by TLR4 activation and may contribute to depressive phenotypes" DO - http://dx.doi.org/10.1089/neu.2014.9935.abstracts 0 1102 E. V. Montsevichiute-Erigene 1966 "[Further study of the immunological stimulation of tumor growth in rat vaccination with the tissue of rat sarcoma 45, treated with Lonin-3]" Patol.Fiziol.Eksp.Ter. 10 4 57-62 http://www.ncbi.nlm.nih.gov/pubmed/5237744 0 1103 "Y. F. Li, Y. Q. Liu, M. Yang, H. L. Wang, W. C. Huang, Y. M. Zhao and Z. P. Luo" 2004 The cytoprotective effect of inulin-type hexasaccharide extracted from Morinda officinalis on PC12 cells against the lesion induced by corticosterone Life Sci. 75 13 1531-1538 "High concentration of corticosterone (Cort) 0.2 mM was incubated with PC12 cells to simulate the lesion state of brain neurons in depressive illness, it was found that the inulin-type oligosaccharides extracted from Morinda officinalis, inulin-type hexasaccharide (IHS) at the doses of 0.625, 1.25 microM or desipramine (DIM) 0.25, 1 microM protected the PC12 cells from the lesion induced by Cort. With Fura-2/AM labeling assay, DIM 0.25, 1 microM or IHS 2.5, 10 microM attenuated the intracellular Ca2+ overloading induced by Cort 0.1 mM for 48 h in PC12 cells. Using RT-PCR, treatment with Cort 0.1 mM for 48 h decreased the nerve growth factor (NGF) mRNA level in PC12 cells, IHS 5, 10 microM reversed this change. In summary, IHS attenuate the intracellular Ca2+ overloading and thereby up-regulate the NGF mRNA expression in Cort-treated PC12 cells, which may be consisted at least part of the cytopretective effect of IHS. These results also extend evidence for our hypothesis that neuroprotective action is one of the common mechanisms for antidepressants" http://www.ncbi.nlm.nih.gov/pubmed/15261759 0 1104 "T. R. Minor, M. Rowe, P. K. Cullen and S. Furst" 2008 Enhancing Brain Adenosine Signaling With the Nucleoside Transport Blocker NBTI (S-(4-Nitrobenzyl)-6-Theoinosine) Mimics the Effects of Inescapable Shock on Later Shuttle-Escape Performance in Rats "Behavioral Neuroscience.122 (6) ()(pp 1236-1247), 2008.Date of Publication: December 2008." 6 1236-1247 "Experience with unsignaled, inescapable shock represents a profound challenge to brain metabolic function and physiology. The authors have argued that behavioral impairment following this traumatic stress is a consequence of enhanced brain adenosine signaling, which promotes metabolic recovery by profoundly inhibiting neural activation. The authors tested this hypothesis by artificially increasing extracellular brain adenosine concentration by blocking uptake transport with NBTI in rats given only restraint stress in five experiments. NBTI impaired shuttle-escape performance in the manner of inescapable shock in a dose-dependent manner and acted synergistically with an ineffective number of inescapable shocks to maximally impair test performance. These deficits produced by inescapable shock and NBTI were reversed by the nonselective adenosine receptor antagonist caffeine, and the highly selective A2A receptor antagonist CSC (8-(3-chloro-styrl)caffeine). The highly selective A1 receptor antagonist DPCPX (8-Cyclopentyl-1,3-Dipropylxanthine) failed to improve performance in rats preexposed to inescapable shock or pretreated with NBTI. These data suggest that enhanced adenosine signaling at a brain A2A receptor impairs escape performance following inescapable shock in the learned helplessness paradigm. © 2008 American Psychological Association" DO - http://dx.doi.org/10.1037/a0013143 0 1105 F. Spah 1986 Bioelectrical and mechanical effects of tiapamil (Ro 11-1781) on isolated guinea pig myocardium Cardiovasc.Res. 20 1 42-51 "In isolated electrically stimulated guinea pig papillary muscles tiapamil exerts a negative inotropic action that corresponds to its presumptive inhibitory effects on the slow-channel-mediated transmembrane Ca2+ influx. However, contractile depression is always accompanied by marked alterations of the normal Na+-carried action potential. Thus Na+-dependent upstroke velocity (dV/dtmax) declines while the length of the plateau phase increases. These observations indicate that tiapamil, besides inhibiting Ca2+ inflow, also interferes with the fast inward Na+ current and possibly also reduces the repolarising K+ efflux. After partial depolarisation with a K+-rich tyrode solution (19 mmol X litre-1 K+). tiapamil lowers the Ca2+-dependent contractile force as it reduces the bioelectric parameters (upstroke velocity, amplitude, duration) of the Ca2+-mediated action potentials. Moreover, in partially depolarised myocardium, the Mg2+-induced bioelectric membrane activity is suppressed by tiapamil. Tiapamil probably operates as an agent with mixed Na+-, K+-, Ca2+- and Mg2+-antagonistic effects and, in this respect, differs considerably from the more specific Ca2+ antagonists such as verapamil, D 600 (gallopamil), nifedipine (and other 1,4-dihydropyridines) or diltiazem. However, tiapamil by virtue of its combined damping actions on both transmembrane Na+ and Ca2+ conductivities (together with prolongation of the action potential plateau), is a drug which exerts, simultaneously, the fundamental myocardial membrane effects of antiarrhythmic agents of group I, III and IV, according to the classification of Singh and Vaughan Williams. Thus these bioelectrical observations are in accordance with the results of clinical studies on tiapamil, which have demonstrated directly its antiarrhythmic efficacy" http://www.ncbi.nlm.nih.gov/pubmed/3708640 0 1106 "J. N. Boyd, E. S. Graham, T. C. Graham and B. C. Tennant" 1985 A comparison of the response of woodchucks and rats to variations in dietary lipotrope and lipid content J.Nutr. 115 9 1136-1146 "A soy protein-based experimental diet for woodchucks (Marmota monax) is described. The diet supported growth of juvenile woodchucks for 12 wk. With this diet, the effects on both woodchucks and rats of increasing dietary corn oil from 5 to 15% and of deleting supplemental lipotropic factors (choline, methionine, folic acid and vitamin B-12) were studied in a 2 X 2 factorial experiment. Both increased lipid and lipotrope deletion resulted in decreased growth in rats, but only increased lipid caused growth depression in woodchucks. Lipotrope depletion resulted in elevated serum markers of hepatic injury and hepatic lipid accumulation in rats but not in woodchucks. Hematological changes induced by the low lipotrope diets included decreased packed cell volume, total hemoglobin and mean corpuscular volume (MCV) in rats but increased MCV in woodchucks. The woodchuck appears to be more resistant than the rat to induction of hepatic injury by lipotrope deficiency" http://www.ncbi.nlm.nih.gov/pubmed/4032061 0 1107 M. Talajic and S. Nattel 1986 Frequency-dependent effects of calcium antagonists on atrioventricular conduction and refractoriness: demonstration and characterization in anesthetized dogs Circulation 74 5 1156-1167 "Calcium-channel blockers are known to affect slow inward current in a frequency-dependent fashion. The purpose of these experiments was to study use-dependent effects of verapamil, diltiazem, and nifedipine on atrioventricular conduction in vivo. Loading and maintenance infusion techniques were developed to study each drug at a series of stable plasma concentrations in autonomically blocked dogs anesthetized with morphine and alpha-chloralose. All three agents produced changes in atrioventricular conduction and refractoriness that increased with increasing stimulation frequency. The time dependence of drug-induced changes in atrioventricular conduction was characterized both by varying the coupling of single test stimuli and by abruptly changing activation frequency. The time constants for onset of (tau on) and recovery from (tau off) block were typical for each drug, with nifedipine having a faster time constant (tau off = 0.36 +/- 0.12 sec) than verapamil (tau off = 3.2 +/- 1.0 sec, tau on = 28 +/- 8 sec) or diltiazem (tau off = 2.7 +/- 1.2 sec, tau on = 13 +/- 4 sec). The time constants for each drug were independent of concentration but the magnitude of time-dependent change increased with increasing drug concentration. We conclude that calcium-channel blockers have important frequency-dependent effects on atrioventricular conduction in vivo. This frequency dependence may result in selective depression of atrioventricular conduction in the presence of supraventricular tachyarrhythmias, with important potential implications for the clinical use of these agents" http://www.ncbi.nlm.nih.gov/pubmed/3769173 0 1108 J. W. Phillis and D. H. York 1968 "Nicotine, smoking and cortical inhibition" Nature 219 5149 89-91 http://www.ncbi.nlm.nih.gov/pubmed/5659634 0 1109 J. L. Holtzman and J. R. Gillette 1968 The effect of phenobarbital on the turnover of microsomal phospholipid in male and female rats J.Biol.Chem. 243 11 3020-3028 http://www.ncbi.nlm.nih.gov/pubmed/5653188 0 1110 S. E. Bates and A. M. Gurney 1999 Use-dependent facilitation and depression of L-type Ca2+ current in guinea-pig ventricular myocytes: modulation by Ca2+ and isoprenaline Cardiovasc.Res. 44 2 381-389 "OBJECTIVE: An increase in stimulation frequency can facilitate or depress cardiac Ca2+ current (ICa). The aim was to examine the Ca2+ dependence of these effects, to determine if facilitation is sustained, and to elucidate the mechanism by which isoprenaline modulates facilitation. METHODS: We examined the effects of increasing the stimulation frequency for 1 min, from 0.05 to 1 Hz, on ICa recorded from guinea-pig ventricular myocytes, using the whole-cell, voltage-clamp technique. RESULTS: 1 Hz stimulation caused a facilitation of ICa that peaked in 5 s and was followed by depression towards the basal level. Metabolic inhibitors or replacement of extracellular Ca2+ with Ba2+ abolished facilitation without affecting depression, implying that they are independent processes and that facilitation required ATP and Ca2+. Subtraction of the depression observed in either condition, from the response to 1 Hz stimulation recorded under control conditions, revealed that ICa facilitation was well maintained during 1 Hz stimulation. Increased intracellular Ca2+ buffering reduced both phases of the response. Furthermore, varying the extracellular Ca2+ concentration ([Ca2+]o) revealed a Ca(2+)-dependent enhancement of depression and a bell-shaped dependence of facilitation on [Ca2+]o. Facilitation increased with [Ca2+]o up to 1 mM, then declined at higher concentrations due to partial masking by the overlaping depression. Isoprenaline produced concentration-dependent inhibition of facilitation and enhancement of depression when pipettes contained 2 mM EGTA, but not BAPTA. For an equivalent increase in ICa amplitude, the effects of isoprenaline and elevated [Ca2+]o on the response to 1 Hz stimulation were quantitatively the same. CONCLUSIONS: Facilitation is sustained during increased activity, but appears transient due to overlapping depression. Both responses are promoted by increased submembrane [Ca2+]. Isoprenaline appears to modulate facilitation and depression as a consequence of increased Ca2+ influx, rather than cAMP-dependent phosphorylation. The apparent block of facilitation by isoprenaline may result from masking by the enhanced depression" http://www.ncbi.nlm.nih.gov/pubmed/10690314 0 1111 "J. W. Holladay, M. J. Dewey and S. D. Yoo" 1998 Pharmacokinetics and antidepressant activity of fluoxetine in transgenic mice with elevated serum alpha-1-acid glycoprotein levels Drug Metab Dispos. 26 1 20-24 "Fluoxetine, a novel selective serotonin reuptake inhibitor utilized in the treatment of depression, is avidly bound to serum albumin and alpha-1-acid glycoprotein (AAG). AAG is an acute phase protein, and its serum levels are elevated in a variety of pathophysiological conditions including inflammation, depression, cancer, and acquired autoimmune deficiency syndrome. Further, the pharmacokinetic disposition and pharmacological activity of several highly bound drugs have been reported to be significantly altered as a result of elevated serum AAG. We investigated the effects of elevated serum AAG levels on the pharmacokinetic disposition, antidepressant activity, and steady state profile of fluoxetine and its demethylated metabolite, norfluoxetine. This was approached utilizing a novel strain of transgenic mice that expressed genetically elevated serum AAG levels severalfold over those of control mice. Serum and brain drug concentrations were determined by HPLC after fluoxetine administration. In transgenic mice, the volume of distribution and the terminal elimination half-life of fluoxetine were significantly reduced. Further, significant reductions in brain-to-serum fluoxetine concentration ratios and antidepressant activity were observed in transgenic mice, despite having higher serum drug levels than control mice. This trend in the serum continued at steady state, and brain fluoxetine levels were significantly lower in transgenic mice. The results of this study provide valuable insights regarding the consequences of elevated serum AAG levels, often seen in several disease states, on the pharmacokinetic disposition of fluoxetine" http://www.ncbi.nlm.nih.gov/pubmed/9443847 1 1112 "Y. Arai, G. Z. Mentis, J. Y. Wu and M. J. O'Donovan" 2007 Ventrolateral origin of each cycle of rhythmic activity generated by the spinal cord of the chick embryo PLoS.One. 2 5 e417 "BACKGROUND: The mechanisms responsible for generating rhythmic motor activity in the developing spinal cord of the chick embryo are poorly understood. Here we investigate whether the activity of motoneurons occurs before other neuronal populations at the beginning of each cycle of rhythmic discharge. METHODOLOGY/PRINCIPAL FINDINGS: The spatiotemporal organization of neural activity in transverse slices of the lumbosacral cord of the chick embryo (E8-E11) was investigated using intrinsic and voltage-sensitive dye (VSD) imaging. VSD signals accompanying episodes of activity comprised a rhythmic decrease in light transmission that corresponded to each cycle of electrical activity recorded from the ipsilateral ventral root. The rhythmic signals were widely synchronized across the cord face, and the largest signal amplitude was in the ventrolateral region where motoneurons are located. In unstained slices we recorded two classes of intrinsic signal. In the first, an episode of rhythmic activity was accompanied by a slow decrease in light transmission that peaked in the dorsal horn and decayed dorsoventrally. Superimposed on this signal was a much smaller rhythmic increase in transmission that was coincident with each cycle of discharge and whose amplitude and spatial distribution was similar to that of the VSD signals. At the onset of a spontaneously occurring episode and each subsequent cycle, both the intrinsic and VSD signals originated within the lateral motor column and spread medially and then dorsally. By contrast, following a dorsal root stimulus, the optical signals originated within the dorsal horn and traveled ventrally to reach the lateral motor column. CONCLUSIONS/SIGNIFICANCE: These findings suggest that motoneuron activity contributes to the initiation of each cycle of rhythmic activity, and that motoneuron and/or R-interneuron synapses are a plausible site for the activity-dependent synaptic depression that modeling studies have identified as a critical mechanism for cycling within an episode" http://www.ncbi.nlm.nih.gov/pubmed/17479162 0 1113 Y. Gutman and P. Boonyaviroj 1974 Suppression by noradrenaline of catecholamine secretion from adrenal medulla Eur.J.Pharmacol. 28 2 384-386 http://www.ncbi.nlm.nih.gov/pubmed/4423752 0 1114 K. H. Dangman and B. F. Hoffman 1983 Antiarrhythmic effects of ethmozin in cardiac Purkinje fibers: suppression of automaticity and abolition of triggering J.Pharmacol.Exp.Ther. 227 3 578-586 "The effects of ethmozin were studied on automatic and triggered impulse initiation in isolated canine cardiac Purkinje fibers using standard microelectrode technique. In driven Purkinje fibers with normal (greater than or equal to -80 mV) maximum diastolic potentials, ethmozin (2-4 mg/l or 4.3-8.6 muM) slightly increased the slope of phase 4 depolarization. However, the rate of normal automatic firing in such fibers was decreased by ethmozin and the threshold (take-off) potential of the pacemaker cells was shifted in the depolarizing direction (toward zero potential). In fibers treated with barium chloride (0.10-0.50 mM), ""abnormal automaticity"" occurred from maximum diastolic potentials of -38 to -68 MV. Ethmozin (2-4 mg/l) consistently slowed and abolished this abnormal automaticity. This appeared to be associated with a decrease in the rate of diastolic depolarization. When lidocaine, 4 or 10 mg/l (17 or 42 muM), was tested on abnormal automaticity induced by barium, it too was found to decrease the rate of diastolic depolarization and decrease the automatic rate. However, lidocaine never terminated barium-induced abnormal automaticity. Ethmozin also consistently abolished abnormal automaticity in Purkinje fibers taken from the endocardial surface of 24- or 48-h infarct zones. Finally, ethmozin (1-4 mg/l or 2.2-8.6 muM) depressed the amplitude of delayed after depolarizations and terminated triggered activity in Purkinje fibers taken from 24-hr infarct zones. Each of these actions could contribute to the antiarrhythmic effects of ethmozin" http://www.ncbi.nlm.nih.gov/pubmed/6317840 0 1115 "M. Pompili, M. Innamorati, M. Raja, I. Falcone, G. Ducci, G. Angeletti, D. Lester, P. Girardi, R. Tatarelli and P. E. De" 2008 Suicide risk in depression and bipolar disorder: Do impulsiveness-aggressiveness and pharmacotheraphy predict suicidal intent? "Neuropsychiatric Disease and Treatment.4 (1 B) ()(pp 247-255), 2008.Date of Publication: 2008." 1 B 247-255 "The aims of the present study were to examine clinical, personality, and sociodemographic predictors of suicide risk in a sample of inpatients affected by major affective disorders. The participants were 74 inpatients affected by major depressive disorder or bipolar disorder-I. Patients completed a semi-structured interview, the Beck Hopelessness Scale, the Aggression Questionnaire, the Barratt Impulsiveness Scale, and the Hamilton scales for depression and anxiety. Over 52% of the patients were high suicide risks. Those at risk reported more severe depressive-anxious symptomatology, more impulsivity and more hostility. Impulsivity, the use of antidepressants, anxiety/somatization, and the use of mood stabilizers (a negative predictor) resulted in accurate predicting of suicide intent. Impulsivity and antidepressant use were the strongest predictors even after controlling for several sociodemographic and clinical variables. © 2008 Pompili et al, publisher and licensee Dove Medical Press Ltd" 0 1116 M. Tashiro and K. Yanai 2007 Molecular imaging of histamine receptors in human brain "Brain and Nerve.59 (3) ()(pp 221-231), 2007.Date of Publication: March 2007." 3 221-231 "Brain histamine is involved in a wide range of physiological functions such as regulation of sleep-wake cycle, arousal, appetite control, cognition, learning and memory mainly through the 4 receptor subtypes: H1, H2, H3 and H4. Neurons producing histamine, histaminergic neurons, are exclusively located in the tuberomammillary nucleus of the posterior hypothalamus and are transmitting histamine to almost all regions of the brain. Roles of brain histamine have been studied using animals including knock-out mice and human subjects. For clinical studies, molecular imaging technique such as positron emission tomography (PET), with ligands such as [11C]doxepin and [11C] pyrilamine, has been a useful tool. A series of clinical studies on histamine H1 antagonists, or antihistamines, have demonstrated that antihistamines can be classified into sedative, mildly-sedative and non-sedative drugs according to their blood-brain barrier (BBB) permeability, showing apparent clinical usefulness regarding QOL, work efficiency and traffic safety of allergic patients. PET has also been used for elucidation of aging effects and pathophysiological roles of histaminergic nervous system in various neuropsychiatric disorders such as Alzheimer's disease, schizophrenia and depression, where H1 receptor binding potentials were lower than age-matched healthy controls. It has been also demonstrated that brain histamine functions as an endogenous anti-epileptic. In addition, H3 receptors are located in the presynaptic sites of not only histaminergic nerves but also in other nervous systems such as serotonergic, cholinergic and dopaminergic systems, and to be regulating secretion of various neurotransmitters. Nowadays, H3 receptors have been thought to be a new target of drug treatment of various neuropsychiatric disorders. There are still many research topics to be investigated regarding molecular imaging of histamine and histamine receptors. The authors hope that this line of research contributes more for the promotion of QOL in patients and people in daily lives" 0 1117 W. Grossmann and I. Jurna 1974 Depression by morphine of activity in the ventrolateral tract evoked from cutaneous A-fibres Eur.J.Pharmacol. 29 1 171-174 http://www.ncbi.nlm.nih.gov/pubmed/4435039 0 1118 "D. S. Macedo, R. S. Santos, L. D. Belchior, M. A. Neto, S. M. Vasconcelos, V. T. Lima, M. M. Fonteles, G. S. Viana and F. C. de Sousa" 2004 "Effect of anxiolytic, antidepressant, and antipsychotic drugs on cocaine-induced seizures and mortality" Epilepsy Behav. 5 6 852-856 "Cocaine abuse may lead to overdose (related to seizures and/or status epilepticus) and to diseases (schizophrenia, depression, and anxiety). This work was designed to study the influence of drugs used to treat psychopathologies associated with cocaine abuse on cocaine-induced seizures and mortality in mice. Fluoxetine (10, 20, 40 mg/kg), imipramine and buspirone (5, 10 mg/kg), pimozide (10, 20 mg/kg), lithium (56.3, 112.5 mg/kg), and naltrexone (25, 50 mg/kg) were administered intraperitoneally, 30 minutes prior to cocaine (90 mg/kg, ip). The animals were observed (30 minutes) to determine: latency to first seizure, number of seizures, and number of deaths after cocaine overdose. Fluoxetine, imipramine, buspirone, and pimozide had pro- or anticonvulsant effects depending on the dose. Smaller doses protected and higher doses increased cocaine-induced seizures and/or mortality. Naltrexone worsened and lithium protected against seizures. Thus, these results suggest that caution should be taken in the selection of pharmacotherapy and dosages for patients with cocaine addiction because of the possibility of potentiating cocaine toxicity" http://www.ncbi.nlm.nih.gov/pubmed/15582832 0 1119 C. Agostini 1978 Effect of sodium octanoate on leucine incorporation into protein of rat liver slices and of Yoshida ascites hepatoma cells Experientia 34 2 232-233 "7.38 X 10(-4) M octanoate does not significantly modify leucine incorporation into protein of rat liver slices, while in hepatoma cells a 19% inhibition has been noted. 3.69 x 10(-3) M octanoate reduces leucine incorporation to about the same extent (71-76%) in both liver slices and hepatoma cells" http://www.ncbi.nlm.nih.gov/pubmed/203476 0 1120 "A. J. Worth, N. Marshall and K. G. Thompson" 2005 Necrotising fasciitis associated with Escherichia coli in a dog N.Z.Vet.J. 53 4 257-260 "CASE HISTORY: Lameness and limb pain associated with a laceration in the inner thigh of a Border Collie dog progressed over 4 days to extensive necrosis of the full-thickness of skin and subcutaneous (S/C) tissue. A successful outcome was achieved using surgical debridement and intensive supportive care, followed by limited local closure, axial pattern flap development, and free skin grafting. CLINICAL FINDINGS: Clinical findings included severe pain, depression, pyrexia and hypoalbuminaemia, and full-thickness loss of skin from the caudal thigh to the hock. Histopathologically, debrided tissue showed extensive necrosis of the dermis, adipose and muscle tissues, and the presence of numerous Gram-negative rods. Escherichia coli was cultured from deep tissue samples. DIAGNOSIS: Necrotising fasciitis (NF) associated with E. coli infection. CLINICAL RELEVANCE: NF associated with E. coli has not been previously reported in dogs. The importance of early diagnosis and surgical debridement is noted and the relevant medical literature is reviewed" http://www.ncbi.nlm.nih.gov/pubmed/16044187 0 1121 "E. Strackx, D. L. van den Hove, J. Prickaerts, L. Zimmermann, H. W. Steinbusch, C. E. Blanco, A. W. Gavilanes and J. S. Vles" 2010 Fetal asphyctic preconditioning protects against perinatal asphyxia-induced behavioral consequences in adulthood Behav.Brain Res. 208 2 343-351 "Perinatal asphyxia is one of the major causes of neuronal injury and impaired development in infants. We recently have shown that a brief episode of experimental fetal asphyxia (FA) can provoke an endogenous neuroprotection against subsequent severe perinatal asphyxia (SPA). The long-lasting functional consequences of FA preconditioning are not clear yet. The aim of the study was to determine if FA preconditioning can provide a long-lasting behavioral protection against SPA. FA was induced, as a preconditioning stimulus, by clamping the uterine vasculature for 30 min on E17. At birth, SPA was induced by placing the uterine horns in a water bath for 19 min. At 6 months of age, functional outcome was assessed using different behavioral tests: the open field for locomotor activity, the elevated zero maze for anxiety-related behavior, the forced swim test for depression-related behavior and the object recognition task for cognition. Data showed that FA preconditioning improved postnatal mortality after SPA. At the age of 6 months, the total distance moved in the open field and elevated zero maze was significantly less in the SPA group compared to the control groups. In addition, cognitive performance in the object recognition task was impaired in the SPA offspring compared to the control groups. Most importantly, FA preconditioning was able to preserve both locomotor activity and cognition function. In conclusion, FA preconditioning induces a long-lasting, functional protection against SPA. Therefore, this model seems to offer good opportunities for the identification and characterization of the underlying mechanisms of preconditioning" http://www.ncbi.nlm.nih.gov/pubmed/19962408 0 1122 "J. J. Kim, M. R. Foy and R. F. Thompson" 1996 Behavioral stress modifies hippocampal plasticity through N-methyl-D-aspartate receptor activation Proc.Natl.Acad.Sci.U.S.A 93 10 4750-4753 "Behavioral stress has detrimental effects on subsequent cognitive performance in many species, including humans. For example, humans exposed to stressful situations typically exhibit marked deficits in various learning and memory tasks. However, the underlying neural mechanisms by which stress exerts its effects on learning and memory are unknown. We now report that in adult male rats, stress (i.e., restraint plus tailshock) impairs long-term potentiation (LTP) but enhances long-term depression (LTD) in the CA1 area of the hippocampus, a structure implicated in learning and memory processes. These effects on LTP and LTD are prevented when the animals were given CGP39551 (the carboxyethylester of CGP 37849; DL-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, before experiencing stress. In contrast, the anxiolytic drug diazepam did not block the stress effects on hippocampal plasticity. Thus, the effects of stress on subsequent LTP and LTD appear to be mediated through the activation of the NMDA subtype of glutamate receptors. Such modifications in hippocampal plasticity may contribute to learning and memory impairments associated with stress" http://www.ncbi.nlm.nih.gov/pubmed/8643474 0 1123 "E. MacDonald, M. Marscelos and U. Nousianinen" 1975 Central and peripheral catecholamine levels after pyrazole treatment Acta Pharmacol.Toxicol.(Copenh) 37 2 106-112 http://www.ncbi.nlm.nih.gov/pubmed/1173726 0 1124 "A. K. Dondua, A. W. Dorresteijn, R. P. Kostiuchenko, Z. Fedorova and A. Fisher" 1996 [The effect of aphidicolin on trochoblast differentiation in the early ontogeny of polychaetes] Ontogenez 27 6 419-426 The differentiation of trochoblasts in Nereis virens and Platynereis dumerlii embryos was investigated during different periods of time after fertilization by means of the DNA replication block. It was shown that the quantal cycle of ciliogenesis is not connected directly with the time of primary trochoblast founder cell formation. Development of the cilia on trochoblasts in P. dumerlii needed normal DNA replication at the fifth cycle. Ciliogenesis in N. virens completely stopped after the inhibition of replication of the fourth cycle and only partly when the fifth and sixth rounds of DNA replication were affected. The data obtained are discussed from the standpoint of Newport and Kirschner's depletion hypothesis http://www.ncbi.nlm.nih.gov/pubmed/9053830 0 1125 "N. Bierne, P. Borsa, C. Daguin, D. Jollivet, F. Viard, F. Bonhomme and P. David" 2003 Introgression patterns in the mosaic hybrid zone between Mytilus edulis and M. galloprovincialis Mol.Ecol. 12 2 447-461 "Hybrid zones are fascinating systems to investigate the structure of genetic barriers. Marine hybrid zones deserve more investigation because of the generally high dispersion potential of planktonic larvae which allows migration on scales unrivalled by terrestrial species. Here we analyse the genetic structure of the mosaic hybrid zone between the marine mussels Mytilus edulis and M. galloprovincialis, using three length-polymorphic PCR loci as neutral and diagnostic markers on 32 samples along the Atlantic coast of Europe. Instead of a single genetic gradient from M. galloprovincialis on the Iberian Peninsula to M. edulis populations in the North Sea, three successive transitions were observed in France. From South to North, the frequency of alleles typical of M. galloprovincialis first decreases in the southern Bay of Biscay, remains low in Charente, then increases in South Brittany, remains high in most of Brittany, and finally decreases again in South Normandy. The two enclosed patches observed in the midst of the mosaic hybrid zone in Charente and Brittany, although predominantly M. edulis-like and M. galloprovincialis-like, respectively, are genetically original in two respects. First, considering only the various alleles typical of one species, the patches show differentiated frequencies compared to the reference external populations. Second, each patch is partly introgressed by alleles of the other species. When introgression is taken into account, linkage disequilibria appear close to their maximum possible values, indicating a strong genetic barrier within all transition zones. Some pre- or postzygotic isolation mechanisms (habitat specialization, spawning asynchrony, assortative fertilization and hybrid depression) have been documented in previous studies, although their relative importance remains to be evaluated. We also provided evidence for a recent migratory 'short-cut' connecting M. edulis-like populations of the Charente patch to an external M. edulis population in Normandy and thought to reflect artificial transfer of spat for aquaculture" http://www.ncbi.nlm.nih.gov/pubmed/12535095 0 1126 "N. Dale, T. Pearson and B. G. Frenguelli" 2000 Direct measurement of adenosine release during hypoxia in the CA1 region of the rat hippocampal slice J.Physiol 526 Pt 1 143-155 "We have used an enzyme-based, twin-barrelled sensor to measure adenosine release during hypoxia in the CA1 region of rat hippocampal slices in conjunction with simultaneous extracellular field recordings of excitatory synaptic transmission. When loaded with a combination of adenosine deaminase, nucleoside phosphorylase and xanthine oxidase, the sensor responded linearly to exogenous adenosine over the concentration range 10 nM to 20 microM. Without enzymes, the sensor when placed on the surface of hippocampal slices recorded a very small net signal during hypoxia of 40 +/- 43 pA (mean +/- s.e.m.; n = 7). Only when one barrel was loaded with the complete sequence of enzymes and the other with the last two in the cascade did the sensor record a large net difference signal during hypoxia (1226 +/- 423 pA; n = 7). This signal increased progressively during the hypoxic episode, scaled with the hypoxic depression of the simultaneously recorded field excitatory postsynaptic potential and was greatly reduced (67 +/- 6.5 %; n = 9) by coformycin (0.5-2 microM), a selective inhibitor of adenosine deaminase, the first enzyme in the enzymic cascade within the sensor. For 5 min hypoxic episodes, the sensor recorded a peak concentration of adenosine of 5.6 +/- 1.2 microM (n = 16) with an IC(50) for the depression of transmission of approximately 3 microM. In slices pre-incubated for 3-6 h in nominally Ca(2+)-free artificial cerebrospinal fluid, 5 min of hypoxia resulted in an approximately 9-fold greater release of adenosine (48.9 +/- 17.7 microM; n = 6). High extracellular Ca(2+) (4 mM) both reduced the adenosine signal recorded by the sensor during hypoxia (3.5 +/- 0.6 microM; n = 4) and delayed the hypoxic depression of excitatory synaptic transmission" http://www.ncbi.nlm.nih.gov/pubmed/10878107 0 1127 "G. Aste, T. M. Di, J. M. Steiner, D. A. Williams and A. Boari" 2005 Pancreatitis associated with N-methyl-glucamine therapy in a dog with leishmaniasis "Veterinary Research Communications.29 (Suppl 2) ()(pp 269-272), 2005.Date of Publication: August 2005." Suppl 2 269-272 DO - http://dx.doi.org/10.1007/s11259-005-0059-4 0 1128 I. I. Malyshev and F. Z. Meerson 1991 [Adaptation of the body to stressors prevents the cardiotoxic effect of rifampicin but not polymyxin B] Biull.Eksp.Biol.Med. 112 10 344-345 It was established on isolated rat hearts that adaptation of the organism to stress exposure effectively limits toxic effect of chronic rifampicin administration (7 mg/kg/day for 8 days) and does not affect the depression of contractile function induced by chronic polymyxin B administration (0.12 mg/kg/day for 8 days). Possible mechanism of the effect of organism's adaptation to stress on the resistance of heart to antibiotics is under discussion http://www.ncbi.nlm.nih.gov/pubmed/1804336 0 1129 W. Ladisich 1974 Influence of stress upon brain serotonin metabolism after progesterone treatment and upon plasma progesterone in the rat "Journal de Pharmacologie.5 (Sup.2) ()(pp 55), 1974.Date of Publication: 1974." Sup. 2 55 0 1130 R. A. Harris 1981 Ethanol and pentobarbital inhibition of intrasynaptosomal sequestration of calcium Biochem.Pharmacol. 30 23 3209-3215 http://www.ncbi.nlm.nih.gov/pubmed/7317104 0 1131 "G. L. Gerdeman, J. Ronesi and D. M. Lovinger" 2002 Postsynaptic endocannabinoid release is critical to long-term depression in the striatum Nat.Neurosci. 5 5 446-451 "The striatum functions critically in movement control and habit formation. The development and function of cortical input to the striatum are thought to be regulated by activity-dependent plasticity of corticostriatal glutamatergic synapses. Here we show that the induction of a form of striatal synaptic plasticity, long-term depression (LTD), is dependent on activation of the CB1 cannabinoid receptor. LTD was facilitated by blocking cellular endocannabinoid uptake, and postsynaptic loading of anandamide (AEA) produced presynaptic depression. The endocannabinoid necessary for striatal LTD is thus likely to be released postsynaptically as a retrograde messenger. These findings demonstrate a new role for endocannabinoids in the induction of long-term synaptic plasticity in a circuit necessary for habit formation and motor control" http://www.ncbi.nlm.nih.gov/pubmed/11976704 0 1132 "C. Aoki, J. Lee, H. Nedelescu, T. Ahmed, A. Ho and J. Shen" 2009 Increased levels of NMDA receptor NR2A subunits at pre- and postsynaptic sites of the hippocampal CA1: an early response to conditional double knockout of presenilin 1 and 2 J.Comp Neurol. 517 4 512-523 "Greater than 90% of familial Alzheimer's disease (AD) is linked to mutations of presenilin (PS), and the loss of PS function altogether within mouse brains by conditional double knockout of the PS 1 and 2 genes (PS-cDKO) leads to age-dependent emergence of AD phenotypes, including neurodegeneration and reduced synaptic plasticity in the hippocampal CA1. The goal of our study was to identify the ultrastructural and molecular changes at synapses in the hippocampal CA1 of this PS-cDKO mouse model of AD. We examined the asymmetric (excitatory) synapses formed on apical dendrites of CA1 pyramidal neurons at 2 months postnatal, an age when AD-like symptoms emerge but brain morphology, as assessed by light microscopy, is still normal. Our quantitative electron microscopic analyses confirm that PS-cDKO hippocampi at 2 months postnatal do not yet exhibit synapse losses or spine size alterations. However, immunocytochemistry reveals that the same region exhibits a 28% increase in the proportion of spines labeled for the NR2A subunits of NMDA receptors (NMDAR), with a 31% increase specifically at postsynaptic densities and a concomitant reduction of these subunits at nonsynaptic sites within spine heads. In contrast, no change in levels or the distribution pattern of NR2B subunit levels were detected within spine heads. Presynaptically, NR2A levels are elevated at axo-spinous junctions and these may contribute to the timing-dependent, long-term depression. These observations point to an early-onset trapping of NMDAR at synapses that are subtle but may underlie the reduced synaptic plasticity at 2 months of age and excitotoxicity at later stages" http://www.ncbi.nlm.nih.gov/pubmed/19795494 0 1133 "A. A. Mathe, H. Husum, K. A. El, P. Jimenez-Vasquez, S. H. Gruber, G. Wortwein, G. Nikisch, P. Baumann, H. Agren, W. Andersson, A. Sodergren and F. Angelucci" 2007 Search for biological correlates of depression and mechanisms of action of antidepressant treatment modalities. Do neuropeptides play a role? Physiol Behav. 92 01-Feb 226-231 "Dysregulation of the monoaminergic systems is likely a sufficient but not a necessary cause of depression. A wealth of data indicates that neuropeptides, e.g., NPY, CRH, somatostatin, tachykinins and CGRP play a role in affective disorders and alcohol use/abuse. This paper focuses on NPY in etiology and pathophysiology of depression. Decreased peptide and mRNA NPY were found in hippocampus of both the genetic, e.g., the FSL strain, and environmental rat models of depression, e.g., chronic mild stress and early life maternal separation paradigms. Rat models of alcoholism also show altered NPY. Furthermore, NPY is also reduced in CSF of depressed patients. Antidepressive treatments tested so far (lithium, topiramate, SSRIs, ECT and ECS, wheel running) increase NPY selectively in rat hippocampus and in human CSF. Moreover, NPY given icv to rat has antidepressive effects which are antagonized by NPY-Y1 blockers. The data support our hypothesis that the NPY system dysregulation constitutes one of the biological underpinnings of depression and that one common mechanism of action of antidepressive treatment modalities may be effects on NPY and its receptors. In a novel paradigm, early life maternal separation was superimposed on ""depressed"" FSL and control rats and behavioral and brain neurochemistry changes observed in adulthood. The consequences were more deleterious in genetically vulnerable FSL. Early antidepressive treatment modulated the adult sequelae. Consequently, if these data are confirmed, the ethical and medical question that will be asked is whether it is permissible and advisable to consider prophylactically treating persons at risk" http://www.ncbi.nlm.nih.gov/pubmed/17572454 1 1134 "H. L. Komiskey, T. M. Cook, C. F. Lin and W. L. Hayton" 1981 Impairment of learning or memory in the mature and old rat by diazepam Psychopharmacology (Berl) 73 3 304-305 http://www.ncbi.nlm.nih.gov/pubmed/6787652 0 1135 H. Haas 1970 "[Changes in the mechanogram and other circulatory parameters induced by isoprenaline and adrenaline under the effect of verapamil, quinidine and adrenergic substances]" Arzneimittelforschung. 20 4 501-509 http://www.ncbi.nlm.nih.gov/pubmed/5467814 0 1136 "K. Briseid, A. Korbu, F. C. Arntzen and I. Baksaas" 1975 Potentiation by beta-adrenoceptor blocking agents of the inhibitory effect of adrenaline on carrageenin-induced rat paw oedema Acta Pharmacol.Toxicol.(Copenh) 37 2 165-176 http://www.ncbi.nlm.nih.gov/pubmed/1173731 0 1137 L. Horlick 1968 Effect of diethylstilbestrol on skin sterols of the male rat J.Lipid Res. 9 6 773-781 "Diethylstilbestrol (DES) was injected in doses ranging from 600 micro g to 0.4 micrograms/kg body weight into mature male rats over a 3 wk period. Profound effects on skin morphology and on sterol content of skin were noted. The sebaceous glands atrophied and the epidermis lost granularity. The concentrations of all skin sterols, with the exception of cholesterol, were reduced. At a dose level of DES of 4 micrograms/kg there was still a perceptible reduction in the concentration of Delta(7)-cholestenol. Incubation of skin fragments with acetate-2-(14)C for 2 hr demonstrated a reduced uptake of (14)C into the nonsaponifiable fraction of skin lipids at all dose levels studied. Preliminary thin-layer chromatography of the nonsaponifiable fraction revealed that the uptake of (14)C into cholesterol was only slightly decreased; uptake into cholesterol precursors was decreased somewhat more. The epidermis and dermis were separated by incubation of skin with elastase and hyaluronidase. The epidermis contained at least three times as much sterol per mg dry weight as did the dermis. Unesterified cholesterol was the major sterol present in both layers; the other sterols were present mainly as esters. DES injection resulted in no change in the free sterol content but markedly reduced the ester content of the epidermis and dermis" http://www.ncbi.nlm.nih.gov/pubmed/5685269 0 1138 C. D. Barnes and O. Pompeiano 1971 Vestibular nerve activation of a brain stem cholinergic system influencing the spinal cord Neuropharmacology 10 4 425-436 http://www.ncbi.nlm.nih.gov/pubmed/5094309 0 1139 "O. Almog, I. Benhar, G. Vasmatzis, M. Tordova, B. Lee, I. Pastan and G. L. Gilliland" 1998 Crystal structure of the disulfide-stabilized Fv fragment of anticancer antibody B1: conformational influence of an engineered disulfide bond Proteins 31 2 128-138 "A recombinant Fv construct of the B1 monoclonal antibody that recognizes the LewisY-related carbohydrate epitope on human carcinoma cells has been prepared. The Fv is composed of the polypeptide chains of the VH and VL domains expressed independently and isolated as inclusion bodies. The Fv is prepared by combining and refolding equimolar amounts of guanidine chloride solubilized inclusion bodies. The Fv is stabilized by an engineered interchain disulfide bridge between residues VL100 and VH44. This construct has a similar binding affinity as that of the single-chain construct (Benhar and Pastan, Clin. Cancer Res. 1:1023-1029, 1995). The B1 disulfide-stabilized Fv (BldsFv) crystallizes in space group P6(1)22 with the unit cell parameters a = b = 80.1 A, and c = 138.1 A. The crystal structure of the BldsFv has been determined at 2.1-A resolution using the molecular replacement technique. The final structure has a crystallographic R-value of 0.187 with a root mean square deviation in bond distance of 0.014 A and in bond angle of 2.74 degrees. Comparisons of the BldsFv structure with known structures of Fv regions of other immunoglobulin fragments shows closely related secondary and tertiary structures. The antigen combining site of BldsFv is a deep depression 10-A wide and 17-A long with the walls of the depression composed of residues, many of which are tyrosines, from complementarity determining regions L1, L3, H1, H2, and H3. Model building studies indicate that the LewisY tetrasaccharide, Fuc-Gal-Nag-Fuc, can be accommodated in the antigen combining site in a manner consistent with the epitope predicted in earlier biochemical studies (Pastan, Lovelace, Gallo, Rutherford, Magnani, and Willingham, Cancer Res. 51:3781-3787, 1991). Thus, the engineered disulfide bridge appears to cause little, if any, distortion in the Fv structure, making it an effective substitute for the B1 Fab" http://www.ncbi.nlm.nih.gov/pubmed/9593187 0 1140 "K. F. Ma, X. Y. Zhang and L. Y. Qi" 2007 [Protective effects of triterpenoids on primarily cultured rat hepatocytes injured by D-galactosamine and carbon tetrachloride] Zhejiang.Da.Xue.Xue.Bao.Yi.Xue.Ban. 36 3 247-254 "OBJECTIVE: To investigate the protective effects and mechanism of triterpenoids on primarily cultured rat hepatocytes injured by D-galactosamine (D-GalN) or carbon tetrachloride (CCl4). METHODS: Rat hepatocytes were isolated by two-step collagenase perfusion and cultured in RPMI 1640 medium. Protective effects of asiatic acid (AA) and beta-glycyrrhetinic acid (GA) were evaluated on hepatocytes injured by D-GalN (2 mmol/L) or CCl4 (10 mmol/L). Cell morphology was observed by light microscope, cell viability was measured by MTT assay, AST and LDH were determined by an automatic analyzer. Fluorescence assay was applied to test reactive oxygen species (ROS), nitric oxide end products (NOx) and reduced glutathione (GSH), and JC-1 staining was used to determine mitochondria membrane potential (DeltaPsim). RESULTS: AST and LDH in medium were decreased when treated with AA and GA after D-GalN injury (P<0.05), furthermore AA enhanced the hepatocyte viability (P<0.05). Moreover, AA and GA significantly reduced ROS and NOx generation, and ameliorated DeltaPsim lost induced by D-GalN. AA also inhibited GSH decrease due to D-GalN and CCl4 treatment. CONCLUSION: Both AA and GA could protect hepatocytes from D-GalN and CCl4 injuries, which is associated with reducing intracellular ROS and NOx, reversing GSH depression and ameliorating DeltaPsim lost" http://www.ncbi.nlm.nih.gov/pubmed/17571307 0 1141 "M. A. Raghanti, T. Conley, J. Sudduth, J. M. Erwin, C. D. Stimpson, P. R. Hof and C. C. Sherwood" 2013 Neuropeptide Y-immunoreactive neurons in the cerebral cortex of humans and other haplorrhine primates Am.J.Primatol. 75 5 415-424 "We examined the distribution of neurons immunoreactive for neuropeptide Y (NPY) in the posterior part of the superior temporal cortex (Brodmann's area 22 or area Tpt) of humans and nonhuman haplorrhine primates. NPY has been implicated in learning and memory and the density of NPY-expressing cortical neurons and axons is reduced in depression, bipolar disorder, schizophrenia, and Alzheimer's disease. Due to the role that NPY plays in both cognition and neurodegenerative diseases, we tested the hypothesis that the density of cortical and interstitial neurons expressing NPY was increased in humans relative to other primate species. The study sample included great apes (chimpanzee and gorilla), Old World monkeys (pigtailed macaque, moor macaque, and baboon) and New World monkeys (squirrel monkey and capuchin). Stereologic methods were used to estimate the density of NPY-immunoreactive (-ir) neurons in layers I-VI of area Tpt and the subjacent white matter. Adjacent Nissl-stained sections were used to calculate local densities of all neurons. The ratio of NPY-ir neurons to total neurons within area Tpt and the total density of NPY-ir neurons within the white matter were compared among species. Overall, NPY-ir neurons represented only an average of 0.006% of the total neuron population. While there were significant differences among species, phylogenetic trends in NPY-ir neuron distributions were not observed and humans did not differ from other primates. However, variation among species warrants further investigation into the distribution of this neuromodulator system" http://www.ncbi.nlm.nih.gov/pubmed/23042407 0 1142 "J. R. McWilliam, B. S. Meldrum and S. A. Checkley" 1981 Enhanced growth hormone response to clonidine after repeated electroconvulsive shock in a primate species "Psychoneuroendocrinology.6 (1) ()(pp 77-79), 1981.Date of Publication: 1981." 1 77-79 "The plasma growth hormone response to clonidine, 0.02 mg/kg, i.v., is enhanced 15 days after a course of 7 electroconvulsive shocks (ECS) in baboons, Papio papio. This supports the hypothesis, based on behavioural observations in rodents, that the therapeutic action of electroconvulsive treatment (ECT) in depressive illness is associated with enhanced responses to monoamines" DO - http://dx.doi.org/10.1016/0306-4530%2881%2990050-0 1 1143 "H. Fujita, A. Koizumi, N. Hayashi and M. Ikeda" 1986 Reduced synthesis of 5-aminolevulinate dehydratase in styrene-treated rats Biochim.Biophys.Acta 867 3 89-96 "5-Aminolevulinate dehydratase (porphobilinogen synthase; 5-aminolevulinate hydro-lyase, EC 4.2.1.24) preparations purified from rat liver and erythrocytes are indistinguishable in terms of molecular weight, subunit size, immunoreactivity, amino-acid composition and kinetic properties, suggesting that the enzyme from liver and erythrocytes are identical. Intraperitoneal injection of styrene to rats decreased 5-aminolevulinate dehydratase activity in both erythrocyte (to 8% of the control) and the liver (to 40% of the control). Studies utilizing polysome-directed cell-free translation indicated that hepatic synthesis of the enzyme was inhibited by styrene at the transcriptional level. In vitro addition of styrene 7,8-oxide, a major intermediate of styrene, to purified 5-aminolevulinate dehydratase resulted in a loss of immunoassayable enzyme protein to less than 1% of the untreated control. These findings suggest that the decrease in 5-aminolevulinate dehydratase caused by in vivo treatment of styrene is partially due to a transcription-dependent decrease in the enzyme synthesis, and partially to post-translational alteration of the structure of the enzyme protein" http://www.ncbi.nlm.nih.gov/pubmed/3718991 0 1144 W. Kostowski and M. Obersztyn 1988 Chronic administration of desipramine and imipramine but not zimelidine attenuates clonidine-induced depression of avoidance behavior in rats Pol.J.Pharmacol.Pharm. 40 4 341-349 "Clonidine (CLO) given intraperitoneally in a dose of 0.05 mg/kg decreased the open-field behavior in rats and completely abolished avoidance acquisition. Short term (4 days) administration of desipramine (DMI) and imipramine (IMI) practically failed to change the depressive effects of CLO whilst chronic (21 days) treatment significantly reduced the CLO action on both avoidance and open-field behavior. Contrary to tricyclic antidepressants, zimelidine (ZIM) given either acutely or chronically did not affect the avoidance deficit but given chronically attenuated the CLO-induced sedation in the open field. The results suggest that ""classic"" tricyclic antidepressants acting strongly upon noradrenaline uptake are more potent in preventing avoidance deficit induced by the alpha 2-adrenoceptor agonist, CLO than drugs acting more selectively upon serotonin uptake" http://www.ncbi.nlm.nih.gov/pubmed/2851779 1 1145 "E. Martini, F. Chiesa, R. Oberosler, E. Seren and V. Beghelli" 1970 The endocellular distribution and the enzymatic oxidation and reduction of the liposoluble neutral fractions (LNF) acting on the blood pressure Enzymologia. 38 3 189-199 http://www.ncbi.nlm.nih.gov/pubmed/4191100 0 1146 B. Gustafsson and P. Zangger 1978 Effect of repetitive activation on the afterhyperpolarization in dorsal spinocerebellar tract neurones J.Physiol 275 303-319 "1. The changes in the afterhyperpolarization (a.h.p.) with repetitive activation have been studied in dorsal spinocerebellar tract cells of the cat using intracellular recording techniques. 2. The a.h.p. following a single spike was conditioned at different interspike intervals by a single preceding spike. In the majority of neurones the a.h.p. following a spike added approximately linearly with that generated by a preceding spike. 3. In other cells the a.h.p. following a spike was instead depressed by a preceding spike. THis depression was approximately constant at interspike intervals less than the a.h.p. duration (50-100 msec). Thereafter the a.h.p. slowly recovered during the next 100-300 msec. There was no associated decrease in the initial brief hyperpolarizing undershoot. 4. With shortlasting repetitive activation at high frequency (greater than 100 impulses/sec) the a.h.p, peak amplitude increased progressively with successive spikes (5-15 spikes). No change in the time constant of decay was observed. A good correspondence was found between the observed increase in peak amplitude of the a.h.p.s and that given by a theoretical linear superposition of the successive a.h.p.s. 5. Changes in the brief hyperpolarizing undershoot with repetitive activation is also described" http://www.ncbi.nlm.nih.gov/pubmed/633119 0 1147 G. R. Hogan 1992 Cadmium treatment and lead-induced suppression of splenic erythropoiesis J.Toxicol.Environ.Health 35 1 01-Jun "Young adult female mice were injected with lead acetate (d 0). Following injection, determinations were made of the percentages of radioactive iron (59Fe) uptake into the hemoglobin of erythrocytes produced by spleen. Control 59Fe uptake percentage vacillated between 4.2 and 5.5 within the 7-d period of observation. On d 4 following lead treatment, splenic percentages were dramatically reduced below those of the saline-injected controls; by d 6 the splenic 59Fe uptake of lead-treated mice was comparable to that of controls. For rodents injected with cadmium chloride on 0, the 59Fe uptake values showed a statistically significant elevation by d 2, which was extended beyond that of the controls' d 4 value. For those animals receiving both lead and cadmium (d 0), the uptake percentages paralleled those of the controls throughout the 7-d period of observation. These data suggest that the inhibitory effect of lead on erythropoiesis of the spleen is blocked by a concurrent cadmium treatment. Results are interpreted in regard to a possible vulnerable target and competition for the target by lead and cadmium" http://www.ncbi.nlm.nih.gov/pubmed/1728662 0 1148 D. R. Cook and B. W. Brandom 1982 "Enflurane, halothane, and isoflurane inhibit removal of 5-hydroxytryptamine from the pulmonary circulation" Anesth.Analg. 61 8 671-675 "We were interested in determining the effect of enflurane, halothane, and isoflurane on the uptake and removal of 5-hydroxytryptamine (5-HT) and phenylethylamine (PEA) from the lung. Isolated rabbit lungs were perfused in a recirculating system in vitro with 0.1 microM [14C]5-HT or 0.1 microM [14C]PEA in Krebs-Ringer solution. The rate of removal and percentage of removal of the bioamines were determined before and after either 1, 2, or 4 MAC multiples of the potent anesthetics. Because of variation in removal of bioamines among lungs from different animals, the effects of anesthetics on bioamine removal were determined by calculating the percentage of inhibition of removal using data from the control and test period for each lung. At 2 MAC concentrations, the anesthetics inhibited 5-HT removal 11.1%, at 4 MAC concentrations the anesthetics inhibited 5-HT removal 29.8% and significantly prolonged the half-life (t 1/2) of 5-HT removal. There was significant (10.8%) inhibition of PEA removal at 4 MAC concentrations for the three anesthetics. As uptake of 5-HT is the rate-limiting step in 5-HT removal, these data demonstrate a uniform depression of 5-HT uptake by the three potent anesthetics. The rate-limiting step of PEA uptake, metabolism by monoamine oxidases, is inhibited at 4 MAC concentrations of anesthetics" http://www.ncbi.nlm.nih.gov/pubmed/7201270 0 1149 "J. Liu, J. L. Dupree, M. Gacias, R. Frawley, T. Sikder, P. Naik and P. Casaccia" 2016 Clemastine Enhances Myelination in the Prefrontal Cortex and Rescues Behavioral Changes in Socially Isolated Mice J.Neurosci. 36 3 957-962 "Altered myelin structure and oligodendrocyte function have been shown to correlate with cognitive and motor dysfunction and deficits in social behavior. We and others have previously demonstrated that social isolation in mice induced behavioral, transcriptional, and ultrastructural changes in oligodendrocytes of the prefrontal cortex (PFC). However, whether enhancing myelination and oligodendrocyte differentiation could be beneficial in reversing such changes remains unexplored. To test this hypothesis, we orally administered clemastine, an antimuscarinic compound that has been shown to enhance oligodendrocyte differentiation and myelination in vitro, for 2 weeks in adult mice following social isolation. Clemastine successfully reversed social avoidance behavior in mice undergoing prolonged social isolation. Impaired myelination was rescued by oral clemastine treatment, and was associated with enhanced oligodendrocyte progenitor differentiation and epigenetic changes. Clemastine induced higher levels of repressive histone methylation (H3K9me3), a marker for heterochromatin, in oligodendrocytes, but not neurons, of the PFC. This was consistent with the capability of clemastine in elevating H3K9 histone methyltransferases activity in cultured primary mouse oligodendrocytes, an effect that could be antagonized by cotreatment with muscarine. Our data suggest that promoting adult myelination is a potential strategy for reversing depressive-like social behavior. SIGNIFICANCE STATEMENT: Oligodendrocyte development and myelination are highly dynamic processes influenced by experience and neuronal activity. However, whether enhancing myelination and oligodendrocyte differentiation is beneficial to treat depressive-like behavior has been unexplored. Mice undergoing prolonged social isolation display impaired myelination in the prefrontal cortex. Clemastine, a Food and Drug Administration-approved antimuscarinic compound that has been shown to enhance myelination under demyelinating conditions, successfully reversed social avoidance behavior in adult socially isolated mice. This was associated with enhanced myelination and oligodendrocyte differentiation in the prefrontal cortex through epigenetic regulation. Thus, enhancing myelination may be a potential means of reversing depressive-like social behavior" http://www.ncbi.nlm.nih.gov/pubmed/26791223 1 1150 "J. E. Deady, D. D. Koblin, E. I. Eger, J. E. Heavner and B. D'Aoust" 1981 Anesthetic potencies and the unitary theory of narcosis Anesth.Analg. 60 6 380-384 "Anesthetic potencies of nitrous oxide, isoflurane, enflurane, halothane, cyclopropane, or chloroform were measured in male (CD-1) mice using three end points: (a) the ability to maintain an upright position (the righting-response ED50, RR ED50); (b) the response to a tail-clamp stimulus (MAC); and (c) the response to heat applied to the tail (tail-flick ED50, TF ED50). The ratio of RR ED50 to MAC ranged from mean values of 0.475 for isoflurane, 0.507 for cyclopropane, 0.524 for enflurane, and less than 0.55 for N2O, to 0.600 for halothane and 0.621 for chloroform. The ratios of RR EDS50 to MAC for halothane differed significantly from the ratios for isoflurane and enflurane. The mean values for TF ED50/MAC and RR ED50/TG ED50 ranged from 0.688 to 1.01 and 0.664 to 0.682, respectively, for isoflurane, enflurane, and halothane. The nitrous oxide RR ED50/TF ED50, however, was 1.34. The ratios of TF ED50 to MAC were significantly different for halothane and isoflurane. The different end points were measured in an attempt to determine whether the response in mice anesthetized with a particular agent was the same with varying stimuli. The differences found suggest that a unitary mechanism of anesthetic action cannot completely explain the depression defined by these three end points" http://www.ncbi.nlm.nih.gov/pubmed/7195159 0 1151 "A. M. Landau, S. Dyve, A. K. O. Alstrup, S. Jakobsen, A. Gjedde and D. J. Doudet" 2010 Focused Conference Group: FC17 - Newapproaches and targets in psychiatry acute vagal nerve stimulation promotes noradrenaline release in minipig brain Basic and Clinical Pharmacology and Toxicology.Conference: 16th World Congress of Basic and Clinical Pharmacology - WorldPharma 2010 Copenhagen Denmark.Conference Start: 20100717 Conference End: 20100723.Conference Publication: (var.pagings).107 ()(pp var.pagings 155 "Vagal Nerve Stimulation (VNS) has emerged in recent years, first as a novel anti-epileptic and more recently, as a possible anti-depressant treatment. We hypothesized that the beneficial effects of VNS are mediated, at least in part, through augmentation of the inhibitory effects of cortical monoaminergic neurotransmission, specifically noradrenergic. Using positron emission tomography (PET), we determined the neurotransmitter changes in brain associated with acute VNS stimulation of anesthetized Gottingen minipigs. We used the alpha2 adrenoceptor antagonist [11C]yohimbine, which previously was shown to be sensitive to competition from the endogenous ligand(s), as a surrogate marker of cortical noradrenaline release. PET scans were acquired 4-6 weeks after the implant of a VNS in the minipig before (OFF condition) and within 30 minutes after the initiation of stimulation at a current intensity of 1mA (ON condition). Preliminary data show decreased binding of [11C]yohimbine to alpha2 adrenoceptors in the acute compared with the baseline scans. Kinetic analysis using the Logan multilinear graphical analysis method in the first two pigs of the study demonstrated decreased binding in the frontal cortex (3-18%), temporal cortex (12-20%) and striatum (17-27%), suggesting increased noradrenaline levels at these sites. The results are consistent with literature reporting decreased noradrenaline neurotransmission with depressive symptoms, and a rapid release of noradrenaline associated with anti-depressant therapies, suggesting a possible mechanism of action for the antidepressant effects of VNS" DO - http://dx.doi.org/10.1111/j.1742-7843.2010.00599.x 0 1152 "H. S. Rosenkranz, A. Mednis, P. A. Marks and H. M. Rose" 1967 Metabolic effects of phenethyl alcohol on mammalian cells Biochim.Biophys.Acta 149 2 513-518 http://www.ncbi.nlm.nih.gov/pubmed/6081518 0 1153 "L. Lundstrom, B. Kuhn, J. Beck, E. Borroni, J. G. Wettstein, T. J. Woltering and S. Gatti" 2009 Mutagenesis and molecular modeling of the orthosteric binding site of the mGlu2 receptor determining interactions of the group II receptor antagonist 3H-HYDIA "ChemMedChem.4 (7) ()(pp 1086-1094), 2009.Date of Publication: 06 Jul 2009." 7 1086-1094 "Modulation of metabotropic glutamate 2/3 receptors represents a promising target for the treatment of neuropsychiatric disorders such as schizophrenia and depression. The novel mGlu2/3 ligand HYDIA ((1S,2R,3R,5R,6S)-2-amino-3- hydroxybicyclo [3.1.0]hexane-2,6-dicarboxylic acid) is a conformationally restricted and hydroxylated glutamate analogue. HYDIA is a potent and selective competitive antagonist of L-glutamate at the mGlu2/3 receptors in spite of being structurally very similar to the bicyclic LY354740, which is a potent and selective mGlu2/3 agonist. By comparing these two ligands, this study delineate the interaction mode of 3H-HYDIA at the mGlu2 receptor, using both mutagenesis studies and computational modeling. Binding of HYDIA in the closed conformation model of mGlu2 results in repulsive interaction with the Y216 residue, preventing closure of the binding pocket and thus receptor activation. Consequently, HYDIA is proposed to bind in an open conformation model of mGlu2. Mutation of the structurally important Y216 residue in the binding site caused complete loss of affinity of both 3H-LY354740 and 3H-HYDIA. T168 in lobe I was shown to have an important role in HYDIA binding, and in the open conformation model this residue is interacting with the amino group of HYDIA. The Y144 residue in lobe I is shown to be engaged in both receptor interlobe binding and ligand interaction. Receptor mutations at this position (Y144G, Y144S and Y144A) showed dramatic impact on binding affinity and functional effect of HYDIA. The mGlu2 receptor mutants with increased structural flexibility at this position, which is crucial for pocket closure, were clearly preferred. These studies highlight the unique properties of the novel 3H-HYDIA ligand and provide further support to our understanding of binding and signal transduction mechanisms of the mGlu2 receptor. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA" DO - http://dx.doi.org/10.1002/cmdc.200900028 0 1154 "P. J. Goadsby, M. Adner and L. Edvinsson" 1996 Characterization of endothelin receptors in the cerebral vasculature and their lack of effect on spreading depression J.Cereb.Blood Flow Metab 16 4 698-704 "The changes in cerebral blood flow that accompany spreading depression are well-described, as are parallel changes in cellular activity, with a wave of hyperemia followed by a prolonged oligemic phase. In this study, a cat model of the CBF changes associated with spreading depression and in vitro pharmacology were used to determine if there is a role for the powerful peptide vasoconstrictor endothelin in this response. For the pharmacological studies, the middle cerebral artery was harvested from cats postmortem. For the physiological studies, cats were anesthetized with halothane induction and alpha-chloralose (60 mg/kg, intraperitoneal loading; 20 mg/kg i.v. 2-h maintenance). CBF was monitored continuously in the parietal cortex using laser Doppler flowmetry (CBFLDF) after exposure of the dura mater. The in vitro work demonstrated that endothelin-1 (ET-1) mediates a strong and potent contraction of cerebral vessels. Both the selective ETA receptor antagonist FR139317 and the combined ETA and ETB receptor antagonist Bosentan caused a rightward shift of the concentration-response curve without attenuation of the maximum effect. The calculated pA2 values were 6.28 and 6.90, respectively. The slope did not differ from unity, suggesting that the ET-1-mediated contraction is evoked by a single population of ETA receptors, which were effectively antagonized by these compounds. Spreading depression was induced with a needle stick injury to the cortex. Local administration of the endothelin antagonists FR139317 (10 microM) and Bosentan (10 microM) did not affect resting blood flow in the cortex. Induction of spreading depression following local administration of FR139317 and Bosentan resulted in responses no different from those in control cortex. These data demonstrate that endothelin does not play a significant role in the vasoconstrictor portion of the CBF change seen in spreading depression, nor does it affect resting flow. Since it is widely held that spreading depression, or a very similar mechanism, underlies the aura phase of migraine, it may be suggested from these studies that endothelin antagonists are unlikely to be useful in migraine" http://www.ncbi.nlm.nih.gov/pubmed/8964810 0 1155 K. Starke 1972 Interactions of guanethidine and indirect-acting sympathomimetic amines Arch.Int.Pharmacodyn.Ther. 195 2 309-314 http://www.ncbi.nlm.nih.gov/pubmed/5015937 0 1156 "M. Yilmaz, H. Celebi, D. Akcali and N. Gurel" 2014 Pre-treatment of bupivacaine-induced cardiovascular depression using different lipid formulations of propofol Acta Anaesthesiol.Scand. 58 3 298-302 "BACKGROUND: Pre-treatment with lipid emulsions has been shown to increase lethal doses of bupivacaine, and the lipid content of propofol may alleviate bupivacaine-induced cardiotoxicity. The aim of this study is to investigate the effects of propofol in intralipid or medialipid emulsions on bupivacaine-induced cardiotoxicity. METHODS: Rats were anaesthetised with ketamine and were given 0.5 mg/kg/min propofol in intralipid (Group P), propofol in medialipid (Group L), or saline (Group C) over 20 min. Thereafter, 2 mg/kg/min bupivacaine 0.5% was infused. We recorded time to first dysrhythmia occurrence, respective times to 25% and 50% reduction of the heart rate (HR) and mean arterial pressure, and time to asystole and total amount of bupivacaine consumption. Blood and tissue samples were collected following asystole. RESULTS: The time to first dysrhythmia occurrence, time to 25% and 50% reductions in HR, and time to asystole were longer in Group P than the other groups. The cumulative bupivacaine dose given at those time points was higher in Group P. Plasma bupivacaine levels were significantly lower in Group P than in Group C. Bupivacaine levels in the brain and heart were significantly lower in Group P and Group L than in Group C. CONCLUSION: We conclude that pre-treatment with propofol in intralipid, compared with propofol in medialipid or saline, delayed the onset of bupivacaine-induced cardiotoxic effects as well as reduced plasma bupivacaine levels. Further studies are needed to explore tissue bupivacaine levels of propofol in medialipid and adapt these results to clinical practice" http://www.ncbi.nlm.nih.gov/pubmed/24438483 0 1157 "L. M. Donini, L. Serra-Majem, M. Bullo, A. Gil and J. Salas-Salvado" 2015 "The Mediterranean diet: Culture, health and science" "British Journal of Nutrition.113 (S2) ()(pp S1-S3), 2015.Date of Publication: 07 Jul 2015." S2 S1-S3 DO - http://dx.doi.org/10.1017/S0007114515001087 0 1158 "K. Comai, P. Prose, S. J. Farber and J. R. Paulsrud" 1974 Correlation of renal medullary prostaglandin content and renal interstitial cell lipid droplets Prostaglandins 6 5 375-379 http://www.ncbi.nlm.nih.gov/pubmed/4851198 0 1159 "K. Kawamura, J. Maeda, A. Hatori, T. Okauchi, Y. Nagai, M. Higuchi, T. Suhara, T. Fukumura and M. R. Zhang" 2011 In vivo and in vitro imaging of I(2) imidazoline receptors in the monkey brain Synapse 65 5 452-455 "I(2) imidazoline receptors (I(2)Rs) are associated with depression, Alzheimer's disease, and Huntington's disease. However, in vivo imaging of I(2)Rs in the monkey brain has not been reported until now. We performed in vitro and in vivo imaging of (I(2)Rs) in the monkey brain using (1)(1)C-labeled 2-(3-fluoro-4-tolyl)-4,5-dihydro-1H-imidazole ([(1)(1)C]FTIMD) which has high and selective affinity of I(2)Rs. In an auto-radiography (ARG) study, the distribution pattern of [(1)(1)C]FTIMD in the monkey brain was similar to that of [(3)H]idazoxan binging to I(2)Rs in the human brain, which was previously described. The specific binding of [(1)(1)C]FTIMD accounted for >97% of total binding in brain regions existing I(2) Rs. In positron emission tomography (PET) studies, the radioactivity was accumulated in brain regions existing I(2)Rs ligand BU224, the accumulated radioactivity was decreased to approximately 66%-75% of the baseline measurement at 15-45 min after injection of [(1)(1)C]FTIMD. These results suggest that [(1)(1)C]FTIMD shows the specific-binging to I(2)Rs in the monkey brain as depicted by PET and ARG. We performed the first in vivo imaging of I(2)Rs using [(1)(1)C]FTIMD in the monkey brain" http://www.ncbi.nlm.nih.gov/pubmed/21370281 0 1160 "T. Iijima, C. Shimase, Y. Iwao and H. Sankawa" 1998 "Relationships between glutamate release, blood flow and spreading depression: real-time monitoring using an electroenzymatic dialysis electrode" Neurosci.Res. 32 3 201-207 "Spreading depression (SD) in a flow-restricted area of the brain may be prolonged and may become potentially harmful by releasing glutamate. We induced SD in an oligemia model and examined the subsequent glutamate release. In 18 anesthetized male Fischer rats, a laser Doppler flowmeter, an electroenzymatic electrode for continuous measurement of glutamate, and a calomel electrode for measuring DC potential were placed through a cranial window positioned 3 mm away from a second window where KCl-soaked cotton was placed to initiate SD. The left carotid artery or both the common carotid arteries were ligated to suppress reactive hyperemia of SD. SD produced an increase in glutamate from 24.8 +/- 13.8 to 33.5 +/- 25.3 microM (peak value) (P < 0.0001). After ligation of both carotid arteries, the duration of SD increased from 1.5 +/- 0.6 min (before ligation) to 6.4 +/- 5.1 min (P < 0.05). Glutamate reached a peak level of 63.9 +/- 72.3 microM, then quickly returned to the control value. However, there was no positive correlation between the duration of SD and glutamate concentration. It is concluded that prolonged SD is not accompanied by a progressive increase in glutamate. Therefore, glutamate release induced by SD may not exert harmful effects on neurons" http://www.ncbi.nlm.nih.gov/pubmed/9875562 0 1161 "T. Yaguchi, T. Nagata and T. Nishizaki" 2009 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine improves cognitive decline by enhancing long-term depression Behav.Brain Res. 204 1 129-132 "1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPhtCho) (1 microM) enhanced long-term depression (LTD), a synaptic plasticity relevant to learning and memory, in the CA1 region of rat hippocampal slices, where expression of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunit GluR1 on the plasma membrane was decreased. In the water maze test, oral administration with POPhtCho (5 mg/kg) significantly shortened the prolonged retention latency for rats intraperitoneally injected with scopolamine (1 mg/kg), while the acquisition latency was not affected. For humans with mild cognitive impairment and dementia (average of Mini Mental State Examination score, 18), oral intake with POPhtCho (300 mg/day, once after breakfast) everyday raised the score to over 20, corresponding to normal cognitive functions, throughout 6 months after intake. The results of the present study, thus, indicate that POPhtCho could ameliorate cognitive disorders, possibly by enhancing LTD" http://www.ncbi.nlm.nih.gov/pubmed/19482045 0 1162 "H. Nawrath, P. Gruschwitz and X. Zong" 1981 A negative inotropic effect of acetylcholine in the presence of several phosphodiesterase inhibitors Experientia 37 7 755-756 "The phosphodiesterase inhibitors papaverine, theophylline and 3-isobutyl-1-methylxanthine (IBMX) reveal a negative inotropic effect of acetylcholine in cat ventricular heart muscle. This effect in unrelated to beta-adrenoceptor stimulation and possibly mediated by the accumulation of cyclic GMP" http://www.ncbi.nlm.nih.gov/pubmed/6168488 0 1163 R. L. St Pierre 1968 Alteration of humoral antibody production following in vivo administration of phytohemagglutinin Experientia 24 4 390-391 http://www.ncbi.nlm.nih.gov/pubmed/4973979 0 1164 M. Mikuni 1995 [Effect of interleukin-2 and interleukin-6 on ovary in the ovulatory period--establishment of the new ovarian perfusion system and influence of interleukins on ovulation rate and steroid secretion] Hokkaido Igaku Zasshi 70 4 561-572 "Cytokines are not only mediators of inflammation and the immune system but are also important factors in cell proliferation, differentiation, and cell-to-cell communication. Cytokines have been identified within follicular fluid and some authors indicated that they are playing some roles in ovulation and ovarian steroidogenesis. Interleukin-2 (IL-2), mainly secreted by activated T-cells, influences other T-cells, B-cells, Macrophages, NKcells, etc. and is a major proliferating and differentiation factor of lymphocytes. Interleukin-6 (IL-6) is known to be secreted from and influence immune cells and/or non-immune cells such as fibroblasts, hepatic cells, endothelial cells, etc. The in vitro ovarian perfusion system has some advantages, compared with in vivo study, that is, it is devoid of systemic or unnecessary factors which are not focused on. In this study, the effects of IL-2 and IL-6 on ovulation and steroidogenesis were examined using the newly developed in vitro ovarian perfusion system and the culture of follicular granulosa cells. In the perfusion experiment, 100 ng/ml of IL-6 suppressed LH (100ng/ml)-induced estradiol (E2) secretion but did not influence progesterone (P4) secretion, while IL-2 had no effect on steroid secretion. Both IL-2 (100ng/ml) and IL-6 (100ng/ml) significantly suppressed LH-induced ovulation (ovulation rate; 8.3 +/- 1.5, mean +/- SE), to 2.2 +/- 1.1 and 3.2 +/- 1.0, respectively. Addition of 1.0, 3.0, 10 ng/ml of IL-6 decreased FSH (50ng/ml)-induced E2 secretion dose-dependently in the culture experiments of granulosa cells. IL-6 also suppressed FSH-induced P4 secretion in concentrations of 3.0 and 10 ng/ml. On the other hand, IL-2 concentrations of 10 and 30 ng/ml increased FSH-induced P4 secretion although 100 ng/ml of IL-2 showed no effect. Any dosage of IL-2 did not influence E2 secretion induced by FSH. All of these results obtained in the present study suggest that IL-2 and IL-6 may directly and/or indirectly suppress some mechanisms of ovulation, but with still unclarified different pathways" http://www.ncbi.nlm.nih.gov/pubmed/7590603 0 1165 "E. Z. Dajani, D. R. Driskill, R. G. Bianchi and P. W. Collins" 1975 Comparative gastric antisecretory and antiulcer effects of prostaglandin E1 and its methyl ester in animals Prostaglandins 10 2 205-215 "The influence of methyl esterification of the carboxyl group of PGE1 on the gastric antisecretory and antiulcer activities were studied. The gastric antisecretory effects of PGE1 free acid and PGE1 methyl ester (PGE1ME) were studied in the Heidenhain pouch dog. Secretion was stimulated with constant intravenous infusion of histamine dihydrochloride. When a steady-state plateau of gastric secretion had been reached, the prostaglandins were administered either by a single intravenous bolus (10.0 mug/kg) or by continuous infusion (1.0 mug/kg/min). PGE1ME was found to be slightly more potent and longer-acting than PFE1 when administered by a single i.v. bolus. PGE1ME was also shown to be more potent than PGE1 when infused intravenously for a two-hour period. PGE1ME caused a significant alteration in gastric juice concentration of hydrogen and sodium ions in an inverse relationship. Potassium and chloride concentration were not altered from pre-existing steady-state values following administration of either form of prostaglandin. Similarly, PGE1ME was also found to possess significantly greater antiulcer activity in the rat forced-exertion ulcer test. These findings support the hypothesis that methyl esterification of the prostaglandin molecule will increase some of the biological actions of PGE1 through inhibition of metabolic beta-oxidation of the carboxylic side chain" http://www.ncbi.nlm.nih.gov/pubmed/1178902 0 1166 "T. E. Romero, C. B. Higgins, S. Kirkpatrick and W. F. Friedman" 1977 Effects of contrast material on dimensions and hemodynamics of the newborn heart: a study in conscious newborn lambs Invest Radiol. 12 6 510-514 "Injections of contrast material (Hypaque M-75%) and normal saline into the left ventricle (LV) of 1- to 3-month-old conscious lambs, during continuous monitoring of LV internal dimensions and pressures, revealed instaneous increases in LV end diastolic and end systolic volumes and LV end diastolic pressure. After contrast material, these alterations were sustained. Contrast injections were also accompanied by a mild depression in LV contractile state (dp/dt/P), systemic vasodilatation and persistent augmentation of cardiac output. The immediate effects on LV dimensions are primarily a consequence of acute volume expansion of the LV by the injection while the sustained changes likely reflect an expanded intravascular volume" http://www.ncbi.nlm.nih.gov/pubmed/145418 0 1167 "L. P. Guan, L. M. Tang, C. Y. Pan, S. L. Zhao and S. H. Wang" 2014 Evaluation of potential antidepressant-like activity of chalcone-1203 in various murine experimental depressant models Neurochem.Res. 39 2 313-320 "Two classic animal behavior despair tests-the forced swimming test (FST) and the tail suspension test (TST) were used to evaluate antidepressant-like activity of a new chalcone compound, chalcone-1203 in mice. It was observed that chalcone-1203 at dose of 1, 5, and 10 mg/kg significantly reduced the immobility time in the FST and TST in mice 30 min after treatment. In addition, chalcone-1203 was found to exhibit significant oral activity in the FST in mice. It also produced a reduction in the ambulation in the open-field test in mice not previously habituated to the arena, but no effect in the locomotor activity in mice previously habituated to the open-field. The main monoamine neurotransmitters and their metabolites in mouse brain regions were also simultaneously determined by HPLC-ECD. It was found that chalcone-1203 significantly increased the concentrations of the main neurotransmitters 5-HT and NE in the hippocampus, hypothalamus and cortex. Chalcone-1203 also significantly reduced the ratio of 5-HIAA/5-HT in the hippocampus and cortex, shown down 5-HT metabolism compared with mice treated with stress vehicle. In conclusion, chalcone-1203 produced significant antidepressant-like activity, and the mechanism of action may be due to increased 5-HT and NE in the mouse hippocampus and cortex" http://www.ncbi.nlm.nih.gov/pubmed/24343532 1 1168 "Y. X. Xu, A. Ayala, B. Monfils, W. G. Cioffi and I. H. Chaudry" 1997 Mechanism of intestinal mucosal immune dysfunction following trauma-hemorrhage: increased apoptosis associated with elevated Fas expression in Peyer's patches J.Surg.Res. 70 1 55-60 "Although intestinal mucosal immune dysfunction occurs after trauma and hemorrhage and appears to contribute to infectious complications, the mechanism is not known. In this regard, the inappropriate induction of immune cell apoptosis may contribute to the immune dysfunction following trauma and hemorrhage. To study this, we examined Peyer's patch cells for evidence of apoptosis and changes in Fas protein expression, as well as alterations in the relative lymphocyte subpopulations after trauma and hemorrhagic shock. Male C3H/HeN mice underwent sham operation, trauma (i.e., laparotomy), hemorrhagic shock (mean arterial blood pressure of 35 +/- 5 mmHg for 90 min, followed by adequate crystalloid resuscitation), or trauma plus hemorrhage. Peyer's patch cells were isolated at 24 and 72 hr after the procedure. The percentage of apoptotic cells, Fas protein expression, and cell percentage of phenotype were determined by flow cytometry. The results indicate that trauma alone induced no significant change in the measured parameters. However, (i) there were a significant decrease in total viable cell yield and an increased apoptosis in Peyer's patch cells at 24 and 72 hr following hemorrhage or trauma plus hemorrhage; (ii) the increased apoptosis in Peyer's patch was predominantly in cells of the B-cell lineage; (iii) the increased apoptosis was associated with an elevated Fas expression. In conclusion, hemorrhage alone or trauma plus hemorrhage can induce increased apoptosis in Peyer's patch cells, which is associated with the increased Fas expression. Thus, apoptotic involution may play an important role in the depression of intestinal mucosal immune function after trauma and hemorrhagic shock" http://www.ncbi.nlm.nih.gov/pubmed/9228928 0 1169 "D. G. Herrera, D. Maysinger, R. Gadient, C. Boeckh, U. Otten and A. C. Cuello" 1993 Spreading depression induces c-fos-like immunoreactivity and NGF mRNA in the rat cerebral cortex Brain Res. 602 1 99-103 "Application of potassium chloride (KCl) to the brain surface elicits spreading depression which leads to a marked induction of the proto-oncogene c-fos in the treated cerebral cortex at the earliest time examined (90 min). High levels of c-fos immunoreactivity are observed up to 6 h after KCl treatment. The areas affected include the cingulate, entorhinal and frontoparietal cortex throughout the treated hemisphere. The c-fos expression preceded an increase in both NGFmRNA and NGF-like protein(s). A maximal increase in c-fos was detected within 3 h, whereas NGFmRNA peaked at 12 h and NGF-like protein(s) reached their maximum level 24 h after KCl application. The most prominent increase in NGFmRNA was measured in the entorhinal cortex (50-fold), but other cortical areas also showed a moderate increase of 2-3-fold. In conclusion, our results provide evidence that increases in c-fos and NGF expression are early adaptive responses following brain injury" http://www.ncbi.nlm.nih.gov/pubmed/8448663 0 1170 "O. Virit, A. Dalkilic, M. Bulut, F. Bulbul, A. Altindag, F. Armutcu, E. Kocoglu, S. Citak and H. A. Savas" 2010 Decreased superoxide dismutase activity after ECT and correlation between higher oxidant levels and poor response to ECT in depression. [Turkish] Noropsikiyatri Arsivi 47 3 2010 "Objective: The literature regarding effects of electroconvulsive therapy (ECT) on oxidative metabolism (OM) reports conflicting changes in oxidant and antioxidant status in animal studies. The goal of this first human study was to investigate the changes in oxidants and antioxidants in plasma of depressed patients after ECT. Methods: Fourteen unipolar and two bipolar patients were included in the study. The blood samples were obtained within one hour before the 1st and within one hour after the 7th ECT sessions. Oxidants malondialdehyde (MDA), nitric oxide (NO), and xanthine oxidase (XO) and antioxidant superoxide dismutase (SOD) were measured in the plasma. Results: Before the 1st and after the 7th ECT sessions, the Hamilton Depression Rating Scale (HDRS) scores were 32.63+/-9.54 and 16.50+/-7.22, respectively (t=7.92, df=15, p<0.001). After the 7th ECT, SOD values were significantly lower than pre-ECT SOD values (p<0.05, Z= -3,459). There were no significant difference between pre-and post-ECT values of MDA, NO, and XO (p>0.05). However, pre-ECT SOD values were significantly and positively correlated with pre-ECT HDRS scores (r=0.641, p=0.007). Conclusion: The decrease in antioxidant enzyme SOD after ECT may damage the neurons by increasing oxidative stress. Thus, possible benefits of antioxidant supplementation during ECT should be investigated. Additionally, higher pre-ECT oxidant levels may predict a poor response to ECT in depression. © Archives of Neuropsychiatry, published by Galenos Publishing" 0 1171 P. L. Jorgensen and J. C. Skou 1971 Purification and characterization of (Na+ + K+)-ATPase. I. The influence of detergents on the activity of (Na+ + K+)-ATPase in preparations from the outer medulla of rabbit kidney Biochim.Biophys.Acta 233 2 366-380 http://www.ncbi.nlm.nih.gov/pubmed/4254310 0 1172 D. L. Toan and W. Schultz 1985 Responses of rat pallidum cells to cortex stimulation and effects of altered dopaminergic activity Neuroscience 15 3 683-694 "The aim of the study was to investigate the influences of dopamine on oligosynaptic corticopallidal neurotransmission. Different cortical areas were electrically stimulated and the responses in the pallidum were recorded by single-cell electrophysiology. Out of 377 pallidal neurons, 192 (51%) responded to stimulation of at least one of the cortical areas investigated. Convergence between frontal cortex and at least one of the other cortical areas was seen in 59 of 110 (54%) pallidal neurons responding to frontal cortex stimulation. Nearly three-quarters (73%) of all responsive pallidal neurons showed a short latency reduction of activity following the stimulus, the rest responded with pure activation or an activation-depression sequence. The dopaminergic influences on this corticopallidal impulse transmission were assessed by the systemic administration of the dopamine receptor-blocking neuroleptics, haloperidol and fluphenazine, as well as by conditioning electrical stimulation of the substantia nigra. Neuroleptic administration augmented the responses to cortical stimulation in 12 of 34 pallidal neurons. Stimulation of the substantia nigra diminished the responses in 24 and augmented them in 6 of 63 of the tested neurons. We propose from the present results, and in agreement with data from conceptually different studies done by others, that dopaminergic influences reduce the flow of information from the cortex to the pallidum. This may constitute a focussing mechanism by which only information form the strongest cortical inputs would pass to the pallidum while less prominent activity would be lost" http://www.ncbi.nlm.nih.gov/pubmed/2866467 0 1173 "H. Ozturk, A. Onen, H. Ozturk and H. Buyukbayram" 2006 Exogenous human recombinant interleukin-10 protects the kidney against hypoxia-induced renal injury in immature rats Int.J.Urol. 13 4 397-400 "AIM: The purpose of this study was to determine the effects of exogenous human recombinant interleukin-10 (rhIL-10) on hypoxia-induced renal injury in immature rats. METHOD: The study was performed on 1-day-old Sprague-Dawley rat pups. Group 1 (n = 8) served as non-hypoxic controls. Group 2 (untreated, n = 8) rats were subjected to hypoxia-reoxygenation (H/O) and were then returned to their mothers. Group 3 (rhIL-10 treated, n = 8) rats were subjected to H/O, were returned to their mothers, and were treated with rhIL-10 (75 microg/kg subcutaneously) for the next 3 days. All animals were killed on day 4 and renal specimens were obtained to determine the tissue level of malondialdehyde (MDA) and histological changes. RESULTS: In the untreated group, moderate or severe renal tubular necrosis was observed However, the tubular necrosis score was significantly less in the rhIL-10 treated rats than in the untreated rats (P < 0.05). In the untreated group, MDA levels were significantly increased compared with the control and rhIL-10 groups (P < 0.001 and P < 0.05, respectively). In the rhIL-10 treated group, MDA levels were not significantly different compared with the control group. CONCLUSION: RhIL-10 has a protective effect against hypoxia-induced renal injury in immature rats by depression of tissue MDA level and renal tubular necrosis score" http://www.ncbi.nlm.nih.gov/pubmed/16734858 0 1174 "F. F. Youssef, J. I. Addae and T. W. Stone" 2006 NMDA-induced preconditioning attenuates synaptic plasticity in the rat hippocampus Brain Res. 1073-1074 183-189 "It was recently demonstrated that glutamate could precondition hippocampal slices against the damaging effects of hypoxia, and we have now extended this observation by investigating (i) the ability of glutamate receptor agonists to act as preconditioning agents and (ii) the effects of preconditioning on synaptic plasticity. Using rat hippocampal slices, 15 microM NMDA applied for 10 min (chemical insult) caused abolition of the population spike potentials (PS) followed by approximately 33% recovery at 60 min post-insult. In comparison, a 5 min preconditioning exposure of 10 microM NMDA given 30 min prior to the insult significantly improved the recovery to 69%. Preconditioning did not alter paired pulse facilitation; however, it significantly enhanced paired pulse depression and reduced population spike long-term potentiation (PS-LTP) and LTP in field recordings. This effect on PS-LTP appeared to be NMDA receptor dependent and was blocked by the nitric oxide synthase inhibitors nitro-L-arginine methyl ester (L-NAME) and 7-nitro indazole (7-NI) but not by the adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). We conclude that preconditioning by NMDA can improve recovery following acute insults but may have deleterious effects on neuronal plasticity" http://www.ncbi.nlm.nih.gov/pubmed/16472785 0 1175 M. Nishio and Y. Watanabe 2010 Hippocampal leptin suppresses methamphetamine-induced hyperlocomotion Basic Clin.Pharmacol.Toxicol. 107 4 842-846 "Leptin is an anorexigenic peptide which is synthesized in white adipose tissue. The actions of leptin are mediated by the leptin receptor which is abundantly localized in the hypothalamus and is involved in energy regulation and balance. Recently, there has been evidence suggesting that the leptin receptor is also present in the hippocampus and may be involved with hippocampal excitability and long-term depression. To investigate the physiological function of leptin signalling in the hippocampus, we studied the effects of leptin on methamphetamine-induced ambulatory hyperactivity by utilizing intra-hippocampal infusion (i.h.) in mice. Our results show that the infusion of leptin (5 ng each bilaterally i.h.) does not affect the basal ambulatory activity but significantly suppresses methamphetamine-induced ambulatory hyperactivity as compared to saline-infused controls. Interestingly, higher dose of leptin increases the suppression of the methamphetamine-induced ambulatory hyperactivity. The i.h. infusion of leptin did not activate the JAK-STAT pathway, which is the cellular signalling pathway through which leptin acts in the hypothalamus. The infusion of leptin also did not affect activation of p42/44 MAPK which is known to be another leptin-induced signalling pathway in the brain. These results demonstrate that leptin has a novel potential suppressive effect on methamphetamine-induced hyperlocomotion and also suggest that there must be an alternative pathway in the hippocampus through which leptin signalling is being mediated" http://www.ncbi.nlm.nih.gov/pubmed/20486923 0 1176 "K. J. Bernstein, M. Verosky and L. Triner" 1984 Halothane inhibition of canine myocardial adenylate cyclase--modulation by endogenous factors Anesth.Analg. 63 3 285-289 "We have hypothesized that the halothane-induced depression of myocardial contractility can be explained, at least in part, by halothane's depression of adenylate cyclase, previously demonstrated in whole homogenates of myocardial tissue. Canine myocardial sarcolemmal membranes, which contain the adenylate cyclase of myocardial cells, were separated from other cellular constituents. Halothane did not depress catecholamine-stimulated adenylate cyclase activity in this preparation. Reconstitution of the sarcolemmal membrane preparation with a 100,000 X g adenylate cyclase-free supernatant restored the depressant effect of halothane on adenylate cyclase stimulated by guanosine triphosphate (GTP) 100 microM alone (-55%, P less than 0.01) or in combination with l-isoproterenol 1 microM (-38%, P less than 0.05) or 2.5 microM (-40%, P less than 0.01). Dilution of the supernatant to half-strength decreased the magnitude of the halothane-induced depression of adenylate cyclase activity to 19% (P less than 0.01); at one-quarter dilution, the effect was no longer significant. This study demonstrates the presence of endogenous modulators of the action of halothane on canine myocardial adenylate cyclase that can be reversibly separated from the adenylate cyclase complex" http://www.ncbi.nlm.nih.gov/pubmed/6703345 0 1177 "P. Brust, W. Deuther-Conrad, G. Becker, M. Patt, C. K. Donat, S. Stittsworth, S. Fischer, A. Hiller, B. Wenzel, S. Dukic-Stefanovic, S. Hesse, J. Steinbach, B. Wunsch, S. Z. Lever and O. Sabri" 2014 Distinctive in vivo kinetics of the new sigma1 receptor ligands (R)-(+)- and (S)-(-)-18F-fluspidine in porcine brain J.Nucl.Med. 55 10 1730-1736 "Because of their involvement in growth and survival signaling cascades, the sigma(1) receptors (sigma(1)Rs) represent a novel target for the treatment of cancer and several brain diseases such as depression and neurodegeneration. From a series of sigma1R-specific (18)F-fluoroalkylated spirocyclic piperidines, we have chosen (18)F-fluspidine for detailed investigation of the in vivo kinetics of the (R)-(+)- and (S)-(-)-enantiomers to identify their potential for imaging in humans. METHODS: Enantiopure tosylate precursors for radiolabeling were obtained using chiral preparative high-performance liquid chromatography and used for radiosynthesis of both (18)F-fluspidine enantiomers by nucleophilic substitution with K-(18)F-F-Kryptofix 222-carbonate complex in a synthesis module. Brain pharmacokinetics were investigated by dynamic PET studies in piglets under baseline and blocking conditions using the highly selective sigma1R agonist SA4503. Standardized uptake values (SUVs) were calculated for 24 MR-defined brain regions. Total distribution volume (V(T)) and binding potentials (k3'/k4) of (S)-(-)- and (R)-(+)-(18)F-fluspidine were estimated. Furthermore, V(T) values were estimated by graphical analysis using Logan plots. RESULTS: The (S)- and (R)-tosylates were obtained in excellent enantiomeric purities (>98% and >96% enantiomeric excess, respectively). (S)-(-)- and (R)-(+)-(18)F-fluspidine were synthesized within approximately 70 min (radiochemical yield, 35%-45%; specific activity, 650-870 GBq/mumol; radiochemical purity, >99%). Both radiotracers displayed different brain uptake kinetics. Although the initial brain uptake was similar, the SUV at the end of the study differed significantly (P < 0.05), with (R)-(+)-(18)F-fluspidine showing about 60%-150% higher values. Administration of SA4503 reduced SUV almost equally for both radiotracers by approximately 65%. Furthermore, k(3)' was significantly decreased under blocking conditions in almost all regions ((S)-(-)-(18)F-fluspidine, -90%-95%; (R)-(+)-(18)F-fluspidine, -70%-90%) whereas effects on k(4) differed according to the particular brain region. V(T) estimated by both graphical analysis using Logan plots and full nonlinear kinetic analysis revealed significant inhibition for both radiotracers under blocking conditions. CONCLUSION: Both (S)-(-)- and (R)-(+)-(18)F-fluspidine appear to be suitable for sigma1R imaging in humans. The different pharmacokinetics of (S)-(-)-(18)F-fluspidine and (R)-(+)-(18)F-fluspidine may have the potential for application in the diagnostics of different pathologic conditions" http://www.ncbi.nlm.nih.gov/pubmed/25071097 0 1178 H. W. Lu and L. O. Trussell 2016 Spontaneous Activity Defines Effective Convergence Ratios in an Inhibitory Circuit J.Neurosci. 36 11 3268-3280 "Many neurons fire spontaneously, and the rate of this firing is subject to neuromodulation. How this firing affects functional connectivity within a neural network remains largely unexplored. Here we show that changes in spontaneous firing of cartwheel interneurons in the mouse dorsal cochlear nucleus (DCN) alter the effective convergence ratio of interneurons onto their postsynaptic targets through short-term synaptic plasticity. Spontaneous firing of cartwheel cells led to activity-dependent synaptic depression of individual cartwheel synapses. Depression was rapid and profound at stimulation frequencies between 10 and 200 Hz, suggesting the presence of high release probability (Pr) vesicles at these inhibitory synapses. Weak, transient synaptic facilitation could be induced after synapses were predepressed, indicating that low-Pr vesicles are also recruited, and may thus support steady-state transmission. A two-pool vesicle depletion model with 10-fold differences in Pr could account for the synaptic depression over a wide range of stimulus conditions. As a result of depression during high spontaneous activity, more cartwheel interneurons were required for effective inhibition. Convergence of four interneurons was sufficient to compensate for the effects of depression during physiologically expected rates of activity. By simulating synaptic release during spontaneous firing, we found that recruitment of low-Pr vesicles at the synapse plays a critical role in maintaining effective inhibition within a small population of interneurons. The interplay between spontaneous spiking, short-term synaptic plasticity, and vesicle recruitment thus determines the effective size of a convergent neural network. SIGNIFICANCE STATEMENT: We examined the relationship between the structure of a small neural circuit and the properties of its individual synapses. Successful synaptic inhibition of a target cell firing requires a critical inhibitory synaptic strength. Synapses often become depressed during spontaneous presynaptic activity, and this increases the number of presynaptic neurons needed to mediate inhibition. We show that depression is limited by the presence of a pool of vesicles that resist depletion. Thus, the size of this vesicle pool determines the size of the circuit needed to mediate inhibition during different patterns of activity" http://www.ncbi.nlm.nih.gov/pubmed/26985036 0 1179 "C. E. McAllister, Z. Mi, M. Mure, Q. Li and N. A. Muma" 2014 GPER1 stimulation alters posttranslational modification of RGSz1 and induces desensitization of 5-HT1A receptor signaling in the rat hypothalamus Neuroendocrinology 100 02-Mar 228-239 "Hyperactivity of the hypothalamic-pituitary-adrenal axis is a consistent biological characteristic of depression, and response normalization coincides with clinical responsiveness to antidepressant medications. Desensitization of serotonin 1A receptor (5-HT1AR) signaling in the hypothalamic paraventricular nucleus of the hypothalamus (PVN) follows selective serotonin reuptake inhibitor (SSRI) antidepressant treatment and contributes to the antidepressant response. Estradiol alone produces a partial desensitization of 5-HT1AR signaling and synergizes with SSRIs to result in a complete and more rapid desensitization than with SSRIs alone as measured by a decrease in the oxytocin and adrenocorticotrophic hormone (ACTH) responses to 5-HT1AR stimulation. G protein-coupled estrogen receptor 1 (GPER1) is necessary for estradiol-induced desensitization of 5-HT1AR signaling, although the underlying mechanisms are still unclear. We now find that stimulation of GPER1 with the selective agonist G-1 and nonselective stimulation of estrogen receptors dramatically alter isoform expression of a key component of the 5-HT1AR signaling pathway, RGSz1, a GTPase-activating protein selective for Galphaz, the Galpha subunit necessary for 5-HT1AR-mediated hormone release. RGSz1 isoforms are differentially glycosylated, SUMOylated, and phosphorylated, and differentially distributed in subcellular organelles. High-molecular-weight RGSz1 is SUMOylated and glycosylated, localized to the detergent-resistant microdomain (DRM) of the cell membrane, and increased by estradiol and G-1 treatment. Because activated Galphaz also localizes to the DRM, increased DRM-localized RGSz1 by estradiol and G-1 could reduce Galphaz activity, functionally uncoupling 5-HT1AR signaling. Peripheral G-1 treatment produced a partial reduction in oxytocin and ACTH responses to 5-HT1AR stimulation similar to direct injections into the PVN. Together, these results identify GPER1 and RGSz1 as novel targets for the treatment of depression" http://www.ncbi.nlm.nih.gov/pubmed/25402859 1 1180 "R. M. Santiago, T. Zaminelli, T. B. Bassani, S. L. Boschen, M. M. Lima, C. C. Da, R. Andreatini and M. A. Vital" 2015 The mechanism of antidepressant-like effects of piroxicam in rats J.Pharmacol.Pharmacother. 6 1 07-Dec "OBJECTIVE: To investigate the antidepressant-like effect of piroxicam with a focus on serotonergic neurotransmission. MATERIALS AND METHODS: Rats were randomly distributed into the following groups: 0.9% saline control; 3 mg/kg pizotifen; 10 mg/kg sertraline; 10 mg/kg piroxicam; 10 mg/kg sertraline + 10 mg/kg piroxicam; 10 mg/kg sertraline + 3 mg/kg pizotifen; and 10 mg/kg piroxicam + 3 mg/kg pizotifen. All the drugs were dissolved in 0.9% saline. Three administrations of the drugs (piroxicam and sertraline) were performed 1, 5 and 24 h before testing the animals in the open field followed by the forced swim test (FST). Piroxicam and sertraline were administered orally by gavage and pizotifen was administered intraperitoneally 30 min before gavage. Immediately after the FST, the hippocampi were rapidly dissected for neurochemical analysis in high-performance liquid chromatography. RESULTS: Acute treatment with piroxicam promoted an antidepressant-like effect in the FST, which was associated with an increase in serotonin levels in the hippocampus. This effect was potentiated in the piroxicam + sertraline group but counteracted by administration of the non-selective serotonin receptor antagonist pizotifen. CONCLUSION: These results suggest that the antidepressant-like effect of piroxicam in the FST is mediated by the serotonin system; however, by different mechanisms from those of sertraline" http://www.ncbi.nlm.nih.gov/pubmed/25709346 1 1181 "W. A. Zuccarello, G. J. Frishmuth and E. G. Rice" 1974 The quantitative measurement of steroids secreted by isolated adrenals from sodium depleted rats Steroids 23 3 443-454 http://www.ncbi.nlm.nih.gov/pubmed/4828063 0 1182 "S. J. Colloby, A. Vasudev, J. T. O'Brien, M. J. Firbank, S. W. Parry and A. J. Thomas" 2011 Relationship of orthostatic blood pressure to white matter hyperintensities and subcortical volumes in late-life depression Br.J.Psychiatry 199 5 404-410 "BACKGROUND: Structural brain abnormalities are associated with late-life major depression, with numerous studies reporting increased white matter hyperintensities (WMH) and reduced cortical/subcortical grey matter volumes. There is strong evidence linking vascular disease to WMH, but limited evidence on its association with subcortical volumes. AIMS: To investigate the relationship of orthostatic blood pressure changes to WMH and subcortical grey matter volumes in late-life depression. METHOD: Thirty-eight people with depression and a similarly aged comparison group (n = 30) underwent fluid attenuated inversion recovery (FLAIR) and T(1)-weighted magnetic resonance imaging as well as systematic orthostatic blood pressure assessments. Volumetric estimates of WMH and subcortical grey matter were obtained for each participant and the relationship to blood pressure drop on active stand was examined. RESULTS: An association between orthostatic systolic blood pressure drop and WMH volumes in temporal and parietal regions was found in the depression group (age-corrected partial correlation r' = 0.31-0.35, P<0.05). Subcortical volumes were not related to blood pressure changes or WMH volumes in either group. CONCLUSIONS: We found evidence for an association between the degree of orthostatic systolic blood pressure drop and WMH volume in the depression group. Since blood pressure drops lead to WMH in animals our findings suggest systolic blood pressure drops may be a factor contributing to these lesions in late-life depression" http://www.ncbi.nlm.nih.gov/pubmed/21903666 0 1183 "M. M. Katz, C. L. Bowden, N. Berman and A. Frazer" 2006 Resolving the onset of antidepressants' clinical actions: critical for clinical practice and new drug development J.Clin.Psychopharmacol. 26 6 549-553 http://www.ncbi.nlm.nih.gov/pubmed/17110809 0 1184 K. Takasaki 1971 Systemic arterial pressure changes cased by sympathomimetic amines and influence of norepinephrine infusion on chronically reserpinized dogs Kurume Med.J. 18 2 111-116 http://www.ncbi.nlm.nih.gov/pubmed/4396621 0 1185 "C. Liu, S. Min, K. Wei, D. Liu, J. Dong, J. Luo and X. B. Liu" 2012 Effect of electroconvulsive shock on the glutamate level and the hyperphosphorylation of protein tau in depression rat models whose olfactory bulbs were removed Zhongguo Yi.Xue.Ke.Xue.Yuan Xue.Bao. 34 3 216-221 "OBJECTIVE: To explore the effect of the electroconvulsive shock (ECS) on the glutamate level and the hyperphosphorylation of tau protein in depressed rats. METHODS: The depression rat models whose olfactory bulbs were removed were established. Using the analysis of variance of factorial design, we set up two intervention factors including electric current (three levels: 25, 50, and 75 mA) and duration (three levels: 3, 6, and 9 times), which constituted 9 combinations (n=6). Fifty-four adult depression rat models whose olfactory bulbs were removed were randomly divided into nine experimental groups (n=6 in each group). The hippocampus was removed within 12 hours after the ECS finished. The level of glutamate in the hippocampus was detected by high-performance liquid chromatography, and that of Tau protein, which includes p-PHF-1(Ser396/404), p-AT8(Ser199/202), and p-12E8(Ser262), in the hippocampus with Western blot analysis. RESULTS: The glutamate level and the hyperphosphorylation of tau protein in the hippocampus of depressed rats remarkably increased. The changes of the hyperphosphorylation of tau protein were correlated with the electric current and duration of ECS, and these two factors showed an synergic effect. CONCLUSION: ECS enhances the hyperphosphorylation of tau protein in the hippocampus of depressed rats by up-regulating the glutamate level" http://www.ncbi.nlm.nih.gov/pubmed/22776652 1 1186 "T. Sasaki, K. Beppu, K. F. Tanaka, Y. Fukazawa, R. Shigemoto and K. Matsui" 2012 Application of an optogenetic byway for perturbing neuronal activity via glial photostimulation Proc.Natl.Acad.Sci.U.S.A 109 50 20720-20725 "Dynamic activity of glia has repeatedly been demonstrated, but if such activity is independent from neuronal activity, glia would not have any role in the information processing in the brain or in the generation of animal behavior. Evidence for neurons communicating with glia is solid, but the signaling pathway leading back from glial-to-neuronal activity was often difficult to study. Here, we introduced a transgenic mouse line in which channelrhodopsin-2, a light-gated cation channel, was expressed in astrocytes. Selective photostimulation of these astrocytes in vivo triggered neuronal activation. Using slice preparations, we show that glial photostimulation leads to release of glutamate, which was sufficient to activate AMPA receptors on Purkinje cells and to induce long-term depression of parallel fiber-to-Purkinje cell synapses through activation of metabotropic glutamate receptors. In contrast to neuronal synaptic vesicular release, glial activation likely causes preferential activation of extrasynaptic receptors that appose glial membrane. Finally, we show that neuronal activation by glial stimulation can lead to perturbation of cerebellar modulated motor behavior. These findings demonstrate that glia can modulate the tone of neuronal activity and behavior. This animal model is expected to be a potentially powerful approach to study the role of glia in brain function" http://www.ncbi.nlm.nih.gov/pubmed/23185019 0 1187 "G. G. Bazazian, V. E. Pastorova and L. A. Liapina" 1976 "[Thrombocyte aggregation in depression of the function of the anticoagulation system of blood, caused by atherogenic diet]" Kardiologiia. 16 5 139-141 http://www.ncbi.nlm.nih.gov/pubmed/950749 0 1188 "D. S. O'Riordain, M. V. Mendez, M. G. O'Riordain, R. G. Molloy, R. G. Holzheimer, K. Collins, I. Saporoschetz, J. A. Mannick and M. L. Rodrick" 1993 Molecular mechanisms of decreased interleukin-2 production after thermal injury Surgery 114 2 407-414 "BACKGROUND: Among the fundamental immunologic abnormalities induced by serious traumatic or thermal injury are alterations in T cell activation, reduced lymphocyte interleukin-2 (IL-2) production, and associated depression of T lymphocyte proliferation. This study attempts to localize the cellular mechanisms underlying abnormal IL-2 production in thermal injury. METHODS: Following National Institutes of Health guidelines, 150 A/J mice were anesthetized, subjected to a 20% full-thickness scald burn injury or sham burn, and killed at intervals from 4 to 21 days later; splenocytes were harvested for in vitro studies. For measurement of IL-2 production, cells were cultured with either concanavalin A or a combination of the phorbol ester PMA, which directly activates protein kinase C, and the calcium ionophore A23187, which increases intracellular calcium. Cytokine mRNA expression was measured by Northern blot analysis and IL-2 production by bioassay. RESULTS: Both IL-2 production and IL-2 mRNA expression were consistently suppressed in concanavalin A-stimulated cells from burned mice compared with sham burns. This suppression of IL-2 and IL-2 mRNA also occurred when T cells were activated with PMA and A23187, bypassing the earlier stages of the signal transduction mechanism. IL-1 beta and tumor necrosis factor-alpha mRNA expression were consistently increased in burned animals, indicating that decreased IL-2 mRNA expression was specific to IL-2 and not representative of a global decrease in cytokine mRNA expression. CONCLUSIONS: These results suggest that the principal cellular abnormalities that result in altered T cell activation and IL-2 production after thermal injury lie downstream of the initiating signal transduction events and before IL-2 gene transcription" http://www.ncbi.nlm.nih.gov/pubmed/8342142 0 1189 A. Mangoni 1974 "The ""kynurenine shunt"" and depression" Adv.Biochem.Psychopharmacol. 11 0 293-298 http://www.ncbi.nlm.nih.gov/pubmed/4276862 0 1190 "J. W. Quintino-dos-Santos, C. J. Muller, C. S. Bernabe, C. A. Rosa, S. Tufik and L. C. Schenberg" 2014 Evidence that the periaqueductal gray matter mediates the facilitation of panic-like reactions in neonatally-isolated adult rats PLoS.One. 9 3 e90726 "Plenty of evidence suggests that childhood separation anxiety (CSA) predisposes the subject to adult-onset panic disorder (PD). As well, panic is frequently comorbid with both anxiety and depression. The brain mechanisms whereby CSA predisposes to PD are but completely unknown in spite of the increasing evidence that panic attacks are mediated at midbrain's dorsal periaqueductal gray matter (DPAG). Accordingly, here we examined whether the neonatal social isolation (NSI), a model of CSA, facilitates panic-like behaviors produced by electrical stimulations of DPAG of rats as adults. Eventual changes in anxiety and depression were also assessed in the elevated plus-maze (EPM) and forced-swimming test (FST) respectively. Male pups were subjected to 3-h daily isolations from post-natal day 2 (PN2) until weaning (PN21) allotting half of litters in individual boxes inside a sound-attenuated chamber (NSI, n = 26) whilst siblings (sham-isolated rats, SHAM, n = 27) and dam were moved to another box in a separate room. Non-handled controls (CTRL, n = 18) remained undisturbed with dams until weaning. As adults, rats were implanted with electrodes into the DPAG (PN60) and subjected to sessions of intracranial stimulation (PN65), EPM (PN66) and FST (PN67-PN68). Groups were compared by Fisher's exact test (stimulation sites), likelihood ratio chi-square tests (stimulus-response threshold curves) and Bonferroni's post hoc t-tests (EPM and FST), for P<0.05. Notably, DPAG-evoked panic-like responses of immobility, exophthalmus, trotting, galloping and jumping were markedly facilitated in NSI rats relative to both SHAM and CTRL groups. Conversely, anxiety and depression scores either did not change or were even reduced in neonatally-handled groups relative to CTRL, respectively. Data are the first behavioral evidence in animals that early-life separation stress produces the selective facilitation of panic-like behaviors in adulthood. Most importantly, results implicate the DPAG not only in panic attacks but also in separation-anxious children's predispositions to the late development of PD" http://www.ncbi.nlm.nih.gov/pubmed/24594924 1 1191 "U. Hoffmann, J. Pomper, J. Graulich, M. Zeller, S. Schuchmann, S. Gabriel, R. F. Maier and U. Heinemann" 2006 Changes of neuronal activity in areas CA1 and CA3 during anoxia and normoxic or hyperoxic reoxygenation in juvenile rat organotypic hippocampal slice cultures Brain Res. 1069 1 207-215 "In neonates, asphyxia is usually followed by hyperoxic treatment. In order to study whether hyperoxic reoxygenation might cause additional impairment of neuronal function, we subjected organotypic hippocampal slice cultures of juvenile rats (7 DIV, P6-8) to 30 min anoxia followed by 60 min hyperoxic or normoxic reoxygenation (95% or 19% O2, respectively). Spontaneous and evoked field potentials as well as [Ca2+]o were recorded in the pyramidal layer of area CA1 or area CA3. In area CA1, 30 min of anoxia led to decline of evoked field potential amplitudes by on average 67% and to profound changes in field potential characteristics and Ca2+ homeostasis which were not related to outcome after reoxygenation. Hyperoxic reoxygenation resulted first in a fast recovery of the field potential amplitude to 82% of the control value and then, in 75% of slice cultures, in a large negative field potential shift accompanied by a prolonged decrease of [Ca2+]o and loss of excitability outlasting the experiment. Recovery of field potential amplitude under normoxic conditions stayed poor, with a first increase to 51% and a second decrease to 22%. In contrast, field potential amplitude in area CA3 recovered to 80% of the initial amplitude, irrespective of the reoxygenation mode. The selective loss of function during hyperoxic reoxygenation in area CA1 might be a first sign of neuronal injury that we observed 1 h after end of hyperoxic reoxygenation in a previous study. Whether the poor outcome after normoxic reoxygenation would favour long-term recovery remains to be determined" http://www.ncbi.nlm.nih.gov/pubmed/16380097 0 1192 "T. I. Cremers, K. Rea, F. J. Bosker, H. V. Wikstrom, S. Hogg, A. Mork and B. H. Westerink" 2007 Augmentation of SSRI effects on serotonin by 5-HT2C antagonists: mechanistic studies Neuropsychopharmacology 32 7 1550-1557 "The treatment of depression may be improved by using an augmentation approach involving selective serotonin reuptake inhibitors (SSRIs) in combination with compounds that focus on antagonism of inhibitory serotonin receptors. Using microdialysis coupled to HPLC, it has recently been shown that the systemic co-administration of 5-HT(2C) antagonists with SSRIs augmented the acute effect of SSRIs on extracellular 5-HT. In this paper, we have investigated the mechanism through which this augmentation occurs. The increase in extracellular 5-HT was not observed when both compounds were locally infused. However, varying the route of administration for both compounds differentially revealed that an augmentation took place when the 5-HT(2C) antagonist was locally infused into ventral hippocampus and the SSRI given systemically, but not when systemic 5-HT(2C) antagonist was co-administered with the local infusion of citalopram. This suggests that the release of extracellular serotonin in ventral hippocampus may be controlled by (an)other brain area(s). As 5-HT(2C) receptors are not considered to be autoreceptors, this would implicate that other neurotransmitter systems are involved in this process. To investigate which neurotransmitter systems were involved in the interaction, systemic citalopram was challenged with several glutamatergic, GABA-ergic, noradrenergic, and dopaminergic compounds to determine their effects on serotonin release in ventral hippocampus. It was determined that the involvement of glutamate, norepinephrine, and dopamine in the augmentation did not seem likely, whereas evidence implicated a role for the GABA-ergic system in the augmentation" http://www.ncbi.nlm.nih.gov/pubmed/17203017 0 1193 "V. T. Antonenko, A. I. Treshchinskii, I. Korolev and I. P. Shlapak" 1988 [A low-molecular blood serum factor suppressing myocardial function in traumatic shock complicated by massive blood loss] Anesteziol.Reanimatol. 5 42-44 http://www.ncbi.nlm.nih.gov/pubmed/3218778 0 1194 "A. Besnard, T. Langberg, S. Levinson, K. Scobie, D. Leonardo, R. Hen and A. Sahay" 2014 KLF9 transcriptionally promotes resilience to chronic stress "Neuropsychopharmacology.Conference: 53rd Annual Meeting of the American College of Neuropsychopharmacology, ACNP 2014 Phoenix, AZ United States.Conference Start: 20141207 Conference End: 20141211.Conference Publication: (var.pagings).39 ()(pp S126-S12" var.pagings S126-S127 "Background: There is growing appreciation that psychiatric disorders such as depression and post-traumatic stress disorder arise from inefficient adaptation to risk factors such as stress. Understanding how transcriptional programs respond to stress to confer vulnerability or resilience through their actions on neural circuits will inform strategies to promote adaptive responses in neural circuits to stress. We recently identified Kruppel-like factor 9 (Klf9) as a transcriptional repressor of dendritic spines. Klf9 expression is upregulated by acute restraint stress and glucocorticoids, but is downregulated in response to chronic restraint stress. Based on these observations, we hypothesized that acute silencing of Klf9 promotes resilience to stress induced changes in hippocampal synaptic connectivity, conflict and fear processing, and depressionlike behaviors. Methods: To test our hypothesis, we developed novel transgenic tools to robustly and reversibly silence Klf9 in excitatory forebrain neurons of adult mice at baseline and prior to exposure to chronic restraint stress or chronic administration of glucocorticoids. Using triple transgenic mice to link changes in hippocampal circuitry with behavior, we genetically visualized dendritic spines in hippocampal subpopulations of neurons following acute forebrain silencing of Klf9 and these different stressors. Results: Inducible silencing of Klf9 in excitatory forebrain neurons in adulthood did not affect contextual encoding or depression-like behaviors at baseline, but produced antidepressant- like behavioral responses in the sucrose preference and forced-swim tests and prevented stress-induced enhancement of fear memory following chronic restraint stress. Furthermore, Klf-9 downregulation blunted the corticosterone response to an acute stressor challenge. These protective effects of inducible Klf9 silencing were mirrored by reversal of chronic restraint stress induced changes in dendritic spines in ventral CA1. Consistent with the moderating effects of inducible Klf9 silencing to chronic restraint stress, inducible silencing Klf9 in excitatory forebrain neurons in adulthood prevented corticosteroneinduced overgeneralization of fear and increase in innate anxiety. Conclusions: Our studies begin to uncover a novel transcriptional mechanism that regulates adaptive responsiveness of neural circuits to multiple forms of stress to confer behavioral resilience. Because Klf9 expression is upregulated in the hippocampus of patients with major depressive disorder and by glucocorticoids, our results suggest that targeting Klf9 or Klf9 dependent circuit changes may confer resilience to stress related psychopathologies" DO - http://dx.doi.org/10.1038/npp.2014.280 0 1195 "E. E. Sinnett, E. A. Wahrenbrock and G. L. Kooyman" 1981 "Cardiovascular depression and thermoregulatory disruption caused by pentothal/halothane anesthesia in the harbor seal, Phoca vitulina" J.Wildl.Dis. 17 1 121-130 "Anesthesia was induced in the harbor seal (Phoca vitulina) with an intravenous injection of 10 mg/kg thiopental sodium; this was followed by halothane (1%) anesthesia for up to 9.5 h. Cardiac output was reduced to 30% of the pre-anesthesia value (from an average of 11.5 1/min to 3.5 1/min) while systemic blood pressure fell from an average of 150/110 to 80/60. Arterial oxygen partial pressures were somewhat depressed (58-72 Torr) during ventilation with air. Heart rate became stable at 90-100 beats/min. Hypothermia was an occasional problem during the first hour of anesthesia, but this trend reversed and gave way to hyperthermia during prolonged anesthesia" http://www.ncbi.nlm.nih.gov/pubmed/7253094 0 1196 "K. Koyano, K. Kuba and S. Minota" 1985 Long-term potentiation of transmitter release induced by repetitive presynaptic activities in bull-frog sympathetic ganglia J.Physiol 359 219-233 "Long-lasting potentiation of transmitter release induced by repetitive presynaptic activities in bull-frog sympathetic ganglia was studied by recording intracellularly fast excitatory post-synaptic potentials (fast e.p.s.p.s.). Following a brief period of post-tetanic potentiation or depression (less than 10 min), the amplitude of the fast e.p.s.p. was potentiated for a period between several tens of minutes and more than 2 h in response to tetanic stimulation of the preganglionic nerve in twenty-one out of twenty-eight cells. Quantal analysis revealed that this long-term potentiation of the fast e.p.s.p. (l.t.p.) was accompanied by an increase in quantal content m (in nine out of twenty-one cells), quantal size (four cells) or both (eight cells). The increased quantal content (presynaptic l.t.p.) declined exponentially (ten cells) or decayed gradually to a certain enhanced level which lasted several hours. In contrast, the increased quantal size grew with a relatively long latency (10-25 min) and remained relatively constant for at least 2 h. The magnitude of presynaptic l.t.p. increased with increased duration of the presynaptic tetanus (33 Hz) from 2 to 5 s. No l.t.p. was elicited by a 1-s tetanus, whereas the time course appears to be independent of the tetanus duration and the magnitude of l.t.p. There was a positive correlation between the magnitude of presynaptic l.t.p. and the pre-tetanic quantal content up to m = 3, but the former deviated from linear regression when the value of the latter exceeded 3. No l.t.p. occurred when quantal content was less than 0.5. A tetanus (33 Hz, 10 s) applied in Ca2+-free solution elicited no presynaptic l.t.p., while the same tetanus in normal Ringer solution produced a large presynaptic l.t.p. Presynaptic l.t.p. was enhanced in magnitude at low temperature (8-10 degrees C). These results demonstrate the existence of a use-dependent, long-term potentiation of transmitter release in bull-frog sympathetic ganglia. Several possible mechanisms are discussed in terms of Ca2+-buffering mechanisms of the presynaptic nerve terminals" http://www.ncbi.nlm.nih.gov/pubmed/2860240 0 1197 "I. K. Hwang, K. Y. Yoo, T. H. Han, C. H. Lee, J. H. Choi, S. S. Yi, S. Y. Lee, P. D. Ryu, Y. S. Yoon and M. H. Won" 2009 Enhanced cell proliferation and neuroblast differentiation in the rat hippocampal dentate gyrus following myocardial infarction Neurosci.Lett. 450 3 275-280 "Basic and clinical studies have revealed that depression is frequently observed following myocardial infarction (MI). We observed changes in neurons in the subgranular zone of the hippocampal dentate gyrus (DG) 14 days after chronic cardiac ischemia. Cresyl violet staining was conducted to examine neurodegeneration. Cresyl violet-positive neurons in the hippocampus in the MI-operated group were similar to those in the sham-operated group, and Fluoro-Jade B-positive cells were not observed in either group. Next, we observed changes in cell proliferation using Ki67 and in the differentiation of neuroblasts using doublecortin (DCX) in the DG. The number of Ki67- and DCX-positive cells in the subgranular zone of the DG in the MI-operated group was significantly increased compared to that in the sham-operated group. In addition, DCX-positive processes were prominent in the MI group. These results suggest that MI may influence cell proliferation and affect neuroblast differentiation in the subgranular zone of the DG" http://www.ncbi.nlm.nih.gov/pubmed/19071196 0 1198 D. J. Grove 1969 Melanophore dispersion in the minnow Phoxinus phoxinus (L.) Comp Biochem.Physiol 28 1 55-65 http://www.ncbi.nlm.nih.gov/pubmed/5777402 0 1199 "U. M. Aswar, P. P. Kalshetti, S. M. Shelke, S. H. Bhosale and S. L. Bodhankar" 2012 "Effect of newly synthesized 1,2,4-triazino[5,6-b]indole-3-thione derivatives on olfactory bulbectomy induced depression in rats" Asian Pac.J.Trop.Biomed. 2 12 992-998 "OBJECTIVE: To study the derivatives of 1,2,4-triazino[5,6-b]indole-3-thione for antidepressant activity in olfactory bulbectomized (OBX) rats. Out of various derivatives tested for acute tail suspension test, the two derivatives showing prominent action were selected for bilateral olfactory bulbectomy model of chronic depression in rats. METHODS: The sub acute effects of 14-day oral pretreatment of two derivatives labeled as 3a (70 mg/kg) and 3r (70 mg/kg), imipramine (20 mg/kg), fluoxetine (30 mg/kg) and moclobemide (15 mg/kg) were evaluated on bilateral bulbectomy induced rise in body weight, hyperphagia, hyperactivity, and on sexual dysfunction. The serum sodium concentration, body temperature, and heart rate were also recorded. RESULTS: The derivatives 3a and 3r showed reversal of drop in body weight, reversed OBX induced hyperactivity, normalized body temperature, heart rate, and serum sodium concentration. In elevated maze test, moclobemide, 3a, 3r treatment significantly reduced time spent in open arm as compared to OBX rats. 3a and 3r also improved sexual behavior parameters. CONCLUSIONS: The present study shows promising antidepressant action and provides a proof of concept for the chronic treatment of 3a, 3r to treat depression" http://www.ncbi.nlm.nih.gov/pubmed/23593581 1 1200 N. E. Anden and M. Henning 1974 Urinary excretion of noradrenaline after treatment with alpha-methyldopa: inhibition by a central nervous mechanism Acta Physiol Scand. 90 1 69-72 http://www.ncbi.nlm.nih.gov/pubmed/4814544 0 1201 "J. Madar, N. Sildan and E. A. Pora" 1972 Age-dependent action of hydrocortisone hemisuccinate upon intravenous glucose tolerance in white rats Arch.Int.Physiol Biochim. 80 2 367-371 http://www.ncbi.nlm.nih.gov/pubmed/4114884 0 1202 "M. L. Cohen, K. S. Wiley and I. H. Slater" 1979 In vitro relaxation of arteries and veins by prazosin: alpha-adrenergic blockade with no direct vasodilation Blood Vessels 16 3 144-154 "Controversy exists regarding the mechanism by which prazosin lowers blood pressure without a marked increase in heart rate; a mechanism involving both sympatholytic activity and direct smooth muscle relaxation has been suggested. alpha-Adrenergic receptor blockade by prazosin is well documented and occurred to exogenous norepinephrine and to field stimulation in vitro in rat arteries and veins. A parallel shift of the norepinephrine concentration response curves in the aorta and mesenteric artery contrasted with a nonparallel shift and a marked depression of maximal norepinephrine responses in the inferior vena cava, portal, iliac and femoral veins. Nonspecific direct acting vasodilators will antagonize contractile responses to all agonists. However, prazosin (10(-8) M) specifically antagonized norepinephrine-induced responses. Concentration response curves to potassium chloride or to serotonin were not affected in these rat tissues. In addition, prazosin (up to 10(-6) M) did not significantly relax aortic tissue previously contracted with potassium chloride or serotonin, whereas the vasodilator, nitroglycerin, produced a clear relaxation. Prazosin only reduced the tone of vessels contracted with norepinephrine. These data indicate that prazosin exhibits minimal, if any, direct smooth muscle relaxant properties in concentrations higher than those producing alpha-adrenergic receptor blockade, and relaxes rat veins by a mechanism involving alpha-adrenergic receptor blockade" http://www.ncbi.nlm.nih.gov/pubmed/221060 0 1203 "R. A. Brown, L. Jefferson, N. Sudan, T. C. Lloyd and J. Ren" 1999 Acetaldehyde depresses myocardial contraction and cardiac myocyte shortening in spontaneously hypertensive rats: role of intracellular Ca2+ Cell Mol.Biol.(Noisy.-le-grand) 45 4 453-465 "Acetaldehyde (ACA), the major metabolite of ethanol, exerts both stimulatory and depressive actions on myocardial tissue. We have recently shown that ACA depresses myocardial contraction, cardiac myocyte shortening and intracellular Ca2+ transients in normal rat heart. The purpose of the present study was to determine the influence of hypertension on ACA-induced myocardial actions. Mechanical properties of left ventricular papillary muscles and ventricular myocytes isolated from both 25-week-old normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were evaluated using force-transducer and video edge-detection, respectively. Papillary muscles and cardiac myocytes were electrically stimulated to contract at 0.5 Hz. Contractile properties analyzed include: peak tension development (PTD), peak twitch amplitude (PTA), time-to-PTD/PTA (TPT/TPS), time-to-90% relaxation/relengthening (RT90/TR90) and maximal velocities of contraction/shortening and relaxation/relengthening (+/-VT/+/-dL/dt). Intracellular Ca2+ transients were measured as fura-2 fluorescence intensity (FFI) changes. ACA (1-30 mM) depressed PTD without affecting other mechanical indices in both WKY and SHR myocardium, with maximal inhibition of 64 and 69%, respectively. SHR myocytes exhibited increased cell dimension, baseline PTA and resting intracellular Ca2+ levels, compared to WKY counterparts. ACA (0.03-30 mM) depressed PTA without affecting TPT, TR90 and +/-dL/dt. The maximal inhibitions were 31 and 36% in WKY and SHR groups, respectively. Interestingly, ACA exerted a biphasic effect on FFI, displaying potentiation at lower doses (<3 mM) and inhibition at higher doses (>3 mM). The maximal increase in FFI changes were 19 and 22% at 0.3 mM and the maximal decreases were 37 and 29% at 30 mM ACA, in WKY and SHR myocytes, respectively. Neither resting intracellular Ca2+ levels (FFI) nor fluorescence decay time (FDT) were affected by ACA. The increase in FFI was attenuated by propranolol (1 microM), whereas the decrease in FFI was reversed by BayK 8644 (1 microM). These results suggest that hypertension does not appear to alter ACA-induced myocardial depression. The mechanism underlying ACA-induced myocardial actions may involve increased beta-adrenergic activity at low doses and reduced Ca2+ entry and/or release at high doses" http://www.ncbi.nlm.nih.gov/pubmed/10432192 0 1204 "N. A. Shanahan, L. P. Velez, V. L. Masten and S. C. Dulawa" 2011 Essential role for orbitofrontal serotonin 1B receptors in obsessive-compulsive disorder-like behavior and serotonin reuptake inhibitor response in mice Biol.Psychiatry 70 11 1039-1048 "BACKGROUND: Perseveration and sensorimotor gating deficits are core features of obsessive-compulsive disorder (OCD). Serotonin 1B receptor (5-HT1BR) agonists exacerbate OCD symptoms in patients and induce perseveration and sensorimotor gating deficits in mice. Serotonin reuptake inhibitors (SRIs), but not noradrenaline reuptake inhibitors (NRIs), reduce OCD symptoms following 4 to 8 weeks of treatment. Using mice, we compared the effects of chronic SRI versus NRI treatment on 5-HT1BR-induced OCD-like behavior and 5-HT1BR sensitivity in orbitofrontal-subcortical OCD circuits. Furthermore, we localized the 5-HT1BR population that mediates OCD-like behavior. METHODS: Mice chronically received the SRI clomipramine or the NRI desipramine and were examined for 5-HT1BR-induced OCD-like behavior or 5-HT1BR binding and G-protein coupling in caudate putamen, nucleus accumbens, and orbitofrontal cortex. Separate mice were tested for OCD- or depression-like behavior following 4, 14, 21, 28, or 56 days of SRI treatment. Finally, OCD-like behavior was assessed following intra-orbitofrontal 5-HT1BR agonist infusion or intra-orbitofrontal 5-HT1BR antagonist infusion coupled with systemic 5-HT1BR agonist treatment. RESULTS: Effective, but not ineffective, OCD treatments reduced OCD-like behavior in mice with a time course that parallels the delayed therapeutic onset in OCD patients and downregulated 5-HT1BR expression in the orbitofrontal cortex. Intra-orbitofrontal 5-HT1BR agonist infusion induced OCD-like behavior, and intra-orbitofrontal 5-HT1BR antagonist infusion blocked OCD-like effects of systemic 5-HT1BR agonist treatment. CONCLUSIONS: These results indicate that orbitofrontal 5-HT1BRs are necessary and sufficient to induce OCD-like behavior in mice and that SRI pharmacotherapy reduces OCD-like behavior by desensitizing orbitofrontal 5-HT1BRs. Our findings suggest an essential role for orbitofrontal 5-HT1BRs in OCD pathophysiology and treatment" http://www.ncbi.nlm.nih.gov/pubmed/21920503 0 1205 "J. Xiong, Y. Li and J. Nie" 2003 Effects of simulated microgravity on nitric oxide level in cardiac myocytes and its mechanism Sci.China C.Life Sci. 46 3 302-309 "The depression of cardiac contractility induced by space microgravity is an important issue of aerospace medicine research, while its precise mechanism is still unknown. In the present study, we explored effects of simulated microgravity on nitric oxide (NO) level, inducible nitric oxide synthase (iNOS) expression and related regulative mechanism using electron spin resonance (ESR) spectroscopy, immunocytochemistry and in situ hybridization. We found a remarkable increase of NO level and up-regulation of iNOS and iNOS mRNA expression in rat cardiac myocytes under simulated microgravity. Staurosporine (a nonselective protein kinase inhibitor), calphostin C (a selective protein kinase C inhibitor), partially inhibited the effect of simulated microgravity. Thus regulative effect of simulated microgravity on iNOS expression is mediated at least partially via activation of protein kinase C. These results indicate that NO system in cardiac myocytes is sensitive to simulated microgravity and may play an important role in the depression of cardiac contractility induced by simulated microgravity" http://www.ncbi.nlm.nih.gov/pubmed/18763145 0 1206 D. W. Cheung and E. E. Daniel 1980 Imidazole inhibits a temperature-dependent component of mammalial skeletal muscle action potential Nature 283 5746 485-486 "Temperature-dependent transition of conductance in ionic channels has been described in several membrane systems. We report here an abrupt change in the maximal rate of rise of the action potentials of the rat extensor digitorum longus (EDL) at 32 degrees C, indicating alteration in the functional characteristics of the sodium channels. Tetrodotoxin (TTX) and imidazole were used to investigate further the change in properties of the sodium channels with respect to temperature. TTX is known for its specificity in blocking sodium channels. It has been proposed that the guanidinium group of the TTX molecule is essential for its activity. Other guanidinium compounds have also been shown to be effective in blocking the sodium channels. In this study, imidazole, a compound structurally similar to guanidine, was also tested. We find that TTX and imidazole affect the maximal rate of rise of the action potential in a temperature-dependent manner" http://www.ncbi.nlm.nih.gov/pubmed/7352030 0 1207 "G. Agam, Y. Bersudsky, G. T. Berry, D. Moechars, Y. Lavi-Avnon and R. H. Belmaker" 2009 Knockout mice in understanding the mechanism of action of lithium Biochem.Soc.Trans. 37 Pt 5 1121-1125 "Lithium inhibits IMPase (inositol monophosphatase) activity, as well as inositol transporter function. To determine whether one or more of these mechanisms might underlie lithium's behavioural effects, we studied Impa1 (encoding IMPase) and Smit1 (sodium-myo-inositol transporter 1)-knockout mice. In brains of adult homozygous Impa1-knockout mice, IMPase activity was found to be decreased; however, inositol levels were not found to be altered. Behavioural analysis indicated decreased immobility in the forced-swim test as well as a strongly increased sensitivity to pilocarpine-induced seizures. These are behaviours robustly induced by lithium. In homozygous Smit1-knockout mice, free inositol levels were decreased in the frontal cortex and hippocampus. These animals behave like lithium-treated animals in the model of pilocarpine seizures and in the Porsolt forced-swim test model of depression. In contrast with O'Brien et al. [O'Brien, Harper, Jove, Woodgett, Maretto, Piccolo and Klein (2004) J. Neurosci. 24, 6791-6798], we could not confirm that heterozygous Gsk3b (glycogen synthase kinase 3beta)-knockout mice exhibit decreased immobility in the Porsolt forced-swim test or decreased amphetamine-induced hyperactivity in a manner mimicking lithium's behavioural effects. These data support the role of inositol-related processes rather than GSK3beta in the mechanism of the therapeutic action of lithium" http://www.ncbi.nlm.nih.gov/pubmed/19754464 1 1208 S. G. Armstrong and K. W. Renton 1994 Factors involved in the down-regulation of cytochrome P450 during Listeria monocytogenes infection Int.J.Immunopharmacol. 16 9 747-754 "The activation of host defense mechanisms has been shown to cause a depression in hepatic cytochrome P450-mediated metabolism in rodents and humans. In a previous study, it was demonstrated that the Gram-positive bacteria Listeria monocytogenes causes a down-regulation of hepatic cytochrome P450 and related substrate metabolism as a result of a pretranslational depression of apoprotein synthesis. The objectives of this study were to determine whether the effect of listeria on hepatocyte cytochrome P450 involves hepatic nonparenchymal cells and whether the hemolysin, secreted only by hemolytic forms of the bacteria, plays any part in mediating this effect. Total cytochrome P450 levels as well as ethoxyresorufin-O-dealkylase (EROD) and benzyloxyresorufin-O-dealkylase (BROD) activities were significantly reduced in hepatic microsomes isolated from mice infected in vivo for 48 h with 15U listeria, whereas the same dose of the avirulent non-hemolytic M3D strain had no effect. Listeria (15U) significantly depressed hepatocyte EROD and BROD activities after 24 h incubations with liver cell cultures containing hepatocytes and nonparenchymal cells, as the result of both a direct effect on the hepatocyte and an interaction of listeria with hepatic nonparenchymal cells. The M3D strain of listeria had no effect on cytochrome P-450-mediated metabolism in isolated cells, confirming that hemolysin is an essential component of the mechanism responsible for the down-regulation of cytochrome P450 during listeria infections" http://www.ncbi.nlm.nih.gov/pubmed/7806432 0 1209 "T. Vargish, K. C. Beamer, T. Daly and T. R. Riggs" 1987 Morphine sulfate depression of cardiac function is attenuated by opiate receptor antagonism with naloxone Circ.Shock 23 3 189-195 "In previous work, morphine sulfate was shown to decrease heart rate (HR) and cardiac output (CO) in a dose-related fashion. It was hypothesized that this effect was mediated by opiate receptors located in the myocardium. The present study evaluated the effect of opiate receptor antagonism with naloxone using a modified Langendorff rat heart perfusion apparatus. Sixty-five rat hearts were excised and perfused with Krebs-Henseleit buffer (KHB) solution, to which morphine sulfate and naloxone (NAL) were added in different concentrations. In the initial studies, NAL (10(-5) M) was added to the perfusate prior to the incremental additions of morphine. This resulted in no antagonism of the previously described opiate agonist effects. Norepinephrine (NE; 10(-9) M) was then added to the perfusate prior to the NAL or morphine. The NE did not affect the dose-related decrease in HR and CO when morphine was added but did permit the attenuation of the morphine effect by the addition of increasing concentrations of NAL up to 10(-5) M. These results suggest that the agonist effect can be attenuated by opiate receptor antagonism with NAL; the data also suggest a possible interrelationship between opiate and catecholamine receptor activity in the myocardium" http://www.ncbi.nlm.nih.gov/pubmed/2827907 0 1210 "H. Allonen, E. Iisalo and L. Nuortio" 1975 "Effect of reserpine, desipramine and phenytoin on digoxin induced arrhythmias and myocardial uptake of digoxin in guinea pigs" Acta Pharmacol.Toxicol.(Copenh) 37 1 Aug-16 http://www.ncbi.nlm.nih.gov/pubmed/1174283 0 1211 "J. I. Andres, J. Alcazar, J. M. Alonso, A. I. de Lucas, L. Iturrino, I. Biesmans and A. A. Megens" 2006 "Synthesis of 7-amino-3a,4-dihydro-3H-[1]benzopyrano[4,3-c]isoxazole derivatives displaying combined alpha2-adrenoceptor antagonistic and 5-HT reuptake inhibiting activities" "Bioorganic and Medicinal Chemistry.14 (13) ()(pp 4361-4372), 2006.Date of Publication: 01 Jul 2006." 13 4361-4372 "Following a program searching for dual 5-HT reuptake inhibitors and alpha2-adrenoceptor antagonists started at Johnson & Johnson Pharmaceutical Research & Development, we now report on the synthesis of a series of 7-amino-3a,4-dihydro-3H-[1]benzopyrano[4,3-c]isoxazole derivatives, some of which proved to be the most potent alpha2-adrenoceptor blockers within this chemical class of tricyclic isoxazolines, while keeping potent 5-HT reuptake inhibiting activity. © 2006 Elsevier Ltd. All rights reserved" DO - http://dx.doi.org/10.1016/j.bmc.2006.02.043 0 1212 "E. Kuteeva, T. Wardi, T. Hokfelt and S. O. Ogren" 2007 Galanin enhances and a galanin antagonist attenuates depression-like behaviour in the rat Eur.Neuropsychopharmacol. 17 1 64-69 "The effect of intracerebroventricular infusion of galanin and/or the galanin antagonist M35 was studied in the forced swim test. Animals were pre-exposed to water for 15 min 24 h prior to test. Immobility and climbing were assessed during the second, 5 min exposure to water. Rats receiving a single infusion of galanin (3 nmol) displayed a significant increase of immobility. This effect was blocked by co-administration of M35 (1 nmol). M35 alone (1 nmol) produced a significant decrease of immobility. The results further support the hypothesis that galanin may play a role in mood disorders, and that galanin antagonists may represent new candidates for antidepressant treatment" http://www.ncbi.nlm.nih.gov/pubmed/16624535 1 1213 "S. J. Cragg, C. J. Hille and S. A. Greenfield" 2002 Functional domains in dorsal striatum of the nonhuman primate are defined by the dynamic behavior of dopamine J.Neurosci. 22 13 5705-5712 "The dorsal striatum comprises a continuum of distinct functional domains, limbic, associative, and sensorimotor. In the primate it exclusively subdivides further into two nuclei, the putamen and caudate. Dopamine (DA) transmission is differentially affected between these nuclei in neurodegenerative diseases such as Parkinson's and by psychostimulants such as cocaine. Because rodent systems can offer only limited insight into DA systems of the human brain, a fuller appreciation of DA transmission and its role in dysfunction requires direct study in primates. DA behavior was explored in the major functional domains of the caudate nucleus and compared with the putamen, using fast-scan cyclic voltammetry in striatal sections from the marmoset (Callithrix jacchus). There was domain-specific variation in extracellular DA transients [i.e., concentration ([DA](o)) released by a single stimulus and the rate maximum of DA uptake, V(max)]. Across nuclei, functional rather than anatomical regions were differentiated by these dynamics. The largest, fastest DA transients were at motor-associated loci. Evoked [DA](o) at physiological frequencies was differently frequency-sensitive between functional domains but not between anatomical nuclei. In contrast, presynaptic depression was not an index of regional differentiation, recovering with similar kinetics at all loci. Within a given functional domain of dorsal striatum, the dynamics of DA release and uptake are similar for the putamen and the caudate nucleus. Conversely, distinct functional domains are defined by these DA dynamics, in a manner more marked in primates than in rodents. These data from the primate brain highlight differences in DA availability that may be central to DA function and dysfunction in the human" http://www.ncbi.nlm.nih.gov/pubmed/12097522 0 1214 "R. C. Barber, D. L. Maass, D. J. White and J. W. Horton" 2008 Increasing percent burn is correlated with increasing inflammation in an adult rodent model Shock 30 4 388-393 "Burn injury has been associated with systemic/compartmental inflammatory responses and myocardial dysfunction. We hypothesized that burn size correlates with the extent of cardiac inflammatory response/contractile dysfunction. Adult male Sprague-Dawley rats were divided to receive anesthesia, a 3-degree burn covering 20%, 30%, 40%, or 60% total body surface area (TBSA) plus fluid resuscitation (lactated Ringer, 4 mL/kg per percent burn); sham burn animals were included as controls. There were seven rats in each group. Rats were euthanized Twenty-four h postburn, and TNF-alpha, IL-1beta, and IL-6 were measured in the plasma and in supernatant from isolated cardiac myocytes by enzyme-linked immunosorbent assay. In addition, left ventricular function (Langendorff) was studied in vitro, and troponin levels were measured by enzyme-linked immunosorbent assay. There were progressive, statistically significant increases in plasma and myocyte inflammatory cytokine levels, as well as plasma troponin with increasing burn size. Similarly, left ventricular pressure (in millimeters of mercury) and +/-dP/dtmax (in millimeters of mercury per second) progressively fell with increasing burn size. However, myocardial contractile depression induced by 60% TBSA burn was similar to that produced by 40% TBSA burn. These data suggest that the degree of inflammatory response, cardiac tissue injury, and myocardial contractile depression were correlated directly with the percent TBSA burn. However, unlike inflammation and cardiac tissue damage, myocardial contractile depression reached a plateau, with maximal myocardial contraction and relaxation defects observed at 40% TBSA burn, which were not further aggravated by a larger (60%) burn" http://www.ncbi.nlm.nih.gov/pubmed/18277951 0 1215 "T. Tanaka, N. Murata and Y. Yamauchi" 1999 The effect of nipradilol on the isoproterenol-induced depression of contractions in the cat soleus muscle Jpn.J.Pharmacol. 81 3 286-291 "The effect of nipradilol on the isoproterelol-induced depression of contractions of the soleus muscle of the anesthetized cats was studied. Isoproterenol (0.3 microg/kg) injected intravenously decreased the tension and degree of fusion of incomplete tetanic contractions of the soleus muscle of the anesthetized cats. The effect of isoproterenol was blocked by nipradilol (> or = 3 microg/kg), desnitro-nipradilol (> or = 10 microg/kg) and propranolol (> or = 10 microg/kg), but not by nitroglycerin (10-100 microg/kg). Nipradilol (30 microg/kg) and desnitronipradilol (300 microg/kg) almost completely antagonized the depressor effects of isoproterenol. These results coupled with evidence that nipradilol does not penetrate the blood-brain barrier indicate that nipradilol exerts an anti-tremor action by blocking peripheral beta2-adrenoceptors" http://www.ncbi.nlm.nih.gov/pubmed/10622217 0 1216 "A. R. Prossin, A. E. Koch, P. L. Campbell, T. Barichello, S. S. Zalcman and J. K. Zubieta" 2016 Acute experimental changes in mood state regulate immune function in relation to central opioid neurotransmission: a model of human CNS-peripheral inflammatory interaction Mol.Psychiatry 21 2 243-251 "Although evidence shows depressed moods enhance risk for somatic diseases, molecular mechanisms underlying enhanced somatic susceptibility are ill-defined. Knowledge of these molecular mechanisms will inform development of treatment and prevention strategies across comorbid depressive and somatic illnesses. Existing evidence suggests that interleukin-18 (IL-18; an IL-1 family cytokine) is elevated in depression and implicated in pathophysiology underlying comorbid medical illnesses. We previously identified strong associations between baseline IL-18 and mu-opioid receptor availability in major depressive disorder (MDD) volunteers. Combined with the evidence in animal models, we hypothesized that experimental mood induction would change IL-18, the extent proportional to opioid neurotransmitter release. Using the Velten technique in a [(11)C]carfentanil positron emission tomography neuroimaging study, we examined the impact of experimentally induced mood (sad, neutral) on plasma IL-18 and relationships with concurrent changes in the central opioid neurotransmission in 28 volunteers (healthy, MDD). Results showed mood induction impacted IL-18 (F2,25=12.2, P<0.001), sadness increasing IL-18 (T27=2.6, P=0.01) and neutral mood reducing IL-18 (T27=-4.1, P<0.001). In depressed volunteers, changes in IL-18 were more pronounced (F2,25=3.6, P=0.03) and linearly proportional to sadness-induced mu-opioid activation (left ventral pallidum, bilateral anterior cingulate cortices, right hypothalamus and bilateral amygdala). These data demonstrate that dynamic changes of a pro-inflammatory IL-1 superfamily cytokine, IL-18, and its relationship to mu-opioid neurotransmission in response to experimentally induced sadness. Further testing is warranted to delineate the role of neuroimmune interactions involving IL-18 in enhancing susceptibility to medical illness (that is, diabetes, heart disease and persistent pain states) in depressed individuals" http://www.ncbi.nlm.nih.gov/pubmed/26283642 0 1217 G. B. Frank and M. S. C. Wong 1974 Evidence for narcotic drug receptors on membranes of excitable cells "Federation Proceedings.33 (3) ()(pp I), 1974.Date of Publication: 1974." 3 I 0 1218 "N. V. Kudryashov, T. S. Kalinina and T. A. Voronina" 2015 [Unpredictable chronic mild stress effects on antidepressants activities in forced swim test] Ross.Fiziol.Zh.Im I.M.Sechenova 101 2 163-170 "The experiments has been designed to study unpredictable chronic mild stress effect on anti-depressive activities of amitriptyline (10 mg/kg) and fluoxetine (20 mg/kg) in forced swim test in male outbred mice. It is shown that acute treatment with fluoxetine does not produce any antidepressant effects in mice following stress of 14 days while the sub-chronic injections of fluoxetine result in more deep depressive-like behavior. In 28 daily stressed mice, antidepressant effect of fluoxetine is observed independently of the injection rates. Amitriptyline demonstrates the antidepressant activity regardless of the duration of stress or administration scheduling, but at the same time the severity of anti-immobilization effect of amitriptyline in stressed mice is weaker in compare to non-stressed trails. Thus, the injection rates and duration of unpredictable mild chronic stress are the parameters that determine the efficiency of antidepressants in the mouse forced swimming test" http://www.ncbi.nlm.nih.gov/pubmed/26012108 1 1219 N. M. Smol'nikova and S. N. Strekalova 1982 [Effect of ethanol in antenatal exposure on the early stages of progeny development] Farmakol.Toksikol. 45 6 68-71 http://www.ncbi.nlm.nih.gov/pubmed/7152006 0 1220 "D. S. Hodgson, E. P. Steffey, J. L. Grandy and M. J. Woliner" 1986 "Effects of spontaneous, assisted, and controlled ventilatory modes in halothane-anesthetized geldings" Am.J.Vet.Res. 47 5 992-996 "Cardiopulmonary effects of spontaneous, assisted, and controlled ventilatory modes were determined with 6 young, healthy geldings anesthetized with halothane at a constant dose (1.3 minimum alveolar concentration). All horses were in lateral recumbency, and all modes of ventilation were studied at least once during each anesthetic exposure. Cardiac output did not differ between spontaneous and assisted ventilation modes, but both modes were associated with significantly (P less than 0.05) higher cardiac output than that with controlled ventilation. The PaCO2 differed significantly (P less than 0.01) between all modes of ventilation. Although controlled ventilation maintained a normal PaCO2, assisted ventilation reduced PaCO2 as compared with spontaneous ventilation with less cardiovascular depression than that with controlled ventilation. Mixed venous O2 tensions were higher with spontaneous and assisted ventilation modes than with controlled ventilation. Except for shorter inspiratory time and smaller inspiratory/expiratory ratio associated with spontaneous ventilation, there were no ventilatory mode-related effects on ventilatory variables" http://www.ncbi.nlm.nih.gov/pubmed/3717746 0 1221 "D. M. Jackson, S. B. Ross and L. G. Larsson" 1989 Dopamine D-2 receptor agonist-induced behavioural depression: critical dependence upon postsynaptic dopamine D-1 function. A behavioural and biochemical study Naunyn Schmiedebergs Arch.Pharmacol. 340 4 355-365 "The dopamine (DA) D-2 receptor agonists quinpirole (threshold dose, 0.01 mg/kg IP), pergolide (0.025 mg/kg), B-HT 920 (0.003 mg/kg) and (-)-3-PPP (4 mg/kg) produced dose-dependent locomotor depression (immobility) in mice as assessed by a subjective scoring system, with the immobility being characterized by a frozen posture. The animals were still but had their eyes open. The immobility was accompanied by reductions in sniffing, rearing and grooming. The depression (and the associated reduction in the various behaviours) produced by quinpirole (0.1 mg/kg), pergolide (0.1 mg/kg) and B-HT 920 (0.1 mg/kg) was substantially (but not always completely) reversed by the selective D-1 receptor agonist SKF38393 (up to 12 mg/kg) and the non-selective D-1 receptor agonist CY208243 (up to 3 mg/kg). The immobility induced by (-)-3-PPP (16 mg/kg) was also reversed by CY208243 and SKF38393, but the reversal was due to an increase in grooming behaviour in mice challenged with the D-1 receptor agonists, whether or not the animals had also received (-)-3-PPP. There was no reversal of the depression of rearing or sniffing. In contrast, CY208243 and SKF38393 also antagonized the immobility induced by B-HT 920, but the reversal was accompanied by at least partial reversals of the depression of sniffing, rearing and grooming. The reversal of quinpirole-induced immobility by SKF38393 and CY208243 was antagonized by SCH23390 (0.1 mg/kg). The selective D-2 receptor antagonist raclopride (0.025 to 0.4 mg/kg) could not reverse quinpirole-induced immobility. High doses of either raclopride (0.4 mg/kg) or SCH23390 (greater than 0.1 mg/kg) significantly increased immobility. Although raclopride itself (0.2 mg/kg) produced a substantial increase in DOPAC and homovanillic acid (HVA) levels in the striatum, it did not antagonize the autoreceptor mediated effects of quinpirole (0.1 mg/kg) in reducing the striatal dihydroxyphenylacetic acid (DOPAC) to DA ratio. However, the same dose of raclopride was partly effective in reducing the effects of lower doses of quinpirole (0.01 and 0.03 mg/kg) on the striatal DOPAC to DA ratio. Raclopride (0.2 mg/kg) also partially but significantly reduced the locomotor stimulant effects of d-amphetamine in reserpinized mice. Biochemical analyses in the striata indicated that CY208243 slightly retarded DA turnover (as assessed by the DOPAC/DA ratio). SKF38393 itself also slightly reduced DA turnover. In automated activity cages, using mice depleted of DA with reserpine and alpha-methyltyrosine, all the D-2 receptor agonists tested, in combination with SKF38393, produced an increase in activity.(ABSTRACT TRUNCATED AT 400 WORDS)" http://www.ncbi.nlm.nih.gov/pubmed/2573842 1 1222 "K. Yamanouchi, A. Fukuda, F. Kobune, Y. Yoshikawa and F. Chino" 1974 Pathogenesis of rinderpest virus infection in rabbits. II. Effect of rinderpest virus on the immune functions of rabbits Infect.Immun. 9 2 206-211 "Rinderpest virus infection was shown to induce marked suppression of both humoral antibody response and cell-mediated immunity in rabbits. The virus exhibited a suppressive effect on primary antibody response as indicated by a decrease in numbers of plaque-forming cells (immunoglobulin [Ig]M) and hemagglutinating antibody titers of both IgM and IgG types to sheep red blood cells, whereas there was no detectable effect of the virus on the production of memory cells. Virus-induced suppression of cell-mediated immunity was demonstrated by a decreased rate of proliferative response of peripheral lymphocytes to phytohemagglutinin stimulus and by a depression of delayed-type skin reactions to purified protein derivative. Such suppressive effects were indicated to persist for 14 days or longer. Alteration in phagocytic activity of the reticuloendothelial system was not observed. The relevance of the virus-induced histological lesions in the lymphoid tissues to the virus-induced immunosuppression was discussed" http://www.ncbi.nlm.nih.gov/pubmed/4593340 0 1223 "J. L. Wang, P. Liu, H. H. Tu, Z. X. Wang and G. Y. Chen" 2007 [Effects of kaixinsan on behavior and expression of p-CREB in hippocampus of chronic stress rats] Zhongguo Zhong.Yao Za Zhi. 32 15 1555-1558 "OBJECTIVE: To study the effects of kaixinsan on behavior and expression of p-CREB in hippocampus of the chronic stress rats. METHOD: The male Wistar rats which gained the similar scores by Open-field test were selected, then the depression model rat was produced by separation and chronic unpredictable mild stress. Open-field test was performed to detect the behavior of rats and immunohistochemistry was used to observe the changes of p-CREB expression in hippocampus. RESULT: On the 22nd day, the body weight and sacchar-intake of the depression model rats were all lower than those of the normal rats and the body weight and sacchar-intake of the rats treated by drugs were higher compared with model rats (P < 0.01). The depressive behavior in kaixinsan 4 g x kg(-1) group was significantly improved compared with the model group, the crossing scores and rearing scores were all increased (P < 0.01) and the expression of p-CREB in CA1, CA3 and DG in hippocampus was higher than that in the model group (P < 0.05 and P < 0.01). CONCLUSION: Kaixinsan might improve depressive behavior by increasing expression of p-CREB in CA1, CA3 and DG in hippocampus of the chronic stress rats" http://www.ncbi.nlm.nih.gov/pubmed/17972588 1 1224 "H. L. Verjans, F. H. De Jong, B. A. Cooke, H. J. van der Molen and K. B. Eik-Nes" 1974 Effect of oestradiol benzoate on pituitary and testis function in the normal adult male rat Acta Endocrinol.(Copenh) 77 4 636-642 http://www.ncbi.nlm.nih.gov/pubmed/4479701 0 1225 I. E. Kisin and L. A. Serebriakov 1969 [Role of autoregulation of vessels in effect of neurotropic vasodilator agents] Farmakol.Toksikol. 32 6 673-678 http://www.ncbi.nlm.nih.gov/pubmed/4392694 0 1226 "L. A. Pohorecky, E. Makowski, B. Newman and E. Rassi" 1979 Cholinergic mediation of motor effects of ethanol in rats Eur.J.Pharmacol. 55 1 67-72 "The role of cholinergic neurons in the motor depressant effects of ethanol was examined. Choline chloride pretreatment (30-90 mg/kg i.p.) potentiated the hypomotility produced by 2 g/kg of ethanol. Physostigmine pretreatment (0.2 mg/kg i.p.) also enhanced the motor depression produced by ethanol. Conversely, in animals pretreated with scopolamine (0.25 and 0.5 mg/kg) the depressant effect of ethanol was less. The potentiation produced by choline was not associated with changes in levels of ethanol in blood. It is concluded that cholinergic neurons are involved in the motor activity changes produced by ethanol. Such a mechanism may operate in conjunction with the dopaminergic neuronal system" http://www.ncbi.nlm.nih.gov/pubmed/436943 0 1227 "P. Blier, G. Gobbi, N. Haddjeri, L. Santarelli, G. Mathew and R. Hen" 2004 Impact of substance P receptor antagonism on the serotonin and norepinephrine systems: relevance to the antidepressant/anxiolytic response J.Psychiatry Neurosci. 29 3 208-218 "Substance P (neurokinin-1 [NK1]) receptor antagonists appear to be effective antidepressant and anxiolytic agents, as indicated in 3 double-blind clinical trials. In laboratory animals, they promptly attenuate the responsiveness of serotonin (5-hydroxytryptamine [5-HT]) and norepinephrine (NE) neurons to agonists of their cell-body autoreceptors, as is the case for some antidepressant drugs that are currently in clinical use. Long-term, but not subacute, antagonism of NK1 receptors in rats increases 5-HT transmission in the hippocampus, a property common to all antidepressant treatments tested thus far. This enhancement seems to be mediated by a time-dependent increase in the firing rate of 5-HT neurons. Mice with the NK1 receptor deleted from their genetic code also have an increased firing rate of 5-HT neurons. Taken together, these observations strongly suggest that NK1 antagonists could become a new class of antidepressant and anxiolytic agents" http://www.ncbi.nlm.nih.gov/pubmed/15173897 0 1228 "Z. Y. Chen, D. Jing, K. G. Bath, A. Ieraci, T. Khan, C. J. Siao, D. G. Herrera, M. Toth, C. Yang, B. S. McEwen, B. L. Hempstead and F. S. Lee" 2006 Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior Science 314 5796 140-143 "A common single-nucleotide polymorphism in the brain-derived neurotrophic factor (BDNF) gene, a methionine (Met) substitution for valine (Val) at codon 66 (Val66Met), is associated with alterations in brain anatomy and memory, but its relevance to clinical disorders is unclear. We generated a variant BDNF mouse (BDNF(Met/Met)) that reproduces the phenotypic hallmarks in humans with the variant allele. BDNF(Met) was expressed in brain at normal levels, but its secretion from neurons was defective. When placed in stressful settings, BDNF(Met/Met) mice exhibited increased anxiety-related behaviors that were not normalized by the antidepressant, fluoxetine. A variant BDNF may thus play a key role in genetic predispositions to anxiety and depressive disorders" http://www.ncbi.nlm.nih.gov/pubmed/17023662 0 1229 "I. Peruga, S. Hartwig, J. Thone, B. Hovemann, R. Gold, G. Juckel and R. A. Linker" 2011 Inflammation modulates anxiety in an animal model of multiple sclerosis Behav.Brain Res. 220 1 20-29 "Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by inflammation, but also degenerative changes. Besides neurological deficits, the rate of affective disorders such as depression and anxiety is at least six fold increased. Many aspects of MS can be mimicked in the animal model of myelin oligodendrocyte glycoprotein experimental autoimmune encephalomyelitis (MOG-EAE). Here we investigate behavioral changes in C57BL/6 mice suffering from mild MOG-EAE. In the later phase of the disease, mice were subjected to behavioral tests including the light-dark-box (LD Box), the acoustic startle response (SR) with a pre-pulse inhibition protocol as well as the learned helplessness (LH) paradigm. Behavioral data were correlated with the motor performance in an open field and rotarod test (RR). In the RR and open field, there was no significant difference in the motor performance between controls and mice suffering from mild MOG-EAE. Yet EAE mice displayed an increased anxiety-like behavior with a 23% reduction of the time spent in the bright compartment of the LD Box as well as an increased SR. In the LH paradigm, mice suffering from MOG-EAE were twice as much prone to depressive-like behavior. These changes correlate with an increase of hippocampal tissue tumor necrosis factor alpha levels and neuronal loss in the hippocampus. Modulation of monoaminergic transmission by chronic application of the antidepressant amitriptyline resulted in a decreased startle reaction and increased hippocampal norepinephrine levels. These data imply that chronic inflammation in the CNS may impact on emotional responses in rodent models of anxiety" http://www.ncbi.nlm.nih.gov/pubmed/21255614 0 1230 S. H. Christiansen and D. P. Woldbye 2010 Regulation of the galanin system by repeated electroconvulsive seizures in mice J.Neurosci.Res. 88 16 3635-3643 "Even though induction of seizures by electroconvulsive stimulation (ECS) is a treatment widely used for major depression in humans, the working mechanism of ECS remains uncertain. The antiepileptic effect of ECS has been suggested to be involved in mediating the therapeutic effect of ECS. The neuropeptide galanin exerts antiepileptic and antidepressant-like effects and has also been implicated in the pathophysiology of depression. To explore a potential role of galanin in working mechanisms of ECS, the present study examined effects of repeated ECS on the galanin system using QRT-PCR, in situ hybridization, and [(125) I]galanin receptor binding. ECS was administered to adult mice daily for 14 days, and this paradigm was confirmed to exert antidepressant-like effect in the tail suspension test. Prominent increases in galanin gene expression were found in several brain regions involved in regulation of epileptic activity and depression, including the piriform cortex, hippocampal dentate gyrus, and amygdala. Likewise, GalR2 gene expression was up-regulated in both the central and the medial amygdala, whereas GalR1 gene expression showed a modest down-regulation in the medial amygdala. [(125) I]galanin receptor binding in the piriform cortex, hippocampus, and amygdala was found to be significantly down-regulated. These data show that the galanin system is regulated by repeated ECS in a number of brain regions implicated in seizure regulation and depression. These changes may play a role in the therapeutic effect of ECS" http://www.ncbi.nlm.nih.gov/pubmed/20936701 1 1231 "A. Roitbak, I. Ocherashvili and G. Gedevanishvili" 1985 On the process of inhibition in the superficial neuropil of the cerebral cortex Physiol Bohemoslov. 34 Suppl 133-136 Experiments were carried out on cats under Nembutal anaesthesia. The electrodes were placed on the gyrus suprasylvius. The recording macroelectrode and the K+--sensitive microelectrode were placed between two stimulating electrodes (S1 and S2). A strong stimulus applied through S1 elicited a slow surface negative potential (SNP) and an increase in [K/]0. The change of K+ potential correlated in time with SNP but the decay of K+ potential lasted longer. At this time depression of the dendritic potential (DP)--EPSP of apcial dendrites--evoked by stimulation through S2 took place. The greater the negative shift and the [K/]0 increase the greater was the depression. Tetraethylammonium increased SNP and this correlated with a strong depression of DP. Application of KCl or acetylcholine solutions resulted in DP depression. It may be supposed that the depression of dendritic potentials expresses presynaptic inhibition in the cortical neuropile based on the action of K+ ions http://www.ncbi.nlm.nih.gov/pubmed/2941782 0 1232 "N. Gordon, R. Ilinca, R. Yirmiya and G. Goelman" 2012 Alterations of neuronal effective connectivity during chronic stress-Application for DBS in major depression "Journal of Molecular Neuroscience.Conference: 20th Annual Meeting of the Israel Society for Neuroscience Eilat Israel.Conference Start: 20111211 Conference End: 20111213.Conference Publication: (var.pagings).48 ()(pp S44), 2012.Date of Publication: N" var.pagings S44 "Introduction: An understanding of major depression (MD) in terms of abnormal brain connectivity has recently emerged, setting the ground for recent attempts to treat severe MD through the use of Deep Brain Stimulation. Although initial trials show promising results, no reliable method to date enables to skillfully identify optimal targets for DBS. The very heterogenic nature of term depression stresses the need for a method enabling to locate optimal, individually tailored DBS targets, thus maximizing chances for positive outcomes. Following the emergent notion that the functional connectivity of a given brain region, rather than its local activity alone, might be of higher relevance for the understanding of psycho-pathologies, we aimed to identify the characteristic changes in neuronal connectivity that underlie the development of depressive behavior. We implemented the Chronic Mild Stress (CMS) model in rats and used fMRI to assess the changes in resting-state functional connectivity that corresponded with the development of depressive-like behavior. Results: Global changes in the pattern of connectivity in the stressed animals included: 1) General decrease in total amount of connectivity. 2) Higher dominance of bilateral connections and a decrease in right-hemisphere connections. 3) Relative shift towards subcortical/posterior connections and less cortical/anterior connections. Regions exhibiting changes in connectivity patterns include the prelimbic area, striatum, mamilary bodies, basal nucleus, superior colliculus and the raphe. Connections exhibiting significant changes in stress include basal nucleusnucleus accumbens, prelimbic areastriatum, mamilary bodiesstriatum and mamilary bodieshippocampus. Conclusion: The relevance of the above mentioned results will be discussed. Our results reinforce the notion that MD is characterized by alterations in network connectivity, enabling to skillfully proceed with the search for efficient treatments for depression" DO - http://dx.doi.org/10.1007/s12031-011-9682-4 0 1233 "G. Leroy, F. Phocas, B. Hedan, E. Verrier and X. Rognon" 2015 Inbreeding impact on litter size and survival in selected canine breeds Vet.J. 203 1 74-78 "Data obtained from the French Kennel Club and the Fichier National Canin were used to estimate the effect of inbreeding on average litter size and survival in seven French breeds of dog. Depending on the breed, litter sizes were 3.5-6.3 puppies and longevities were 7.7-12.2 years. Estimated heritabilities were 6.0-10.9% for litter size and 6.1-10.1% for survival at 2 years of age. Regression coefficients indicated a negative effect of inbreeding on both individual survival and litter size. Although the impact of baseline inbreeding within breeds appears to be limited, the improper mating of close relatives will reduce biological fitness through significant reduction of litter size and longevity" http://www.ncbi.nlm.nih.gov/pubmed/25475165 0 1234 "F. Wada, H. Shibata, M. Goto and Y. Sakamoto" 1968 Participation of the microsomal electron transport system involving cytochrome P-450 in omega-oxidation of fatty acids Biochim.Biophys.Acta 162 4 518-524 http://www.ncbi.nlm.nih.gov/pubmed/4387274 0 1235 H. Witschi and M. G. Cote 1976 Biochemical pathology of lung damage produced by chemicals Fed.Proc. 35 1 89-94 "Damage to the lung may be caused by chemicals that gain access to the alveolar zone by inhalation or via the pulmonary circulation. Several agents toxic to the lung have recently been found to bind covalently to pulmonary macromolecules or to disrupt certain metabolic reactions. However, it has also been observed that extensive chemical lung injury is not necessarily preceded by a depression of pulmonary metabolic reactions. One possible explanation for this might be that biochemical changes due to cell death are often masked and/or compensated for by changes associated with lung tissue repair. Substantial cell proliferation as a response to toxic lung damage is a common phenomenon in lung pathology. This makes it necessary to develop models that permit analysis of the biochemical events triggering and accompanying cell growth in lung. We have recently examined some aspects of cell proliferation in mouse lung. Intraperitoneal injection of the antioxidant butylated hydroxytoluene (BHT) produces within 3-5 days extensive hypertrophy, hyperplasia, and general disorganization of the cellular components of the lung. Total lung weight and total DNA per lung almost double within this time and are accompanied by proportional increases in protein and lipids. RNA accumulates at a faster rate than DNA. The changes in lung composition are accompanied by dose-dependent increases in the in vivo incorporation of thymidine into DNA and of leucine into protein. The activities of several enzymes (thymidine kinase, DNA polymerase, uridine kinase, glucose-6-phosphate dehydrogenase, and 5'-nucleotidase) increase substantially after BHT. Administration of BHT to mice seems to offer a convenient tool to study cell growth in the lungs of mice" http://www.ncbi.nlm.nih.gov/pubmed/1245236 0 1236 D. E. Blask and J. L. Nodelman 1980 "An interaction between the pineal gland and olfactory deprivation in potentiating the effects of melatonin on gonads, accessory sex organs, and prolactin in male rats" J.Neurosci.Res. 5 2 129-136 "Male rats (25-26 days of age) housed with 14 hours of light per day (lights on 0600--2000 hours) were either olfactory bulbectomized (rendering them anosmic), bulbectomized plus pinealectomized (Pinx), or left intact. On the day following the operations, intact, anosmic, and anosmic-Pinx animals began receiving single, daily afternoon (1700--1800 hours) subcutaneous injections of 50 microgram of melatonin (MEL) for six weeks, while an additional group of intact controls received injections of diluent. At the end of this period, body, anterior pituitary, testicular, and seminal vesicle weights were significantly reduced in intact-MEL-treated animals. Anosmic animals that had been treated with MEL experienced a further, highly significant, 65%, 90%, and 85% depression in testicular, seminal vesicle, and ventral prostate weights, respectively, as compared with intact control and MEL-treated rats. Additionally, both body and anterior pituitary weights were significantly decreased in MEL-treated, anosmic rats. Anosmic-Pinx rats treated with MEL had organ and body weights that were intermediate between those of intact-MEL and anosmic-MEL-treated animals. Pituitary and serum levels of prolactin (Prl) were significantly lower in anosmic-MEL-treated rats than in intact-MEL-treated groups. Similarly, Prl levels were depressed in the anosmic-Pinx rats treated with MEL; however, serum Prl was not statistically lower than in intact or intact-MEL-treated animals. These results indicate that anosmic male rats have an increased sensitivity to antigonadotrophic and Prl-inhibitory effects of MEL. Futhermore, the data suggest that the presence of the pineal gland in anosmic rats is important in permitting anosmia maximally to sensitize the neuroendocrine-reproductive axis to the antigonadotrophic effects of exogenously administered MEL" http://www.ncbi.nlm.nih.gov/pubmed/7401193 0 1237 G. H. Jarrell 1995 "A male-biased natal sex-ratio in inbred collared lemmings, Dicrostonyx groenlandicus" Hereditas 123 1 31-37 "A captive colony of collared lemmings (Dicrostonyx groenlandicus) from northern Alaska produced a male-biased sex ratio of 67% males for about three generations. These lemmings have a pair of autosomes fused to the sex chromosomes. Thus, males have two copies of some (formerly autosomal) sex-linked genes: One set is X-linked; the other can be described as Y-linked. Given such a karyotype, deleterious recessive alleles on the autosomal portion of the X chromosome are more resistant to selection than truly autosomal loci because they can be eliminated by homozygosity only in females. The male-bias could have resulted from one or more lethals carried on the formerly autosomal arm of the X chromosome. As inbreeding coefficients approached 0.3, the lethal was apparently homozygous in half of the homogametic (female) zygotes. This phenomenon may explain the excess of males and XY females attributed to meiotic drive in Dicrostonyx torquatus from Siberia. If under the natural mating system, inbreeding depression limits fitness, then fusion of autosomal chromatin to the sex chromosomes could be an adaptation to reduce inbreeding depression in heterogametic individuals" http://www.ncbi.nlm.nih.gov/pubmed/8598343 0 1238 "D. Bose, L. V. Hryshko, B. W. King and T. Chau" 1988 Control of interval-force relation in canine ventricular myocardium studied with ryanodine Br.J.Pharmacol. 95 3 811-820 "1. The mechanism of post-extrasystolic, rest and frequency potentiation was studied in canine isolated ventricular muscle. 2. Ryanodine, which impairs Ca availability from the sarcoplasmic reticulum (SR), reduced the amplitude of the extrasystole less than that of the steady state contraction. Ryanodine also inhibited post-extrasystolic potentiation and converted rest-potentiation into rest depression. Rest-potentiation was blocked preferentially by ryanodine compared to post-extrasystolic potentiation. An increase in the contribution of extracellular Ca to the extrasystolic contraction could not entirely account for the post-extrasystolic potentiation. 3. Prolonged rest, by itself, also caused depression of the first post-rest contraction. During rest-potentiation, SR Ca seemed to play a greater role in contraction than transmembrane Ca influx. However, the ability of the 'release pool' of Ca in the SR to be reprimed after a contraction was reduced. This was seen as a decrease in post-extrasystolic potentiation elicited immediately after rest. 4. A decrease in stimulus interval was associated with a transient decrease in contraction amplitude followed by an increase. An abrupt increase in stimulus interval had the opposite effect. Ryanodine blocked the initial transient changes and accelerated the delayed changes. These results suggest that the transient changes in contraction after sudden changes in drive interval are dependent on the SR. 5. Transmembrane Ca entry and the rate of recovery of the Ca release process (repriming) in the SR after a contraction seem to be interval-dependent. The data also indicate that different mechanisms are involved in post-extrasystolic and rest-potentiation. 6. The results are consistent with a model which proposes 'recirculation' of activator Ca within the SR after a contraction or of the presence of an appreciable amount of inactivation of the SR Ca release process during normal stimulation. An increased pool of releasable Ca due to longer recirculation time or a time-dependent decay in the level of inactivation of Ca release from the SR may give rise to rest-potentiation" http://www.ncbi.nlm.nih.gov/pubmed/2463029 0 1239 V. I. Petukhov 1970 [Effect of cholinolytics on the course of traumatic shock] Farmakol.Toksikol. 33 2 170-173 http://www.ncbi.nlm.nih.gov/pubmed/4393233 0 1240 "V. Doyere, M. L. Errington, S. Laroche and T. V. Bliss" 1996 Low-frequency trains of paired stimuli induce long-term depression in area CA1 but not in dentate gyrus of the intact rat Hippocampus 6 1 52-57 "We have examined the efficacy of a recently introduced protocol for inducing homosynaptic long-term depression (LTD) in area CA1 of the anesthetized rat (Thiels et al. [1994] J Neurophysiol 72:3009-3116.). In area CA1 of the awake animal, this protocol, consisting of 200 pairs of pulses delivered at 0.5 Hz, with an interpulse interval of 25 ms, consistently produced LTD, provided the initial pulse was sufficiently strong to produce significant paired-pulse depression of the evoked response. We extended these experiments to the dentate gyrus, using either paired pulses given to the perforant path in the awake adult rat, or, in the anesthetized adult, a two-pathway pairing procedure, in which the first pulse was delivered to the commissural input to the dentate gyrus and the second to the perforant path. In both cases, the first pulse led to substantial suppression of the response evoked by the second pulse. With neither protocol, however, was there any evidence for LTD or depotentiation. Paired-pulse stimulation of the perforant path of young rats (10-11 days) also failed to induce LTD or depotentiation of the population excitatory postsynaptic potential (EPSP). Thus, the dentate gyrus in the intact animal appears to be less susceptible to LTD and depotentiation than area CA1, a conclusion consistent with previous experiments in which we found that stimulation at 1-5 Hz produced LTD/depotentiation in area CA1 of young (but not adult) rats in vivo but was ineffective at any age in the dentate gyrus. Our results do not rule out the possibility that other, untested protocols may produce homosynaptic LTD and/or depotentiation in the dentate gyrus in vivo" http://www.ncbi.nlm.nih.gov/pubmed/8878742 0 1241 "M. Hriscu, G. Saulea, S. Ostriceanu and I. Baciu" 2002 Circadian phagocytic activity in rats under light-dark and constant light regimens Rom.J.Physiol 39-40 17-26 "The phagocytic function was proved to be a periodic, circadian process. Its acrophase appears to be differently timed in species with different activity type, occurring in the evening in diurnal species and at night in nocturnal ones. The main pineal hormone melatonin, whose secretion occurs strictly at dark, has been shown to play a role in the control of inflammation and to exert a certain stimulatory effect upon phagocytosis in vitro. The aim of the present study was to assess whether the phagocytic activity of neutrophils in the blood of rats exhibits a circadian rhythmicity similar to that of other nocturnal rodents (mice) and also if a constant light regimen alters its amplitude and/or chronostructure. Wistar rats were submitted to either an artificial light-dark 12/12 regimen (LD) or to constant light (LL), for 15 days. In vitro phagocytosis of the neutrophils in whole blood against E.coli was assessed at 10:00, 16:00, 22:00, and 04:00 hours. In LD, phagocytosis appears to be a rhythmical function, with statistically significant differences between the highest value at 04:00 hrs and the lowest at 10:00 hrs. Constant light induces a 30% depression of the phagocytic ability throughout the whole 24 hours cycle, without altering its oscillations. The darkness period appears to play the role of a synchronizer; in its absence the rhythm tends to free-run. It may be stated that rhythmical melatonin secretion is responsible only for maintenance of the phagocytic level, probably via the anterior hypothalamic area and thymus, while it cannot account directly for the nocturnal increase of phagocytosis" http://www.ncbi.nlm.nih.gov/pubmed/15984664 0 1242 I. N. Bel'gova 1969 [Effect of salts of ethylenediamine tetraacetic acid and sodium dimercaptopropane sulfonate on hemolytic activity of alpha-toxin of Clostridium perfringens] Farmakol.Toksikol. 32 6 707-710 http://www.ncbi.nlm.nih.gov/pubmed/4315040 0 1243 A. Dorn 1968 "[Inhibitory effect of 2,4-dichlorophenoxyacetate on the histochemical demonstration of phosphorylase using the lead precipitation technic]" Acta Histochem. 30 2 391-392 http://www.ncbi.nlm.nih.gov/pubmed/4235606 0 1244 "R. Goto, H. Kubo and S. Okada" 1991 Effect of reticuloendothelial blockade on tissue distribution of 99mTc-labeled synthetic liposomes in Ehrlich solid tumor-bearing mice Chem.Pharm.Bull.(Tokyo) 39 1 230-232 "The effect of a reticuloendothelial blockade was examined on the tissue distribution of 99mTc-labeled synthetic liposomes prepared from N,N-didodecyl-N alpha-[6-(trimethylammonio)hexanoyl]-L-alaninamide bromide (N+C5Ala2C12) in Ehrlich solid tumor-bearing mice. While a pre-dose of unlabeled phosphatidyl choline liposomes (natural liposomes) hardly influenced the tissue distribution of N+C5Ala2C12 liposomes, the pretreatment of dextran sulfate depressed the uptake in liver accompanied by increasing that in tumor and other tissues except the stomach. However, the extent of liver depression of N+C5Ala2C12 liposomes by dextran sulfate was lower than that of natural liposomes and the pre-dose of unlabeled natural liposomes had a minor effect on the tissue distribution of N+C5Ala2C12 liposomes compared with that of natural liposomes. In the liver uptake of N+C5Ala2C12 liposomes, it was suggested that Kupffer cell phagocytosis was not the main mechanism" http://www.ncbi.nlm.nih.gov/pubmed/2049808 0 1245 W. H. Dantzler and S. K. Bentley 1976 Low Na+ effects on PAH transport and permeabilities in isolated snake renal tubules Am.J.Physiol 230 2 256-262 "Effects of low sodium concentrations on p-aminohippurate (PAH) transport by isolated, perfused snake (Thamnophis spp.) distal-proximal renal tubules were studied. Replacement of sodium in bath with choline led to significant depression of net PAH transport from bath to lumen in less than 10 min and to maximum depression (to 25-30% of control) in about 30 min, but transport still occurred against concentration gradient. In absence of sodium, PAH concentration in cell water was markedly depressed, but was still slightly greater than that in bath or lumen. Apparent permeability of peritubular membrane, determined from PAH efflux from tubules with oil-filled lumens, averaged about 0.5 X 10(-5) cm s-1 in 150 mM sodium and about 1.1 X 10(-5) cm s-1 in sodium-free medium. Data suggest that both decreased rate of active transport and increased apparent permeability of peritubular membrane contribute to depression of net transepithelial PAH transport and cell water PAH concentration in sodium-free medium. When sodium was restored to bath, net PAH transport nearly tripled in 15 min. Reduction of bath sodium concentration to one-half control or perfusion with sodium-free medium in lumen and control medium in bath had no effect on net PAH transport" http://www.ncbi.nlm.nih.gov/pubmed/1259001 0 1246 "R. Collu, F. Fraschini, P. Visconti and L. Martini" 1972 Adrenergic and serotoninergic control of growth hormone secretion in adult male rats Endocrinology 90 5 1231-1237 http://www.ncbi.nlm.nih.gov/pubmed/4401150 0 1247 P. A. Ganesan and S. M. Karim 1974 "Acute toxicity of prostaglandins E2,F2alpha and 15 (S) 15 methyl prostaglandin E2 methyl ester in the baboon" Prostaglandins 7 3 215-221 http://www.ncbi.nlm.nih.gov/pubmed/4411859 0 1248 R. P. Hullin and A. W. Johnson 1970 Effect of lithium salts on uptake of I-125 by rat thyroid gland Life Sci. 9 1 Sep-20 http://www.ncbi.nlm.nih.gov/pubmed/5411555 0 1249 I. K. Pasechnik 1969 [Choleretic properties of compounds obtained from hedge nettle] Farmakol.Toksikol. 32 5 575-577 http://www.ncbi.nlm.nih.gov/pubmed/5364673 0 1250 P. Pichot 1974 Therapy resistant depressions. Methodological problems. Contributions to methodical questions and animal experimental aspects "Pharmakopsychiatrie und Neuropsychopharmakologie.7 (2) ()(pp 80-84), 1974.Date of Publication: 1974." 2 80-84 "In this paper the authors have artificially separated the problems posed by clinical methodology and raised by biological methodology concerning resistance to pharmacotherapy in depression. In fact, the two are closely linked. For instance, the search for the factors responsible for the variation in the plasmatic levels implies the demonstration of a connection between the plasmatic level of the drug and the therapeutic clinical effect obtained on the depressive syndrome. This means that no univocal methodology can be proposed for the time being. Progress in this field depends upon multiple and coordinated approaches" 0 1251 "M. A. Friedman, E. Arnold, Y. Bishop and S. S. Epstein" 1971 "Additive and synergistic inhibition of mammalian microsomal enzyme functions by piperonyl butoxide, safrole and other methylenedioxyphenyl derivatives" Experientia 27 9 1052-1054 http://www.ncbi.nlm.nih.gov/pubmed/5116130 0 1252 "C. Hoyo-Becerra, Z. Liu, J. Yao, B. Kaltwasser, G. Gerken, D. M. Hermann and J. F. Schlaak" 2015 Rapid Regulation of Depression-Associated Genes in a New Mouse Model Mimicking Interferon-alpha-Related Depression in Hepatitis C Virus Infection Mol.Neurobiol. 52 1 318-329 "Major depression is a serious side effect of interferon-alpha (IFN-alpha), which is used in the therapy of hepatitis C virus (HCV) infection. Due to the lack of reproducible animal models, the mechanisms underlying IFN-alpha-related depression are largely unknown. We herein established a mouse model, in which murine IFN-alpha (250 IU/day) and polyinosinic/polycytidylic acid (poly(I:C); 1 mug/day), a toll-like receptor-3 (TLR3) agonist that mimics the effect of HCV double-strand RNA, were continuously infused into the lateral ventricle via miniosmotic pumps over up to 14 days. The delivery of IFN-alpha and poly(I:C), but not of IFN-alpha or poly(I:C) alone, resulted in a reproducible depression-like state that was characterized by reduced exploration behavior in open-field tests, increased immobility in tail suspension and forced swimming tests, and a moderate loss of body weight. In the hippocampus and prefrontal cortex, the pro-inflammatory genes TNF-alpha, IL-6, tissue inhibitor of metalloproteinases-1 (Timp-1), CXC motif ligand-1 (Cxcl1), Cxcl10, and CC motif ligand-5 (Ccl5) were synergistically induced by IFN-alpha and poly(I:C), most pronounced after 14-day exposure. In comparison, the interferon-inducible genes of signal transducer and activator of transcription-1 (Stat1), guanylate binding protein-1 (Gbp1), proteasome subunit-beta type-9 (Psmb9), ubiquitin-conjugating enzyme E2L-6 (Ube2l6), receptor transporter protein-4 (Rtp4), and GTP cyclohydrolase-1 (Gch1), which had previously been elevated in the blood of IFN-alpha-treated patients developing depression, in the brains of suicidal individuals, and in primary neurons exposed to IFN-alpha and poly(I:C), were induced even earlier, reaching maximum levels mostly after 24 hours. We propose that interferon-inducible genes might be useful markers of imminent depression" http://www.ncbi.nlm.nih.gov/pubmed/25159480 1 1253 A. V. Bolotnyi and Z. F. Iurkova 1973 [Data on the toxicological and hygienic evaluation of the new organophosphorus insecticide gardona] Vopr.Pitan. 6 60-65 http://www.ncbi.nlm.nih.gov/pubmed/4804112 0 1254 "C. A. Frye, A. A. Walf, M. E. Rhodes and J. P. Harney" 2004 "Progesterone enhances motor, anxiolytic, analgesic, and antidepressive behavior of wild-type mice, but not those deficient in type 1 5 alpha-reductase" Brain Res. 1004 01-Feb 116-124 "The importance of progesterone's (P(4)) metabolism by the 5 alpha-reductase type I enzyme was examined in homozygous and heterozygous 5 alpha-reductase type I knockout mice and their wild-type siblings. P(4) (1.0 mg) or vehicle was administered and effects on motor, anxiety, nociceptive, and depression behavior were observed. After testing, whole-brain progesterone and 5 alpha-pregnan-3 alpha-ol-20-one (3 alpha,5 alpha-THP) levels were determined by radioimmunoassay. Motor behavior in the horizontal crossing and open field tasks of 5 alpha-reductase-deficient mice administered P(4) was similar to vehicle control mice and significantly reduced compared to wild-type mice administered P(4). In the open field, 5 alpha-reductase-deficient mice administered P(4) had a similar number of central entries as did vehicle control mice, both were lower than central entries of P(4)-administered wild-type mice. However, in the plus maze, P(4) to 5 alpha-reductase-deficient or wild-type mice significantly increased open arm activity compared to vehicle-administered control mice. P(4) to wild-type, but not 5 alpha-reductase-deficient mice, significantly increased latencies to lick front and back paws in response to radiant heat stimuli compared to vehicle administration to control mice. In the forced swim test, 5 alpha-reductase-deficient mice administered P(4) were similar to vehicle control mice and the latency to immobility was significantly decreased, and the duration of immobility was significantly increased, compared to wild-type mice administered P(4). Thus, these data suggest metabolism by the 5 alpha-reductase type I enzyme may mitigate P(4)'s effects on some tasks of motor, anxiety, nociception, and depression behavior" http://www.ncbi.nlm.nih.gov/pubmed/15033426 1 1255 "J. R. Bourke, S. Murdoch, S. W. Manley, T. Matainaho, G. J. Huxham and M. J. Waters" 1991 Epidermal growth factor (EGF) inhibits the secretomotor response of the thyroid: effects of EGF on radioiodine turnover and fluid transport in cultured porcine thyroid cells J.Endocrinol. 128 2 213-218 "Thyrotrophin (4-256 microU/ml) promoted an increase in the rate of release of radioiodine from the organic iodine pool of cultured porcine thyroid cells in follicular formations. This action of TSH was antagonized by low concentrations of epidermal growth factor (EGF; 0.1-5 nmol/l). The maximal effect of EGF was reached by 0.5 nmol/l. EGF (0.5-5 nmol/l) also inhibited the stimulatory effect of 8-chloro cyclic AMP (0.06-1.0 nmol/l) on radioiodine turnover. Exposure of thyroid cultures to media with a calcium concentration of 17.7 mumol/l (1% of normal) resulted in a very marked increase in the rate of release of radioiodine. The effect of TSH in low-calcium media was to inhibit the increased release of radioiodine, and EGF (0.5 nmol/l) antagonized this inhibitory effect of TSH. The calcium ionophore, A23187, stimulated radioiodine release in a dose-dependent fashion, and EGF (1.7 nmol/l) inhibited this response. Fluid transport in thyroid monolayers was stimulated by prostaglandin E2 (PGE2; 1 mumol/l). EGF (5 nmol/l) also stimulated fluid transport, but antagonized the effect of PGE2 added subsequently. It was concluded that EGF exerted acute antagonistic effects on thyroid cell responses in vitro to cyclic AMP and agents promoting accumulation of cyclic AMP in time-frames too short for these inhibitory effects to be attributable to the dedifferentiative effect of the growth factor" http://www.ncbi.nlm.nih.gov/pubmed/2005412 0 1256 J. Hartung 1981 [Comparative dermatology: trichotillomania (author's transl)] Z.Hautkr. 56 10 629-630 http://www.ncbi.nlm.nih.gov/pubmed/7281859 0 1257 "J. Molgo, P. E. del, J. E. Banos and D. Angaut-Petit" 1991 Changes of quantal transmitter release caused by gadolinium ions at the frog neuromuscular junction Br.J.Pharmacol. 104 1 133-138 "1. The actions of the trivalent cation, gadolinium (Gd3+), were studied on frog isolated neuromuscular preparations by conventional electrophysiological techniques. 2. Gd3+ (450 microM) applied to normal or formamide-treated cutaneous pectoris nerve-muscle preparations induced, after a short delay, a complete block of neuromuscular transmission. The reversibility of the effect was dependent on the time of exposure. 3. Gd3+ (5-450 microM) had no consistent effect on the resting membrane potential of the muscle fibres. 4. Gd3+ (5-40 microM) applied to preparations equilibrated in solutions containing high Mg2+ and low Ca2+ reduced the mean quantal content of endplate potentials (e.p.ps) in a dose-dependent manner. Under those conditions, 3,4-diaminopyridine (10 microM) consistently reversed the depression of evoked quantal release. 5. The calcium current entering motor nerve terminals, revealed after blocking presynaptic potassium currents with tetraethylammonium (10 mM) in the presence of elevated extracellular Ca2+ (8 mM), was markedly reduced by Gd3+ (0.2-0.5 mM). 6. Gd3+ (40-200 microM) increased the frequency of spontaneous miniature endplate potentials (m.e.p.ps) in junctions bathed either in normal Ringer solution or in a nominally Ca(2+)-free medium supplemented with 0.7 microM tetrodotoxin. This effect may be due to Gd3+ entry into the nerve endings since it is not reversed upon removal of extracellular Gd3+ with chelators (1 mM EGTA or EDTA). Gd3+ also enhanced the frequency of me.p.ps appearing after each nerve stimulus in junctions bathed in a medium containing high Mg2+ and low Ca2+. 7. Gd3+, in concentrations higher than 100 microM, decreased reversibly the amplitude of m.e.p.ps suggesting a postsynaptic action. 8. It is concluded that the block of nerve-impulse evoked quantal release caused by Gd3 + is related to its ability to block the calcium current entering the nerve endings, supporting the view that Gd3 + blocks N-type Ca2+ channels; while the enhancement of spontaneous quantal release is probably the result of Gd3 + entry into motor nerve endings. Besides its dual prejunctional effects on quantal release it is suggested that Gd3 + exerts a postsynaptic action on the endplate acetylcholine receptor-channel complex" http://www.ncbi.nlm.nih.gov/pubmed/1686201 0 1258 "H. Fujimura, K. Tsurumi, M. Nozaki, H. Imai, K. Niu and Y. Muramatsu" 1981 "[Interaction of phenothiazinic anti-inflammatory agent, protizinic acid, with the biopolymers: Inhibitory effects on functions of platelets (author's transl)]" Nihon Yakurigaku Zasshi 77 1 27-39 "Two types of phenothiazinic anti-inflammatory agents, protizinic acid (PZA) and metiazinic acid (MZA) were examined using 1) heat denaturation test, 2) heat-induced erythrocyte lysis, 3) several platelet functions, 4) model membrane systems containing the same phospholipids and cholesterol compositions as in platelets. PZA and MZA were inhibited with heat denaturation in a similar manner seen with BSA and heat-induced erythrocyte lysis, and effects were more potent than indomethacin (IM). PZA showed inhibitory effects similar to MZA on ADP or collagen-induced platelet aggregation. However, in arachidonic acid (AA)-induced rabbit platelet aggregation, PZA had a more potent effect, similar to effects seen with IM and more potent than those of MZA. PZA inhibited the lethal effect of AA in rabbits at concentrations lower then MZA. To determine the sites of action, we examined the effects on uptake and release reactions of 3H-serotonin. PZA and MZA did not affect the uptake reaction but did reduce the release of serotonin to a greater extent than seen with IM. The tested drugs had little effect on the platelet aggregation in vivo. To investigate the interaction of these drugs with lipid bilayers, we used liposomes as a model membrane, of which the lipids compositions were the same as that of platelets. The tested drugs showed inhibitions of the liposome aggregation with addition of 6 mM Ca2+, in a dose dependent manner and similar to findings in the drug-platelet system. In this experiment, PZA had a more potent interaction with lipid bilayers than did MZA. These results suggest that interactions of PZA with the platelet membrane may be the origin of the PZA-induced inhibition of the platelet aggregation, in addition to the effect on the biosynthesis of prostaglandins" http://www.ncbi.nlm.nih.gov/pubmed/7262705 0 1259 "K. Takeuchi, H. Watanabe, Q. K. Tran, M. Ozeki, D. Sumi, T. Hayashi, A. Iguchi, L. J. Ignarro, K. Ohashi and H. Hayashi" 2004 "Nitric oxide: inhibitory effects on endothelial cell calcium signaling, prostaglandin I2 production and nitric oxide synthase expression" Cardiovasc.Res. 62 1 194-201 "OBJECTIVE: Nitric oxide (NO) produced in large amounts by inducible nitric oxide synthase exerts many harmful effects such as stimulation of inflammation and induction of apoptosis. The effects of excessive NO production on functions of endothelial cells, the major physiological source of NO, are not completely known. The aim of this study was to investigate the role of NO on the regulation of endothelial cell Ca2+ signaling and endothelial cell function. METHODS: Primary porcine aortic endothelial cells (PAECs) were used for all these studies. Intracellular Ca2+ concentrations ([Ca2+]i) were measured using fura-2/AM. Production of prostaglandin I2 (PGI2) and cyclic GMP were assessed using enzyme immunoassays, and endothelial NO synthase protein expression was evaluated by Western blotting. RESULTS: Bradykinin (BK, 10 nM) and thapsigargin (TG, 1 microM) provoked large increases in [Ca2+]i. The NO donor NOC12 reduced these responses, respectively, by 21% and 31% at 100 microM, 60% and 55% at 300 microM, and 74% and 78% at 500 microM. These effects were also observed with other NO donors including spermine NONOate and NOC18, and were completely prevented by carboxy-PTIO (200 microM), an NO scavenger. 8-Bromo-cGMP, however, had no effects on BK- and TG-stimulated Ca2+ responses. A 30-fold increase in PGI2 production was observed in cells stimulated with BK. NOC12 again reduced this response by 12%, 54%, 83% and 95% at 10, 100, 300 and 500 microM, respectively. Endothelial NO synthase protein level was reduced by 2%, 15%, 36 and 47% after 2, 6, 12 and 24 h, respectively, of incubation with NOC18, a NO donor with long half-life. CONCLUSIONS: NO, when produced in large amounts, can inhibit agonist-induced Ca2+ responses independently of cyclic GMP, reduce the production of endothelium-derived relaxing factors (EDRFs) and interfere with endothelial NO synthase protein expression" http://www.ncbi.nlm.nih.gov/pubmed/15023566 0 1260 "W. Swiercz, K. Cios, J. Hellier, A. Yee and K. Staley" 2007 Effects of synaptic depression and recovery on synchronous network activity J.Clin.Neurophysiol. 24 2 165-174 "SUMMARY: The output of an artificial neural network of spiking neurons linked by glutamatergic synapses subject to use-dependent depression was compared with physiologic data obtained from rat hippocampal area CA3 in vitro. The authors evaluated how network burst initiation and termination was affected by activity-dependent depression and recovery under a variety of experimental conditions including neuronal membrane depolarization, altered glutamate release probability, the strength of synaptic inhibition, and long-term potentiation and long-term depression of recurrent glutamatergic synapses. The results of computational experiments agreed with the in vitro data and support the idea that synaptic properties, including activity-dependent depression and recovery, play important roles in the timing and duration of spontaneous bursts of network activity. This validated network model is useful for experiments that are not feasible in vitro, and makes possible the investigation of two-dimensional aspects of burst propagation and termination" http://www.ncbi.nlm.nih.gov/pubmed/17414972 0 1261 "P. Franchimont, A. Demoulin, J. Verstraelen-Proyard, M. T. Hazee-Hagelstein and W. M. Tunbridge" 1979 Identification in human seminal fluid of an inhibin-like factor which selectively regulates FSH secretion J.Reprod.Fertil.Suppl 26 123-133 "Human seminal plasma obtained by centrifugation of human semen contains a factor capable of selectively inhibiting the secretion of FSH both in vivo (reduction of the levels of FSH in rats 24 h after castration) and in vitro (reduction of the FSH released by LH-RH in rat pituitary cell culture). This effect is not due to testosterone, oestradiol-17 beta or progesterone present in the active fractions. The factor has the characteristics of a protein in that its biological activity is destroyed by heat and trypsin digestion. It does not resemble androgen-binding protein. The biological action is not completely specific for FSH as inhibition of LH can be seen with doses usually higher than those which produce inhibition of FSH alone. There is no effect on TSH or prolactin levels in vitro. The factor clearly acts on the release and synthesis of gonadotrophins by gonadotrophs but an effect on the hypothalamus is not excluded. This factor fits the definition of inhibin" http://www.ncbi.nlm.nih.gov/pubmed/293406 0 1262 "C. C. Huang, I. H. Wei, C. L. Huang, K. T. Chen, M. H. Tsai, P. Tsai, R. Tun, K. H. Huang, Y. C. Chang, H. Y. Lane and G. E. Tsai" 2013 Inhibition of glycine transporter-I as a novel mechanism for the treatment of depression Biol.Psychiatry 74 10 734-741 "BACKGROUND: Antidepressants, aiming at monoaminergic neurotransmission, exhibit delayed onset of action, limited efficacy, and poor compliance. Glutamatergic neurotransmission is involved in depression. However, it is unclear whether enhancement of the N-methyl-D-aspartate (NMDA) subtype glutamate receptor can be a treatment for depression. METHODS: We studied sarcosine, a glycine transporter-I inhibitor that potentiates NMDA function, in animal models and in depressed patients. We investigated its effects in forced swim test, tail suspension test, elevated plus maze test, novelty-suppressed feeding test, and chronic unpredictable stress test in rats and conducted a 6-week randomized, double-blinded, citalopram-controlled trial in 40 patients with major depressive disorder. Clinical efficacy and side effects were assessed biweekly, with the main outcomes of Hamilton Depression Rating Scale, Global Assessment of Function, and remission rate. The time course of response and dropout rates was also compared. RESULTS: Sarcosine decreased immobility in the forced swim test and tail suspension test, reduced the latency to feed in the novelty-suppressed feeding test, and reversed behavioral deficits caused by chronic unpredictable stress test, which are characteristics for an antidepressant. In the clinical study, sarcosine substantially improved scores of Hamilton Depression Rating Scale, Clinical Global Impression, and Global Assessment of Function more than citalopram treatment. Sarcosine-treated patients were much more likely and quicker to remit and less likely to drop out. Sarcosine was well tolerated without significant side effects. CONCLUSIONS: Our preliminary findings suggest that enhancing NMDA function can improve depression-like behaviors in rodent models and in human depression. Establishment of glycine transporter-I inhibition as a novel treatment for depression waits for confirmation by further proof-of-principle studies" http://www.ncbi.nlm.nih.gov/pubmed/23562005 1 1263 J. W. McIntyre and J. C. Russel 1971 Renal function and methoxyflurane anaesthesia Can.Anaesth.Soc.J. 18 2 131-136 http://www.ncbi.nlm.nih.gov/pubmed/4252247 0 1264 "S. Quiroz-Gonzalez, B. Segura-Alegria, J. C. Olmos and I. Jimenez-Estrada" 2012 The effect of chronic undernourishment on the synaptic depression of cutaneous pathways in the rat spinal cord Brain Res.Bull. 89 03-Apr 97-101 "The aim of this study was to determine the effect of chronic undernourishment on the amplitude depression of the first negative component in the cord dorsum potentials (N(1)-CDPs) caused by the conditioning stimulation of sensory cutaneous nerves in the rat spinal cord. Single electrical pulses (1Hz; 2 times threshold) applied to the sural (SU) nerve of control rats (n=14) produced CDPs with a first negative component (N(1)-CDPs) larger in amplitude (14.2+/-1.3%, p<0.01) than those recorded in chronically undernourished rats (n=14; 3 times threshold). The conditioning stimulation of the SP nerve (4 shocks at 300Hz, 3xT) in the control rats (n=5) evoked a long-lasting (~200ms) depression of the N(1)-CDP (60.2+/-7.2%). In contrast such depression was smaller in magnitude (42.5+/-5.7%, p<0.01) and time course (100-120ms) in undernourished rats (n=7). The systemic application of picrotoxin (PTX) reduced, but did not abolish the conditioned depression of the N(1)-CDPs and DRPs in both the control and undernourished rats. By assuming that the depression of the N(1)-CDPs is representative of presynaptic mechanisms, it is proposed that chronic undernourishment influence the activation of presynaptic neuronal pathways that regulate the transmitter release of cutaneous afferent fibers in the spinal cord and such effect could act as a compensatory mechanism that counterbalances the decreased activation of spinal neurons by the reduced afferent input in the rat" http://www.ncbi.nlm.nih.gov/pubmed/22828571 0 1265 "T. Namba, M. Takaki, J. Araki, K. Ishioka and H. Suga" 1994 Energetics of the negative and positive inotropism of pentobarbitone sodium in the canine left ventricle Cardiovasc.Res. 28 4 557-564 "OBJECTIVE: Pentobarbitone (sodium) is an anaesthetic widely used in animal experiments. It is known to be a cardiovascular depressant and a coronary dilator, but its effects on myocardial energetics in relation to its negative and positive (due to Gregg's phenomenon) inotropism have not been studied. The aim of this study was therefore to determine whether and how pentobarbitone affects cardiac mechanoenergetics compared with other negative inotropic agents for which data are already available. METHODS: The effects of graded doses of intracoronary pentobarbitone on mechanoenergetics were studied in the excised cross circulated left ventricles of 12 dogs. The framework of the Emax (a contractility index)--VO2 (myocardial oxygen consumption)--PVA (systolic pressure-volume area, a measure of total mechanical energy) relationships was fully utilised. RESULTS: Pentobarbitone increased Emax at low doses in five of the 12 hearts. In two of these five hearts, a marked coronary dilatation was found. Pentobarbitone decreased Emax dose dependently at high doses in all the hearts and lowered the VO2 intercept but not the slope (oxygen cost of PVA) of the VO2-PVA relation. There was no difference in oxygen cost of Emax between pentobarbitone and CaCl2, although they have opposite inotropism. These findings suggest that pentobarbitone depresses myocardial mechanoenergetics via suppression of total calcium handling in the excitation-contraction-relaxation coupling. CONCLUSIONS: Pentobarbitone at low doses partly acts as a positive inotropic agent, but at high doses it acts as a negative inotropic agent like beta blockers and calcium antagonists on cardiac mechanoenergetics in canine blood perfused hearts" http://www.ncbi.nlm.nih.gov/pubmed/8181046 0 1266 J. Vlk 1979 Postnatal development of postganglionic parasympathetic neurones in the heart of the albino rat Physiol Bohemoslov. 28 6 561-568 "Electrical stimulation of the sinoatrial node region of isolated atria in medium containing physostigmine (0.1 micrograms/ml) produces a negative chronotropic effect whose intensity and duration depend mainly on the amount of acetylcholine released from postganglionic parasympathetic fibres endings. This technique was used to study functional maturation of the given neurones during postnatal development of albino rats. Preparations from animals of different ages were stimulated with 2-second bursts of rectangular pulses (frequency 50 Hz, pulse duration 0.02 ms, voltage 22.5--27.5 V) and frequency changes of the preparation were registered by recording extracellular action potentials. At 10 days the negative chronotropic effect is very weak and at 15 days it is only slightly stronger, but at 18 days it is almost the same as in adult animals. At 24 and 34 days the reaction is somewhat stronger than in adulthood. It can be concluded from these observations that functional maturation of the postganglionic parasympathetic neurones innervating the sinoatrial node in albino rats occurs between the 10th and 20th day of postnatal life" http://www.ncbi.nlm.nih.gov/pubmed/160578 0 1267 "D. Dlaboga, H. Hajjhussein and J. M. O'Donnell" 2006 Regulation of phosphodiesterase-4 (PDE4) expression in mouse brain by repeated antidepressant treatment: Comparison with rolipram "Brain Research.1096 (1) ()(pp 104-112), 2006.Date of Publication: 22 Jun 2006." 1 104-112 "Cyclic nucleotide phosphodiesterase-4 (PDE4) is a component of signaling pathways involved in the mediation of antidepressant activity. Of the four PDE4 subtypes, PDE4D appears to be of particular importance, given the finding that PDE4D-deficient mice exhibit an antidepressant-like behavioral phenotype. In mouse hippocampus and cerebral cortex, the effects of repeated treatment with the antidepressants desipramine and fluoxetine or the PDE4 inhibitor rolipram on the expression of PDE4D was compared to that of PDE4A and PDE4B, the other two subtypes expressed in the brain. Expression of PDE4D was increased by all drugs tested, with the exception of desipramine in hippocampus. By contrast, these treatments affected PDE4A and PDE4B expression differentially. In hippocampus, antidepressants increased PDE4A and decreased PDE4B, whereas ROL decreased PDE4A and did not change PDE4B. In cerebral cortex, antidepressants increased PDE4A and did not change PDE4B, whereas ROL did not change PDE4A and increased PDE4B. 3H-Rolipram binding was increased in cytosolic, but not in membrane, fractions of cerebral cortex by all drugs tested; there were no changes observed in hippocampus. Overall, the present results suggest some species-dependence of the regulation of PDE4 subtypes, based on data obtained previously using rats. They also suggest that the PDE4D subtype may be of particular importance as an antidepressant target in that it is regulated by repeated treatment with both norepinephrine and serotonin reuptake inhibitors as well as by the PDE4 inhibitor rolipram, drugs that produce antidepressant effects via different neuropharmacological mechanisms. © 2006 Elsevier B.V. All rights reserved" DO - http://dx.doi.org/10.1016/j.brainres.2006.04.032 0 1268 H. Kaneto and J. Watanabe 1980 [Tolerance to and dependence on opioids in isolated longitudinal muscle of guinea pig ileum. Validity of the muscle preparation as a receptor model for opioids (author's transl)] Nihon Yakurigaku Zasshi 76 5 347-354 "Contractions evoked by electrical stimulation of isolated longitudinal muscle preparations of guinea pig ileum were inhibited by the addition of opioids in the order of morphine = methionine enkephalin greater than pentazocine pethidine. Incubation of the preparation in the medium containing opioids at 4 degrees C for 22 hr resulted in a tolerance to the inhibitory effect in morphine and pethidine but in the case of pentazocine and met-enkephalin tolerance did not develop under the conditions employed. The same treatment with morphine, pethidine and pentazocine resulted in the development of dependence as demonstrated by naloxone provoked contracture or increase in the height of contraction. Opiate and enkephalin receptors are known to be unevenly distributed in the ileum and a significant difference was also observed in the distribution patterns of both receptors. Distribution of the receptors did not parallel the effect of opioids, thereby indicating a multiplicity in receptors. However, under the conditions employed in the present experiments, our results reflect the in vivo effects of opioids, such as analgesic effect or tolerance and dependence liability, and the validity of this preparation for the evaluation of opioids was confirmed" http://www.ncbi.nlm.nih.gov/pubmed/6259029 0 1269 "Z. Zhang, X. Du, C. Zhao, B. Cao, Y. Zhao and X. Mao" 2013 The antidepressant amitriptyline shows potent therapeutic activity against multiple myeloma Anticancer Drugs 24 8 792-798 "Our previous study indicated that the antidepressant amitriptyline showed potent activity in inducing multiple myeloma (MM) cell apoptosis in vitro. In the present study, we further showed that amitriptyline was active against MM in vivo. Oral administration of amitriptyline significantly decreased tumor growth in two MM xenograft models derived from murine and human MM cells, respectively. Molecular pathological analysis showed that amitriptyline induced p53, activated caspase-3, and decreased antiapoptotic Bcl-2 and Mcl-1 in tumor tissues. Amitriptyline also significantly extended the survival period of MM-tumor-bearing mice. In the in-vitro study, we also found that amitriptyline synergistically induced MM cell apoptosis in combination with bortezomib, the most potent anti-MM agent. Because amitriptyline has been proposed to control cancer-associated pain, depression, and anxiety, proper application of amitriptyline will benefit MM patients" http://www.ncbi.nlm.nih.gov/pubmed/23708819 0 1270 "R. Li, F. S. Huang, A. K. Abbas and H. Wigstrom" 2007 Role of NMDA receptor subtypes in different forms of NMDA-dependent synaptic plasticity BMC.Neurosci. 8 55 "BACKGROUND: The involvement of different NMDA receptor (NMDAR) subunits has been implicated in several forms of synaptic plasticity. However, it is still controversial to what extent the involvement is specific, and little is known about the role of NMDAR subunits in certain ""non-conventional"" forms of plasticity. In this study we used subunit-specific blockers to test the roles of" http://www.ncbi.nlm.nih.gov/pubmed/17655746 0 1271 "R. V. Johnston, D. A. Grant, M. H. Wilkinson and A. M. Walker" 1998 Repetitive hypoxia rapidly depresses arousal from active sleep in newborn lambs J.Physiol 510 ( Pt 2) 651-659 "1. Arousal from sleep is an important protective mechanism that is depressed by repeated episodes of hypoxia. We aimed to determine how rapidly arousal depression occurs during repeated hypoxia and to determine if the depression is sleep state specific. 2. Three successive 12 h overnight sleep recordings were performed in six newborn lambs instrumented to record sleep state, blood pressure, heart rate and blood gases. The first (control) and third (recovery) nights were baseline studies (inspired oxygen fraction, FI,O2 = 0.21) to determine the spontaneous arousal probability. During the second (test) study night, lambs were exposed to a 60 s episode of isocapnic hypoxia (FI,O2 = 0.10; inspired carbon dioxide fraction, FI,CO2 = 0.03) during every epoch of sleep. 3. During quiet sleep (QS), the probability of arousing to hypoxia (56%) remained significantly higher than the probability of arousing spontaneously (18%) throughout the repeated hypoxic exposures (chi(2) = 81.5, P < 0.001). By contrast, during active sleep (AS) arousal rapidly became depressed with repetition of the hypoxic stimulus; the probability of arousal in hypoxia (52%) was significantly higher than the probability of spontaneous arousal (12%) during the first ten hypoxic exposures (chi(2) = 18.2, P < 0.001), but there was no difference thereafter. 4. We conclude that, when repeated, moderate hypoxia very rapidly becomes ineffective as an arousing stimulus in AS, but not in QS. These results suggest that the arousal mechanism is particularly vulnerable to failure during AS" http://www.ncbi.nlm.nih.gov/pubmed/9706012 0 1272 "M. J. Niebauer, M. J. Holmberg and I. H. Zucker" 1986 Aortic baroreceptor characteristics in dogs with chronic high output failure Basic Res.Cardiol. 81 2 111-122 "It has been shown that the arterial baroreflex is depressed in heart failure. The role of alterations in afferent discharge as a possible mechanism for this depression has not been investigated previously. Single unit aortic baroreceptor activity was recorded from six normal dogs and from nine dogs, each with a chronic aorto-caval fistula (AVF). At the time of the acute experiment, mean arterial blood pressure (MABP) was not significantly different in the two groups of dogs; however, pulse pressure was significantly higher in the AVF dogs (45.7 +/- 2.4 mm Hg vs, 24.4 +/- 2.0 mm Hg; p less than 0.001). Left ventricular end-diastolic pressure (LVEDP) was higher in the AVF dogs (31.3 +/- 2.0 vs 5.6 +/- 1.8 mm Hg; p less than 0.001). AVF dogs had elevated heart weight/body weight ratios. The relationship of systolic aortic pressure to systolic discharge was examined by changing aortic pressure with aortic and vena caval occluders. The peak gain (normalized to maximum discharge) averaged 2.19 +/- 0.27 in the normal dogs compared to 1.15 +/- 0.09 in the AVF group (p less than 0.01). Saturation pressures and maximum discharge rates were greater in the AVF dogs although the threshold pressures were not different in the two groups. This data suggests that there is an attenuated response of aortic baroreceptor discharge in dogs with chronic volume overload and this abnormality may partially be responsible for the abnormal baroreflex in heart failure" http://www.ncbi.nlm.nih.gov/pubmed/3741352 0 1273 "D. Brewster, P. W. Dettmar and A. G. Lynn" 1980 Modification of the proline residue of TRH enhances biological activity and inhibits degradation "European Journal of Pharmacology.66 (1) ()(pp 65-71), 1980.Date of Publication: 1980." 1 65-71 "An analogue of TRH with a modified proline residue (Pyr-His-MepNH2) has been synthesized and evaluated. In CNS, but not endocrine tests the analogue had improved activity compared to TRH and was more resistant to enzymatic degradation. A metabolite of TRH, His-Pro, was without biological activity. It is concluded that the biological actions attributed to TRH are due to the parent tripeptide rather than His-Pro and that these actions can be enhanced by improving the biological stability of TRH" DO - http://dx.doi.org/10.1016/0014-2999%2880%2990295-2 0 1274 J. Green 1996 Zoledronate: the preclinical pharmacology Br.J.Clin.Pract.Suppl 87 16-18 http://www.ncbi.nlm.nih.gov/pubmed/8995013 1 1275 "D. Artini, W. Logemann, P. Melloni, G. Vita, A. Buttinoni and R. Tommasini" 1970 [Analgesic and antiphlogistic action of amide and amine compounds. 1] Arzneimittelforschung. 20 8 1009-1018 http://www.ncbi.nlm.nih.gov/pubmed/5536494 0 1276 H. Einat 2007 Chronic oral administration of ginseng extract results in behavioral change but has no effects in mice models of affective and anxiety disorders "Phytotherapy Research.21 (1) ()(pp 62-66), 2007.Date of Publication: January 2007." 1 62-66 "Ginseng is a popular 'tonic' herb in Chinese traditional medicine with diverse biological activity. The core of ginseng's therapeutic abilities is thought to be its neuroprotective actions in increasing cellular resilience. These actions coincide with novel theories of affective and anxiety disorders and raise the possibility that ginseng may serve as medication for these common and devastating diseases. The present study was designed to explore the possible effects of chronic ginseng extract, administered in a clinically relevant schedule (similar to antidepressants) in animal models of affective and anxiety disorders. Groups of mice received chronic oral treatment with ginseng extract (500 mg/kg/day for 3 weeks) and were tested in a large open field, in the emergence test for anxiolytic activity, the forced swim test for antidepressant activity and the amphetamine hyperactivity test for mood stabilizing activity. Chronic ginseng had a significant effect on reducing spontaneous locomotor activity in the open field test but not on the distribution of activity and had no influence on the performance of mice in any of the specific models. Although the extract used in this study contained significant levels of ginsenosides, detailed analysis of the brain levels of the active ingredients of ginseng may be needed to make a far reaching conclusion. However, the doses and schedule of administration of ginseng used in the present study induced some behavioral changes but did not influence affective- and anxiety-like measures. Copyright © 2006 John Wiley & Sons, Ltd" DO - http://dx.doi.org/10.1002/ptr.2024 0 1277 R. S. Lasher 1975 Uptake of GABA by neuronal and nonneuronal cells in dispersed cell cultures of postnatal rat cerebellum J.Neurobiol. 6 6 597-608 "A study was made of the time course and kinetics of [3H]GABA uptake by dispersed cell cultures of postnatal rat cerebellum with and without neuronal cells. The properties of GABA neurons were calculated from the biochemical difference between the two types of cultures. It was found that for any given concentration of [3H]GABA, or any time up to 20 min, GABA neurons in cultures 21 days in vitro had an average velocity of uptake several orders of magnitude greater than that of nonneuronal cells. In addition, the apparent Kmvalues for GABA neurons for high and low affinity uptake were 0.33 X 10(-6) M and 41.8 X 10(-4) M, respectively. For nonneuronal cells, the apparent Km for high affinity uptake was 0.29 X 10(-6) M. The apparent Vmax values for GABA neurons for high and low affinity uptake were 28.7 X 10(-6) mol/g DNA/min and 151.5 mmol/g DNA/min, respectively. For nonneuronal cells, the apparent Vmax for high affinity uptake was 0.06 X 10(-6) mol/g DNA/min. No low affinity uptake system for nonneuronal cells could be detected after correcting the data for binding and diffusion. By substituting the apparent kinetic constants in the Michaelis-Menten equation, it was determined that for GABA concentrations of 5 X 10(-9) M to 1 mM or higher over 99% of the GABA should be accumulated by GABA neurons, given equal access of all cells to the label. In addition, high affinity uptake of [3H]GABA by GABA neurons was completely blocked by treatment with 0.2 mM ouabain, whereas that by noneuronal cells was only slightly decreased. Most (75-85%) of the [3H]GABA (4.4 X 10(-6) M) uptake by both GABA neurons and nonneuronal cells was sodium and temperature dependent" http://www.ncbi.nlm.nih.gov/pubmed/1237537 0 1278 "C. G. Benson, M. C. Chase and S. J. Potashner" 1991 Decreased release of D-aspartate in the guinea pig spinal cord after lesions of the red nucleus J.Neurochem. 56 4 1174-1183 "This study attempts to determine if fibers that project from the guinea pig red nucleus to the spinal cord use L-glutamate and/or L-aspartate as transmitters. Unilateral injections of kainic acid were placed stereotaxically in the red nucleus to destroy the cells of origin of the rubrospinal tract. Six days after the injection, Nissl-stained sections through the lesion site showed that the majority of neurons in the red nucleus ipsilateral to the kainic acid injection were destroyed. In addition, the lesioned area included parts of the surrounding midbrain reticular formation. Silver-impregnated, transverse sections of the cervical spinal cord revealed the presence of degenerating fibers contralaterally in laminae IV-VII of the gray matter. Ipsilaterally, very sparse degeneration was evident in laminae VII and VIII of the gray matter. Two to six days after surgery, the electrically evoked, Ca2(+)-dependent release of both D-[3H]aspartate, a marker for glutamatergic/aspartatergic neurons, and gamma-amino[14C]-butyric acid ([14C]GABA) was measured in dissected quadrants of the spinal cervical enlargement. Lesions centered on the red nucleus depressed the release of D-[3H]aspartate by 25-45% in dorsal and ventral quadrants of the cervical enlargement contralaterally. The release of [14C]GABA was depressed by 27% in contralateral ventral quadrants. To assess the contribution of rubro- versus reticulospinal fibers to the deficits in amino acid release, unilateral injections of kainic acid were placed stereotaxically in the midbrain reticular formation lateral to the red nucleus. Nissl-stained sections through the midbrain revealed the presence of extensive neuronal loss in the midbrain and rostral pontine reticular formation, whereas neurons in the red nucleus remained undamaged. In the spinal cord, degenerating axons were present ipsilaterally in laminae VII and VIII of the gray matter. Some fiber degeneration was also evident contralaterally in laminae V and VI of the gray matter. This lesion did not affect the release of either D-[3H]aspartate or [14C]GABA in the spinal cord. The substantial decrements in D-[3H]aspartate release following red nucleus lesions suggests that the synaptic endings of rubrospinal fibers mediate the release of D-[3H]aspartate in the spinal cord. Therefore, these fibers may be glutamatergic and/or aspartatergic. Because other evidence suggests that rubrospinal neurons are probably not GABAergic, the depression of [14C]GABA release probably reflects changes in the activity of spinal interneurons following the loss of rubrospinal input" http://www.ncbi.nlm.nih.gov/pubmed/2002335 0 1279 "P. E. Waibel, C. W. Carlson, J. A. Brannon and S. L. Noll" 2000 Identification of limiting amino acids in methionine- and lysine-supplemented low-protein diets for turkeys Poult.Sci. 79 9 1299-1305 "Large White male turkeys were fed 100, 85, 70, or 60% of NRC (1994) CP during 7 to 28 d (Experiment (EXP) 1), 8 to 12 wk (EXP 2), and 16 to 20 wk (EXP 3) of age. Diets contained corn, soybean, canola, and meat meals and were supplemented with Met and Lys to requirement. The influence of supplementary amino acids (AA) was studied at each protein level. Turkeys fed 85% CP gained BW similarly to those fed 100% of NRC CP (control) during each age range. Supplemental Thr, Val, and Ile during 7 to 28 d or 8 to 12 wk, or Thr during 16 to 20 wk, did not result in positive BW gain response. For turkeys fed 70% CP, BW gain was depressed compared with the normal-CP control in each period. During 7 to 28 d and 8 to 12 wk of age, the combination of Thr, Ile, Val, Arg, and Trp to 100% of NRC reversed the BW depression; here only Thr, Ile, and Val were essential components of the response. The BW depression during 16 to 20 wk was reversed by the combination of Thr, Ile, Val, and Trp. For turkeys fed 60% of CP, BW gain was severely depressed. The combination of Thr, Ile, Val, Trp, and Arg resulted in nearly complete BW recovery during each age" http://www.ncbi.nlm.nih.gov/pubmed/11020075 0 1280 "J. Yin, M. Liu, W. Ren, J. Duan, G. Yang, Y. Zhao, R. Fang, L. Chen, T. Li and Y. Yin" 2015 Effects of dietary supplementation with glutamate and aspartate on diquat-induced oxidative stress in piglets PLoS.One. 10 4 e0122893 "This study aimed to investigate the protective effects of dietary glutamate and aspartate supplementations on diquat-induced oxidative stress in piglets. Diquat injection significantly reduced growth performance, including body weight, average daily weight gain, and feed intake (P<0.05). Meanwhile, diquat administration induced oxidative stress evidenced by the decreased serum nitric oxide (NO) and elevated malondialdeyhde (MDA) concentration (P<0.05). Furthermore, diquat-induced oxidative stress disrupted intestinal absorption system and decreased serum threonine, serine, and glycine levels. Dietary supplementation with glutamate improved final body weight, antioxidant system, and expressions of amino acids transporters and enhanced serum glutamate concentration compared with diquat group (P<0.05). While aspartate failed to alleviate diquat-induced oxidative stress, growth depression, and dysfunction of nutrients absorption except for liver relative weight. In conclusion, dietary supplementation with glutamate confers beneficial effects on diquat-induced oxidative stress in piglets, while aspartate exhibits little effects" http://www.ncbi.nlm.nih.gov/pubmed/25875335 0 1281 "Z. Aira, T. Barrenetxea, I. Buesa and J. J. Azkue" 2015 "Plasticity of alpha2-adrenergic spinal antinociception following nerve injury: selective, bidirectional interaction with the delta opioid receptor" Brain Res. 1594 190-203 "Interactions of opioid receptors with other receptor families can be made use of to improve analgesia and reduce adverse effects of opioid analgesics. We investigated interactions of the alpha2-adrenergic receptor (alpha2AR) with opioid receptors of the mu (MOR) and delta (DOR) types in the spinal dorsal horn in an animal model of neuropathic pain induced by spinal nerve ligation. Nine days after nerve injury, immunoreactivity for the alpha2AR subtype A (alpha2AAR) was increased both in tissue homogenates and at pre- and post-synaptic sites in transverse sections. The efficacy of spinally administered alpha2AAR agonist guanfacine at reducing C-fiber-evoked field potentials was increased in nerve-ligated rats. This reducing effect was impaired by simultaneous administration of DOR antagonist naltrindole, but not MOR antagonist CTOP, suggesting that concurrent DOR activation was required for alpha2AAR-mediated inhibition. While DOR agonist deltorphin II and MOR agonist DAMGO both effectively depressed C-fiber-evoked spinal field potentials, DOR- but not MOR-mediated depression was enhanced by subclinical guanfacine. In conscious, nerve-ligated rats, chronically administered deltorphin II produced stable thermal and mechanical antinociception over the 9 following days after nerve injury without apparent signs of habituation. Such an effect was dramatically enhanced by co-administration of a low dose of guanfacine, which reversed thermal and mechanical thresholds to levels near those prior to injury. The results suggest that spinal, alpha2AAR-mediated antinociception is increased after nerve injury and based on DOR co-activation. We demonstrate in vivo that alpha2AAR/DOR interaction can be exploited to provide effective behavioral antinociception during neuropathic pain" http://www.ncbi.nlm.nih.gov/pubmed/25446445 0 1282 "M. D. Azevedo, K. Jacobsohn and C. M. Rodrigues" 1969 "[Influence of thiamine, in vivo, on the thiaminase activity of guinea pig organs]" Bull.Soc.Chim.Biol.(Paris) 50 10 1791-1796 http://www.ncbi.nlm.nih.gov/pubmed/5799151 0 1283 "A. R. Rutzen, C. W. Roberts, J. Driller, D. Gomez, B. C. Lucas, F. L. Lizzi and D. J. Coleman" 1990 Production of corneal lesions using high-intensity focused ultrasound Cornea 9 4 324-330 "In order to study the potential use of ultrasound as a noninvasive system for altering corneal curvature, we used high-density focused ultrasound at a frequency of 4.8 MHz and 7.9 MHz to produce corneal lesions in the rabbit eye. Intensity and duration threshold exposure conditions were determined for the production of minimally visible lesions. Threshold lesions were initially apparent as discrete white opacities resulting from stromal edema and disruption. Light and scanning electron microscopy of higher-energy, suprathreshold lesions revealed more extensive disruption, including the formation of a superficial stromal depression and a larger zone of edema and disorganization surrounding each lesion. Posterior stromal lamellae, endothelium, and Descemet's membrane were intact. Healing and reepithelialization resulted in a smooth corneal surface with no residual opacification. Threshold determinations predict safe exposure levels to the cornea during insonification of other ocular structures. Selective heating of the peripheral cornea using focused ultrasound may be a useful technique for correcting astigmatism" http://www.ncbi.nlm.nih.gov/pubmed/2078961 0 1284 "L. A. Dethlefsen, C. M. Lehman, J. E. Biaglow and V. M. Peck" 1988 Toxic effects of acute glutathione depletion by buthionine sulfoximine and dimethylfumarate on murine mammary carcinoma cells Radiat.Res. 114 2 215-224 "Glutathione (GSH) depletion to approximately equal to 5% of control for 48 h or longer by 0.05 mM L-buthionine sulfoximine (BSO) led to appreciable toxicity for the 66 murine mammary carcinoma cells growing in vitro [L.A. Dethlefsen et al., Int. J. Radiat. Oncol. Biol. Phys. 12, 1157-1160 (1986)]. Such toxicity in normal, proliferating cells in vivo would be undesirable. Thus the toxic effects after acute GSH depletion to approximately equal to 5% of control by BSO plus dimethylfumarate (DMF) were evaluated in these same 66 cells to determine if this anti-proliferative effect could be minimized. Two hours of 0.025 mM DMF reduced GSH to 45% of control, while 6 h of 0.05 mM BSO reduced it to 16%. However, BSO (6 h) plus DMF (2 h) and BSO (24 h) plus DMF (2 h) reduced GSH to 4 and 2%, respectively. The incorporation (15-min pulses) of radioactive precursors into protein and RNA were unaffected by these treatment protocols. In contrast, cell growth was only modestly affected, but the incorporation of [3H]thymidine into DNA was reduced to 64% of control by the BSO (24 h) plus DMF (2 h) protocol even though it was unaffected by the BSO (6 h) plus DMF (2 h) treatment. The cellular plating efficiencies from both protocols were reduced to approximately equal to 75% of control cells. However, the aerobic radiation response, as measured by cell survival, was not modified at doses of either 4.0 or 8.0 Gy. The growth rates of treated cultures, after drug removal, quickly returned to control rates and the resynthesis of GSH in cells from both protocols was also rapid. The GSH levels after either protocol were slightly above control by 12 h after drug removal, dramatically over control (approximately equal to 200%) by 24 h, and back to normal by 48 h. Thus even a relatively short treatment with BSO and DMF resulting in a GSH depletion to 2-5% of control had a marked effect on DNA synthesis and plating efficiency and a modest effect on cellular growth. One cannot rule out a direct effect of the drugs, but presumably the antiproliferative effects are due to a depletion of nuclear GSH with the subsequent inhibition of the GSH/glutaredoxin-mediated conversion of ribonucleotides to deoxyribonucleotides. However, even after extended treatment, upon drug removal, GSH was rapidly resynthesized and cellular DNA synthesis and growth quickly resumed" http://www.ncbi.nlm.nih.gov/pubmed/3375425 0 1285 "I. Gil-Ad, M. Portnoy, I. Tarasenko, M. Bidder, M. Kramer, M. Taler and A. Weizman" 2014 A novel analog of olanzapine linked to sarcosinyl moiety (PGW5) demonstrates high efficacy and good safety profile in mouse models of schizophrenia Eur.Neuropsychopharmacol. 24 3 425-436 "Schizophrenia is a chronic mental disorder related to hypo-functioning of glutamatergic neurotransmission. N-methyl-D-aspartate-receptor (NMDA-R) positive modulators were reported to reduce schizophrenia symptoms. However, their efficacy is low and inconsistent. We developed a novel antipsychotic possessing an olanzapine moiety linked to the positive modulator of glutamate NMDA-R sarcosine (PGW5) and characterized the pharmacodynamic properties of the novel molecule in-vivo using MK-801 and in-vitro using receptor binding analysis. We investigated the pharmacological activity of PGW5 (olanzapine linked to sarcosinyl moiety) in male mice (BALB/c or C57BL). In an open field test, up to 50mg/kg PGW5 did not affect motility while higher doses were sedative. PGW5 (25-50mg/kg po) antagonized MK-801 (0.15 mg/kg ip) and amphetamine-induced (5mg/kg ip) hyperactivity. PGW5 (25mg/kg po/d) treatment for 15 or 22 days exhibited antidepressant and anxiolytic activity in mice. Moreover, PGW5, but not olanzapine, attenuated phencyclidine (PCP)-induced deficits of social preference in mice and promoted the expression of brain derived neurotrophic factor (BDNF) in the hippocampus and the frontal cortex and glutamic acid decarboxylase (GAD67) in the hippocampus. Mice treated with PGW5 (25 and 50mg/kg/d) for 28 days did not show toxic effects in terms of weight gain and blood-chemistry analysis. CONCLUSIONS: PGW5 is a novel and safe antipsychotic, efficacious against schizophrenia-like positive and negative symptoms at nonsedative doses. The drug shows anxiolytic and antidepressant activity, and improves impaired social performance in phencyclidine (PCP) treated mice. The mechanism underlying its activity seems to involve potentiation of NMDA receptor as well as stimulation of brain BDNF and GAD67 expression" http://www.ncbi.nlm.nih.gov/pubmed/24389121 0 1286 N. Zisapel and M. Laudon 1983 Inhibition by melatonin of dopamine release from rat hypothalamus: regulation of calcium entry Brain Res. 272 2 378-381 "The [Ca2+] dependency of dopamine release evoked by electrical field stimulation of hypothalamic tissue from female rats at the estrous stage was assessed in the presence of melatonin. At concentrations of 10(-9)-10(-6) M, melatonin inhibited the [Ca2+]-dependent dopamine release. Melatonin reduced tissue uptake of 45Ca2+ during stimulation either by an electrical field or by elevated K+ concentration. About 90% of this inhibition by melatonin of 45Ca2+ uptake, as well as of dopamine release, was not observed in the presence of the calcium ionophore A23187. Hence, the inhibitory effect on dopamine release by melatonin may stem from the reduction of calcium entry into the presynaptic nerve endings" http://www.ncbi.nlm.nih.gov/pubmed/6412963 0 1287 "T. Chang, H. Alexopoulos, M. McMenamin, A. Carvajal-Gonzalez, S. K. Alexander, R. Deacon, F. Erdelyi, S. Gabor, B. Lang, F. Blaes, P. Brown and A. Vincent" 2013 Neuronal surface and glutamic acid decarboxylase autoantibodies in nonparaneoplastic stiff person syndrome "JAMA Neurology.70 (9) ()(pp 1140-1149), 2013.Date of Publication: September 2013." 9 1140-1149 "IMPORTANCE: High titers of autoantibodies to glutamic acid decarboxylase (GAD) are well documented in association with stiff person syndrome (SPS). Glutamic acid decarboxylase is the rate-limiting enzyme in the synthesis of gamma-aminobutyric acid (GABA), and impaired function of GABAergic neurons has been implicated in the pathogenesis of SPS. Autoantibodies to GAD might be the causative agent or a disease marker. OBJECTIVE: To investigate the characteristics and potential pathogenicity of GAD autoantibodies in patients with SPS and related disorders. DESIGN: Retrospective cohort study and laboratory investigation. SETTING: Weatherall Institute of Molecular Medicine, University of Oxford. PARTICIPANTS: Twenty-five patients with SPS and related conditions identified from the Neuroimmunology Service. EXPOSURES: Neurological examination, serological characterization and experimental studies. MAIN OUTCOMES AND MEASURES: Characterization of serum GAD antibodies from patients with SPS and evidence for potential pathogenicity. RESULTS: We detected GAD autoantibodies at a very high titer (median, 7500 U/mL) in 19 patients (76%), including all 12 patients with classic SPS. The GAD autoantibodies were high affinity (antibody dissociation constant, 0.06-0.78 nmol) and predominantly IgG1 subclass. The patients' autoantibodies co-localized with GAD on immunohistochemistry and in permeabilized cultured cerebellar GABAergic neurons, as expected, but they also bound to the cell surface of unpermeabilized GABAergic neurons. Adsorption of the highest titer (700 000 U/mL) serum with recombinant GAD indicated that these neuronal surface antibodies were not directed against GAD itself. Although intraperitoneal injection of IgG purified from the 2 available GAD autoantibody-positive purified IgG preparations did not produce clinical or pathological evidence of disease, SPS and control IgG were detected in specific regions of the mouse central nervous system, particularly around the lateral and fourth ventricles. CONCLUSIONS AND RELEVANCE: Autoantibodies to GAD are associated with antibodies that bind to the surface of GABAergic neurons and that could be pathogenic. Moreover, in mice, human IgG from the periphery gained access to relevant areas in the hippocampus and brainstem. Identification of the target of the non-GAD antibodies and peripheral and intrathecal transfer protocols, combined with adsorption studies, should be used to demonstrate the role of the non-GAD IgG in SPS" DO - http://dx.doi.org/10.1001/jamaneurol.2013.3499 0 1288 R. Orias and S. M. McCann 1972 Natriuresis induced by alpha and beta melanocyte stimulating hormone (MSH) in rats Endocrinology 90 3 700-706 http://www.ncbi.nlm.nih.gov/pubmed/5009346 0 1289 "B. Jiang, M. Trevino and A. Kirkwood" 2007 Sequential development of long-term potentiation and depression in different layers of the mouse visual cortex J.Neurosci. 27 36 9648-9652 "Visual deprivation affects the responses of layer IV cells more prominently during early postnatal development, whereas responses in layer II/III remain modifiable until later ages. We examined whether these laminar differences correlate with changes in long-term potentiation (LTP) and long-term depression (LTD) of the ascending pathways to layers IV and II/III in the mouse visual cortex. Our analysis revealed that LTP and LTD in layer IV principal cells is lost shortly after the eyes open, but persists in layers II/III beyond puberty. These results suggest that plasticity proceeds sequentially through cortical layers in a manner that parallels the flow of information during sensory processing" http://www.ncbi.nlm.nih.gov/pubmed/17804625 0 1290 "A. Iring, E. Ruisanchez, M. Leszl-Ishiguro, B. Horvath, R. Benko, Z. Lacza, Z. Jarai, P. Sandor, M. Di, V, P. Pacher and Z. Benyo" 2013 Role of endocannabinoids and cannabinoid-1 receptors in cerebrocortical blood flow regulation PLoS.One. 8 1 e53390 "BACKGROUND: Endocannabinoids are among the most intensively studied lipid mediators of cardiovascular functions. In the present study the effects of decreased and increased activity of the endocannabinoid system (achieved by cannabinoid-1 (CB1) receptor blockade and inhibition of cannabinoid reuptake, respectively) on the systemic and cerebral circulation were analyzed under steady-state physiological conditions and during hypoxia and hypercapnia (H/H). METHODOLOGY/PRINCIPAL FINDINGS: In anesthetized spontaneously ventilating rats the CB1-receptor antagonist/inverse agonist AM-251 (10 mg/kg, i.v.) failed to influence blood pressure (BP), cerebrocortical blood flow (CoBF, measured by laser-Doppler flowmetry) or arterial blood gas levels. In contrast, the putative cannabinoid reuptake inhibitor AM-404 (10 mg/kg, i.v.) induced triphasic responses, some of which could be blocked by AM-251. Hypertension during phase I was resistant to AM-251, whereas the concomitant CoBF-increase was attenuated. In contrast, hypotension during phase III was sensitive to AM-251, whereas the concomitant CoBF-decrease was not. Therefore, CoBF autoregulation appeared to shift towards higher BP levels after CB1-blockade. During phase II H/H developed due to respiratory depression, which could be inhibited by AM-251. Interestingly, however, the concomitant rise in CoBF remained unchanged after AM-251, indicating that CB1-blockade potentially enhanced the reactivity of the CoBF to H/H. In accordance with this hypothesis, AM-251 induced a significant enhancement of the CoBF responses during controlled stepwise H/H. CONCLUSION/SIGNIFICANCE: Under resting physiological conditions CB1-receptor mediated mechanisms appear to have limited influence on systemic or cerebral circulation. Enhancement of endocannabinoid levels, however, induces transient CB1-independent hypertension and sustained CB1-mediated hypotension. Furthermore, enhanced endocannabinoid activity results in respiratory depression in a CB1-dependent manner. Finally, our data indicate for the first time the involvement of the endocannabinoid system and CB1-receptors in the regulation of the cerebral circulation during H/H and also raise the possibility of their contribution to the autoregulation of CoBF" http://www.ncbi.nlm.nih.gov/pubmed/23308211 0 1291 "E. P. Murono, R. C. Derk and Y. Akgul" 2006 In vivo exposure of young adult male rats to methoxychlor reduces serum testosterone levels and ex vivo Leydig cell testosterone formation and cholesterol side-chain cleavage activity Reprod.Toxicol. 21 2 148-153 "Methoxychlor (MC) was developed as a replacement for the banned pesticide DDT. After in vivo administration, it is metabolized in the liver to 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE), which is proposed to be the active agent. Both MC and HPTE have been shown to exhibit weak estrogenic and antiandrogenic activities, and they are thought to exert their effects through estrogen and androgen receptors, respectively. Although in vitro studies using cultured rat Leydig cells have reported that HPTE inhibits both basal and hCG-stimulated testosterone formation, the response of circulating testosterone levels to in vivo MC has been more variable. Therefore, the current studies evaluated whether the daily in vivo administration of MC (0, 5, 40 and 200 mg/kg body weight) for a short duration (days 54-60 of age) by gavage altered serum testosterone levels and ex vivo Leydig cell testosterone formation in young adult male rats. These results demonstrate that both fluid-retained and fluid-expressed seminal vesicle weights declined to 44 and 60% of control, respectively, in the 200 mg/kg MC-exposed animals. Similarly, serum testosterone and dehydroepiandrosterone levels declined to 41 and 45% of control, respectively, in the 200 mg/kg MC-exposed animals; however, serum LH and FSH levels were unaffected. Ex vivo Leydig cell basal testosterone formation over 4h declined to 49% of control in animals exposed to 200 mg/kg MC, and ex vivo Leydig cell P450 cholesterol side-chain cleavage activity declined to 79 and 50% of control in animals exposed to 40 and 200 mg/kg of MC, respectively, supporting previous in vitro studies which demonstrated the sensitivity of this step to MC" http://www.ncbi.nlm.nih.gov/pubmed/16226009 0 1292 G. Kaur and M. S. Kanungo 1970 Alterations in glutamate dehydrogenase of the brain of rats of various ages Can.J.Biochem. 48 2 203-206 http://www.ncbi.nlm.nih.gov/pubmed/5417417 0 1293 "F. Rodriguez, I. Rozas, J. E. Ortega, J. J. Meana and L. F. Callado" 2007 "Guanidine and 2-aminoimidazoline aromatic derivatives as alpha(2)-adrenoceptor antagonists, 1: toward new antidepressants with heteroatomic linkers" J.Med.Chem. 50 18 4516-4527 "The efficient preparation and pharmacological characterization of different families of (bis)guanidine and (bis)2-aminoimidazoline derivatives (""twin"" and ""half"" molecules) as potential alpha(2)-adrenoceptor antagonists for the treatment of depression is presented. The affinity toward the alpha(2)-adrenoceptor of all the compounds prepared was measured in vitro in human brain tissue. Additionally, the activity as agonist or antagonist of those compounds with a pK(i) larger than 7 was determined in functional [(35)S]GTPgammaS binding assays in human brain tissue. Finally, the activity of the most promising compounds was confirmed by means of in vivo microdialysis experiments in rats. Compounds 1, 2b, 3b, 12b, 13b, 17b, 18b, 22b, 25b, 26b, 28b, and 30 showed a good affinity toward the alpha(2)-ARs. In general, the 2-aminoimidazoline derivatives displayed higher affinities than their guanidine analogues. Finally and most importantly, compounds 18b and 26b showed antagonistic properties over alpha(2)-ARs not only in vitro [(35)S]GTPgammaS binding but also in vivo microdialysis experiments. Moreover, both compounds have shown to be able to cross the blood-brain barrier and, therefore, they can be considered as potential antidepressants" http://www.ncbi.nlm.nih.gov/pubmed/17691718 0 1294 R. G. Bridges and J. Ricketts 1968 The effect of 2-aminobutan-1-ols on the growth of the housefly (Musca domestica) Comp Biochem.Physiol 25 2 383-400 http://www.ncbi.nlm.nih.gov/pubmed/5653696 0 1295 "V. Petronilli, B. Persson, M. Zoratti, J. Rydstrom and G. F. Azzone" 1991 Flow-force relationships during energy transfer between mitochondrial proton pumps Biochim.Biophys.Acta 1058 2 297-303 "The effect of inhibitors of proton pumps, of uncouplers and of permeant ions on the relationship between input force, delta mu H+, and output flows of the ATPase, redox and transhydrogenase H(+)-pumps in submitochondrial particles was investigated. It is concluded that: (1) The decrease of output flow of the transhydrogenase proton pump, defined as the rate of reduction of NADP+ by NADH, is linearily correlated with the decrease of input force, delta mu H+, in an extended range of delta mu H+, independently of whether the H(+)-generating pump is the ATPase or a redox pump, or whether delta mu H+ is depressed by inhibitors of the H(+)-generating pump such as oligomycin or malonate, or by uncouplers. (2) The output flows of the ATPase and of the site I redox H(+)-pumps exhibit a steep dependence on delta mu H+. The flow-force relationships differ depending on whether the depression of delta mu H+ is induced by inhibitors of the H(+)-generating pump, by uncouplers or by lipophilic anions. (3) With the ATPase as H(+)-consuming pump, at equivalent delta mu H+ values, the output flow is more markedly inhibited by malonate than by uncouplers; the latter, however, are more inhibitory than lipophilic anions such as ClO4-. With redox site I as proton-consuming pump, at equivalent delta mu H+ values, the output flow is more markedly inhibited by oligomycin than by uncouplers; again, uncouplers are more inhibitory than ClO4-. (4) The results provide further support for a delocalized interaction of transhydrogenase with other H(+)-pumps" http://www.ncbi.nlm.nih.gov/pubmed/1646634 0 1296 "P. M. Cahusac, R. H. Evans, R. G. Hill, R. E. Rodriquez and D. A. Smith" 1984 The behavioural effects of an N-methylaspartate receptor antagonist following application to the lumbar spinal cord of conscious rats Neuropharmacology 23 7A 719-724 "The selective N-methylaspartate (NMA) receptor antagonist 2-amino-5-phosphonopentanoate (AP5) has been applied to the lumbar region of the spinal cord in conscious rats through chronically implanted intrathecal cannulae. Administration of AP5 was compared with administration of 2-amino-4-phosphonobutyrate (AP4), morphine and control injections. Intrathecal injection of AP5 (250 nmol) produced extensor paralysis in the hindquarters and depression of aversive responses to tail heat (54 degrees C), paw heat (hotplate 56.5 degrees C) and paw pressure. Depression of AP5 of the vocal response to aversive electrical stimuli, applied to the tail, suggested that AP5 produced analgesia independently of locomotor paralysis. Intrathecal injection of morphine (20-30 nmol) produced no observed locomotor effects, but depressed responses to all the aversive stimuli. Intrathecal injection of AP4 had no significant effects. When tritiated AP5 was administered intrathecally, the proportion of radioactivity recovered from the lumbar spinal cord suggested that the concentration of AP5, which produced locomotor depression and analgesia, was likely to have been in the range (15-75 microM) known to depress excitatory transmission in isolated spinal cord preparations. It is concluded that synaptic activation of n-methylaspartate receptors is important in spinal pathways which control locomotion, posture and central transmission of nociceptive information" http://www.ncbi.nlm.nih.gov/pubmed/6147787 0 1297 R. Evans 1970 Further studies on the replication of the lactate dehydrogenase-elevating virus (LDH virus) in mouse peritoneal macrophage cultures Proc.Soc.Exp.Biol.Med. 133 3 831-836 http://www.ncbi.nlm.nih.gov/pubmed/5435576 0 1298 N. N. Oleshko 1989 [Effect of damage of the nigro-neostriatal dopaminergic system by MPTP on the transmission of corticofugal impulses to the neurons of the caudate nucleus] Fiziol.Zh. 35 6 33-39 "It is shown in acute experiments on cats (males) that the induced responses as action potentials (AP) by the latent period (LP) less than 8.0 ms in the caudate nucleus neurons (CN) to a single stimulation of the motor zone of the cortex (MI) are more frequently inhibited than facilitated after specifying single stimulation of the compact part of the black substance (BS) in the intervals between stimuli 10-100 ms. As a result of system multiple injection of MPTP neurotoxin during 5 days per 5 mg/kg the number of CN neurons responding to stimulation of MI, AP, LP less than 8.0 Usec and to stimulation of BS-LP less than 10.0 ms reliably decreases. A conclusion is made that dopaminergic nigro-striatum system exerts a protective action on the impulse transfer on monosynaptic connections from the cortex to striatum" http://www.ncbi.nlm.nih.gov/pubmed/2558913 0 1299 "I. P. Stolerman, R. Fink and M. E. Jarvik" 1973 Acute and chronic tolerance to nicotine measured by activity in rats Psychopharmacologia. 30 4 329-342 http://www.ncbi.nlm.nih.gov/pubmed/4722204 0 1300 "B. A. Brewer, R. C. Lacy, M. L. Foster and G. Alaks" 1990 Inbreeding depression in insular and central populations of Peromyscus mice J.Hered. 81 4 257-266 "We tested the hypothesis that small, isolated populations would show less depression in fitness when inbred than would large, central populations. Laboratory stocks of Peromyscus leucopus and P. polionotus were established from insular, peninsular, and central populations. The isolated populations had one-third to one-half the genic diversity of central populations. Responses to inbreeding were highly varied: some populations had smaller litters, others experienced higher mortality, some showed slower growth rates, and one displayed no measurable effects when inbred. These results suggest that inbreeding depression is controlled by a small number of genes and that the size of the genetic load depends on which alleles are present in the founders of a population. The severity of fitness depression in inbred litters did not correlate with initial genic diversity of the stocks nor, therefore, with the size of the wild populations. Fitness measures appeared linearly related to the inbreeding coefficient of the liters, with no diminution of deleterious effects through subsequent generations of inbreeding. Thus overdominance of fitness traits probably contributed as much to the genetic load as did deleterious recessive alleles. The inbreeding level of the dam negatively affected the size, growth, and survival of litters only in genetically diverse populations, indicating that the load of recessive alleles negatively impacting maternal care may have been reduced by selection in the more peripheral populations during past bottlenecks" http://www.ncbi.nlm.nih.gov/pubmed/2273239 0 1301 "E. Edwards, W. Kornrich, H. P. van and F. A. Henn" 1992 In vitro neurotransmitter release in an animal model of depression Neurochem.Int. 21 1 29-35 "Sprague-Dawley rats exposed to uncontrollable shock can be separated by a subsequent shock escape test into two groups: a ""helpless"" (LH) group which demonstrates a deficit in escape behavior, and a ""nonlearned helpless"" (NLH) group which shows no escape deficit and acquires the escape response as readily as naive control rats (NC) do. The present studies were designed to examine the correlations between the behavioral differences and the changes of in vitro neurotransmitter release seen in these three groups of rats. The major finding concerned a significant increase in endogenous and K(+)-stimulated serotonin (5-HT) release in the hippocampal slices of LH rats. There were no apparent differences in acetylcholine, dopamine and noradrenaline release in the hippocampus of LH rats as compared to NLH and NC rats. These results add further support to previous studies in our laboratory which implicate presynaptic 5-HT mechanisms in the behavioral deficit caused by uncontrollable shock" http://www.ncbi.nlm.nih.gov/pubmed/1303140 1 1302 O. Frederiksen 1983 Effect of amiloride on sodium and water reabsorption in the rabbit gall-bladder J.Physiol 335 75-88 "The effects of the Na+-channel-blocking diuretic agent amiloride were assessed in the rabbit gall-bladder epithelium, a low-resistance epithelium with an isosmotic, coupled NaCl transport mechanism. Amiloride caused a rapid, reversible, and dose-dependent decrease in fluid absorption when applied from the mucosal side in concentrations between 8.8 X 10(-5) and 1.76 X 10(-3) M. These concentrations were without effect from the serosal side, suggesting an action of amiloride in the luminal cell membrane as in high-resistance epithelia. Amiloride did not affect the epithelial resistance or the passive serosa-to-mucosa Na+ flux, while net Na+ and water reabsorption were inhibited in parallel. Thus, amiloride did not affect the paracellular tight junction pathway, but inhibited a transcellular, coupled salt and water transport mechanism. The kinetics of the amiloride effect were of a Michaelis-Menten type. The dose of amiloride giving 50% inhibition of fluid absorption (ID50) was 4 X 10(-4) M, a value about three orders of magnitude higher than in high-resistance, Na+-retaining epithelia. The percentage inhibitory effect at each concentration of amiloride increased with increasing rate of spontaneous (control) fluid transport, reaching maximal responses fitting a Michaelis-Menten kinetic with an ID50 of 1.5 X 10(-4) M. No effects of changing the extracellular Na+ concentration between 51 and 145 mequiv/l on the maximal inhibitory effect of amiloride on Na+ and water reabsorption were observed. This suggests a non-competitive type of action of amiloride on a Na+-dependent isosmotic fluid transport mechanism. Removal of mucosal Ca2+ did not alter the effect of amiloride. The implications of these findings are discussed in relation to concepts concerning the mechanism of isosmotic salt and water transport. The data are compatible with the concept that amiloride interferes with a Na+-dependent formation and transcellular transport of isosmotic fluid volumes in a sequestered compartment in the epithelial cells" http://www.ncbi.nlm.nih.gov/pubmed/6875899 0 1303 "A. I. Marzoev, S. L. Turchina and V. A. tnikov" 1985 [Blocking effect of cycloheximide on decreased mitochondrial resistance due to thyroid hormone action] Biull.Eksp.Biol.Med. 99 5 540-542 "Administration of cycloheximide (20-25 micrograms/kg bw twice, interval 24 h) to hyperthyroid rats (300 micrograms/T4/100 g bw i. p. 48 h before sacrifice) inhibited the decrease in mitochondrial resistance to Ca2+ characteristic of hyperthyroidism. It was established in particular that calcium capacitance of the mitochondria and the time of the maintenance of transmembrane potential of these organelles under calcium loading were increased in the mitochondria of hyperthyroid animals given cycloheximide as compared with analogous parameters of the organelles of intact hyperthyroid rats. Moreover, the fluorescence intensity of NADPH in the mitochondria of the first group of animals was 37% greater and the rate of oxidation of these nucleotides several times lower than in the organelles of the second group animals. It is assumed that the described effects of cycloheximide on the mitochondria are linked with the inhibitory effect of the antibiotic on endogenous activity of mitochondrial phospholipase A2" http://www.ncbi.nlm.nih.gov/pubmed/4005406 0 1304 "J. M. Abu-Shaweesh, I. A. Dreshaj, R. J. Martin, K. J. Wirth, U. Heinelt and M. A. Haxhiu" 2002 Inhibition of Na(+)/H(+) exchanger type 3 reduces duration of apnea induced by laryngeal stimulation in piglets Pediatr.Res. 52 3 459-464 "Reflexes from the larynx induce cessation of breathing in newborn animals. The magnitude of respiratory inhibition is inversely related to the level of central chemical input. Recent studies indicate that selective inhibition of Na(+)/H(+) exchanger type 3 (NHE3) activates CO(2)/H(+)-sensitive neurons, resembling the responses evoked by hypercapnic stimuli. Hence, the use of NHE3 inhibitors may reduce reflexly mediated respiratory depression and duration of apnea in the neonatal period. This possibility was examined in decerebrate, vagotomized, ventilated, and paralyzed piglets by testing the effects of i.v. administration of NHE3 blocker S8218 on the response of phrenic nerve amplitude, frequency, and duration of apnea induced by graded electrical stimulation of the superior laryngeal nerve. Superior laryngeal nerve stimulation caused a significant decrease in phrenic nerve amplitude, frequency, minute phrenic activity, and inspiratory time (all p < 0.01) that was proportional to the level of electrical stimulation. Increased levels of stimulation were more likely to induce apnea both during and after cessation of stimulation. NHE3 blocker S8218 reduced the superior laryngeal nerve stimulation-induced decrease in phrenic nerve amplitude, minute phrenic activity, and phrenic nerve frequency (all p < 0.05) and reduced superior laryngeal nerve stimulation-induced apnea and duration of poststimulation apnea (p < 0.05). In six other pigs the brain concentrations of S8218 were measured at different intervals after i.v. administration of the drug and were found to be higher in the brain tissue than plasma at all intervals. These findings suggest that the use of NHE3 blockers may decrease the duration of apnea and possibly reduce the pathophysiologic consequences of potentially life-threatening apnea in infants" http://www.ncbi.nlm.nih.gov/pubmed/12193685 0 1305 "H. Tani, A. E. Bandrowski, I. Parada, M. Wynn, J. R. Huguenard, D. A. Prince and R. J. Reimer" 2007 Modulation of epileptiform activity by glutamine and system A transport in a model of post-traumatic epilepsy Neurobiol.Dis. 25 2 230-238 "Epileptic activity arises from an imbalance in excitatory and inhibitory synaptic transmission. To determine if alterations in the metabolism of glutamate, the primary excitatory neurotransmitter, might contribute to epilepsy we directly and indirectly modified levels of glutamine, an immediate precursor of synaptically released glutamate, in the rat neocortical undercut model of hyperexcitability and epilepsy. We show that slices from injured cortex take up glutamine more readily than control slices, and an increased expression of the system A transporters SNAT1 and SNAT2 likely underlies this difference. We also examined the effect of exogenous glutamine on evoked and spontaneous activity and found that addition of physiological concentrations of glutamine to perfusate of slices isolated from injured cortex increased the incidence and decreased the refractory period of epileptiform potentials. By contrast, exogenous glutamine increased the amplitude of evoked potentials in normal cortex, but did not induce epileptiform potentials. Addition of physiological concentrations of glutamine to perfusate of slices isolated from injured cortex greatly increased abnormal spontaneous activity in the form of events resembling spreading depression, again while having no effect on slices from normal cortex. Interestingly, similar spreading depression like events were noted in control slices at supraphysiological levels of glutamine. In the undercut cortex addition of methylaminoisobutyric acid (MeAIB), an inhibitor of the system A glutamine transporters attenuated all physiological effects of added glutamine suggesting that uptake through these transporters is required for the effect of glutamine. Our findings support a role for glutamine transport through SNAT1 and/or SNAT2 in the maintenance of abnormal activity in this in vitro model of epileptogenesis and suggest that system A transport and glutamine metabolism are potential targets for pharmacological intervention in seizures and epilepsy" http://www.ncbi.nlm.nih.gov/pubmed/17070687 0 1306 "S. Suzuki, L. C. Solberg, E. E. Redei and R. J. Handa" 2001 Prepro-thyrotropin releasing hormone 178-199 immunoreactivity is altered in the hypothalamus of the Wistar-Kyoto strain of rat Brain Res. 913 2 224-233 "The rat prepro-thyrotropin releasing hormone (TRH) 178-199 is derived from prepro-TRH by the actions of the endopeptidases, prohormone convertase 1 (PC1) and PC2. PPTRH 178-199 attenuates the synthesis and secretion of adrenocorticotropic hormone (ACTH) from the anterior pituitary both in vitro and in vivo, suggesting an inhibitory action on hypothalamic-pituitary-adrenal (HPA) axis function. This peptide also acts centrally to increase activity and decrease anxiety related behaviors. To elucidate the involvement of this peptide in these functions, we have compared the expression of PPTRH 178-199, PPTRH mRNA, and PC1 and PC2 mRNAs in the Wistar-Kyoto (WKY) and Wistar strains of rat. WKY rats have been shown to possess neuroendocrine abnormalities (HPA hyper-activity) and hyper-emotional behavioral characteristics. Immunohistochemical analysis of PPTRH 178-199 demonstrated significant strain differences in the paraventricular nucleus (PVN) of the hypothalamus and the parastrial nucleus (PSN). WKY rats had significantly greater numbers of immunoreactive (IR) cell body profiles (P<0.0005) than Wistar rats in the PVN and a significantly lower fiber density (P<0.002) in the PSN. Levels of PPTRH, PC1, and PC2 mRNA were not different between strains in any brain region examined. These data suggest that altered levels of PPTRH 178-199 in WKY rats could cause, at least in part, the hyper-activity of the HPA axis and the hyper-emotional behavioral characteristics seen in this rat strain. Such data fit with the hypothesis that PPTRH 178-199 is involved in the regulation of the HPA axis and behavior" http://www.ncbi.nlm.nih.gov/pubmed/11549391 0 1307 H. Nagayama 1996 Chronic administration of imipramine and lithium changes the phase-angle relationship between the activity and core body temperature circadian rhythms in rats Chronobiol.Int. 13 4 251-259 "Evidence suggests that there is an association between the pathophysiology of depression and a disturbance of circadian rhythms. Accordingly, attention has focused on the possible effects of antidepressants on circadian rhythms. In the present study, we examined the effects of chronic administration of two clinically effective antidepressant agents, imipramine and lithium, on several circadian rhythms in the rat. Activity, core body temperature, and drinking rhythms were assessed in constant darkness (DD) and light-dark (LD) conditions. In DD, lithium significantly lengthened the circadian period of the activity, temperature, and drinking rhythms, while imipramine had no effect. In LD, both drugs significantly delayed the phase of the activity rhythm, but did not change that of the other two rhythms. As a result, the phase-angle differences between the activity and temperature rhythms significantly increased. Neither lithium nor imipramine produced any effect on the resynchronization of these rhythms after an 8-h delay in the LD cycle. These results indicate that although both drugs produced different effects on the circadian period of individual rhythms, both caused a relative phase advance of the temperature rhythm as compared to the activity rhythm, and this effect may be related to the similarity in their antidepressant effects" http://www.ncbi.nlm.nih.gov/pubmed/8889249 0 1308 "T. Maekawa, S. Kim, D. Nakai, C. Makino, T. Takagi, H. Ogura, K. Yamada, B. Chatton and S. Ishii" 2010 Social isolation stress induces ATF-7 phosphorylation and impairs silencing of the 5-HT 5B receptor gene EMBO J. 29 1 196-208 "Many symptoms induced by isolation rearing of rodents may be relevant to neuropsychiatric disorders, including depression. However, identities of transcription factors that regulate gene expression in response to chronic social isolation stress remain elusive. The transcription factor ATF-7 is structurally related to ATF-2, which is activated by various stresses, including inflammatory cytokines. Here, we report that Atf-7-deficient mice exhibit abnormal behaviours and increased 5-HT receptor 5B (Htr5b) mRNA levels in the dorsal raphe nuclei. ATF-7 silences the transcription of Htr5B by directly binding to its 5'-regulatory region, and mediates histone H3-K9 trimethylation via interaction with the ESET histone methyltransferase. Isolation-reared wild-type (WT) mice exhibit abnormal behaviours that resemble those of Atf-7-deficient mice. Upon social isolation stress, ATF-7 in the dorsal raphe nucleus is phosphorylated via p38 and is released from the Htr5b promoter, leading to the upregulation of Htr5b. Thus, ATF-7 may have a critical role in gene expression induced by social isolation stress" http://www.ncbi.nlm.nih.gov/pubmed/19893493 1 1309 "Y.-C. Si, J.-N. Sun and C.-E. Xie" 2004 Effects of hypericin on behavior and brain 5-hydroxytryptamine and noradrenalin expression in rats with depression "Chinese Journal of Clinical Rehabilitation.8 (13) ()(pp 2543-2545), 2004.Date of Publication: May 2004." 13 2543-2545 "Aim: To study the effects of hypericin on the behavior and expressions of 5-hydroxytryptamine(5-HT), noradrenaline(NA) in the brain of rats with depression. Methods: Totally 72 male Wistar rats were selected in this experiment to establish models of chronic stress-induced depression. Open-field test, step-down avoidance test and immunohistochemistry staining were employed to study the effects of the extract of the fruit of Hypericum perforatum (EFHP) on praxiology and cerebral pathology in the rat models. Results: In open-field test, the number of crossing and rearing was significantly lower in chronic stress-induced depression rats than the control rats (P < 0.01). At the doses of 150.0 and 75.0 mg/kg, EFHP increased the number of crossing and rearing (P < 0.05 and P < 0.01, respectively) in comparison with the model group; at the dose of 37.5 mg/kg, EFHP increased the number of crossings to 27 +/- 4, significantly higher than that in the model group (18 +/- 5) (P < 0.05). At the doses of 150 and 75 mg/kg, EFHP significantly decreased the staying time of erroneous reaction in step-down avoidance test to 18 +/- 30 and 23 +/- 43 respectively as compared with the model group (116 +/- 129) (P < 0.05); EFHP also increased the expression of 5-HT, NA in rat brain in comparison with the model group (P < 0.01). Conclusion: Hypericin improves depression in rats through increasing the expressions of NA and 5-HT" 1 1310 "M. Saito, T. Mitsui and T. Mizuno" 2000 [Genistein represses the induction of prostatic buds by testosterone] J.Soc.Biol. 194 2 95-97 "Genistein, a phytoestrogen and a kind of endocrine disrupters, inhibits tyrosine-specific protein kinase activity of the epidermal growth factor (EGF) receptor. It is also effective both in the suppression of the prostatic cell proliferation and the prostate carcinogenesis. We have recently demonstrated that several growth factors, like EGF, transforming growth factor-alpha (TGF-alpha), or keratinocyte growth factor (KGF), can induce prostatic bud formation in the absence of androgen. The present study was performed to investigate whether genistein can suppress testosterone-induced prostatic bud formation. Urogenital sinuses of 16.5-day male rat fetuses were cultured organotypically for 5 days in a serum-free medium containing 10 or 100 ng/ml genistein and 50 ng/ml testosterone. The number and total volume of prostatic buds were analyzed by laser scanning microscopy and computerized. We found that genistein inhibits significantly testosterone-induced prostatic bud formation. In the presence of genistein, cell proliferation of the sinus epithelium was suppressed and the number of prostatic buds and total volume of the buds were reduced as compared with those in the sinuses cultured with testosterone alone. Genistein did not appear to cause necrosis of the sinus. These results support our hypothesis that growth factors like EGF secreted from the sinus mesenchyme activated by testosterone are involved in the induction and stimulation of growth of the prostatic buds" http://www.ncbi.nlm.nih.gov/pubmed/11098434 0 1311 C. B. Higgins and G. K. Feld 1976 Direct chronotropic and dromotropic actions of contrast media: ineffectiveness of atropine in the prevention of bradyarrhythmias and conduction disturbances Radiology 121 1 205-209 "Methyl glucamine sodium diatrizoate (Renografin 76) was directly infused into the isolated arteries to the sino-atrial and atrioventricular nodes of anesthetized dogs, causing a dose-related inhibition of sino-atrial nodal automaticity and atrioventricular nodal conductivity; these effects were not attenuated by autonomic blockade or cervical vagotomy. The important negative chronotropic and dramatropic effects of contrast media used for coronary angiography are direct actions and cannot be effectively blocked by premedication with atropine" http://www.ncbi.nlm.nih.gov/pubmed/959540 0 1312 "A. D. Nozdrachev, A. V. Gnetov, I. Kachalov, L. D. Fedorova and G. I. Sanin" 1976 [Effect of methylene blue on transmission of excitation at peripheral autonomic synapses] Fiziol.Zh.SSSR Im I.M.Sechenova 62 9 1300-1309 http://www.ncbi.nlm.nih.gov/pubmed/188691 0 1313 "D. Lawson, M. J. Frazer and C. Lynch, III" 1990 Nitrous oxide effects on isolated myocardium: a reexamination in vitro Anesthesiology 73 5 930-943 "This study examined in vitro myocardial depression by 50% N2O. Maximal isometric contractions of guinea pig right ventricular papillary muscles were studied in Tyrode's superfusate at 37 degrees C within a gas-tight chamber. Superfusate (pH at 7.45) and chamber were equilibrated with 95% O2/5% CO2. After control measurements in 95% O2, muscles were studied with 50% N2 and 50% N2O (45% O2/5% CO2) in random order with an intervening and final recovery in oxygen. Muscles were field stimulated after rest and at 0.1-3 Hz. At 37 degrees C, muscle performance deteriorated over time with exposure to reduced oxygen; therefore, identical experiments were performed at 30 degrees C in which no systematic deterioration occurred. Peak tension and maximum rate of tension development (dT/dtmax) were compared for each stimulation rate. At both temperatures, N2O caused a 10-15% depression of contractility as compared to that observed with nitrogen. In a second protocol, muscles were studied at 37 degrees C in 26 mM K+ Tyrode's solution with 0.10 microM isoproterenol to study enhanced contractions mediated by slow (Ca2(+)-channel-dependent) action potentials. Rested-state double stimulations were used (stimulus interval, 250-600 ms) resulting in a first rested-state contraction followed by a second contraction (C2) with rapid initial tension development. The muscles were exposed to nitrogen and N2O as in the force-frequency experiments and did not deteriorate over time. In this setting, N2O also caused a 10-15% depression of C2 contractility as compared with nitrogen. Another set of muscles was studied in 95% O2 to which 0.5% halothane or 1% isoflurane was added before exposure to nitrogen and N2O. The combined depressant action of N2O with either halothane or isoflurane did not differ from that predicted by the simple addition of independent effects; there was no evidence of synergism. Furthermore, N2O (50%) alone depressed dT/dtmax in a manner similar to that of 0.5% halothane and different from that of 1.0% isoflurane. Experiments conducted in iso-osmolar 40 mM Na+ Tyrode's solution, in which activator Ca2+ arose from the sarcoplasmic reticulum Ca2+, also showed greater depression by N2O than nitrogen. N2O (50%) is a myocardial depressant independent of concurrent hypoxic effects with a pattern and magnitude of contractile depression similar to that of 0.5% halothane" http://www.ncbi.nlm.nih.gov/pubmed/2240682 0 1314 "L. M. Antunes, J. V. Roughan and P. A. Flecknell" 2003 Excitatory effects of fentanyl upon the rat electroencephalogram and auditory-evoked potential responses during anaesthesia Eur.J.Anaesthesiol. 20 10 800-808 "BACKGROUND AND OBJECTIVE: Previous studies have shown existence of inconsistent data concerning the use of auditory-evoked potential (AEP) and electroencephalogram (EEG) changes to measure the depth of anaesthesia in regimens involving the use of opioids. The present studies characterize the effects of fentanyl on those responses in rats. METHODS: The effects of a bolus of fentanyl (6-10 microg kg(-1) intravenously) alone or following naloxone (100 microg kg(-1) intravenously) were examined using brain responses in rats during light anaesthesia with either propofol (20-30 mg kg(-1) h(-1)) or isoflurane (0.8%). Electrophysiological data were recorded using silver ball electrodes. The rats' tracheas were intubated and a femoral artery cannula was inserted to monitor blood pressure. Body temperature, respiratory and pulse rate, and pedal withdrawal data were also collected. Parameters measured before and following administration of naloxone and fentanyl or of fentanyl alone were compared using repeated-measures ANOVA. RESULTS: Fentanyl significantly increased the latency of the major peak from the AEP during propofol and isoflurane anaesthesia (F = 13.2 and 13.5, respectively; P < 0.05) and the amplitude differential between two waveform complexes, and the second differential index (F = 28.3 and 57.2, respectively; P < 0.01). The spectral edge frequency and median frequency from the EEG tended to increase. These effects were abolished by the prior administration of naloxone. CONCLUSIONS: These excitatory effects were inconsistent with the classical concept of brain activity depression indicating a deepening of anaesthesia" http://www.ncbi.nlm.nih.gov/pubmed/14580049 0 1315 "V. DiTizio, C. Karlgard, L. Lilge, A. E. Khoury, M. W. Mittelman and F. DiCosmo" 2000 Localized drug delivery using crosslinked gelatin gels containing liposomes: factors influencing liposome stability and drug release J.Biomed.Mater.Res. 51 1 96-106 "We describe a drug-delivery vehicle that combines the sustained release properties of liposomes with the structural advantages of crosslinked gelatin gels that can be implanted directly or coated onto medical devices. Liposome inclusion in gelatin gels does not compromise thermal stability nor does it interfere with the resiliency of gels to tensile force. However, electron spin resonance analysis of sequestered DPPC liposomes revealed a slight depression (ca. 1.0 degrees C) of the gel-to-fluid phase transition relative to liposomes in suspension. The level of liposome release from gels was determined by liposome concentration, liposome size, and the presence of poly(ethylene oxide) chains in the gel matrix or in the liposome membrane. Both neutral and charged liposomes displayed relatively high affinities for poly(ethylene glycol)gelatin gels, with only 10-15% release of initially sequestered liposomes while liposomes in which poly(ethylene glycol) was included within the membrane were not as well retained (approximately 65% release). The in vitro efflux of ciprofloxacin from liposomal gels immersed in serum was nearly complete after 24 h compared to 38% release of liposomal chlorhexidine after 6 days. The serum-induced destabilization of liposomal ciprofloxacin depended on the accessibility of serum components to gels as partly immersed gels retained approximately 50% of their load of drug after 24 h. In vivo experiments using a catheterized rabbit model of urinary tract infection revealed the absence of viable Escherichia coli on coated catheter surfaces in seven out of nine cases while all untreated catheter surfaces examined (n = 7) were contaminated" http://www.ncbi.nlm.nih.gov/pubmed/10813750 0 1316 E. Garcia and J. Sotelo 1993 Electroconvulsive shock does not modify striatal contents of dopamine in MPTP-treated mice "Neurochemical Research.18 (5) ()(pp 613-616), 1993.Date of Publication: 1993." 5 613-616 "It has been suggested that the therapeutic response to electroconvulsive therapy in depressed patients could be mediated by functional changes in the dopaminergic pathways; a favorable response to electroconvulsive therapy was also observed recently in patients with Parkinson's disease. To study a possible interference of electroconvulsive shock in the course of MPTP- induced parkinsonism in rodents, we measured the striatal content of dopamine in MPTP-treated mice that received electroconvulsive shock at various intervals in the course of MPTP neurotoxicity. Our results showed no immediate or delayed differences in striatal dopamine content of animals that received MPTP and electroconvulsive shock when compared with animals that received only MPTP, thus suggesting that the strong biological effects of MPTP and electroconvulsive shock on the brain may follow different biochemical mechanisms" 0 1317 "N. Hatakeyama, H. Kubo, N. Shibuya, M. Yamazaki, Y. Ito and Y. Momose" 1993 [Effect of sevoflurane on contraction and membrane potentials in canine right ventricular myocytes] Masui 42 11 1653-1658 "The effects of sevoflurane on contraction and membrane potentials were studied in isolated canine ventricular muscle strips. Sevoflurane depressed electrically-induced contraction in a dose-dependent manner. The inhibitory effect was more pronounced in high-K+ Tyrode solution than in normal Tyrode solution suggesting that sevoflurane inhibits transmembrane Ca2+ influx. In electrophysiological studies, sevoflurane depressed both overshoot and the plateau phase of action potentials. Resting membrane potential was not affected by sevoflurane. We conclude that the depression of myocardial contractility by sevoflurane may be due to block of transmembrane calcium influx" http://www.ncbi.nlm.nih.gov/pubmed/8254876 0 1318 "A. P. Degnan, G. O. Tora, Y. Han, R. Rajamani, R. Bertekap, R. Krause, C. D. Davis, J. Hu, D. Morgan, S. J. Taylor, K. Krause, Y. W. Li, G. Mattson, M. A. Cunningham, M. T. Taber, N. J. Lodge, J. J. Bronson, K. W. Gillman and J. E. Macor" 2015 "Biaryls as potent, tunable dual neurokinin 1 receptor antagonists and serotonin transporter inhibitors" Bioorg.Med.Chem.Lett. 25 15 3039-3043 "Depression is a serious illness that affects millions of patients. Current treatments are associated with a number of undesirable side effects. Neurokinin 1 receptor (NK1R) antagonists have recently been shown to potentiate the antidepressant effects of serotonin-selective reuptake inhibitors (SSRIs) in a number of animal models. Herein we describe the optimization of a biaryl chemotype to provide a series of potent dual NK1R antagonists/serotonin transporter (SERT) inhibitors. Through the choice of appropriate substituents, the SERT/NK1R ratio could be tuned to afford a range of target selectivity profiles. This effort culminated in the identification of an analog that demonstrated oral bioavailability, favorable brain uptake, and efficacy in the gerbil foot tap model. Ex vivo occupancy studies with compound 58 demonstrated the ability to maintain NK1 receptor saturation (>88% occupancy) while titrating the desired level of SERT occupancy (11-84%) via dose selection" http://www.ncbi.nlm.nih.gov/pubmed/26048800 1 1319 J. N. Johannessen and S. P. Markey 1984 Assessment of the opiate properties of two constituents of a toxic illicit drug mixture Drug Alcohol Depend. 13 4 367-374 "The intravenous use of an illicit synthetic drug preparation has caused permanent parkinsonism in a number of addicts. Chemical analysis has revealed the ingredients to be two related compounds 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenyl-4-propionoxypiperidine (MPPP). The opiate properties of these two compounds have been assessed using in vitro receptor binding techniques as well as behavioral tests indicative of opiate action, including analgesia, catatonia, respiratory depression and the loss of righting and corneal reflexes. All opiate activity was found to reside with MPPP, which proved to be a potent mu-type agonist. It is concluded that the opiate properties of MPPP alone explain repeated abuse of MPTP/MPPP mixtures by heroin addicts" http://www.ncbi.nlm.nih.gov/pubmed/6148225 0 1320 "A. Jindal, R. Mahesh, B. Gautam, S. Bhatt and D. Pandey" 2012 "Antidepressant-like effect of etazolate, a cyclic nucleotide phosphodiesterase 4 inhibitor - An approach using rodent behavioral antidepressant tests battery" "European Journal of Pharmacology.689 (1-3) ()(pp 125-131), 2012.Date of Publication: 15 Aug 2012." 01-Mar 125-131 "Etazolate, a pyrazolopyridine class derivative is selective inhibitor of type 4 phosphodiesterase (PDE4), an enzyme catalyzes the hydrolysis of cyclic nucleotide viz. cAMP & regulates cAMP signal transduction. Enhancing cAMP signal transduction by inhibition of PDE4 is known to be beneficial in depression disorders. Thus, the present study was designed to investigate thoroughly the antidepressant potential of etazolate using rodent behavioral models of depression. Acute treatment of etazolate (0.25-1 mg/kg, i.p.) exhibited antidepressant-like effects in forced swim test (FST) & tail suspension test (TST) in mice without influencing the baseline locomotion in actophotometer test. Interaction studies of etazolate sub-effective dose (0.12 mg/kg, i.p.), were carried out with sub-effective dose of conventional antidepressants like fluoxetine (5 mg/kg, i.p.), venlafaxine (4 mg/kg, i.p.) & desipramine (5 mg/kg, i.p.) in FST. Etazolate at sub-effective dose produced synergistic antidepressant-like effect with conventional antidepressants in the mouse FST. In addition, combined treatment of etazolate & conventional antidepressants had no significant effect on baseline locomotion. Moreover, etazolate (0.5 and 1 mg/kg, i.p.) increased head twitch scores in mice & antagonized the reserpine-induced hypothermia in rats. Chronic treatment (14 days) with etazolate (0.5 and 1 mg/kg, p.o.) & fluoxetine (10 mg/kg, p.o.) significantly reversed the behavioral anomalies induced by bilateral olfactory bulbectomy in rats in modified open field exploration. In conclusion, taken together, our results suggested that etazolate exhibited antidepressant-like activity in acute & chronic rodent models of depression & deserves as a therapeutic tool that could help the conventional pharmacotherapy of depression. © 2012 Elsevier B.V. All rights reserved" DO - http://dx.doi.org/10.1016/j.ejphar.2012.05.051 1 1321 "O. Ballot, S. Laouafa, E. Elliot-Portal, R. Tam, N. Voituron, V. Joseph and J. Soliz" 2015 The central chemosensitivity is not altered by cerebral erythropoietin Neurosci.Lett. 609 63-68 "The stimulation of central chemoreceptors by CO2 is considered essential for breathing. The supporting evidence include the fact that central apnea in neonates correlates with immaturity of the CO2-sensing mechanism, and that congenital central hypoventilation syndrome (CCHS) is characterized by the absence of a ventilatory response to elevated PCO2. We reported previously that cerebral erythropoietin (Epo) is a potent respiratory stimulant upon normoxia and hypoxia. The injection of soluble Epo receptor (sEpoR; the natural EpoR competitor to bind Epo) via the cisterna magna (ICI: intra-cisternal injection) decreases basal ventilation in adult and newborn mice. Moreover, sEpoR induces respiratory depression in adult and newborn mice exposed to hypoxia. In this study we tested the hypothesis that endogenous brain Epo also modulates the respiratory stimulation induced by the activation of central CO2 chemoreceptors. Adult and newborn male and female mice received an injection of sEpoR or vehicle via the cisterna magna. Twenty-four hours later basal minute ventilation and the ventilatory response to hypercapnia (5% CO2) were evaluated by plethysmography. Our results did not show a difference in the hypercapnic response between sEpoR and vehicle-injected male or female mice at postnatal or adult ages. We concluded that endogenous brain Epo does not contribute to modulating the PCO2-mediated central activation of breathing" http://www.ncbi.nlm.nih.gov/pubmed/26472708 0 1322 "M. Nagano, S. Mochizuki, T. Kogure, T. Kosuga and N. Saito" 1975 Oxidative phosphorylation in mitochondria isolated from stressed rat heart Recent Adv.Stud.Cardiac.Struct.Metab 8 293-300 "Oxidative phosphorylation was measured polarographically in mitochondria isolated from rat heart. With regard to ADP/O ratio and respiratory control index, no differences were found among mitochondria isolated from normal, acutely (increased pneumatic resistance of the heart-lung preparation) and chronicly (renal hypertension) stressed heart. However, the acute stressed heart induced by strangulating the outflow tract of the heart-lung preparation showed clear depression and tendency to depression, respectively, in the level of ADP/O ratio and respiratory control index in mitochondria. The results indicate that there is no change in the oxidative phosphorylating mechanism of the myocardial mitochondria of nonfailed heart despite acute or chronic pressure loadings; however, there is an uncoupling of oxidative phosphorylation in mitochondria of the failed heart after acute strangulation of the outflow tract" http://www.ncbi.nlm.nih.gov/pubmed/1215639 0 1323 I. Toida 1974 Effects of cord factor on microsomal enzymes Am.Rev.Respir.Dis. 110 5 641-646 http://www.ncbi.nlm.nih.gov/pubmed/4372916 0 1324 S. Skrede 1968 The mechanism of disulphide reduction by mitochondria Biochem.J. 108 4 693-699 "1. Cystamine was reduced to the corresponding thiol by rat liver mitochondria, even in the presence of rotenone or antimycin A. 2. The reduction of disulphides was stimulated by the accumulation of NADH or by the addition of NADH to osmotically ;shocked' mitochondria. 3. Energy made available by oxidative phosphorylation was not essential for the reduction of disulphides. 4. Cystamine was not reduced during the oxidation of NADH by ultrasonically treated particles, which had lost their capacity for oxidation of alpha-oxo acids. 5. In intact mitochondria, arsenite and other inhibitors of vicinal dithiols caused a decrease in the capacity for reduction of disulphides concomitantly with an inhibition of the oxidation of alpha-oxo acids. 6. Isolated lipoamide dehydrogenase reduced cystamine at the expense of NADH, provided that lipoic acid was also present. 7. It is concluded that in mitochondria the reduction of cystamine and related disulphides is probably brought about by interaction with reduced lipoic acid, generated by the alpha-oxo acid dehydrogenase complexes during the oxidation of alpha-oxo acids or by reaction of lipoamide dehydrogenase with NADH" http://www.ncbi.nlm.nih.gov/pubmed/4299131 0 1325 "J. E. Berk, M. M. Nothman and A. D. Callow" 1971 Pancreatic origin of normal serum amylase Gastroenterology 60 5 988-989 http://www.ncbi.nlm.nih.gov/pubmed/5581339 0 1326 "K. Tun, A. Savas, M. F. Sargon, I. Solaroglu and Y. Kanpolat" 2006 The histopathological and electron-microscopic examination of the stereotactic pulsed radiofrequency and conventional radiofrequency thermocoagulation lesions in rat brain Neurol.Res. 28 8 841-844 "OBJECTIVE: Neurodestructive procedures have been used for treating intractable pain for a long time. Pulsed radiofrequency (RF) is a newly defined energy type. Pulsed RF may be used in the treatment of patients with some pain syndromes in whom the pain could not be controlled by the alternative techniques. The objective of the present study was to examine the histological and electron microscopical changes in rat brain after pulsed RF application. METHODS: Forty-five male rats were used in these experiments. Lesions were applied stereotactically to the target areas of the rat brains. Two different RF energy type were used as representative models of pulsed-RF and conventional-RF procedures. The rats were kept alive for 21 days and then killed. The effect of pulsed RF lesions on cerebral tissue ultrastructure was studied. RESULTS: In the pulsed RF group, intracytoplasmic edema, clarity of the mitochondrial cristas and opening in the cell membrane pores were observed on the electron microscopic examination. In the conventional RF group, these findings were more prominent. In the pulsed RF group, the ratio of the effected neurons was 5.5% on light microscopic examination. In the conventional RF group, the ratio of the effected neurons was 14.26% and central necrosis was observed additionally. DISCUSSION: Pulsed RF caused ultrastructural changes in the neurons. The pulsed RF may possibly cause a depression on the cell membrane potential by opening the cell membrane pores and resulting in the ion entrance into the cell cytoplasm and intracytoplasmic edema. However, it seems that all these changes were reversible" http://www.ncbi.nlm.nih.gov/pubmed/17288742 0 1327 "G. J. Kurtzman, L. Platanias, L. Lustig, N. Frickhofen and N. S. Young" 1989 Feline parvovirus propagates in cat bone marrow cultures and inhibits hematopoietic colony formation in vitro Blood 74 1 71-81 "Feline parvovirus (FPV) causes leukopenia in naturally infected cats. We investigated the mechanism of hematopoietic depression by this virus in feline bone marrow cultured in vitro. In suspension cultures we demonstrated FPV propagation and replication using DNA molecular hybridization. Viral RNA and DNA were observed by in situ hybridization in about 10% of marrow cells at day 3. Granulocytes and their precursors were virtually absent from infected cultures after six days. Infected cells showed viral capsid protein predominantly in nuclei by immunofluorescence. In clonal assays, FPV most efficiently inhibited hematopoietic colony formation by myeloid progenitor cells (CFU-GM), but erythroid colony formation (BFU-E and CFU-E-derived) was also depressed in the presence of virus. Inhibition of colony formation could be abrogated by physical inactivation of the virus or preincubation with specific neutralizing antibodies. Recombinant human colony stimulating factors GM-CSF and G-CSF supported feline myelopoiesis in progenitor assays, and FPV completely inhibited factor dependent colony formation" http://www.ncbi.nlm.nih.gov/pubmed/2546625 0 1328 "R. V. Perez, J. Johnson, N. E. Hubbard, K. Erickson, M. Morgan, S. Kim, S. M. Rudich, S. Katznelson and J. B. German" 1998 Selective targeting of Kupffer cells with liposomal butyrate augments portal venous transfusion-induced immunosuppression Transplantation 65 10 1294-1298 "BACKGROUND: Enhanced Kupffer cell production of the immunosuppressive arachidonic acid metabolite prostaglandin E2 (PGE2) has been shown to be a mechanism of the immunosuppressive effect of portal venous transfusions (PVT). Butyrate, a four-carbon short-chain fatty acid, has received increased attention because of its ability to enhance gene transcription. This study tested the hypothesis that the intrahepatic delivery of butyrate enhances Kupffer cell PGE2 production and thus augments the immunosuppressive effect of PVT. METHODS: Butyrate was incorporated into liposomes and administered intravenously to Lewis rats. Control rats were administered liposomes without butyrate. Twenty-four hours after liposome injection, rats were administered a PVT of 1 ml of Wistar-Furth blood. Kupffer cells were isolated, and PGE2 and tumor necrosis factor-alpha levels were measured in the culture medium after 24 hr. Additionally, Kupffer cells from butyrate-treated and control animals were added to one-way mixed lymphocyte reaction cultures. RESULTS: Intrahepatic delivery of butyrate via liposomes increased Kupffer cell PGE2 (3800+/-1220 vs. 1010+/-119 pg/ml, P<0.05) and decreased tumor necrosis factor-alpha (1670+/-81 vs. 3360+/-415 pg/ml, P<0.01) production as compared with controls. Butyrate also augmented the Kupffer cell-mediated immunosuppression as demonstrated by significant depression of the mixed lymphocyte reaction (690+/-119 vs. 3850+/-148 cpm, P<0.01). CONCLUSION: The results support the hypothesis that intrahepatic delivery of butyrate enhances Kupffer cell PGE2 production, and specific targeting of Kupffer cells with liposomes containing immunomodulating agents such as butyrate may be a useful means of augmenting immunosuppression protocols in organ transplantation" http://www.ncbi.nlm.nih.gov/pubmed/9625008 0 1329 "D. Qin, J. Rizak, X. Chu, Z. Li, S. Yang, L. Lu, L. Yang, Q. Yang, B. Yang, L. Pan, Y. Yin, L. Chen, X. Feng and X. Hu" 2015 A spontaneous depressive pattern in adult female rhesus macaques Sci.Rep. 5 11267 "Non-human primates offer unique opportunities to study the development of depression rooted in behavioral and physiological abnormalities. This study observed adult female rhesus macaques within social hierarchies and aimed to characterize the physiological and brain abnormalities accompanying depressive-like behavior. The behaviors of 31 female rhesus macaques from 14 different breeding groups were video recorded, and the footage was analyzed using the focal animal technique. There were 13 monkeys who never displayed huddling behavior (non-huddlers). The remaining 18 monkeys were divided into two groups according the mean time spent in the huddle posture. Four monkeys were designated as high huddlers, whereas the other 14 monkeys were low huddlers. An inverse relationship was discovered between social rank and depression. High huddlers spent more time engaging in physical contact and in close proximity to other monkeys, as well as less time spontaneously and reactively locomoting, than low huddlers and/or non-huddlers. Cortisol levels measured from the hair were elevated significantly in high huddlers compared with low huddlers and non-huddlers, and the measured cortisol levels were specifically higher in high huddlers than subordinate or dominant control monkeys. Regional cerebral blood flow data revealed significant and widespread decreases in high huddlers compared with non-huddlers" http://www.ncbi.nlm.nih.gov/pubmed/26059851 0 1330 "C. J. Fowler, K. F. Tipton, A. V. MacKay and M. B. Youdim" 1982 Human platelet monoamine oxidase--a useful enzyme in the study of psychiatric disorders? Neuroscience 7 7 1577-1594 http://www.ncbi.nlm.nih.gov/pubmed/6956813 0 1331 "Z. Y. Sui, H. J. Chae, G. B. Huang, T. Zhao, M. S. Shrestha and Y. C. Chung" 2012 Effects of chronic mild stress in female bax inhibitor-1-gene knockout mice Clin.Psychopharmacol.Neurosci. 10 3 155-162 "OBJECTIVE: The anti-apoptotic protein Bax inhibitor-1 (BI-1) is a regulator of apoptosis linked to endoplasmic reticulum (ER) stress, and BI-1(-/-) mice exhibit increased sensitivity to tissue damage. The purpose of this study was to investigate the role of BI-1 in the pathogenesis of chronic mild stress (CMS)-induced depression-like behaviors in BI-1(-/-) mice. METHODS: We delivered CMS for 2 or 6 weeks in BI-1-knockout and wild-type mice. Control groups of BI-1-knockout and wild-type mice were left undisturbed. The measured parameters were sucrose consumption at weeks 1, 2, 3, 4, 5, and 6, spontaneous locomotion, and a forced swimming test (FST) at weeks 2 and 6. RESULTS: Significant decreases in sucrose consumption and increases in immobility time in the FST were observed in both stress groups compared with the non-stress groups. Interestingly, at week 2, but not at week 6, BI-1(-/-)-stress mice showed less sucrose intake and greater immobility time than did BI-1(+/+)-stress mice. CONCLUSION: These results suggest that BI-1 may play role in protecting against the depressogenic effects of CMS in the short term, but not in the long term. Further study is required to deepen understanding of the role of BI-1 in protecting against depression" http://www.ncbi.nlm.nih.gov/pubmed/23430888 1 1332 "K. H. Tan, D. J. Meyer, J. Belin and B. Ketterer" 1984 Inhibition of microsomal lipid peroxidation by glutathione and glutathione transferases B and AA. Role of endogenous phospholipase A2 Biochem.J. 220 1 243-252 "Lipid peroxidation in vitro in rat liver microsomes (microsomal fractions) initiated by ADP-Fe3+ and NADPH was inhibited by the rat liver soluble supernatant fraction. When this fraction was subjected to frontal-elution chromatography, most, if not all, of its inhibitory activity could be accounted for by the combined effects of two fractions, one containing Se-dependent glutathione (GSH) peroxidase activity and the other the GSH transferases. In the latter fraction, GSH transferases B and AA, but not GSH transferases A and C, possessed inhibitory activity. GSH transferase B replaced the soluble supernatant fraction as an effective inhibitor of lipid peroxidation in vitro. If the microsomes were pretreated with the phospholipase A2 inhibitor p-bromophenacyl bromide, neither the soluble supernatant fraction nor GSH transferase B inhibited lipid peroxidation in vitro. Similarly, if all microsomal enzymes were heat-inactivated and lipid peroxidation was initiated with FeCl3/sodium ascorbate neither the soluble supernatant fraction nor GSH transferase B caused inhibition, but in both cases inhibition could be restored by the addition of porcine pancreatic phospholipase A2 to the incubation. It is concluded that the inhibition of microsomal lipid peroxidation in vitro requires the consecutive action of phospholipase A2, which releases fatty acyl hydroperoxides from peroxidized phospholipids, and GSH peroxidases, which reduce them. The GSH peroxidases involved are the Se-dependent GSH peroxidase and the Se-independent GSH peroxidases GSH transferases B and AA" http://www.ncbi.nlm.nih.gov/pubmed/6743263 0 1333 A. Goldberg and F. B. McGillion 1973 Proceedings: Central uptake and cardiovascular effects of delta-aminolaevulinic acid Br.J.Pharmacol. 49 1 178P http://www.ncbi.nlm.nih.gov/pubmed/4787551 0 1334 "R. Cardinal, J. L. Ardell, B. Linderoth, M. Vermeulen, R. D. Foreman and J. A. Armour" 2004 Spinal cord activation differentially modulates ischaemic electrical responses to different stressors in canine ventricles Auton.Neurosci. 111 1 37-47 "Spinal cord stimulation (SCS) represents an acceptable treatment modality for patients with chronic angina pectoris refractory to standard therapy, but its mechanism of action remains unclear. To develop an experimental paradigm to study this issue, ameroid (AM) constrictors were implanted around the left circumflex coronary artery (LCx) in canines. Six weeks later, unipolar electrograms were recorded from 191 sites in the LCx territory in the open-chest, anesthetized state under basal pacing at 150 beats/min. We investigated the effect of SCS on ST segment displacements induced in the collateral-dependent myocardium in response to two stressors: (i) transient bouts of rapid ventricular pacing (TRP: 240/min for 1 min) and (ii) angiotensin II administered to right atrial neurons via their coronary artery blood supply. ST segment responses to TRP consisted of ST segment elevation in central areas of the LCx territory and ST depression at more peripheral areas. Such responses were unchanged when TRP was applied under SCS. Shortening of repolarization intervals in the metabolically compromised myocardium in response to TRP was also unaffected by SCS. In contrast, ST segment responses to intracoronary angiotensin II, which consisted of increased ST elevation, were attenuated by SCS in 6/8 preparations. The modulator effects of SCS were greatest at sites at which the greatest responses to angiotensin II occurred in the absence of SCS. These data indicate that spinal cord stimulation may attenuate the deleterious effects that stressors exert on the myocardium with reduced coronary reserve, particularly stressors associated with chemical activation of the intrinsic cardiac nervous system" http://www.ncbi.nlm.nih.gov/pubmed/15109937 0 1335 S. J. Legan and F. J. Karsch 1983 Importance of retinal photoreceptors to the photoperiodic control of seasonal breeding in the ewe Biol.Reprod. 29 2 316-325 "Two experiments were performed to determine whether the eyes are necessary for photoperiodic control of reproduction in ewes. In the first, intact and estradiol-treated ovariectomized (OVX + E) ewes were housed in each of 2 photoperiod-controlled rooms with a vasectomized ram and subjected to 90-day alternations between long and short days. Prior to blinding, long days initiated anestrus in intact ewes and a suppression of serum luteinizing hormone (LH) levels in OVX + E ewes; short days caused onset of estrous cycles and an increase in LH levels in the intact and OVX + E ewes, respectively. After 1.5 years of such photoperiodic control, all ewes were blinded by bilateral orbital enucleation. Photoperiodic control was lost following blinding, but circannual alternations between cyclicity and anestrus or high and low LH levels, were maintained in most ewes for the remaining 2.5 years of the study. In one group of OVX + E ewes, serum LH levels remained synchronized to the 90-day shifts in photoperiod for about 1 year after blinding. Once the sighted ram was removed from the room, however, the 90-day rhythm in LH disappeared and a circannual pattern of LH became evident, suggesting that blind ewes may receive photoperiodic information from a sighted ram. This possibility was supported by the results of the second experiment in which 12 additional OVX + E ewes were blinded and exposed to 90 long days and 90 short days in the absence of a sighted ram. In these ewes, serum LH levels were not controlled by the changes in photoperiod. These results are consistent with the following conclusions: 1) the eyes are necessary for perception of photoperiod in the ewe and 2) ewes have an endogenous circannual rhythm of reproduction and/or they can be controlled by other environmental signals in the absence of photoperiodic input. Further, the results lead to the hypothesis that blind ewes can receive photoperiodic information indirectly from a sighted ram" http://www.ncbi.nlm.nih.gov/pubmed/6685536 0 1336 "I. N. Tyurenkov, V. V. Bagmetova, A. V. Shishkina, V. M. Berestovitskay, O. S. Vasileva and E. S. Ostroglaydov" 2010 Gender differences in action fenotropil and its structural analog - Compound RGPU-95 on anxiety-depressive behavior animals. [Bulgarian] Eksperimental'naya i Klinicheskaya Farmakologiya 73 11 2010 "Fenotropil and its structural analog - compound RGPU-95 to a greater extent reduce the severity of anxious and depressive behavior in male rats than in females. On expression of the anxiolytic compound RGPU-95 significantly exceeds Fenotropil, but inferior to Diazepam; of antidepressant activity - comparable to Melipramin and exceeds Fenotropil" 1 1337 "K. H. Baggaley, S. D. Atkin, P. D. English, R. M. Hindley, B. Morgan and J. Green" 1975 Inhibition of cholesterol biosynthesis by 1-alkylimidazoles Biochem.Pharmacol. 24 20 1902-1903 http://www.ncbi.nlm.nih.gov/pubmed/1191407 0 1338 C. J. Limas and S. S. Spier 1980 Effect of antihypertensive therapy on calcium transport by cardiac sarcoplasmic reticulum of SHRs Cardiovasc.Res. 14 12 692-699 "Cardiac hypertrophy develops during the course of blood pressure elevation in spontaneously hypertensive rats (SHRs) and is associated with defective calcium transport by cardiac sarcoplasmic reticulum (SR). AT 20 weeks of age, calcium uptake is reduced in SHRs (42 +/- 1.3 vs 64 +/- 1.6 nmol X mg-1 X min-1 in age-matched normotensive Wistar-Kyoto rats, P less than 0.01), while Ca2+ ATPase activity is enhanced (44 +/- 1.1 vs 35 +/- 0.7 nmol X mg-1 X min-1 in WKYs, P = 0.02); this results in low stoichiometry between calcium uptake and ATP hydrolysis in SHRs. The steady-state levels of the phosphoprotein intermediate [EP] of the transport ATPase are higher in normotensive rats (0.97 +/- 0.1 vs 0.67 +/- 0.08 nmol X mg-1 in SHRs, P less than 0.01) but the Ca2+- and ATP-dependency are similar in the two groups. In order to study the relative roles of hypertension and cardiac hypertrophy in the depression of SHR function, 20-week old SHRs and normotensive rats were treated for 10 weeks with either hydralazine (100 mg X litre-1) or alpha-methyldopa (8 g X litre-1). Both therapeutic regimens resulted in near normalisation of blood pressure of SHRs (hydralazine: 18.1 +/- 0.5 kPa [136 +/- 4 mmHg]; alpha-methyldopa 17.6 +/- kPa [132 +/- 3 mmHg]). Regression of cardiac hypertrophy, however, was seen only in the alpha-methyldopa-treated group, as judged by changes in left ventricular weight, RNA/DNA ratio, and hydroxyproline content. Furthermore, improvement in calcium transport capacity by the SHR, as reflected in higher calcium uptake and stoichiometric ratio between uptake and ATP hydrolysis, was found after alpha-methyldopa, but not hydralazine treatment. These results indicate that reversal of cardiac hypertrophy is required for improvement in calcium transport by cardiac SR after antihypertensive therapy of SHRs" http://www.ncbi.nlm.nih.gov/pubmed/6455196 0 1339 "T. S. Grabow, D. M. Gaumann and T. L. Yaksh" 1989 Electroencephalographic and behavioral assessment of intracerebroventricular somatostatin and a substance P analogue Brain Res. 489 2 223-230 "Chronically implanted rats were injected either with somatostatin (SST) lumbar intrathecally (i.t.) (100 micrograms, n = 5), into the fourth ventricle (3 micrograms, n = 5; 10 micrograms, n = 6; 30 micrograms, n = 5) or into the lateral ventricle (10 micrograms, n = 6; 30 micrograms, n = 6), or received an injection of the substance P (SP) analogue, [D-Pro2, D-Trp7,9]SP into the fourth ventricle (0.3 micrograms, n = 2; 1 micrograms, n = 4; 3 micrograms, n = 4; 10 micrograms, n = 1) or lateral ventricle (3 micrograms, n = 3). A dose-dependent EEG depressant effect was observed following fourth and lateral ventricular injections of SST and of the SP analogue. Acute death due to respiratory depression was observed following i.t. and fourth ventricular injection of SST, and fourth ventricular injection of the SP analogue. Prominent motor behavior (barrel rotation, circling, cranial stereotypies) was observed, without signs of EEG seizure activity, following intraventricular injection of both drugs. Present findings indicate neurotoxic effects of SST and SP analogue at the cerebral level" http://www.ncbi.nlm.nih.gov/pubmed/2472857 0 1340 "J. Florez, J. A. Armijo and G. Delgado" 1972 Characterization of the acute tolerance and dependence to morphine-induced respiratory depression in decerebrate cats Rev.Esp.Fisiol. 28 3 167-173 http://www.ncbi.nlm.nih.gov/pubmed/4679517 0 1341 "O. Nakagawasai, W. Nemoto, H. Onogi, T. Moriya, J. R. Lin, T. Odaira, F. Yaoita, T. Ogawa, K. Ohta, Y. Endo and K. Tan-No" 2016 "BE360, a new selective estrogen receptor modulator, produces antidepressant and antidementia effects through the enhancement of hippocampal cell proliferation in olfactory bulbectomized mice" Behav.Brain Res. 297 315-322 "We have reported that the carborane compound BE360 is a novel selective estrogen receptor modulator and new therapy option for osteoporosis. The aim of this study was to explore the effects and underlying mechanisms of BE360 on depressive-like behavior and memory impairment in the olfactory bulbectomized (OBX) mice, an experimental animal model of depression and dementia. BE360 was administered subcutaneously to mice using a mini-osmotic pump for 2 weeks. Depressive-like behavior was measured as the reduced intake of a sweet solution in the sucrose preference test. Short-term memory was assessed using the Y-maze test. Cell proliferation was assessed by the analysis of cells expressing 5-bromo-2'-deoxyuridine (BrdU) uptake. The expression of phosphorylated cyclic-AMP response element binding protein (pCREB) and brain-derived neurotrophic factor (BDNF) were measured by immunoblot. The depressive-like behavior and memory impairment in OBX mice were improved by the chronic treatment with BE360. Immunohistochemical analysis showed that the number of BrdU-positive cells in the dentate gyrus of the hippocampus significantly decreased in OBX mice whereas they increased after the chronic treatment with BE360. Immunoblotting studies revealed that pCREB and BDNF were significantly increased in the hippocampus of OBX mice treated with BE360. The present study has shown that BE360 has antidepressant and antidementia effects characterized by hippocampal cell proliferation potentially activated via CREB/BDNF signaling pathways. These results indicate that BE360 may have valuable therapeutic potential against depression and neurodegenerative diseases" http://www.ncbi.nlm.nih.gov/pubmed/26497104 1 1342 "W. Wang, X. Hu, Z. Zhao, P. Liu, Y. Hu, J. Zhou, D. Zhou, Z. Wang, D. Guo and H. Guo" 2008 Antidepressant-like effects of liquiritin and isoliquiritin from Glycyrrhiza uralensis in the forced swimming test and tail suspension test in mice "Progress in Neuro-Psychopharmacology and Biological Psychiatry.32 (5) ()(pp 1179-1184), 2008.Date of Publication: 01 Jul 2008." 5 1179-1184 "Two classic animal behavior despair tests-the Forced Swimming Test (FST) and the Tail Suspension Test (TST) were used to evaluate the antidepressant activity of liquiritin and isoliquiritin from Glycyrrhiza uralensis in mice. It was observed that both liquiritin and isoliquiritin at doses of 10, 20 and 40 mg/kg significantly reduced the immobility time in the FST and TST in mice 30 min after treatment. Measurement of locomotor activity indicated that liquiritin and isoliquiritin had no central nervous system (CNS)-stimulating effects. The main monoamine neurotransmitters and their metabolites in mouse brain regions were also simultaneously determined by HPLC-ECD. It was found that these two compounds significantly increased the concentrations of the main neurotransmitters 5-HT and NE in the hippocampus, hypothalamus and cortex. Liquiritin and isoliquiritin also significantly reduced the ratio of 5-HIAA/5-HT in the hippocampus, hypothalamus and cortex, slowing down 5-HT metabolism compared with mice treated with vehicle + stress. In conclusion, liquiritin and isoliquiritin produced significant antidepressant-like effects, and their mechanism of action may be due to increased 5-HT and NE in the mouse hippocampus, hypothalamus and cortex. © 2008" DO - http://dx.doi.org/10.1016/j.pnpbp.2007.12.021 1 1343 E. I. STan and M. P. Chernikov 1979 [Physiological activity of kappa-casein glycomacropeptide] Vopr.Med.Khim. 25 3 348-352 "Low molecular peptide fragment [molecular weight 700-2,000] was isolated from the preparation of k-caseine glycomacropeptide using gel chromotography on Sephadex G-25 superfine. After intravenous administration the peptide inhibited gastric secretion more distinctly as compared with the initial preparation. The data obtained suggest that the inhibitory effect of glycomacropeptide was caused by fragment but not by the whole molecule" http://www.ncbi.nlm.nih.gov/pubmed/452502 0 1344 C. Gao 1991 [An experimental study on the pathophysiology of septic ventilatory depression] Zhonghua Yi.Xue.Za Zhi. 71 5 "249-52, 18" "Ventilatory depression and apnea are well-known early pulmonary responses of sepsis in infants, yet their underlying mechanisms are not understood. To further elucidate the pathophysiology, we induced Escherichia coli septicemia in piglets and studied the sequential changes in intrapulmonary shunt (QS/QT), physiological dead space (VD/VT), minute ventilation (VE), and blood gases for up to 6 hours of lethal sepsis. Lung lymph was also collected and extravascular lung water (EVLW) was measured. Histology confirmed that interstitial edema developed 1 hour after E. coli infusion. These data suggest that high permeability pulmonary edema and hypoxemia following early intrapulmonary shunt increase may be the causes of septic ventilatory depression" http://www.ncbi.nlm.nih.gov/pubmed/1650639 0 1345 "D. J. Kennaway, T. A. Gilmore and R. F. Seamark" 1982 Effects of melatonin implants on the circadian rhythm of plasma melatonin and prolactin in sheep Endocrinology 110 6 2186-2188 "The effects of implanting Silastic capsules containing melatonin on plasma melatonin and prolactin levels were investigated in pinealectomized (Px) and sham-operated sheep (SPx). Prior to implantation, melatonin was found in plasma samples obtained during the night period from SPx sheep (mean value 150 pg/ml), but could not be (less than 25 pg/ml) detected in plasma samples obtained during the day in SPx sheep or in any sample obtained during the night or day period in Px sheep. Following implantation, a constant basal plasma melatonin level of about 165 pg/ml was established in all sheep with a superimposed nighttime rise in SPx animals suggesting no diminution of endogenous melatonin production during the dark period. Following melatonin treatment, there was a marked depression in plasma prolactin levels in both SPx and Px sheep. These results are interpreted to indicate that 1) there is no negative feedback of melatonin upon its own synthesis and release, 2) that there is no circadian change in the rate of metabolism of melatonin and 3) that constant melatonin availability in sheep caused a depression in plasma prolactin levels similar to that found following exposure of animals to a short day" http://www.ncbi.nlm.nih.gov/pubmed/7075555 0 1346 "R. Hausmann, A. Kless and G. Schmalzing" 2014 Key sites for P2X receptor function and multimerization: Overview of mutagenesis studies on a structural basis "Current Medicinal Chemistry.22 (7) ()(pp 799-818), 2014.Date of Publication: 2014." 7 799-818 "P2X receptors constitute a seven-member family (P2X1-7) of extracellular ATP-gated cation channels of widespread expression. Because P2X receptors have been implicated in neurological, inflammatory and cardiovascular diseases, they constitute promising drug targets. Since the first P2X cDNA sequences became available in 1994, numerous site-directed mutagenesis studies have been conducted to disclose key sites of P2X receptor function and oligomerization. The publication of the 3-A crystal structures of the zebrafish P2X4 (zfP2X4) receptor in the homotrimeric apo-closed and ATP-bound open states in 2009 and 2012, respectively, has ushered a new era by allowing for the interpretation of the wealth of molecular data in terms of specific three-dimensional models and by paving the way for designing more-decisive experiments. Thanks to these structures, the last five years have provided invaluable insight into our understanding of the structure and function of the P2X receptor class of ligandgated ion channels. In this review, we provide an overview of mutagenesis studies of the pre- and post-crystal structure eras that identified amino acid residues of key importance for ligand binding, channel gating, ion flow, formation of the pore and the channel gate, and desensitization. In addition, the sites that are involved in the trimerization of P2X receptors are reviewed based on mutagenesis studies and interface contacts that were predicted by the zfP2X4 crystal structures" 0 1347 "W. P. Drake, S. M. LeGednre and M. R. Mardiney, Jr." 1973 Depression of complement activity in tree strains of mice after tumor transfer Int.J.Cancer 11 3 719-724 http://www.ncbi.nlm.nih.gov/pubmed/4151582 0 1348 "F. Orallo, A. A. Fernandez, M. Campos-Toimil and J. M. Calleja" 1995 Study of the in vivo and in vitro cardiovascular effects of (+)-glaucine and N-carbethoxysecoglaucine in rats Br.J.Pharmacol. 114 7 1419-1427 "1. The cardiovascular and vasorelaxant effects of (+)-glaucine and of a semisynthetic derivative (N-carbethoxysecoglaucine) were studied in rats. 2. N-carbethoxysecoglaucine did not modify either systolic arterial pressure or heart rate values in conscious (25 mg kg-1, p.o.) and anaesthetized normotensive rats (5 mg kg-1, i.v.). Furthermore, this compound showed no activity in the experiments carried out on rat isolated aorta [contractility and 45Ca2+ influx assays (5 microM)] and did not modify the rate and force of contraction in rat isolated atria (5 microM). 3. In conscious normotensive rats, oral administration of (+)-glaucine (25 mg kg-1) did not modify either systolic arterial pressure or heart rate. 4. In anaesthetized normotensive rats, (+)-glaucine (5 mg kg-1, i.v.) produced a remarkable fall in mean arterial pressure (MAP) accompanied by a significant decrease in heart rate. In the same preparation, (+)-glaucine (5 mg kg-1, i.v.) did not modify the cardiovascular effects induced by noradrenaline (NA) (5 micrograms kg-1) and 5-hydroxytryptamine (5-HT) (300 micrograms kg-1) but markedly inhibited those induced by nicotine (200 micrograms kg-1). 5. In isolated intact aorta of rat, (+)-glaucine (0.15-5 microM) competitively inhibited the contractions induced by NA (with a pA2 value of 7.14) and non-competitively those induced by 5-HT (in normal Krebs solution) and Ca2+ (in depolarizing Ca(2+)-free high-K+ 50 mM solution), with depression of the maximal response and with pD2 values of 5.56 and 5.26, respectively. 6. In experiments in Ca2+-free medium, (+)-glaucine (3 microM) inhibited the contractions induced by NA and had no effect on either 5-HT- or caffeine-induced contractions.7. Furthermore, in the experiments with radioactive Ca2+, (+)-glaucine (3 microM) did not modify the basal uptake of 45Ca2+ but strongly inhibited the influx of 45Ca2+ induced by NA, 5-HT and K+.8. (+)-Glaucine (5microM) had no effect on rate and force of contraction in rat isolated atria.9. These results indicate that: (a) the cardiovascular effects (hypotension and bradycardia) of (+)-glaucine in anaesthetized normotensive rats (5 mg kg-1) may be due, at least in part, to a ganglioplexic effect; (b) the vasorelaxant action of ( + )-glaucine (0.15-5 microM) in rat isolated aorta can be attributed to an alpha1-adrenoceptor blocking property (which may explain its inhibition of noradrenaline-induced 45Ca2+influx and contractions in normal Krebs solution and noradrenaline-induced contractions in Ca2+-free medium) and to a Ca2+-antagonist activity (which may be responsible, at least in part, for the inhibition of 45Ca2+ uptake induced by NA, 5-HT and K+ and the contractions induced by both NA and 5-HT in normal Krebs solution and by Ca2+ in Ca2+-free high-K+ medium) and (c) there is no correlation between the mechanisms of action observed for (+ )-glaucine in vivo and in vitro, which suggests that the vasorelaxant activity of this alkaloid does not contribute to its hypotensive activity" http://www.ncbi.nlm.nih.gov/pubmed/7606346 0 1349 "W. Goettsch, Y. Hatori and R. P. Sharma" 1992 Adjuvant activity of all-trans-retinoic acid in C57Bl/6 mice Int.J.Immunopharmacol. 14 2 143-150 "The effects of all-trans-retinoic acid were investigated on the immune responses in C57Bl/6 mice after daily oral administration for one week. In selected experiments the immunosuppressive chemicals, cyclophosphamide and cyclosporin A were used in conjunction with retinoic acid. Retinoic acid stimulated the production of antibodies against sheep red blood cells and DNP-Ficoll; however, retinoic acid did not reverse the depression caused by immunosuppressive chemicals. In non-immunized animals retinoic acid stimulated the production of IL-1 but not of IL-2. The mitogenic responses of splenocytes against concanavalin A, phytohemagglutinin and pokeweed mitogen were depressed after the retinoic acid treatment; those against lipopolysaccharide were not influenced. Treatment with retinoic acid did not alter the mixed leukocyte responses but increased the activity of NK cells. Results indicate that retinoic acid may act as an adjuvant via activating macrophages, however, retinoic acid cannot reverse the immunosuppression induced by potent chemicals" http://www.ncbi.nlm.nih.gov/pubmed/1624215 0 1350 "B. D. Woodward, K. D. Bezanson, L. M. Hillyer and W. H. Lee" 1995 The CD45RA+ (quiescent) cellular phenotype is overabundant relative to the CD J.Nutr. 125 10 2471-2482 "The objective of this investigation was to determine whether an imbalance between naive- and memory-phenotype cells occurs within CD4+ and/or CD8+ splenic T cell subsets in models of protein-energy malnutrition (PEM) which produce wasting disease (loss of approximately 1.6% of body weight per day for 14 d) and profound depression in thymus-dependent immunity. Male and female weanling mice of disparate inbred strains, CBA/J and C57BL/6J, were allocated to the following groups: zero-time control (23 d old and 19 d old, respectively), ad libitum intake of a complete purified diet (19% crude protein, 17 kJ/g gross energy), restricted intake of the complete diet, and (C57BL/6J, only) ad libitum intake of an isocaloric low protein diet (0.6% crude protein). Surface expression of isoforms of CD45, a component of the T cell receptor complex, as well as of the accessory molecule, CD2, were assessed by flow cytometry of splenic mononuclear cell suspensions. Both major T cell subsets in the malnourished groups contained a significantly higher proportion of cells expressing the surface marker, CD45RA, than was found in the spleen cells of the control groups. CD45RA+ (naive-phenotype) T cells represent the extreme of quiescence and stringent activation requirements among thymic lymphocytes. The results provide the first clear evidence of a T cell subset imbalance in PEM which is consistent with depression in acquired immunity and which occurs, apart from antigenic challenge, in a site wherein immune responses take place. The T cell receptor complex may emerge as a focal point of the depressive influence of PEM on the competence of thymic lymphocytes" http://www.ncbi.nlm.nih.gov/pubmed/7562081 0 1351 "R. Capasso, F. Borrelli, F. Capasso, N. Mascolo and A. A. Izzo" 2004 Inhibitory effect of the antidepressant St. John's wort (hypericum perforatum) on rat bladder contractility in vitro Urology 64 1 168-172 "OBJECTIVES: To evaluate the effect of St. John's wort (SJW), an effective and safe herbal antidepressant, on rat bladder contractility. Recent data have suggested a strong association between depression and urinary incontinence. METHODS: Strips were cut from the bladder body and placed in organ baths containing Krebs solution. Contractions were induced by electrical field stimulation (EFS) and, in some experiments, by exogenous alpha,beta (alpha,beta)-methylene adenosine triphosphate. RESULTS: St. John's wort was significantly more active in inhibiting the EFS-induced contractions than the alpha,beta-methylene adenosine triphosphate-induced contractions, suggesting both a presynaptic site of action and a direct inhibition of bladder smooth muscle. The inhibitory effect of SJW on EFS-induced contractions was unaffected by methysergide, haloperidol, phentolamine plus propranolol (antagonists that block the action of the neurotransmitters 5-hydroxytriptamine, dopamine, and noradrenaline on their own receptors), the L-type calcium channel antagonist verapamil, capsazepine (which blocks the vanilloid receptor), or cannabinoid CB1 receptor antagonist SR141716A. However, the opioid receptor antagonist naloxone significantly reduced the inhibitory effect of SJW on EFS-induced contractions. Among the chemical constituents of SJW tested, hyperforin and, to a lesser extent, the flavonoid kaempferol showed inhibitory effects. CONCLUSIONS: The results of our study demonstrated that SJW inhibits excitatory transmission of the rat urinary bladder and also directly inhibits smooth muscle contractility. The inhibitory effect on excitatory transmission could involve, at least in part, opioid receptors. SJW may be evaluated for its possible use in treating urinary incontinence in depressed patients" http://www.ncbi.nlm.nih.gov/pubmed/15245964 0 1352 "Y. Cui, V. Paille, H. Xu, S. Genet, B. Delord, E. Fino, H. Berry and L. Venance" 2015 Endocannabinoids mediate bidirectional striatal spike-timing-dependent plasticity J.Physiol 593 13 2833-2849 "KEY POINTS: Although learning can arise from few or even a single trial, synaptic plasticity is commonly assessed under prolonged activation. Here, we explored the existence of rapid responsiveness of synaptic plasticity at corticostriatal synapses in a major synaptic learning rule, spike-timing-dependent plasticity (STDP). We found that spike-timing-dependent depression (tLTD) progressively disappears when the number of paired stimulations (below 50 pairings) is decreased whereas spike-timing-dependent potentiation (tLTP) displays a biphasic profile: tLTP is observed for 75-100 pairings, is absent for 25-50 pairings and re-emerges for 5-10 pairings. This tLTP induced by low numbers of pairings (5-10) depends on activation of the endocannabinoid system, type-1 cannabinoid receptor and the transient receptor potential vanilloid type-1. Endocannabinoid-tLTP may represent a physiological mechanism operating during the rapid learning of new associative memories and behavioural rules characterizing the flexible behaviour of mammals or during the initial stages of habit learning. ABSTRACT: Synaptic plasticity, a main substrate for learning and memory, is commonly assessed with prolonged stimulations. Since learning can arise from few or even a single trial, synaptic strength is expected to adapt rapidly. However, whether synaptic plasticity occurs in response to limited event occurrences remains elusive. To answer this question, we investigated whether a low number of paired stimulations can induce plasticity in a major synaptic learning rule, spike-timing-dependent plasticity (STDP). It is known that 100 pairings induce bidirectional STDP, i.e. spike-timing-dependent potentiation (tLTP) and depression (tLTD) at most central synapses. In rodent striatum, we found that tLTD progressively disappears when the number of paired stimulations is decreased (below 50 pairings) whereas tLTP displays a biphasic profile: tLTP is observed for 75-100 pairings, absent for 25-50 pairings and re-emerges for 5-10 pairings. This tLTP, induced by very few pairings ( approximately 5-10) depends on the endocannabinoid (eCB) system. This eCB-dependent tLTP (eCB-tLTP) involves postsynaptic endocannabinoid synthesis, requires paired activity (post- and presynaptic) and the activation of type-1 cannabinoid receptor (CB1R) and transient receptor potential vanilloid type-1 (TRPV1). eCB-tLTP occurs in both striatopallidal and striatonigral medium-sized spiny neurons (MSNs) and is dopamine dependent. Lastly, we show that eCB-LTP and eCB-LTD can be induced sequentially in the same neuron, depending on the cellular conditioning protocol. Thus, while endocannabinoids are usually thought simply to depress synaptic function, they also constitute a versatile system underlying bidirectional plasticity. Our results reveal a novel form of synaptic plasticity, eCB-tLTP, which may underlie rapid learning capabilities characterizing behavioural flexibility" http://www.ncbi.nlm.nih.gov/pubmed/25873197 0 1353 "W. T. McKinney, Jr., R. G. Eising, E. C. Moran, S. J. Suomi and H. F. Harlow" 1971 Effects of reserpine on the social behavior of rhesus monkeys Dis.Nerv.Syst. 32 11 735-741 http://www.ncbi.nlm.nih.gov/pubmed/5002259 1 1354 "J. Manny, G. Grindlinger, A. A. Mathe and H. B. Hechtman" 1978 "Positive end-expiratory pressure, lung stretch, and decreased myocardial contractility" Surgery 84 1 127-133 http://www.ncbi.nlm.nih.gov/pubmed/351839 0 1355 S. Molotchnikoff and D. Richard 1980 Reactions of lateral geniculate cells to chemical and electrical excitation of the visual cortex in rabbits J.Neurosci.Res. 5 5 419-429 "In anesthetized and paralyzed rabbits unitary discharges of lateral geniculate nucleus (LGN) were studied after cortical excitation by strychnine and following electrical stimulation of the visual cortex (VC). Results showed that local application of strychnine produced a general increase of the spontaneous and evoked activity of geniculate cells. By contrast, cortical depression with KCl led to a differential decrement of one of the evoked responses (on or off). Electrical cortical stimulation paired with on or off stimuli led to a differential increment of on or off responses. The results support the notion that, in rabbits, the corticogeniculate system is center-surround organized. A diagrammatic model is proposed to account for the relationship between the VC and the LGN in rabbits" http://www.ncbi.nlm.nih.gov/pubmed/7441796 0 1356 A. Y. Bakshaliyeva 2010 Peculiarities of development of the depression state in rats characterized by different individual/typological behavioral statuses "Neurophysiology.42 (2) ()(pp 130-138), 2010.Date of Publication: September 2010." 2 130-138 "We examined the development of a depression state induced by long-lasting stressing of rats preliminarily selected according to their active or passive behavior pattern. Stress was induced using a technique of sensory contact with aggressive individuals. The pathologically modified state in animals of the above groups developed according to dissimilar scenarios. As a result, a depressive state similar to anxious depression developed in active animals, while psychoemotional disorders similar to a melancholy-type depression were formed in passive rats. Therefore, the symptomatic heterogeneity of depression is, to a considerable extent, determined by individual/typological peculiarities of behavior (passive vs active) and can be rather clearly identified using the sensory contact technique. © 2010 Springer Science+Business Media, Inc" DO - http://dx.doi.org/10.1007/s11062-010-9141-9 1 1357 "A. C. Ferraz, A. M. Delattre, R. G. Almendra, M. Sonagli, C. Borges, P. Araujo, M. L. Andersen, S. Tufik and M. M. Lima" 2011 "Chronic omega-3 fatty acids supplementation promotes beneficial effects on anxiety, cognitive and depressive-like behaviors in rats subjected to a restraint stress protocol" Behav.Brain Res. 219 1 116-122 "Recent evidence has demonstrated dietary influence on the manifestation of different types of behaviors induced by stressor tasks. The present study examined the impact of omega-3 polyunsaturated fatty acids (PUFAs) supplementation in an early phase of the brain development with the goal of preventing or even attenuating the occurrence of stress-related behaviors such as depressive-like behaviors, anxiety and cognitive dysfunctions in male rats subjected to restraint stress. Our results indicated that the supplementation regimen successfully counteracted the anxiogenic effects of stress as evidenced by the rats' increased exploration time in the aversive arms of the elevated plus maze. The forced swimming test indicated that immobility and swimming were more deeply influenced by PUFAs supplementation, thereby demonstrating an antidepressant effect. Furthermore, cognitive function was shown to be intensely affected by restraint stress, but the effects were surprisingly counteracted by the PUFAs supplementation. Lastly, plasmatic corticosterone levels were demonstrated to be drastically increased by the restraint stress; however, PUFAs supplementation promoted a reduction of this stress-related hormone to levels that were comparable to those observed in the control group. Our results suggested that the mechanisms underlying these effects are possibly associated with the reduction of corticosterone levels promoted by the PUFAs supplementation in the stress-induced animals. Further studies to examine the participation of PUFAs in mediating different behaviors in rats subjected to restraint stress are warranted" http://www.ncbi.nlm.nih.gov/pubmed/21192985 1 1358 "C. Lacerra, I. D. Martijena, S. G. Bustos and V. A. Molina" 1999 Benzodiazepine withdrawal facilitates the subsequent onset of escape failures and anhedonia: influence of different antidepressant drugs Brain Res. 819 01-Feb 40-47 "The effect of benzodiazepine (BDZ) withdrawal on escape acquisition and on the behavioral response to two different reinforcing stimuli was investigated. In addition, the influence of antidepressant drugs (AD) differing in their mechanism of action on these behavioral outputs was also evaluated. Rats subjected to withdrawal from a chronic treatment with diazepam (DZM; 2 mg/kg per day, i.p.) during 21 days were subsequently exposed to a brief inescapable shock session (IS) and 48 h later to an active avoidance test. Only withdrawn animals exposed to the IS exhibited enhanced escape failures. In an additional experiment, withdrawn rats were repeatedly administered with vehicle (VEH), desipramine (DMI; 5 mg/kg, i.p.), fluoxetine (FLU; 5 mg/kg, i.p.) or phenelzine (PHEN; 5 mg/kg, i.p.) and subsequently exposed to IS and to active avoidance task. A significant reversal of escape deficit was only observed following DMI and PHEN but not after FLU. Furthermore, withdrawn rats showed a reduced preference for a sexually relevant olfactory cue, this reduced sensitivity was only normalized following DMI but not after the administration of FLU or PHEN. Finally, rats exposed to abrupt cessation of chronic BDZ administration did not exhibit preference for a context previously associated with amphetamine (AMP) under the conditioned place preference (CPP) procedure. All these findings are indicative that BDZ withdrawal facilitates the subsequent occurrence of behavioral changes-escape failures and reduced behavioral response to rewarding stimuli-suggested to parallel important symptoms of human depression. In addition, DMI seems to be much more effective in restoring such behavioral abnormalities as compared to a MAO inhibitor and to a inhibitor of 5-HT uptake" http://www.ncbi.nlm.nih.gov/pubmed/10082859 1 1359 "Y. X. Chen, S. W. Chen, X. R. Zhang, S. Liu, W. F. Xie and S. Li" 2005 [Inhibition of proliferation of hepatic stellate cells by taurine is mediated via regulating cell cycle proteins] Zhonghua Gan Zang.Bing.Za Zhi. 13 8 571-574 "OBJECTIVE: To explore the possible mechanism(s) of taurine-inhibiting the proliferation of hepatic stellate cells (HSC), this study investigated the effect of taurine on the HSC cell cycle and its regulatory protein expression. METHODS: Cell proliferation was assessed by MTT assay. Cell cycle was analyzed by flow cytometry. Cell cycle regulatory protein Cyclin D1 and P21waf1 expression were determined by immunocytochemistry and image-analysis system, and real-time quantitative PCR. RESULTS: HSC proliferation was markedly inhibited when HSC were treated with taurine at concentrations of 5, 10, 20, 30, 40 and 50 mmol/L for 48 hours, and the inhibition rates were 6.7%, 14.4%, 23.3%, 32.2%, 36.7% and 45.6% respectively (P < 0.05-0.01). In the flow cytometry analysis, it was found that taurine could block HSC in the G0/G1 phase from entering the S phase, resulting in more cells in the G0/G1 phase and fewer in the S phase. The percentage of the cells in the G0/G1 phase and the S phase at the dosage of 40 mmol/L were 68.2%+/-1.4% and 26.2+/-1.3% respectively, which was significantly different in comparison to the controls (56.2%+/-1.7% and 38.5%+/-0.8% respectively, P < 0.01). HSC expressed cyclin D1 and P21waf1. Taurine inhibited cyclin D1 expression and induced P21waf1 expression. The cyclin D1 protein and mRNA in the HSC treated with 40 mmol/L taurine were significantly reduced compared with the controls [protein (optical density value): 0.13+/-0.02 versus 0.18+/-0.02, P < 0.01; mRNA: 5776.7+/-3345.0 versus 18,400.6+/-1374.8 copies/10(6) GAPDH, P < 0.01]; and the P21waf1 protein and mRNA were markedly increased compared with the controls [protein (optical density value): 0.19+/-0.02 versus 0.14+/-0.01, P < 0.01; mRNA: 44,866.7+/-3910.7 versus 16,933.3+/-960.9 copies/10(6) GAPDH, P less than 0.05]. CONCLUSIONS: Cyclin D1 and P21waf1 were cell cycle regulatory proteins in HSC, and taurine can inhibit the HSC cyclin D1 expression and stimulate P21waf1 expression, facilitate arresting cells in G0/G1 phase, and suppress cell proliferation" http://www.ncbi.nlm.nih.gov/pubmed/16092977 0 1360 "J. Shikata, K. Kohno, T. Shida, S. Miyaji and F. Kohdaira" 1989 The causes and value of hyperphosphatemia in experimental strangulation obstruction Surgery 106 5 879-883 "In model experiments with mongrel dogs, intestinal strangulation obstruction was induced by occluding the superior mesenteric veins, and a rise in the inorganic phosphate value of the blood was observed. The high inorganic phosphate values of the fluid exuding from the strangulated bowel suggest that intestinal factors associated with the strangulated bowel may be partly responsible for this elevated phosphatemia. However, hyperphosphatemia was also found in a model experiment in which the route through which the fluid was absorbed into the blood from the peritoneal cavity was interrupted by keeping the strangulated bowel in an intestinal bag. After this, in the model experiments in which a systemic blood pressure depression curve with a percentage reduction similar to that of the decreasing arterial blood pressure resulting from strangulation was produced (by exsanguination, and even by exsanguination with adequate perfusion of the gut), plasma inorganic phosphate values also increased. Therefore it is undeniable that systemic factors other than the above-mentioned local factors are related to the rise in plasma inorganic phosphate values in experimental strangulation obstruction. Because it is not possible to assert that phosphatemia is specific to intestinal strangulation, the importance of a rise in inorganic phosphate values in the early diagnosis of intestinal strangulation cannot be considered very great" http://www.ncbi.nlm.nih.gov/pubmed/2814822 0 1361 "A. Garjani, S. Andalib, S. Biabani, H. Soraya, Y. Doustar, A. Garjani and N. Maleki-Dizaji" 2011 Combined atorvastatin and coenzyme Q10 improve the left ventricular function in isoproterenol-induced heart failure in rat Eur.J.Pharmacol. 666 01-Mar 135-141 "The effect of atorvastatin on cardiac remodeling, function, and homodynamic parameters in isoproterenol-induced heart failure was evaluated in the present study. A subcutaneous injection of isoproterenol (5mg/kg/day) for 10 days was used for the induction of heart failure. Isoproterenol administration produced intensive myocardial necrosis and fibrosis with a significant decrease in the arterial pressure indices, heart rate, contractility (LVdP/dt(max)) and relaxation (LVdP/dt(min)), but an increase in the left ventricular end-diastolic pressure. Rats were randomly assigned to control, treatment with only atorvastatin, and treatment with atorvastatin plus coenzyme Q10. Histopathological analysis showed a marked attenuation of myocyte necrosis and interstitial fibrosis in all atorvastatin treated groups (P<0.001). A low dose of atorvastatin (5mg/kg/day) significantly improved the left ventricular systolic pressure, contractility and relaxation (P<0.01). On the contrary, a high dose of atorvastatin (20mg/kg/day) worsened the isoproterenol-induced left ventricular dysfunction by a further reduction of LVdP/dt(max) from +2780 +/- 94 to +1588 +/- 248 (mmHg/s; P<0.01) and LVdP/dt(min) from -2007 +/- 190 to -2939 +/- 291 (mmHg/s; P<0.05). Co-administration of coenzyme Q10 with atorvastatin reversed the hemodynamic depression and the left ventricular dysfunction to a high level (P<0.001). There was a lower level of LVEDPs in the atorvastatin+coenzyme Q10 treated groups (3 +/- 1 and 4 +/- 1.4 versus 8 +/- 3.5 and 14 +/- 3.6 mmHg, respectively), thereby suggesting improvement in the myocardial stiffness by the combined coenzyme Q10 and atorvastatin treatment. The atorvastatin therapy attenuated myocardial necrosis and fibrosis in isoproterenol-induced heart failure. However, a high dose of the drug considerably worsened the left ventricular dysfunction and hemodynamic depression, which was reversed by coenzyme Q10 co-administration" http://www.ncbi.nlm.nih.gov/pubmed/21570962 0 1362 "V. Ventafridda, M. Bianchi, C. Ripamonti, P. Sacerdote, C. F. De, E. Zecca and A. E. Panerai" 1990 Studies on the effects of antidepressant drugs on the antinociceptive action of morphine and on plasma morphine in rat and man "Pain.43 (2) ()(pp 155-162), 1990.Date of Publication: 1990." 2 155-162 "In the rat we studied the effect of 3 tricyclic antidepressants: chlorimipramine, amitriptyline and nortriptyline, and the atypical antidepressant trazodone on pain thresholds when administered alone or together with morphine. Moreover, we evaluated the effect of the antidepressants on free morphine plasma concentrations both in the rat and in man. We observed that chlorimipramine and amitriptyline, two tricyclic antidepressants active on the serotoninergic system, induce analgesia and potentiate morphine analgesia in a dose-related fashion. The noradrenergic tricyclic nortriptyline and trazodone did not elicit analgesia and inconsistently affected morphine analgesia. In the rat, all drugs tested increased plasma concentrations of morphine with the exception of amitriptyline. In man, only chlorimipramine and amitriptyline increased the plasma concentration of the free opiate" DO - http://dx.doi.org/10.1016/0304-3959%2890%2991068-T 0 1363 "E. Kostarczyk, E. Fonberg and J. C. Prechtl" 1986 Changes in socio-emotional behavior under imipramine treatment in normal and amygdalo-hypothalamic dogs Acta Neurobiol.Exp.(Wars.) 46 4 187-203 "The effects of imipramine on learned social responses were examined in ten dogs with dorsomedial amygdalar lesions and/or lateral hypothalamic lesions. Six of the ten dogs were also tested preoperatively. The social responses were instrumentally conditioned using social interaction with the experimenter as reinforcement (petting and verbal reassurance). In the non-lesioned dogs imipramine treatment produced a dose-dependent deterioration of performance during drug administration followed by a long-term amelioration of performance. In the lesioned dogs imipramine produced various changes in performance depending on the pretreatment level of responding. When the pretreatment level of performance was high drug administration resulted in a long-term deterioration, and when performance was poor imipramine produced a continuous and long-term increase. It is suggested that imipramine facilitates the recovery of performance, but suppresses well-performed responses" http://www.ncbi.nlm.nih.gov/pubmed/3788669 0 1364 "J. Y. Chen, P. Lonjers, C. Lee, M. Chistiakova, M. Volgushev and M. Bazhenov" 2013 Heterosynaptic plasticity prevents runaway synaptic dynamics J.Neurosci. 33 40 15915-15929 "Spike timing-dependent plasticity (STDP) and other conventional Hebbian-type plasticity rules are prone to produce runaway dynamics of synaptic weights. Once potentiated, a synapse would have higher probability to lead to spikes and thus to be further potentiated, but once depressed, a synapse would tend to be further depressed. The runaway synaptic dynamics can be prevented by precisely balancing STDP rules for potentiation and depression; however, experimental evidence shows a great variety of potentiation and depression windows and magnitudes. Here we show that modifications of synapses to layer 2/3 pyramidal neurons from rat visual and auditory cortices in slices can be induced by intracellular tetanization: bursts of postsynaptic spikes without presynaptic stimulation. Induction of these heterosynaptic changes depended on the rise of intracellular calcium, and their direction and magnitude correlated with initial state of release mechanisms. We suggest that this type of plasticity serves as a mechanism that stabilizes the distribution of synaptic weights and prevents their runaway dynamics. To test this hypothesis, we develop a cortical neuron model implementing both homosynaptic (STDP) and heterosynaptic plasticity with properties matching the experimental data. We find that heterosynaptic plasticity effectively prevented runaway dynamics for the tested range of STDP and input parameters. Synaptic weights, although shifted from the original, remained normally distributed and nonsaturated. Our study presents a biophysically constrained model of how the interaction of different forms of plasticity--Hebbian and heterosynaptic--may prevent runaway synaptic dynamics and keep synaptic weights unsaturated and thus capable of further plastic changes and formation of new memories" http://www.ncbi.nlm.nih.gov/pubmed/24089497 0 1365 "R. Dang, H. Cai, L. Zhang, D. Liang, C. Lv, Y. Guo, R. Yang, Y. Zhu and P. Jiang" 2016 Dysregulation of Neuregulin-1/ErbB signaling in the prefrontal cortex and hippocampus of rats exposed to chronic unpredictable mild stress Physiol Behav. 154 145-150 "Exposure to chronic stress increases the likelihood of developing depression, but the underlying mechanisms remain equivocal. While recent evidence has indicated that Neuregulin-1 (NRG1) and its ErbB receptors play an essential role in neural development and function, and NRG1 has emerged as a novel modulator involved in the response of brain to stress, there is limited evidence concerning the effects of chronic stress exposure on NRG1/ErbB signaling. To fill this critical gap, we examined the protein expression of NRG1 and ErbB receptors in the brain of rats following chronic unpredictable mild stress (CUMS) exposure. After 6weeks of CUMS procedures, the rats were induced to a depression-like state. The stressed rats displayed elevated expression of NRG1 and phosphorylated ErbB4 (pErbB4) in the prefrontal cortex, whereas ErbB2 and pErbB2 were inhibited. In the hippocampus, CUMS also attenuated activation of the both ErbB receptors and suppressed the downstream Akt and ERK phosphorylation. Meanwhile, administration of sertraline enhanced NRG1/ErbB signaling and partly normalized the stress-induced behavioral changes and the disturbances of NRG1/ErbB system in CUMS rats. Combined, our data firstly showed the aberrant changes of NRG1/ErbB system in the brain of the animal model of depression, providing new evidence for the involvement of NRG1/ErbB pathway in the development and treatment of depression" http://www.ncbi.nlm.nih.gov/pubmed/26626816 1 1366 J. H. Johnson and J. M. Jensen 1998 Hepatotoxicity and secondary photosensitization in a red kangaroo (Megaleia rufus) due to ingestion of Lantana camara J.Zoo.Wildl.Med. 29 2 203-207 "Three red kangaroos (Megaleira rufus), an adult male, an adult female, and a yearling, were exposed in bedding and food to coastal bermuda hay that contained the toxic plant Lantana camara. The adult male exhibited signs of anorexia, depression, lethargy, and jaundice. The adult female was presented dead. After 1 wk, following exposure to sunlight, the adult male and a yearling joey developed exudative dermatitis of the ear margins, eyelids, muzzle, and scrotum and opacity of the corneas. The adult male had a leucocytosis, anemia, bilirubinemia, bilirubinuria, hyperproteinemia, and elevated alanine aminotransferase, gamma glutamyl transpeptidase, alkaline phosphatase, and bile acid serum levels. Postmortem examination of the adult male revealed jaundice, and the liver was swollen, mottled, and pale yellow to reddish yellow. The gall bladder was markedly distended. Histopathologically, there was hepatocellular enlargement with vesiculation of the nuclei and sporadic feathery degeneration of the cytoplasm. The yearling joey survived and was treated symptomatically with i.v. fluids and antibiotics. The history, clinical signs, diagnostic findings, necropsy findings, and exposure to the toxic plant Lantana camara support the diagnosis of secondary photosensitization and hepatoxicity" http://www.ncbi.nlm.nih.gov/pubmed/9732038 0 1367 D. C. Jackson 2000 How a Turtle's Shell Helps It Survive Prolonged Anoxic Acidosis News Physiol Sci. 15 181-185 "Anoxic turtles accumulate high levels of lactate in blood. To avoid fatal acidosis, turtles exploit buffer reserves in their large mineralized shell. The shell acts by releasing calcium and magnesium carbonates and by storing and buffering lactic acid. Together with profound metabolic depression, shell buffering permits survival without oxygen for several months at 3 degrees C" http://www.ncbi.nlm.nih.gov/pubmed/11390905 0 1368 J. L. Boak and T. C. Agwunobi 1978 A study of technetium-labelled sulphide colloid uptake by regional lymph nodes draining a tumour-bearing area Br.J.Surg. 65 6 374-378 "With appropriate controls, experimental groups of inbred C3H mice bearing a syngeneic mammary carcinoma challenge in their right rear footpads were injected in both rear footpads with 99TcmASC. Mice were sacrificed 15 and 90 min after the labelled colloid injection. Popliteal and sacral lymph nodes were weighed and counted in a well scintillation counter. A marked inhibition of labelled colloid uptake was demonstrated in regional lymph nodes draining a tumour-bearing area. Rabbits bearing VX2 carcinoma in a forelimb received 99TcmASC into each front footpad. Depression of labelled colloid uptake by regional lymph nodes draining tumour was evident on gamma-camera scanning" http://www.ncbi.nlm.nih.gov/pubmed/656753 0 1369 A. Ahmed and M. Lahkar 2016 Effect of nimesulide in reversing reserpine induced depression in mice "International Journal of Pharmaceutical Sciences and Research.7 (1) ()(pp 336-339), 2016.Date of Publication: 2016." 1 336-339 "To demonstrate the effect of Nimesulide in reversing Reserpine induced depression in mice. Materials and Methods: This test was done using 20-25gm of healthy albino mice of either sex in the Department of Pharmacology of Gauhati medical college. They were housed in standard laboratory condition at 25degreeC and fed on standard diet and water ad libitum. Five groups were selected each containing six mice. The groups were Group I (Normal Control), Group II (Disease Control), Group III (Fluoxetine 10mg/kg i.p), Group IV (Nimesulide 2.5mg/kg i, p) and Group V (Nimesulide 5mg/kg i.p)Reserpine (2mg/kg i.p) was used to induce depression in all the groups except the Normal Control. After 24 hours, the standard and test drugs were given and the mice were subjected to tail suspension test (TST) after 30 mins and forced swim test (FST) after 1 hour of injecting the drugs. Result: Mean+/-SEM values were calculated for each group. The data were analyzed using ANOVA and post analysis was done by Dunnett's test. Results were found to be significant (p <.05). The period of immobility was found to be reduced in the test groups in a dose dependent manner as compared to the Disease Control.However, the episodes and the duration of immobility was minimum in the Standard group. Conclusion: Nimesulide has been found to be effective in reversing reserpine induced depression in mice" DO - http://dx.doi.org/10.13040/IJPSR.0975-8232.7%281%29.336-39 1 1370 "S. M. le Grand, W. Supornsilpchai, C. Saengjaroentham and A. Srikiatkhachorn" 2011 Serotonin depletion leads to cortical hyperexcitability and trigeminal nociceptive facilitation via the nitric oxide pathway Headache 51 7 1152-1160 "OBJECTIVE: To investigate the role of nitric oxide (NO) in the development of cortical hyperexcitability and trigeminal nociceptive facilitation induced by serotonin (5-HT) depletion. BACKGROUND: Nitric oxide and 5-HT are important in the pathogenesis of primary headaches. An increase in cortical excitability and trigeminal nociception has been demonstrated in animals with low 5-HT levels. Although the mechanism underlying this increase is unclear, an alteration of the NO system is one possible explanation. METHODS: Male Wistar rats were divided into control and 5-HT-depleted groups. 5-HT was depleted by i.p. injection of parachlorophenylalanine (100 mg/kg). Three days after injection, a microelectrode was inserted into the cerebral cortex for electrocorticograph recording and waves of cortical spreading depression (CSD) were triggered with KCl application. N-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg by i.v. injection) or saline was given after the second CSD wave. Following the experiment, the cerebral cortex and brain stem were removed for anti-neuronal nitric oxide synthase (nNOS) and anti-Fos immunohistochemistry. RESULTS: Relative to the control group, the 5-HT-depleted group exhibited a higher frequency of CSD waves, more nNOS-immunoreactive cells in both the cerebral cortex and brainstem and more Fos-immunoreactive cells in the trigeminal nucleus caudalis (TNC). In the control group, L-NAME application led to fewer nNOS-immunoreactive cells in the cerebral cortex and TNC, and fewer Fos-immunoreactive cells in the TNC; however, L-NAME was without effect on the CSD pattern. By contrast, in addition to decreased nNOS and Fos expression, L-NAME significantly reduced the frequency of CSD events in the 5-HT-depleted group. CONCLUSIONS: Inhibition of NO production can counter both the cortical hyperexcitability and facilitation of trigeminal nociception that develop in the depleted 5-HT state. Therefore, NO is likely involved in the increase in both CSD events and CSD-evoked trigeminal nociception under decreased 5-HT conditions" http://www.ncbi.nlm.nih.gov/pubmed/21649655 0 1371 "W. E. Hoffman, J. M. Feld, P. Larscheid, J. M. Cook, R. F. Albrecht and D. J. Miletich" 1984 "Cerebrovascular and cerebral metabolic effects of flurazepam and a benzodiazepine antagonist, 3-hydroxymethyl-beta-carboline" Eur.J.Pharmacol. 106 3 585-591 "There is a need in clinical practice for an antagonist which can reverse the sedative action of benzodiazepines. Recently, 3-hydroxymethyl-beta-carboline (3-HMC) has been reported to inhibit the sleep inducing effects of flurazepam. The effects of flurazepam (0.5, 5 and 50 mg/kg) on cerebral blood flow (CBF) and cerebral O2 consumption (CMRO2) were evaluated in rats and the ability of 3-HMC to reverse these changes was determined. Regional CBF was measured with radioactive microspheres and cortical CMRO2 was calculated from sagittal sinus-arterial O2 content differences and cortical CBF. Flurazepam produced dose dependent decreases in CBF and CMRO2 which were significant at 5 and 50 mg/kg. 3-HMC (5 mg/kg) inhibited flurazepam induced changes at the 5 mg/kg dose but had little effect on the CBF and CMRO2 depression produced by 50 mg/kg flurazepam. At a dose of 25 mg/kg, 3-HMC inhibited the effects of both 5 and 50 mg/kg flurazepam. Blood pressure and heart rate were also decreased by flurazepam but these variables were not reversed as effectively by 3-HMC treatment. The results indicate that 3-HMC is an active antagonist of the cerebrovascular and cerebral metabolic depression produced by flurazepam and can stimulate CBF and CMRO2 at high doses when given alone" http://www.ncbi.nlm.nih.gov/pubmed/6519176 0 1372 "T. R. Insel, E. A. Lane, M. Sheinin and M. Linnoila" 1987 Acute and chronic effects of desipramine administration to rhesus monkeys Eur.J.Pharmacol. 136 1 63-68 "Rhesus monkeys were studied for changes in noradrenergic functioning before and after chronic oral administration (28 days) of the tricyclic antidepressant desipramine (DMI). Decreases in cerebrospinal fluid concentration of the norepinephrine metabolite MHPG were evident following the first dose (5.0 mg/kg) of DMI, but not after chronic administration of the drug. The alpha 2-adrenoceptor agonist clonidine reduced plasma norepinephrine prior to DMI treatment, but not after 28 days of treatment with DMI. These adaptive changes in noradrenergic function were evident in spite of very low plasma levels of DMI due to rapid metabolism of the drug in the rhesus monkey. The development of changes compatible with alpha 2-adrenoceptor subsensitivity in the presence of plasma levels of the drug that are well below those considered therapeutic in the treatment of depression suggests that such a receptor change may be dissociated from the drug's antidepressant effect" http://www.ncbi.nlm.nih.gov/pubmed/3595717 0 1373 E. M. Peganov 1980 [Inactivation of sodium permeability of a nerve fiber membrane by means of formamide] Dokl.Akad.Nauk SSSR 250 1 229-232 http://www.ncbi.nlm.nih.gov/pubmed/6247129 0 1374 "A. M. Pare, W. P. Pare and J. Kluczynski" 1999 Negative affect and voluntary alcohol consumption in Wistar-Kyoto (WKY) and Sprague-Dawley rats Physiol Behav. 67 2 219-225 "Based on the assumption that the Wistar-Kyoto (WKY) rat strain represents an animal model for depressive behavior, the purported relationship between depression and alcohol consumption was investigated in three experiments. WKY rats consumed more alcohol than Sprague-Dawley (S-D) rats when offered a choice between a 7% alcohol solution and tap water. Subsequently, the severity of stress-induced stomach ulcers was significantly less in WKY rats that had access to alcohol. In Experiment 2, WKY and S-D rats were assigned to either an alcohol access treatment or to a water-only treatment for 27 days and subsequently observed in the open-field test (OFT) and the elevated plus-maze (EPM). Access to alcohol reduced response latency in the OFT, and increased the percent time in the open arm and the total number of arm entries in the EPM for WKY rats. In Experiment 3, the antidepressant, imipramine, reduced alcohol consumption in both strains and significantly increased percent time in the open arms of the EPM for WKY rats. These studies support the assumption that depression and alcohol consumption may be related" http://www.ncbi.nlm.nih.gov/pubmed/10477053 1 1375 "Y. Wang, S. Li, F. Piao, Y. Hong, P. Liu and Y. Zhao" 2009 "Arsenic down-regulates the expression of Camk4, an important gene related to cerebellar LTD in mice" Neurotoxicol.Teratol. 31 5 318-322 "To elucidate the molecular mechanism of arsenic (As) on motor learning and memory, concentration of As in cerebellar tissue of mice exposed to 1 ppm and 4 ppm As(2)O(3) subchronically was determined by ICP-MS, neurobehavioral changes associated with memory was examined by the Morris Water Maze test, and the critical gene expression profiles related to the Creb-dependent phase of cerebellar long-term depression (LTD) were analyzed by GeneChip. Our results showed the increased level of As concentration in cerebellar tissue of the exposed mice in a dose-response manner, longer escape latency in the experimental group than controls and the down-regulated expression of Ca(2+)/calmodulin dependent protein kinase IV (Camk4), a very important regulator in the LTD pathway. We further analyzed the influence of As on cerebellar Camk4 expression by Western blot. The quantity of Camk4 band in the group exposed to 4 ppm As(2)O(3) significantly decreased compared to the control group, agreeing well with gene microarray results. It is indicated that the accumulated As induced learning and memory impairment and impeded the Camk4 expression. Therefore, the Camk4 may be target of As-induced neurotoxicity. Furthermore, the intervention of antioxidants taurine or vitamin C did not prevent Camk4 from down-regulation, indicating that the down-regulation of Camk4 expression by As may be via an oxidation-independent way" http://www.ncbi.nlm.nih.gov/pubmed/19410645 0 1376 "D. Zhou, H. Jin, H. B. Lin, X. M. Yang, Y. F. Cheng, F. J. Deng and J. P. Xu" 2010 Antidepressant effect of the extracts from Fructus Akebiae Pharmacol.Biochem.Behav. 94 3 488-495 "Fructus Akebiae is a common ingredient in many traditional Chinese medicine complex prescriptions for the treatment of mental disorders. Previous studies indicate that the main chemical compositions of Fructus Akebiae are triterpenoid saponins with hederagenin as their sapogenin. In the present study, we enriched hederagenin from the extracts of Fructus Akebiae with a purity of approximately 70%. Using behavioral tests sensitive to antidepressant drugs, we demonstrated that acute and sub-chronic administration of the extracts of Fructus Akebiae produced antidepressant-like effects, as evidenced by decreases in the duration of immobility in forced swim and tail suspension tests in mice and reversal of chronic unpredicted mild stress-induced inhibition of sucrose consumption in rats. In addition, the extracts decreased the levels of plasma adrenocorticotrophic hormone and serum corticosterone in rats exposed to chronic unpredicted mild stress. Both behavioral and biochemical effects of the extracts were mimicked by the proven antidepressant escitalopram. These results suggest that the extracts of Fructus Akebiae exert antidepressant activity. Administration of the extracts may be beneficial for patients with depressive disorders" http://www.ncbi.nlm.nih.gov/pubmed/19931301 1 1377 "V. Milesi, A. Rebolledo, A. G. Alvis, J. Raingo and A. O. Grassi de Gende" 2001 Voltage-activated sodium current is inhibited by capsaicin in rat atrial myocytes Biochem.Biophys.Res.Commun. 282 4 965-970 "The effects of capsaicin, the active principle of hot pepper genus Capsicum, were studied on voltage-activated, tetrodotoxin-sensitive Na+ currents in isolated rat atrial cells using the patch clamp technique in the whole-cell configuration. 0.4 and 4 microM of capsaicin produced a significant tonic block on voltage-activated Na+ current (I(Na)) evoked by a depolarizing step to -40 mV from a holding potential of -100 mV (49 +/- 7% n = 11, P < 0.05 and 72 +/- 13% n = 4, P < 0.05 respectively). We didn't observe any use-dependent block of capsaicin in our experimental conditions. Capsaicin slowed the time decay of inactivation of I(Na), and increased the time constant of the recovery of inactivation. Capsaicin and tetrodotoxin (TTX) depressed contractility of isolated electrically driven left rat atria, being the depression of maximal velocity of force development (dF/dt(max)) with respect to control values of 19 +/- 3% at 1 microM of capsaicin and 22 +/- 2% at 1 microM of TTX. These results show an inhibitory effect of capsaicin on I(Na) in isolated atrial cells that may modify the electrical and contractile function of the rat heart" http://www.ncbi.nlm.nih.gov/pubmed/11352646 0 1378 "M. Kobayashi, T. Nino, T. Mori, S. Fukuyo and T. Yazawa" 1971 "[Influence of various drugs on liver glycogen and blood sugar levels in reserpinized rats. Combined effect of MAOI, 5HTP, DOPA, ACTH and cortisone]" Nihon Yakurigaku Zasshi 67 3 265-273 http://www.ncbi.nlm.nih.gov/pubmed/4326925 0 1379 "T. Kanno, A. Tanaka and T. Nishizaki" 2015 "Linoleic acid derivative DCP-LA ameliorates stress-induced depression-related behavior by promoting cell surface 5-HT1A receptor translocation, stimulating serotonin release, and inactivating GSK-3beta" Mol.Neurobiol. 51 2 523-532 "Impairment of serotonergic neurotransmission is the major factor responsible for depression and glycogen synthase kinase 3beta (GSK-3beta) participates in serotonergic transmission-mediated signaling networks relevant to mental illnesses. In the forced-swim test to assess depression-like behavior, the immobility time for mice with restraint stress was significantly longer than that for nonstressed control mice. Postsynaptic cell surface localization of 5-HT1A receptor, but not 5-HT2A receptor, in the hypothalamus for mice with restraint stress was significantly reduced as compared with that for control mice, which highly correlated to prolonged immobility time, i.e., depression-like behavior. The linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) restored restraint stress-induced reduction of cell surface 5-HT1A receptor and improved depression-like behavior in mice with restraint stress. Moreover, DCP-LA stimulated serotonin release from hypothalamic slices and cancelled restraint stress-induced reduction of GSK-3beta phosphorylation at Ser9. Taken together, the results of the present study indicate that DCP-LA could ameliorate depression-like behavior by promoting translocation of 5-HT1A receptor to the plasma membrane on postsynaptic cells, stimulating serotonin release, and inactivating GSK-3beta" http://www.ncbi.nlm.nih.gov/pubmed/24788685 1 1380 L. Ahtee and M. Svartstrom-Fraser 1975 Effect of ethanol dependence and withdrawal on the catecholamines in rat brain and heart Acta Pharmacol.Toxicol.(Copenh) 36 4 289-298 http://www.ncbi.nlm.nih.gov/pubmed/1173314 0 1381 V. Walia 2016 Influence of stress and fluoxetine on immobility period of mice in tail suspension test and forced swim test "Asian Journal of Pharmaceutical and Clinical Research.9 (2) ()(pp 302-305), 2016.Date of Publication: March-April 2016." 2 302-305 Objective: To investigate the influence of immobilization stress of 2 hrs and FLX on the immobility period of unstressed and stressed mice and to determine how stress and FLX modulates the effect of each other. Methods: Mice were stressed by immobilization for 2 hrs and the immobility period of both unstressed and stressed mice were determined by using tail suspension test (TST) and forced swim test (FST). Results: Immobilization stress of 2 hrs increased the immobility period of mice in both TST and FST. FLX reduced the immobility period of both unstressed and stressed mice in both TST and FST. Both immobilization stress of 2 hrs and FLX modulated the effect of each other. Immobility period of mice in which FLX was administered before the immobilization stress of 2 hrs had no significant difference from the immobility period of mice in which FLX was administered after the immobilization stress of 2 hrs. Conclusion: It has been concluded that the immobility period of mice in which FLX was administered before the immobilization stress of 2 hrs had no significant difference from the immobility period of mice in which FLX was administered after the immobilization stress of 2 hrs 0 1382 "P. J. Conroy, B. R. von, W. Passalacqua and R. M. Sutherland" 1980 The effect of misonidazole on some physiologic parameters in mice J.Pharmacol.Exp.Ther. 212 1 47-52 "The physiologic effects of misonidazole (Ro-07-0582) were studied in BALB/cKa mice injected i.p. at 0.5 to 1.5 mg/g b.wt. A 2--4 degree C reduction of body core temperature was observed in unanesthetized mice: the duration and degree of effect were dependent on dose. Normal core temperatures were restored when the serum level of misonidazole had fallen to 0.5 microM (100 micrograms/ml). Misonidazole (1 mg/g) produced a rapid postinjectional drop of heart rate (40%), respiration (45%) and body core (4 degrees C) temperatures which gradually returned to preinjection values 6 to 8 hr later. In addition, misonidazole administration (1 mg/g) enhanced the overall effect on body temperature induced by hexobarbital anesthesia by a factor of approximately 3. These results are discussed in relation to the use of mouse model tumor systems to give an estimate of the magnitude of the cytotoxic effect of misonidazole expected in humans" http://www.ncbi.nlm.nih.gov/pubmed/7351625 0 1383 "V. O. Rechinskii, R. S. Bibilashvili, A. A. Khorlin, S. L. Grokhovskii and A. L. Zhuze" 1981 "[""Bis-netropsin"" as a selective inhibitor of DNA-dependent RNA synthesis]" Dokl.Akad.Nauk SSSR 259 1 244-247 http://www.ncbi.nlm.nih.gov/pubmed/6169496 0 1384 "K. Berghauzen-Maciejewska, J. Wardas, B. Kosmowska, H. Domin, M. Smialowska, U. Glowacka and K. Ossowska" 2016 Adaptive down-regulation of the serotonin transporter in the 6-hydroxydopamine-induced rat model of preclinical stages of Parkinson's disease and after chronic pramipexole treatment Neuroscience 314 22-34 "Our recent study has indicated that a moderate lesion induced by bilateral 6-hydroxydopamine (6-OHDA) injections into the ventrolateral region of the caudate-putamen (CP) in rats, modeling preclinical stages of Parkinson's disease, induces a ""depressive-like"" behavior which is reversed by chronic treatment with pramipexole (PRA). The aim of the present study was to examine the influence of the above lesion and chronic PRA treatment on binding to the serotonin transporter (SERT) in different brain regions. As before, 6-OHDA (15 mug/2.5 mul) was administered bilaterally into the CP. PRA (1mg/kg) was injected subcutaneously twice a day for 2 weeks. Serotonergic and dopaminergic neurons of the dorsal raphe (DR) were immunostained for tryptophan hydroxylase and tyrosine hydroxylase, respectively, and were counted stereologically. Binding of [(3)H]GBR 12,935 to the dopamine transporter (DAT) and [(3)H]citalopram to SERT was analyzed autoradiographically. Intrastriatal 6-OHDA injections decreased the number of dopaminergic, but not serotonergic neurons in the DR. 6-OHDA reduced the DAT binding in the CP, and SERT binding in the nigrostriatal system (CP, substantia nigra (SN)), limbic system (ventral tegmental area (VTA), nucleus accumbens (NAC), amygdala, prefrontal cortex (PFCX), habenula, hippocampus) and DR. A significant positive correlation was found between DAT and SERT binding in the CP. Chronic PRA did not influence DAT binding but reduced SERT binding in the above structures, and deepened the lesion-induced losses in the core region of the NAC, SN, VTA and PFCX. The present study indicates that both the lesion of dopaminergic neurons and chronic PRA administration induce adaptive down-regulation of SERT binding. Moreover, although involvement of stimulation of dopaminergic transmission by chronic PRA in its ""antidepressant"" effect seems to be prevalent, additional contribution of SERT inhibition cannot be excluded" http://www.ncbi.nlm.nih.gov/pubmed/26628402 1 1385 "V. Chauvel, J. Schoenen and S. Multon" 2013 Influence of ovarian hormones on cortical spreading depression and its suppression by L-kynurenine in rat PLoS.One. 8 12 e82279 "Migraine is sexually dimorphic and associated in 20-30% of patients with an aura most likely caused by cortical spreading depression (CSD). We have previously shown that systemic L-kynurenine (L-KYN), the precursor of kynurenic acid, suppresses CSD and that this effect depends on the stage of the estrous cycle in female rats. The objectives here are to determine the influence of ovarian hormones on KCl-induced CSD and its suppression after L-KYN by directly modulating estradiol or progesterone levels in ovariectomized rats. Adult female rats were ovariectomized and subcutaneously implanted with silastic capsules filled with progesterone or 17beta-estradiol mixed with cholesterol, with cholesterol only or left empty. Two weeks after the ovariectomy/capsule implantation, the animals received an i.p. injection of L-KYN (300 mg/kg) or NaCl as control. Thirty minutes later CSDs were elicited by applying KCl over the occipital cortex and recorded by DC electrocorticogram for 1 hour. The results show that both estradiol and progesterone increase CSD frequency after ovariectomy. The suppressive effect of L-KYN on CSD frequency, previously reported in normal cycling females, is not found anymore after ovariectomy, but reappears after progesterone replacement therapy. Taken together, these results emphasize the complex role of sex hormones on cortical excitability. The CSD increase by estradiol and, more surprisingly, progesterone may explain why clinically migraine with aura appears or worsens during pregnancy or with combined hormonal treatments" http://www.ncbi.nlm.nih.gov/pubmed/24340013 0 1386 "A. Ellison, J. Jones, C. Inchley and S. Consuegra" 2013 Choosy males could help explain androdioecy in a selfing fish Am.Nat. 181 6 855-862 "Androdioecy (the coexistence of males and hermaphrodites) is considered a transitional state derived from pure hermaphroditism or dioecy, but the processes selecting for this rare breeding system are unclear, particularly in animals. In androdioecious species, the proportion of males in relation to hermaphrodites is usually so reduced that it is not known whether there is scope for mate choice, particularly when simultaneous hermaphrodites can self-fertilize. We investigated the potential role of male mate choice in the persistence of androdioecy in animals using a self-fertilizing androdioecious fish (Kryptolebias marmoratus) as a model. Hermaphrodites preferred to associate with males but showed no preference based on genetic similarity. In contrast, males displayed a strong preference for genetically dissimilar hermaphrodites, based, apparently, on olfactory cues. We suggest that disassortative male mate choice could be a critical factor in stabilizing androdioecy in cases where high selfing rates are associated with inbreeding depression" http://www.ncbi.nlm.nih.gov/pubmed/23669547 0 1387 W. S. Swecker and C. D. Thatcher 1988 The investigation of nutritional disorders Vet.Clin.North Am.Food Anim Pract. 4 1 127-144 "The following list is presented as a summary of guidelines that may be helpful in the investigation of a nutritional disorder. 1. Identify the perceived herd or flock problem. The client's complaint usually reflects an appearance of clinical signs or a depression in production parameters. The practitioner should also identify subclinical manifestations and other concurrent problems. 2. Identify the affected population or subpopulation. Groups should be identified according to breed, sex, age, reproductive status, growth phase, and lactation status. It is critical to identify the affected population, as a diet can be adequate for one population and deficient or excessive for another. For example, 24-month-old Angus heifers in the first 60 days of lactation would have greater risk of protein-energy malnutrition than would 5-year-old Angus cows in their second trimester of gestation if both were fed a marginal hay ration. 3. Identify the nutritional requirements for the affected population. The National Research Council publications serve as a guideline in determining nutrient requirements. 4. Identify factors that influence nutrient requirements and feed intake. Environmental factors, such as ambient temperature, can affect both nutrient requirements and feed intake of the population. Housing conditions, such as muddy lots, can increase maintenance requirements. 5. Sample and evaluate the feedstuffs. Nutrient(s) must be bioavailable--that is, they must be in a form that can be ingested, digested, and absorbed by the animal. 6. Sample and evaluate water sources for quantity and quality. 7. Evaluate feed bunk management practices. 8. Examine the herd. Both affected and normal populations should be examined. 9. Evaluate and submit to a laboratory any animal samples that may relate to the disorder. 10. Assemble the data and develop a hypothesis to support a diagnosis. 11. Provide a written account of all recommendations for the producer" http://www.ncbi.nlm.nih.gov/pubmed/3259454 0 1388 "J. M. Smith, G. M. Mkoji and R. K. Prichard" 1989 Depression of hydrogen peroxide dependent killing of schistosomula in vitro by peritoneal exudate cells from Schistosoma mansoni infected mice Am.J.Trop.Med.Hyg. 40 2 186-194 "Peritoneal exudate cells from mice infected with Schistosoma mansoni (S-PEC) can kill a small proportion of schistosomula in vitro in the presence of immune serum. S-PEC produce a low level of respiratory burst. However, schistosomula mortality in their presence is not reduced when exogenous antioxidants are added, suggesting that with S-PEC, oxidative killing may not be important. Hydrogen peroxide (H2O2) and superoxide production by S-PEC, and cells from Bacillus Calmette-Guerin (BCG) and thioglycollate (THGL) injected mice, nonspecifically stimulated with opsonized zymosan, were measured. Levels of H2O2 produced by S-PEC were significantly lower than BCG or THGL PEC, and were below the threshold for schistosomula killing. This correlated with lower levels of cell-mediated killing of schistosomula in vitro by S-PEC than by BCG-PEC. Superoxide levels, however, were similar between the 3 cell populations. It therefore appears that the efficiency of PEC to kill schistosomules in vitro correlates with H2O2 rather than superoxide levels. It was found that there was a sharp concentration threshold in H2O2 mediated killing of schistosomula. A depression in the levels of H2O2 produced may be a mechanism by which the parasite can partially evade the host immune system" http://www.ncbi.nlm.nih.gov/pubmed/2537585 0 1389 "N. Shintani, Y. Onaka, R. Takenaga, T. Kanoh, R. Haba, A. Hayata, H. Hirai, K. Nagata, M. Nakamura, A. Baba and H. Hashimoto" 2012 Selective involvement of prostanoid receptor CRTH2 in depression-like behaviors Journal of Neurochemistry.Conference: 11th Biennial Meeting of the Asian-Pacific Society for Neurochemistry / 55th Annual Meeting of the Japanese Society for Neurochemistry Kobe Japan.Conference Start: 20120929 Conference End: 20121002.Conference Publi var.pagings 73 "Recent clinical studies indicate that inhibition of prostanoid signaling could ameliorate depressive symptoms. In lipopolysaccharide (LPS)-induced sickness behavior model, we recently found genetic ablation of CRTH2, one of prostaglandin D2 receptor subtype, blocked the LPS-induced impairment of social behaviors. The present study further explored the behavioral impacts of CRTH2-deficiency in several animal models. CRTH2-deficient (KO) mice were injected singly with LPS, repeatedly with corticosterone (CORT), or inoculated with adenocarcinoma cells. For a basic behavioral characterization, SHIRPA, a comprehensive behavioral assessment was employed. The other behaviors including immobility in the forced swim test (FST) were also analyzed. SHIRPA revealed normal behaviors in KO mice, but these mice displayed reduced immobility in the FST. In LPS and CORT models, prolonged immobility in the FST was observed in wild-type but not in KO mice. In CORT and tumor-inoculated models, decreases in social behaviors and novel object exploration were also attenuated in KO mice. These results indicate that the CRTH2- signaling has a critical role specifically in depression-like behaviors, and therefore could be a target for therapeutic intervention" DO - http://dx.doi.org/10.1111/j.1471-4159.2012.07905.x 0 1390 "F. Leuschner, W. Neumann and I. S. Doppelfeld" 1978 General pharmacology of amitriptylinoxide "Arzneimittel-Forschung/Drug Research.28 (10 B) ()(pp 1883-1893), 1978.Date of Publication: 1978." 10 B 1883-1893 "Assessment focussed on general pharmacological properties of the tricyclic antidepressant amitriptylinoxide, which is a metabolite of amitriptyline or, in chemical terms, its N-oxide. Synergistic action with sympathetic neurotransmitters was observed. The intensification of adrenergic reactions stated in the anaesthetised cat and isolated seminal vesicles of guinea-pigs was comparable to that produced by amitriptyline. No inhibition of the MAO-system could be detected. Moreover effects registered in animal tests laid out to reflect central anticholinergic action (pilocarpine stereotypism, antagonistic action against nicotine, tremorine and paraoxon) yielded no decisive difference between amitriptylinoxide and amitriptyline. Peripheral anticholinergic action, on the other hand, which was investigated in the isolated intestine (guinea-pig) and through evaluating pilocarpine-induced salivation (rat, rabbit) and mydriasis (mouse), was found to be considerably weaker after amitriptylinoxide than after amitriptyline (factor 3 to 15). Tests in the anaesthetised dog served to establish the threshold dose causing cardiovascular impairment. The level obtained was 3.16 mg/kg i.v. (elevation of heart rate, diminished stroke volume). First lowering of blood pressure occurred at 10 mg/kg i.v. The isolated heart and atrium of guinea-pigs were investigated for signs of negative inotropic and bradycardiac effects, comparing amitriptylinoxide with amitriptyline. Cardiotoxic activity of the oxide was essentially lower than that of the reference substance (approx. by factor of 10). Comparison with amitriptyline, imipramine and desipramine in the isolated atrium proved amitriptylinoxide to be the only drug not provoking negative inotropism up to the concentration of 10-4 g/ml bath liquid. To a certain extent tests in anaesthetised rats and dogs confirmed the antagonistic action of tricyclic antidepressants against the antihypertensive effect of clonidine referred to in literature. However, application of amitriptylinoxide or amitriptyline did not lead to the complete suppression of a clonidine-induced reduction of blood pressure. In the first place results seem to indicate a delayed onset of action and a shift in the peak effect of clonidine after prior application of the antidepressants. Amitriptylinoxide was less active than amitriptyline. 5. pharmacologic screening supplied evidence for a certain antihistamine, antiserotonin and musculotropic spasmolytic activity. Amitriptylinoxide displayed no specific analgesic, anti-inflammatory or local anaesthetic properties. Mild, dose-related diuresis was observed in rats. Simultaneous consideration of neuropharmacological data and the results obtained in general pharmacological assessment point to a certain superiority of amitriptylinoxide over other tricyclic antidepressants; this applies to amitriptyline in particular. Amitriptylinoxide can be expected to provide higher antidepressant potency but weaker sedation together with clearly less severe cardiac and peripheral anticholinergic side effects" 0 1391 A. J. Hansen and C. E. Olsen 1980 Brain extracellular space during spreading depression and ischemia Acta Physiol Scand. 108 4 355-365 "The change of extracellular space volume of rat brain cortex during ischemia and cortical spreading depression, CSD (Leao 1944) was evaluated by a new method. The cortical surface was irrigated with isotonic CSF containing the extracellular markers 50 mM cholin or 50 mM trimethyltris(hydroxymethyl)methyl ammonium ion (N-TRIS), and their extracellular concentrations were monitored by ion-selective microelectrodes. When steady-state for the concentration of these markers was attained, CSD evoked a reversible increase of the concentration of the markers, indicating shrinkage of the interstitial volume of distribution. During ischemia an initial slow rate of concentration increase was observed, followed a few minutes later by a rapid increase concomitant with the sharp rise in extracellular potassium concentration. During CSD and ischemia, the maximal increases of choline and N-TRIS concentration reflected a shrinkage of the extracellular space amounting to about 50% of the initial volume" http://www.ncbi.nlm.nih.gov/pubmed/7415848 0 1392 N. P. Shugalev 1983 [Effect of stimulation of GABA-ergic structures of the substantia nigra and caudate nucleus on food-getting behavior in the cat] Zh.Vyssh.Nerv.Deiat.Im I.P.Pavlova 33 3 486-492 "A study was made of the functional significance of GABA-ergic structures of the substantia nigra (SN) and the caudate nucleus (CN) and their role in food-procuring behaviour of cats. Analysis was made of behavioral and EEG-effects of local GABA and the GABA antagonist, picrotoxin, microinjections into the studied brain structures. Stimulation of the GABA-ergic structures of the SN produced a sedative effect and depression of the cat food-procuring behaviour. Effects of stimulation of the CN GABA-ergic structures were to a great degree reverse. The conclusion has been made that GABA-ergic structures of the SN and the CN play different roles in controlling the CN inhibitory influence upon food-procuring behaviour" http://www.ncbi.nlm.nih.gov/pubmed/6613342 0 1393 "H. Stoeckel, J. H. Hengstmann and J. Schuttler" 1979 Pharmacokinetics of fentanyl as a possible explanation for recurrence of respiratory depression Br.J.Anaesth. 51 8 741-745 "The pharmacokinetics of fentanyl are complicated by an additional increase in plasma concentration during the elimination phase of the drug. We have confirmed that fentanyl is excreted in the gastric juice and reabsorbed from the alkaline medium of the small intestine. In addition, the stomach wall in rats has an important storage capacity for fentanyl. A maximum of about 20% of the dose was found in the stomach wall after i.v. injection. In man the resected part of the stomach contained 16% of the dose, 10 min after injection. These observations could be important in explaining the occurrence of respiratory depression in the period after operation" http://www.ncbi.nlm.nih.gov/pubmed/497071 0 1394 "J. D. Amsterdam, N. Berwish, L. Potter and K. Rickels" 1987 Open trial of gepirone in the treatment of major depressive disorder "Current Therapeutic Research - Clinical and Experimental.41 (2) ()(pp 185-193), 1987.Date of Publication: 1987." 2 185-193 "Gepirone hydrochloride is a putative antidepressant and anxiolytic compound that is similar to buspirone, but structurally distinct from benzodiazepines. Chronic administration of gepirone to animals results in alteration of central nervous system serotonergic neurotransmitter systems, suggesting a potential antidepressant action. The present study was an open-label assessment of the potential antidepressant action of gepirone in patients with major depression. We demonstrated a significant overall antidepressant effect of gepirone. Nonmelancholic patients improved slightly more than melancholic patients, and patients with greater symptom severity improved more rapidly than less severely depressed patients. These data suggest that gepirone may represent a potential antidepressant agent" 0 1395 N. Toda 1972 "Modification by Ca ++ removal, Mg ++ and Sr ++ of the membrane effect and the inotropic effect of norepinephrine in rabbit left atria" J.Pharmacol.Exp.Ther. 180 3 698-709 http://www.ncbi.nlm.nih.gov/pubmed/5012788 0 1396 "H. Tamura, T. Tsumoto and Y. Hata" 1992 Activity-dependent potentiation and depression of visual cortical responses to optic nerve stimulation in kittens J.Neurophysiol. 68 5 1603-1612 "1. To see whether long-lasting changes in synaptic efficacy are induced in the developing visual cortex (VC), field potentials evoked by test stimulation given alternatively to each of the optic nerves (ONs) were recorded from VC of kittens ranging in age from 4 to 8 wk. In some experiments, field potentials were recorded simultaneously from the dorsal lateral geniculate nucleus (LGN) in addition to VC. 2. Tetanic stimulation was applied to one of the ONs for 1-60 min at 5 Hz. Homosynaptic potentiation of cortical responses, defined as an increase lasting > 2.5 h in the cortical field potential evoked by test stimulation of the ON that was tetanized, was induced without any changes in LGN responses in 3 of the 12 kittens tested. Heterosynaptic depression, defined as a decrease lasting > 0.5 h in the field potential evoked by stimulation of the ON that was not tetanized, was also induced in two of those three kittens. 3. To elucidate a role of inputs originating from spontaneous activity of retinal ganglion cells in induction of potentiation and depression in the cortex, tetrodotoxin (TTX) was injected into both eyes of 11 kittens. After we confirmed the suppression of retinal activity by TTX, tetanic stimulation was applied to ON. Homosynaptic potentiation of cortical responses was induced in 6 of the 11 kittens, and the ratio of the mean amplitude of posttetanic responses to that of pretetanic responses for the 11 kittens was on average larger than that for the 12 control kittens. Heterosynaptic depression was not observed in any of the 11 kittens. 4. To see a role of postsynaptic activity in induction of potentiation and depression, gamma-aminobutyric acid (GABA) was applied continuously to the VC by an infusion pump in 10 kittens. Tetanic stimulation was given to ON while cortical activities were suppressed by GABA. After recovery of cortical activities, homosynaptic depression was found to be induced in 3 of the 10 kittens, but homosynaptic potentiation was not observed at all. The ratio of amplitude of posttetanic to pretetanic responses at the tetanized side for the 10 kittens was on average smaller than that for the 11 TTX-injected kittens. 5. These results can be accounted for by the modified covariance model in which the relation of postsynaptic activity and direction of changes in synaptic efficacy is formulated.(ABSTRACT TRUNCATED AT 400 WORDS)" http://www.ncbi.nlm.nih.gov/pubmed/1479433 0 1397 L. A. Dawson and H. Q. Nguyen 2000 The role of 5-HT(1A) and 5-HT(1B/1D) receptors on the modulation of acute fluoxetine-induced changes in extracellular 5-HT: the mechanism of action of (+/-)pindolol Neuropharmacology 39 6 1044-1052 "Some clinical evidence has suggested that (+/-)pindolol can be effective at producing a shortened time to onset of antidepressant activity when co-administered with a serotonin specific reuptake inhibitor (SSRI). This effect has been attributed to the antagonist effects of pindolol at the 5-HT(1A) receptor. In the present study, we compared the pharmacology of (+/-)pindolol, WAY-100635 (a 5-HT(1A) antagonist), GR127935 (a 5-HT(1B/1D) antagonist), and isamoltane (a 5-HT(1B) antagonist), when given acutely in combination with fluoxetine, using in vivo microdialysis in the frontal cortex of the freely moving rat. We have determined that the acute fluoxetine-induced increases in extracellular 5-HT can be augmented by (+/-)pindolol, WAY100635, GR127935 and isamoltane with maximum increases of 216+/-32%, 235+/-49%, 240+/-18% and 171+/-47% of preinjection control levels, respectively. Combination of both 5-HT(1A) and 5-HT(1B/1D) autoreceptor antagonists with fluoxetine produced additive increases in extracellular 5-HT (i.e. WAY100635+GR127935+fluoxetine and WAY100635+isamoltane+fluoxetine produced a four- and five-fold potentiation, respectively), suggesting that this strategy may be useful in further augmenting the action of a SSRI in the treatment of depression. In addition, by comparing the combined administration of (+/-)pindolol with either WAY100635, GR127935 or isamoltane, we have determined that (+/-)pindolol produces much of its acute potentiation of fluoxetine-induced increases in extracellular 5-HT via its action at the 5-HT(1B/D) receptor in addition to any activity it has at the presynaptic 5-HT(1A) receptor" http://www.ncbi.nlm.nih.gov/pubmed/10727715 0 1398 L. Reif-Lehrer and H. Amos 1968 Hydrocortisone requirement for the induction of glutamine synthetase in chick-embryo retinas Biochem.J. 106 2 425-430 Hydrocortisone has been found to induce glutamine synthetase activity in chick-embryo retinas in culture. Evidence is presented to show that the hydrocortisone is definitely required for transcription; its requirement for translation has not been ruled out. The possible identity of hydrocortisone with an active component of calf-serum diffusate reported earlier is discussed. The data also indicate that the glutamine synthetase messenger RNA is stable for at least several hours http://www.ncbi.nlm.nih.gov/pubmed/5637352 0 1399 V. A. Zhukova 1969 [Combined effect of cardiac glycosides and diuretics of some functions of heart] Farmakol.Toksikol. 32 6 690-692 http://www.ncbi.nlm.nih.gov/pubmed/5381599 0 1400 "P. Darcy, J. P. Kelly, B. E. Leonard and J. A. Henry" 2002 The effect of lofepramine and other related agents on the motility of Tetrahymena pyriformis Toxicol.Lett. 128 01-Mar 207-214 "Tricyclic antidepressants (TCAs) were introduced almost 50 years ago. Whilst there is no doubt that TCAs are effective in treating depression, they are also more cardiotoxic when taken in overdose than other antidepressant groups. Lofepramine is a more recently introduced modified TCA, which in animals and man has low toxicity when compared to older TCAs. Paradoxically, lofepramine is extensively metabolised to desipramine, which has considerable toxicity, both experimentally and in overdose. The toxicity of such compounds is attributed, in part, to a membrane stabilising effect (MSA) on cell membranes. This MSA causes gross effects to the cell structure and in turn, normal cell activity. The aim of this study was to compare the MSA of lofepramine with that of desipramine and amitriptyline in order to see if this might help to explain the low toxicity of lofepramine. The local anaesthetic agent lignocaine was also studied for comparison. Each compound was enclosed in a beta-cyclodextrin to increase its solubility in aqueous medium. The extent of MSA was determined as a measure of the effect on the swimming speed of the protozoan Tetrahymena pyriformis using a video image analysis system. The IC50s for the various drugs were then correlated with their respective octanol-water partition coefficient values (Pow). Amitriptyline had an IC50 of 1.26+/-0.29 mM, desipramine 75.99+/-14.40 mM, while lofepramine had an IC50 of 357.40+/-25.00 mM. Lignocaine had an IC50 of 85.73+/-18.30 mM. There was also a significant correlation between the IC50 values and the Pow values" http://www.ncbi.nlm.nih.gov/pubmed/11869831 0 1401 G. Pesce and F. J. Stefano 1982 Cardiovascular effects of 2-Br-alpha-ergocriptine in urethane anesthetized rats Acta Physiol Lat.Am. 32 2 117-122 "Experiments were designed to study the cardiovascular effects of Bromocriptine (2-Br-alpha-ergocriptine) in the normotensive anesthetized rats. The intravenous administration of bromocriptine (20 micrograms/kg and 200 micrograms/kg) produced a long-lasting and not dose-dependent fall in the mean blood pressure and heart rate. The pressor response to phenylephrine, an alpha adrenergic agonist, was antagonized by bromocriptine in a dose-dependent manner. At a dose of 20 micrograms/kg bromocriptine behaved as a competitive antagonist, whereas at the dose of 200 micrograms/kg produced an insurmountable blockade of the response to phenylephrine. Previous administration of phentolamine (5 mg/kg) prevented the insurmountable blockade of alpha adrenoceptors by bromocriptine. This observation suggests that both drugs compete for the same receptor. It is concluded that blockade of peripheral alpha-adrenoceptors may contribute to cardiovascular effects of bromocriptine" http://www.ncbi.nlm.nih.gov/pubmed/7170990 0 1402 "J. A. Sokal, B. Baranski, J. Majka, R. Rolecki, J. Stetkiewicz, L. Ivanova-Chemishanska, T. Vergieva, G. Antonov, E. Mirkova, J. Kolakowski, S. Szendzikowski and K. Wroblewska" 1980 Experimental studies on the chronic toxic effects of vinyl chloride in rats J.Hyg.Epidemiol.Microbiol.Immunol. 24 3 285-294 "Male rats were exposed to vinyl chloride at the concentrations of 50, 500, and 20 000 ppm, 5 hours daily, 5 days a week for 10 months. Morphological lesions in the liver and the testes detected by light and electron microscope and depression in body weight increase intensified with the duration of exposure. Increased relative weights of some organs and slight hematological and biochemical changes in blood during the course of the experiment were also observed. Some toxic effects including morphological liver injuries arose at the smallest exposure level, i. e., 50 ppm. Assuming 50 ppm as the threshold concentration for rats, the 5 ppm level has been estimated as the safe exposure limit in industry in relation to systemic effects of vinyl chloride" http://www.ncbi.nlm.nih.gov/pubmed/6449527 0 1403 "M. B. Hennessy, N. P. Stafford, B. Yusko-Osborne, P. A. Schiml, E. D. Xanthos and T. Deak" 2015 Naproxen attenuates sensitization of depressive-like behavior and fever during maternal separation Physiol Behav. 139 34-40 "Early life stress can increase susceptibility for later development of depressive illness though a process thought to involve inflammatory mediators. Isolated guinea pig pups exhibit a passive, depressive-like behavioral response and fever that appear mediated by proinflammatory activity, and which sensitize with repeated separations. Treatment with an anti-inflammatory can attenuate the behavioral response during the initial separation and separation the following day. Here we used the cyclooxygenase inhibitor naproxen to examine the role of prostaglandins in mediating the depressive-like behavior and core body temperature of young guinea pigs during an initial separation, separation the next day, and separation 10 days after the first. The passive, depressive-like behavior as well as fever sensitized with repeated separation. Three days of injection with 14 mg/kg of naproxen prior to the initial separation reduced depressive-like behavior during all three separations. A 28 mg/kg dose of naproxen, however, had minimal effect on behavior. Fever during the early separations was moderated by naproxen, but only at the higher dose. These results suggest a role of prostaglandins in the behavioral and febrile response to maternal separation, and particularly in the sensitization of depressive-like behavior following repeated separation" http://www.ncbi.nlm.nih.gov/pubmed/25449392 1 1404 "Q. Robberechts, M. Wijnants, M. Giugliano and S. E. De" 2010 Long-term depression at parallel fiber to Golgi cell synapses J.Neurophysiol. 104 6 3413-3423 "Golgi cells (GoCs) are the primary inhibitory interneurons of the granular layer of the cerebellum. Their inhibition of granule cells is central to operate the relay of excitatory inputs to the cerebellar cortex. Parallel fibers (PFs) establish synapses to the GoCs in the molecular layer; these synapses contain AMPA, N-methyl-D-aspartate (NMDA), and mostly group II metabotropic glutamate receptors. Long-term changes in the efficacy of synaptic transmission at the PF-GoC synapse have not been described previously. We used whole cell patch-clamp recordings of GoCs in acute rat cerebellar slices to study synaptic plasticity. We report that high-frequency burst stimulation of PFs, using a current-clamp or voltage-clamp induction protocol, gave rise to long-term depression (LTD) at the PF-GoC synapse. This form of LTD was not associated with persistent changes of paired-pulse ratio, suggesting a postsynaptic origin. Furthermore, LTD induction was not dependent on activation of NMDA receptors. PF-GoC LTD does require activation of specifically group II metabotropic glutamate receptors and of protein kinase A" http://www.ncbi.nlm.nih.gov/pubmed/20861429 0 1405 "P. Ney, R. K. Pandita, D. T. Newgreen, A. Breidenbach, T. Stohr and K. E. Andersson" 2008 "Pharmacological characterization of a novel investigational antimuscarinic drug, fesoterodine, in vitro and in vivo" BJU.Int. 101 8 1036-1042 "OBJECTIVE: To investigate the primary pharmacology of fesoterodine (a novel antimuscarinic drug developed for treating overactive bladder) and SPM 7605 (its active metabolite, considered to be the main pharmacologically active principle of fesoterodine in man) against human muscarinic receptor subtypes, and to investigate in vitro and in vivo functional activity of these agents on the rat bladder compared with existing standard agents. MATERIALS AND METHODS: The displacement of radioligand binding by fesoterodine, SPM 7605 and standard agents in membrane preparations of Chinese hamster ovary (CHO) cells expressing the different human muscarinic receptors (M1-M5) was characterized. Agonistic and antagonistic activities were studied using different CHO cell lines stably expressing the human recombinant muscarinic receptor subtypes. The effects of fesoterodine and SPM 7605 on isolated bladder strips contracted by carbachol or electrical field stimulation (EFS) were investigated. In vivo the effects of fesoterodine and SPM 7605 on micturition variables were assessed using continuous cystometry in conscious female Sprague-Dawley rats, and compared to those of oxybutynin and atropine. RESULTS: In vitro SPM 7605 potently inhibited radioligand binding at all five human muscarinic receptor subtypes with equal affinity across all five. Fesoterodine had a similar balanced selectivity profile but was less potent than SPM 7605. Both substances were competitive antagonists of cholinergic agonist-stimulated responses in human M1-M5 cell lines and had a similar potency and selectivity profile to the radioligand-binding studies. In rat bladder strips, fesoterodine and SPM 7605 caused a rightward shift of the concentration-response curve for carbachol with no depression of the maximum, and concentration-dependently reduced contractions induced by EFS. The potency of both drugs was similar to that of atropine and oxybutynin. In the presence of the esterase inhibitor neostigmine, the concentration-response curve of fesoterodine was shifted to the right, suggesting that part of the activity was caused by metabolism to SPM 7605 by tissue enzymes. In vivo, low doses (0.01 mg/kg) of fesoterodine and SPM 7605 reduced micturition pressure and increased intercontraction intervals and bladder capacity, but did not affect residual volume. CONCLUSIONS: Fesoterodine and its active metabolite, SPM 7605, are nonsubtype selective, competitive antagonists of human muscarinic receptors, but SPM 7605 has greater potency than the parent compound. Pharmacodynamic studies in the rat bladder in vitro confirm the competitive muscarinic antagonist profile of these agents in a native tissue preparation, and in vivo studies in the rat showed effects on bladder function consistent with a muscarinic antagonist profile" http://www.ncbi.nlm.nih.gov/pubmed/18279452 0 1406 "H. Nishijima, K. Yonemoto and T. Sakai" 1972 [Effect of temperature and agents on Ca-uptake of the fragmented sarcoplasmic reticulum] Nihon Seirigaku Zasshi 34 1 28-39 http://www.ncbi.nlm.nih.gov/pubmed/4260671 0 1407 "J. I. Borroto, A. Creus, R. Marcos and J. Zapatero" 2005 In vivo genotoxic evaluation of the furylethylene derivative 1-(5-bromofur-2-yl)-2-nitroethene in mouse bone marrow Environ.Toxicol.Pharmacol. 20 1 241-245 "The genotoxic potential of the compound 1-(5-bromofur-2-yl)-2-nitroethene (2-betaNF) has been tested by using the in vivo mouse bone marrow micronucleus assay. Its ability to induce clastogenicity or aneugenicity, through the induction of micronucleated polychromatic erythrocytes (MNPCE) in the bone marrow cells has been evaluated. Treatment groups of five CD-1 male mice were administered once intraperitoneally at the doses of 10, 20, and 30mg/kg, and their bone marrows were sampled at 24 and 48h after the administration, at the first sampling time animals administered with the three doses were used, and in the second sampling time, only animals administered with the highest dose were used. All animals treated with the highest dose of the test compound (30mg/kg) showed evident clinical symptoms of toxicity such as irritation, hunched posture, slight ataxia, dyspnoea, piloerection, and palpebral ptosis. However, no marked depression of bone marrow cell proliferation was observed, and no significant increases in the frequency of MNPCE were obtained in any of the concentrations tested at any sampling times. The positive control treated-animals were administered with cyclophosphamide at the dose of 40mg/mL. The compound caused a significant increase in the number of MNPCE in all treated animals, demonstrating the sensitivity of the mouse strain used. From the results obtained, it is concluded that the compound 2-betaNF is neither clastogenic nor aneugenic in the erythrocytes from the bone marrow of treated mice at the doses tested" http://www.ncbi.nlm.nih.gov/pubmed/21783595 0 1408 L. L. Southern and D. H. Baker 1983 Excess manganese ingestion in the chick Poult.Sci. 62 4 642-646 "Two experiments were conducted with young chicks to investigate effects of excess manganese, (Mn) ingestion and to compare MnCl2 . 4H2O, MnSO4 . H2O, MnO2, and MnCO3 as sources of dietary Mn activity. Each source of Mn was added to a conventional corn-soybean meal diet to supply 3000, 4000, or 5000 mg/kg Mn. High levels of dietary Mn from MnSO4 . H2O and MnCl2 . 4H2O depressed growth slightly; MnO2 and MnCO3 did not affect chick performance. Manganese dioxide contained less Mn activity than MnCO3, MnSO4 . H2O, or MnCl2 . 4H2O as assessed by relative depressions in hemoglobin and hematocrit and by relative increases in bile, liver, and bone Mn concentrations. Neutralization of the chloride ion in MnCl2 . 4H2O with NaHCO3 did not ameliorate the adverse effects of excess, MnCl2 . 4H2O ingestion. Bone and bile Mn concentrations reflected Mn intake better than liver Mn concentration or rate and efficiency of weight gain" http://www.ncbi.nlm.nih.gov/pubmed/6866900 0 1409 X. Ji and G. E. Martin 2012 New rules governing synaptic plasticity in core nucleus accumbens medium spiny neurons Eur.J.Neurosci. 36 12 3615-3627 "The nucleus accumbens is a forebrain region responsible for drug reward and goal-directed behaviors. It has long been believed that drugs of abuse exert their addictive properties on behavior by altering the strength of synaptic communication over long periods of time. To date, attempts at understanding the relationship between drugs of abuse and synaptic plasticity have relied on the high-frequency long-term potentiation model of T.V. Bliss & T. Lomo [(1973) Journal of Physiology, 232, 331-356]. We examined synaptic plasticity using spike-timing-dependent plasticity, a stimulation paradigm that reflects more closely the in vivo firing patterns of mouse core nucleus accumbens medium spiny neurons and their afferents. In contrast to other brain regions, the same stimulation paradigm evoked bidirectional long-term plasticity. The magnitude of spike-timing-dependent long-term potentiation (tLTP) changed with the delay between action potentials and excitatory post-synaptic potentials, and frequency, whereas that of spike-timing-dependent long-term depression (tLTD) remained unchanged. We showed that tLTP depended on N-methyl-d-aspartate receptors, whereas tLTD relied on action potentials. Importantly, the intracellular calcium signaling pathways mobilised during tLTP and tLTD were different. Thus, calcium-induced calcium release underlies tLTD but not tLTP. Finally, we found that the firing pattern of a subset of medium spiny neurons was strongly inhibited by dopamine receptor agonists. Surprisingly, these neurons were exclusively associated with tLTP but not with tLTD. Taken together, these data point to the existence of two subgroups of medium spiny neurons with distinct properties, each displaying unique abilities to undergo synaptic plasticity" http://www.ncbi.nlm.nih.gov/pubmed/23013293 0 1410 "A. Bonito-Oliva, D. Masini and G. Fisone" 2014 A mouse model of non-motor symptoms in Parkinson's disease: focus on pharmacological interventions targeting affective dysfunctions Front Behav.Neurosci. 8 290 "Non-motor symptoms, including psychiatric disorders, are increasingly recognized as a major challenge in the treatment of Parkinson's disease (PD). These ailments, which often appear in the early stage of the disease, affect a large number of patients and are only partly resolved by conventional antiparkinsonian medications, such as L-DOPA. Here, we investigated non-motor symptoms of PD in a mouse model based on bilateral injection of the toxin 6-hydroxydopamine (6-OHDA) in the dorsal striatum. This model presented only subtle gait modifications, which did not affect horizontal motor activity in the open-field test. Bilateral 6-OHDA lesion also impaired olfactory discrimination, in line with the anosmia typically observed in early stage parkinsonism. The effect of 6-OHDA was then examined for mood-related dysfunctions. Lesioned mice showed increased immobility in the forced swim test and tail suspension test, two behavioral paradigms of depression. Moreover, the lesion exerted anxiogenic effects, as shown by reduced time spent in the open arms, in the elevated plus maze test, and by increased thigmotaxis in the open-field test. L-DOPA did not modify depressive- and anxiety-like behaviors, which were instead counteracted by the dopamine D2/D3 receptor agonist, pramipexole. Reboxetine, a noradrenaline reuptake inhibitor, was also able to revert the depressive and anxiogenic effects produced by the lesion with 6-OHDA. Interestingly, pre-treatment with desipramine prior to injection of 6-OHDA, which is commonly used to preserve noradrenaline neurons, did not modify the effect of the lesion on depressive- and anxiety-like behaviors. Thus, in the present model, mood-related conditions are independent of the reduction of noradrenaline caused by 6-OHDA. Based on these findings we propose that the anti-depressive and anxiolytic action of reboxetine is mediated by promoting dopamine transmission through blockade of dopamine uptake from residual noradrenergic terminals" http://www.ncbi.nlm.nih.gov/pubmed/25221486 1 1411 "N. A. Wright, H. S. Al-Dewachi, D. R. Appleton and A. J. Watson" 1978 The effect of single and of multiple doses of prednisolone tertiary butyl acetate on cell population kinetics in the small bowel mucosa of the rat Virchows Arch.B Cell Pathol. 28 4 339-350 "The effect of single and of multiple doses of prednisolone upon cell population kinetics in the rat jejunal crypt was investigated, using autoradiography and stathmokinetic techniques with vincristine. Single injections of prednisolone (2.5 mg/kg body weight) induced a depression both flash thymidine labelling and mitotic indices; this change was shown to be due to a decreased cell production rate. Recovery of these proliferative indices occurred over seven days after injection; measurement of crypt size parameters showed a transient decrease in crypt population. Multiple daily injections of prednisolone (1 mg/kg body weight) produced a more sustained decrease in labelling and mitotic indices, which lasted as long as injections were continued (7 days); stathmokinetic techniques showed decreases in cell production rates, and the crypt population was also depressed throughout this period. It is concluded that prednisolone depresses cell proliferative rates in rat jejunal mucosa" http://www.ncbi.nlm.nih.gov/pubmed/103298 0 1412 "F. F. Bermudez, J. M. Forbes and M. H. Injidi" 1983 "Involvement of melatonin and thyroid hormones in the control of sleep, food intake and energy metabolism in the domestic fowl" J.Physiol 337 19-27 "Growing male domestic fowl of an egg-laying strain were fed ad libitum and injected intraperitoneally with melatonin or intramuscularly with triiodothyronine (T3) to study the effects on sleep, food intake, blood glucose, e.e.g., oxygen consumption and carbon dioxide production. Melatonin caused a dose-related depression of food intake with sleep and aphagia lasting for 2 1/2 hr following 8 mg, drowsiness and greatly reduced intake following 4 and 2 mg and a slight reduction in food intake after 1 mg. T3 injection was followed by increased feeding within the range 50-200 micrograms. The higher dose (200 micrograms) completely prevented the effects of 10 mg melatonin injected simultaneously. Melatonin (10 mg) depressed plasma glucose levels whereas T3 (200 micrograms) elevated blood glucose. Either darkness or melatonin (10 mg) caused an increase in amplitude and a decrease in frequency of the e.e.g. Birds fasted for 3 hr before injection showed significantly lower oxygen consumption and carbon dioxide production when given melatonin (10 mg); T3 had no effect within the 4 hr period after injection and did not modify the effects of melatonin. It is postulated that the rapid effects of melatonin and T3 which were observed result from direct effects of these hormones on the central nervous system" http://www.ncbi.nlm.nih.gov/pubmed/6410055 0 1413 Y. Furuya and H. Ogura 1997 Competitive NMDA and strychnine-insensitive glycine-site antagonists disrupt prepulse inhibition Pharmacol.Biochem.Behav. 57 4 909-913 "Prepulse inhibition (PPI) is thought to reflect the operation of a sensorimotor gating system in the brain. Sensorimotor gating abnormalities have been identified in schizophrenic patients, and various neural systems are involved in this function. To study the modulation of the sensorimotor gating system by the N-methyl-D-aspartate (NMDA) receptor channel complex, the effects of noncompetitive and competitive NMDA antagonists on PPI were examined in rats. PPI was not disrupted by CGS 19755, a competitive NMDA antagonist, at 30 min after subcutaneous (s.c.) administration. However, CGS 19755 (40 mg/kg s.c.) decreased PPI at 120 min after administration with a marked decrease of startle amplitude. Late onset of the effect of CGS 19755 was also observed in the increase of spontaneous locomotor activity (SLA). On the other hand, phencyclidine, a noncompetitive NMDA antagonist, disrupted PPI at 30 min after administration and increased SLA from 20 min after administration. PPI was also disrupted by bilateral intracerebroventricular administration of 5,7-dichlorokyn urenate (10 and 20 micrograms/side X 2), an antagonist at the strychnine-insensitive glycine receptor, which is an allosteric binding site in the NMDA receptor-channel complex. It is concluded that the NMDA receptor-channel complex plays an important role in regulation of PPI" http://www.ncbi.nlm.nih.gov/pubmed/9259023 0 1414 "E. Arrhenius, L. Renberg, L. Johansson and M. A. Zetterqvist" 1977 Disturbance of microsomal detoxication mechanisms in liver by chlorophenol pesticides Chem.Biol.Interact. 18 1 35-46 "The pesticide pentachlorophenol known as an uncoupler of mitochondrial oxidative phosphorylation was shown to disturb liver microsomal detoxication functions by a selective inhibition of the terminal oxygenation enzyme P-450. At lower concentrations the flavin moiety of this enzyme chain is not inhibited but rather is stimulated, whereby a qualitative shift in detoxication of aromatic amines from C-oxygenation to N-oxygenation is obtained. The effects were due to the pentachlorophenol itself and not to a metabolite. Similar effects of varying strength were also obtained with other chlorophenol pesticides; 2,4,di-, 2,4,6,-tri and 2,3,4,6-tetrachlorophenol, di- and hexachlorophen, tri- and nonachloro-2-hydroxydiphenyl ethers. The relevance of these findings to the possible synergistic influence of chlorophenols on the carcinogenic effects of polyaromatic amines and hydrocarbons is discussed" http://www.ncbi.nlm.nih.gov/pubmed/890839 0 1415 "J. A. Baird, J. R. Hales and W. J. Lang" 1974 "Thermoregulatory responses to the injection of monoamines, acetylcholine and prostaglandins into a lateral cerebral ventricle of the echidna" J.Physiol 236 3 539-548 "1. The putative neurotransmitter substances 5-hydroxytryptamine (5-HT), noradrenaline (NA), acetylcholine (ACh) and prostaglandins E(1) (PGE(1)) and E(2) (PGE(2)) have been injected into a lateral cerebral ventricle of the conscious echidna (Tachyglossus aculeatus); thermoregulatory responses in thermoneutral (ambient dry bulb temperature, T(db), of approximately 22 degrees C), cool (T(db) of approximately 14 degrees C) and warm (T(db) of approximately 26 degrees C) environments were determined.2. Under all conditions, all of the drugs tested either caused deep body temperature to fall or else had no effect; the fall was brought about by peripheral vasodilatation and/or reduced metabolic rate due to a decrease in shivering or to general relaxation.3. Responses of the many placental mammals to 5-HT, NA and ACh vary widely, and the echidna, a monotreme, appears to exhibit responses most like those of the rat.4. Placental mammals tested to date invariably exhibit a hyperthermic response to prostaglandins, and the hypothermic responses of this monotreme is therefore unique. The present study included the confirmation of a hyperthermic response to PGE(1) and PGE(2) in cats and rats.5. It is concluded that the concept of thermoregulation by amines and other substances in the hypothalamus of placental mammals may also be applicable to the monotremes which have evolved separately from the marsupials and placental mammals for about 180 million years" http://www.ncbi.nlm.nih.gov/pubmed/4822575 0 1416 "C. Castellano, M. Battaglia and M. Sansone" 1992 Oxiracetam prevents haloperidol-induced passive avoidance impairment in mice Pharmacol.Biochem.Behav. 42 4 797-801 "The nootropic drug oxiracetam (50 mg/kg) prevented passive avoidance impairment induced by posttraining administration of haloperidol (0.25 and 0.5 mg/kg). Conversely, oxiracetam did not antagonize either locomotor depression or suppression of active avoidance responses induced by the dopamine receptor blocking agent. The results indicate that prevention of haloperidol-induced retention impairment, by oxiracetam, may be due to a not yet defined protective action, common to other nootropic agents, on different types of experimental amnesias, rather than to a specific interaction with dopaminergic mechanisms" http://www.ncbi.nlm.nih.gov/pubmed/1513861 0 1417 "W. K. Kim, P. G. Jang, M. S. Woo, I. O. Han, H. Z. Piao, K. Lee, H. Lee, T. H. Joh and H. S. Kim" 2004 A new anti-inflammatory agent KL-1037 represses proinflammatory cytokine and inducible nitric oxide synthase (iNOS) gene expression in activated microglia Neuropharmacology 47 2 243-252 "Excessive proinflammatory cytokine and NO production by activated microglia play a role in neurodegenerative disorders. In this study, we found that a new compound KL-1037 suppressed LPS-induced NO release/inducible nitric oxide synthase expression in BV2 mouse microglial cells. In addition, KL-1037 prominently diminished LPS-induced production of pro-inflammatory cytokines such as TNF-alpha, IL-1 beta and IL-6, while it increased anti-inflammatory IL-10 and TGF-beta 1 production. By RNase protection assay and RT-PCR, we showed that KL-1037 regulated iNOS and cytokines at transcriptional or post-transcriptional level. Further analysis of molecular mechanisms revealed that KL-1037 prominently increased intracellular cAMP levels and potentiated LPS-induced pCREB expression. However, LPS-induced MAP kinase or NF-kappa B activities were slightly or little changed by KL-1037. Treatment with cAMP antagonist or IL-10 neutralizing antibody completely reversed upregulation of IL-10 and partially repression of TNF-alpha or NO induced by KL-1037. These data suggest that microglial inactivation by KL-1037 is at least in part due to activation of PKA pathway and/or upregulation of IL-10. Thus, repressing proinflammatory cytokines and iNOS gene expression in activated microglia by KL-1037 may provide potential therapeutic strategies for various neurodegenerative diseases including ischemic cerebral disease" http://www.ncbi.nlm.nih.gov/pubmed/15223303 0 1418 N. Konow and D. R. Bellwood 2005 "Prey-capture in Pomacanthus semicirculatus (Teleostei, Pomacanthidae): functional implications of intramandibular joints in marine angelfishes" J.Exp.Biol. 208 Pt 8 1421-1433 "We examined prey-capture morphology and kinematics in the angelfish, Pomacanthus semicirculatus (Cuvier 1931), to evaluate the magnitude and role of functional specialisation. The feeding apparatus of P. semicirculatus possess three biomechanical mechanisms of particular interest: (1) a novel intramandibular joint, permitting dentary rotation and protruded jaw closure; (2) an opercular linkage facilitating mandible depression; and (3) a suspensorial linkage with two novel points of flexion, permitting anterior rotation of the suspensorium and augmenting mandible protrusion. Prey-capture kinematics were quantified using motion analysis of high-speed video, yielding performance profiles illustrating timing of onset, duration and magnitude of movement in these three biomechanical systems, and other variables traditionally quantified in studies of teleostean ram-suction feeding activity. Mandible depression and suspensorial rotation both augmented mandible protrusion, and coincided during jaw protrusion, typically increasing head length by 30%. Jaw closure appeared to result from contraction of the adductor mandibulae segment A2, which rotated the dentary by approximately 30 degrees relative to the articular. This resulted in jaw closure with the mandible fully depressed and the jaws at peak-protrusion. Feeding events were concluded by a high-velocity jaw retraction (20-50 ms), and completed in 450-750 ms. Feeding kinematics and morphology of Pomacanthus differed from other biting teleosts, and more closely resemble some long-jawed ram-suction feeders. The structural and functional modifications in the Pomacanthus feeding apparatus are matched to an unusual diet of structurally resilient and firmly attached benthic prey" http://www.ncbi.nlm.nih.gov/pubmed/15802666 0 1419 "X. Fauvergue, J. C. Malausa, L. Giuge and F. Courchamp" 2007 Invading parasitoids suffer no Allee effect: a manipulative field experiment Ecology. 88 9 2392-2403 "One frequent explanation for the failure of biological invasions is the Allee effect: due to positive density dependence, initially small invading populations may fail to establish and spread. Populations released for biological control are similar to fortuitous invading populations and may therefore suffer from Allee effects. However, unlike fortuitous invasions, biological control allows the experimental manipulation of initial population size and, thus, offers a unique opportunity to test for the occurrence of Allee effects. We manipulated the initial size of 45 populations of a parasitoid wasp introduced for the biological control of a phytophagous insect and followed the population dynamics of both parasitoids and hosts during three years. Our results suggest an absence of Allee effects but clear negative density dependence instead: (1) the probability of establishment after three years was not affected by initial population size; (2) net reproductive rate was highest at low parasitoid density and high host density; (3) the sex ratio, reflecting the proportion of virgin females, did not increase at low density, suggesting that low densities did not impede mate-finding; (4) the depression of host populations did not depend upon the number of parasitoids introduced. This is, to our knowledge, the first experimental test of the Allee effect in an invading parasitoid. It leads us to propose that a number of behavioral and life-history features of many parasitoids could protect them from Allee effects" http://www.ncbi.nlm.nih.gov/pubmed/17918416 0 1420 "E. Estrada-Camarena, A. Fernandez-Guasti and C. Lopez-Rubalcava" 2003 Antidepressant-like effect of different estrogenic compounds in the forced swimming test Neuropsychopharmacology 28 5 830-838 "The present study evaluated the possible antidepressant-like action of the natural estrogen 17beta-estradiol (E(2), 2.5-10 microg/rat), the synthetic steroidal estrogen ethinyl-estradiol (EE(2), 1.25-10.0 microg/rat), and the nonsteroidal synthetic estrogen, diethyl-stilbestrol (DES, 0.25-1.0 mg/rat) in ovariectomized adult female Wistar rats using the forced swimming test (FST). The behavioral profile induced by the estrogens was compared with that induced by the antidepressants fluoxetine (FLX, 2.5-10 mg/kg) and desipramine (DMI, 2.5-10 mg/kg). In addition, the temporal course of the antidepressant-like action of the estrogenic compounds was analyzed. FLX and DMI induced an antidepressant-like effect characterized by a reduced immobility and increased swimming for FLX and decreased immobility and increased climbing for DMI. Both E(2) and EE(2) produced a decrease in immobility and an increase in swimming, suggesting an antidepressant-like action. DES did not affect the responses in this animal model of depression at any dose tested. The time course analysis of the actions of E(2) (10 microg/rat) and EE(2) (5 microg/rat) showed that both compounds induced an antidepressant-like effect observed 1 h after their injection lasting for 2-3 days" http://www.ncbi.nlm.nih.gov/pubmed/12637949 1 1421 "M. J. Meyler, H. Wesseling and S. Agoston" 1976 The effects of dantrolene sodium on cardiac and skeletal muscle in rats Eur.J.Pharmacol. 39 1 127-131 Dantrolene sodium in different concentrations was administered to the spontaneously beating heart placed in a modified Langendorff apparatus. Heart frequency and contractility were recorded. Dantrolene sodium was also administered to the rat diaphragm. Twitch tension after indirect supramaximal stimulation was recorded. Dantrolene sodium produced a long lasting dose-dependent reduction of the contractility of the isolated rat heart up to 75% of control values. It had no effect on the heart frequency. The drug also decreased the force of contraction of the rat skeletal muscle in vitro to the same extent. The diaphragm appeared to be more sensitive to low concentrations of dantrolene sodium than was heart muscle i.e. the dose-response curve on rat diaphragm was flatter. It may be concluded however that higher concentrations of dantrolene sodium may effect the contractility of heart muscle as well and that this may have clinical implications http://www.ncbi.nlm.nih.gov/pubmed/964299 0 1422 "J. A. Terron, A. Sanchez-Lopez, J. E. Ramirez-San, C. Castillo and C. M. Villalon" 1996 Influence of 5-hydroxytryptamine on the pressor responses induced by norepinephrine and electrical sympathetic stimulation in the pithed rat Arch.Med.Res. 27 3 291-297 "Serotonin (5-hydroxytryptamine; 5-HT) modifies the responses to several vasoconstrictor stimuli prejunctionally and/or postjunctionally. The present study analyzed the effects of 5-HT on the pressor responses induced by norepinephrine (NE) or electrical sympathetic stimulation in pithed rats. Responses to intravenous (i.v.) NE (0.03-3 micrograms/kg) or electrical stimulation at increasing frequencies (0.1-3 Hz) were evaluated before and during continuous i.v. infusions of physiological saline (0.01 ml/min) or 5-HT (1-10 micrograms/kg x min). The effects of 5-HT on the tachycardic responses to NE and sympathetic stimulation were studied in parallel. The increases in diastolic blood pressure and heart rate produced by NE were not modified by 5-HT. In contrast, 5-HT significantly and dose-dependently inhibited the increases in diastolic blood pressure - but not those in heart rate - produced by stimulation of the appropriate spinal segments. These effects of 5-HT were more pronounced on the responses to lower frequencies of stimulation. It is suggested that 5-HT inhibits the electrically induced pressor responses by a prejunctional mechanism which would lead to a reduction of neurotransmitter release from the sympathetic nerves supplying the systemic vasculature. The selective stimulation of this inhibitory mechanism might represent a new approach for the development of novel antihypertensive agents" http://www.ncbi.nlm.nih.gov/pubmed/8854384 0 1423 K. Okada 1970 Effects of divalent cations on the spontaneous transmitter release at the amphibian neuromuscular junction in the presence of ethanol Jpn.J.Physiol 20 1 97-111 http://www.ncbi.nlm.nih.gov/pubmed/5311129 0 1424 "D. S. Lee, P. Choy, M. Davi, R. Caces, D. Gibson, S. U. Hasan, D. Cates and H. Rigatto" 1989 Decrease in plasma prostaglandin E2 is not essential for the establishment of continuous breathing at birth in sheep J.Dev.Physiol 12 3 145-151 "Depression of prostanoid concentrations by indomethacin induces continuous breathing in fetal sheep, but it is not known whether this is associated with changes in fetal behaviour. Furthermore, the relationship between changes in prostaglandin E2 (PGE2) concentration after delivery and the appearance of continuous breathing has not been examined. We hypothesized that the decrease in fetal PGE2 by infusion of indomethacin would induce continuous breathing and a change in behaviour such that the fetus should come to resemble a newborn lamb; and coinciding with the establishment of continuous breathing at birth, PGE2 concentrations would decrease to a critical level below that present in the fetus. We found that continuous breathing in fetal sheep induced by infusion of indomethacin was related to a decrease in PGE2 from 436 +/- 114 to 189 +/- 73 pg/ml (P less than 0.005) but that this was not associated with fetal wakefulness. In addition, measurements of carotid arterial PGE2 concentrations showed that the beginning of continuous breathing after birth occurred at a plasma concentration of PGE2 of 1245 +/- 260 pg/ml, a value about three times higher than the 422 +/- 53 pg/ml measured in the fetus during breathing activity. Together these findings suggest that PGE2 is not primarily involved in the establishment of continuous breathing at birth" http://www.ncbi.nlm.nih.gov/pubmed/2625514 0 1425 "M. V. Schmidt, M. Paez-Pereda, F. Holsboer and F. Hausch" 2012 The prospect of FKBP51 as a drug target ChemMedChem. 7 8 1351-1359 "The FK506 binding protein 51 (FKBP51) is best known as an Hsp90-associated co-chaperone that regulates the responsiveness of steroid hormone receptors. In human genetic association studies, FKBP51 has repeatedly been associated with emotion processing and numerous stress-related affective disorders. It has also been implicated in contributing to the glucocorticoid hyposensitivity observed in New World primates. More recently, several research groups have consistently shown a protective effect of FKBP51 knockout or knockdown on stress endocrinology and stress-coping behavior in animal models of depression and anxiety. The principal druggability of FKBP51 is exemplified by the prototypic FKBP ligands FK506 and rapamycin. Moreover, FKBP51 is highly suited for X-ray co-crystallography, which should facilitate the rational drug design of improved FKBP51 ligands. In summary, FKBP51 has emerged as a promising new drug target for stress-related disorders that should be amenable to drug discovery" http://www.ncbi.nlm.nih.gov/pubmed/22581765 0 1426 "N. M. Czekala, J. K. Hodges, G. E. Gause and B. L. Lasley" 1980 Annual circulating testosterone levels in captive and free-ranging male armadillos (Dasypus novemcincuts) J.Reprod.Fertil. 59 1 199-204 "Mean circulating concentrations and seasonal changes in plasma testosterone over 3 years were similar in free-ranging and captive male armadillos. The highest concentrations were seen in the summer months, i.e. at the time of maximum breeding, but the relatiely high values at other times and the inability of ACTH to restore dexamethasone-suppressed testosterone concentrations confirms that testicular function continues throughout the year. There was a gradual rise in plasma testosterone to adult levels from the 5th to the 9th month of life in captive-born males, indicating that sexual maturity is reached within the first year of life and that captivity is not deleterious to Leydig cell function" http://www.ncbi.nlm.nih.gov/pubmed/6249926 0 1427 "A. K. Jaiswal, S. N. Upadhyay, K. S. Satyan and S. K. Bhattacharya" 1996 Behavioural effects of prenatal and postnatal undernutrition in rats Indian J.Exp.Biol. 34 12 1216-1219 "Effects of pre- and post-natal undernutrition on anxiety and depression paradigms were studied in albino rats. Prenatal undernutrition was induced in rat pups by restricting the dam's daily food during the gestation period whereas postnatal undernutrition in rat pups was induced by rotating them between lactating and non-lactating maternalised females daily for 12 hr during suckling period from 2nd to 18th day after birth. At 2.5 to 3 months of age all the rat pups were subjected to (i) elevated plus maze behaviour, (ii) open-field behaviour, and (iii) swimming induced behavioural despair tests. The results indicate that postnatal undernutrition caused significantly increased anxiety in the elevated plus maze as well as in open-field behaviour tests. Whereas prenatal undernourishment caused lesser degree of anxiogenic behaviours in the elevated plus maze test. Prenatally undernourished rats showed increased anxiety in the open-field behaviour test. Both, pre- and post-natal undernutrition also lead to increased depressive behaviour in the behavioural despair test and postnatal undernourishment caused greater degree of behavioural despair" http://www.ncbi.nlm.nih.gov/pubmed/9246914 1 1428 T. Dinan 2011 Debate: The amine hypothesis is a dead end for drug development PRO: Monoamine Debate "International Journal of Psychiatry in Clinical Practice.Conference: 11th International Forum on Mood and Anxiety Disorders Budapest Hungary.Conference Start: 20111109 Conference End: 20111111.Conference Publication: (var.pagings).15 ()(pp 6), 2011.D" var.pagings 6 "For over half a century the pharmaceutical industry has largely focused on antidepressant development by targeting the monoaminergic system. Both the noradrenergic neuronal network, largely centred on the nucleus locus coeruleus and the serotonergic raphe nuclei have been the object of attention. This approach led to the development of the SSRIs which reduced the side-effects burden on patients but no significant improvement has taken place in terms of efficacy. At this point it must be obvious to all that the line of research is in a cul-de-sac and that further investment of resources in such a strategy is futile. One of the major deficits in the monoamine hypothesis of depression which has led to a search for monoamine acting drugs, lies in the fact that far too much credence has been given to data acquired from studies in rodents. Proportionately, there are far more monoamine neurones in a rat than a human brain. The result is that the role of monoamines in psychiatric illnesses has been greatly exaggerated. At this point almost every diagnosis in DSM-IV has been linked to monoamine malfunction. Given the relatively small number of monoamine neurones in the human brain this situation is ridiculous. A simple monoamine hypothesis is far too simplistic to explain the complexity of major depression. The industry faces the challenge of exiting the intellectual current cul-de-sac or exiting antidepressant research altogether. Sadly many companies have taken the latter route. Far more sophisticated psychobiological models need to be used in drug development, which take on board the full complexity of the depressive syndrome. It is obvious that in the overwhelming majority of patients that stress plays a major role, we need therefore to focus on stress mechanisms. Furthermore, it is beyond doubt that most depressed patients have a pro-inflammatory phenotype characterised by elevations in pro-inflammatory cytokines. This inflammatory component offers a potential drug-development target as do a variety of other biological processes associated with depression such as changes in trophic factors and in pivotal microRNAs. Surely the time has come to forego our obsession with monoamines" DO - http://dx.doi.org/10.3109/13651501.2011.626556 0 1429 D. M. Mirvis 1983 Differential electrocardiographic effects of myocardial ischemia induced by atrial pacing in dogs with various locations of coronary stenosis Circulation 68 5 1116-1126 "The spatial distribution of abnormal repolarization potentials caused by regional myocardial ischemia was determined in 45 dogs. Ameroid constrictors were placed around the left circumflex artery in 10, the left anterior descending artery in 10, and the right coronary artery in 10. Ten dogs without constrictors served as controls. Electrocardiographic events were determined from body surface isopotential distributions, which were computed from potentials sensed by 84 torso electrodes. In control dogs, pacing to heart rates of 230 to 250 beats/min increased the intensity of positive and negative surface extrema during the ST segment without altering their spatial features. Two weeks after placement of the ameroid constrictors, tachycardia induced abnormal negative potentials during the ST segment. Localization of these ischemic forces varied with the placement of the constrictor in a manner consistent with the affected perfusion territories. However, much of the torso surface was involved by all lesions, and only small zones of ST segment depression unique to specific lesions could be identified. In five additional dogs a constrictor was placed on the right coronary artery 3 months after implantation of a device on the circumflex vessel. ST segment patterns during pacing in dogs with two lesions were consistent with the sum of the two individual lesions. Thus, the regional nature of myocardial ischemia is detectable in the body surface isopotential distributions, but the degree of spatial overlap may limit the value of such techniques in extending the usefulness of clinical exercise-stress electrocardiography" http://www.ncbi.nlm.nih.gov/pubmed/6616791 0 1430 "M. Iijima, A. Ito, S. Kurosu and S. Chaki" 2010 Pharmacological characterization of repeated corticosterone injection-induced depression model in rats Brain Res. 1359 75-80 "Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis has been reported in patients with psychotic major depression (PMD), and a higher rate of cortisol hypersecretion is observed in PMD than in nonpsychotic patients. Approximately 19% of patients who meet the criteria for major depressive disorder (MDD) have psychotic features. Accumulated studies have indicated that repeated corticosterone (CORT) injections induce depressive behavioral and neurochemical manifestations in rodents. However, the pharmacological characterization of this model has not been fully established. In the present study, we investigated the pharmacological characteristics of this model. Rats received CORT injections (20 mg/kg, subcutaneously), once per day for 21 consecutive days prior to a behavioral test. The rats were then tested for depressive behavior using a forced swimming test. The repeated CORT injections increased the immobility time in the forced swimming test, indicating an increase in depressive-like behavior. An acute treatment with a glucocorticoid receptor antagonist, mifepristone, counteracted the depressive-like behavior. In contrast, an acute treatment with a selective serotonin reuptake inhibitor (SSRI), fluvoxamine, and a tricyclic antidepressant (TCA), imipramine, did not have any effect on this condition, while a combination of fluvoxamine and risperidone exerted an antidepressant-like effect. This observation is of interest in the light of the clinical findings that a combination of antidepressants and antipsychotics, but not SSRIs and TCAs, is effective for the treatment of patients with PMD. Based on previous findings and the present results, this model could be used as an animal model of PMD and may be useful for evaluating the antidepressant-like potential of compounds targeting the HPA axis" http://www.ncbi.nlm.nih.gov/pubmed/20813098 1 1431 K. L. Hansen 1973 The effect of castrix (crimidin) on pyridoxal-5'-phosphate and the activity of pyridoxal kinase Acta Vet.Scand. 14 4 495-500 http://www.ncbi.nlm.nih.gov/pubmed/4755759 0 1432 T. B. Gloveli 1985 [Effects of excluding reticuloseptal input on hippocampal electrical activity in the cat] Fiziol.Zh.SSSR Im I.M.Sechenova 71 1 80-86 "The effect of interruption of the reticulo-septal input on the electrical activity of CA1 and CA3 areas of the dorsal hippocampus was studied in cats. Lesion of the medial septal nuclei or the i.v. injection of chlorpromazine in low doses led to depression of the hippocampal theta activity. The reticulo-septal input is responsible for generation and the course of tonic sensory responses of the hippocampal neurons in both areas. The existence of the remaining principal types of sensory responses (phasic, complex) mainly depends upon the cortical input. The reticulo-septal input takes part only in the prolongation of these responses" http://www.ncbi.nlm.nih.gov/pubmed/3972140 0 1433 R. N. Willette and H. N. Sapru 1982 Peripheral versus central cardiorespiratory effects of morphine Neuropharmacology 21 10 1019-1026 "The administration of morphine sulfate (MS, 2 mg/kg) into the right atrium in decerebrate rats, produced a dramatic bradycardia, apnea, and a slight transient biphasic blood pressure response within 1 sec. The bradycardia was slowly restored to control levels within 8-10 min and was prevented by pretreatment with atropine. Apnea (7.3 +/- 2.2 sec) was followed by a period of rapid shallow breathing. Acute tolerance to these effects developed to subsequent doses of morphine. In paralyzed artificially ventilated animals, morphine produced: (1) cessation of phrenic nerve (PN) activity which was followed by bursts of shortened duration; and (2) concomitant excitation of the recurrent laryngeal nerve (RLN), this activity exhibited a continuous discharge which was asynchronous with that of phrenic nerve. These actions of morphine were qualitatively similar to those observed with phenyldiguanide (PDG) and were found to be reflexogenic, i.e. emanating from the lungs via stimulation of pulmonary C-fibers. Bilaterally vagotomized animals only responded to morphine with respiratory depression, characterized by a severe decrease in respiratory rate and minute ventilation. On the other hand, animals with intact vagi showed stimulation of rate and minute ventilation following a brief period of apnea. They were less sensitive than vagotomized animals to the depressant action during the first 8 min after administration of morphine. All the effects of morphine were blocked by pretreatment with naloxone (50-400 micrograms/kg, i.v.). These results indicate that the initial cardiorespiratory effects of morphine are due to a peripheral reflex action arising from the stimulation of opiate receptors associated with pulmonary C-fibers, e.g. J-fibers" http://www.ncbi.nlm.nih.gov/pubmed/6292766 0 1434 A. Cihak and H. INOUE 1979 Synthesis of DNA in the liver and testes of cadmium-tested partially hepatectomized rats J.Biochem. 86 3 657-662 "Cadmium affects the induction of thymidine and thymidylate kinases in regenerating rat liver. EDTA administered simultaneously with cadmium reverses its inhibitory action on enzyme synthesis, and prevents the depression of thymidine incorporation into DNA observed in cadmium-treated animals. Zinc does not abolish the inhibitory action of cadmium on the synthesis of DNA in regenerating liver, and the incorporation of thymidine into DNA in the testes was inhibited more by intraperitoneal injection of cadmium plus zinc than by injection of cadmium alone. Inhibition of thymidine incorporation into DNA in the liver and testes was proportional to the amount of cadmium administered up to about 2 mg CdCl2/kg body weight, but surprisingly, higher doses of cadmium caused less inhibition" http://www.ncbi.nlm.nih.gov/pubmed/229099 0 1435 "L. Becker, R. Ferreira and M. Thomas" 1973 Effect of propranolol and isoprenaline on ST segment and regional left ventricular blood flow in experimental myocardial ischaemia Br.Heart J. 35 5 551 http://www.ncbi.nlm.nih.gov/pubmed/4716019 0 1436 "B. M. Costa, M. W. Irvine, G. Fang, R. J. Eaves, M. B. Mayo-Martin, D. A. Skifter, D. E. Jane and D. T. Monaghan" 2010 A novel family of negative and positive allosteric modulators of NMDA receptors J.Pharmacol.Exp.Ther. 335 3 614-621 "The N-methyl-D-aspartate (NMDA) receptor family regulates various central nervous system functions, such as synaptic plasticity. However, hypo- or hyperactivation of NMDA receptors is critically involved in many neurological and psychiatric conditions, such as pain, stroke, epilepsy, neurodegeneration, schizophrenia, and depression. Consequently, subtype-selective positive and negative modulators of NMDA receptor function have many potential therapeutic applications not addressed by currently available compounds. We have identified allosteric modulators with several novel patterns of NMDA receptor subtype selectivity that have a novel mechanism of action. In a series of carboxylated naphthalene and phenanthrene derivatives, compounds were identified that selectively potentiate responses at GluN1/GluN2A [e.g., 9-iodophenanthrene-3-carboxylic acid (UBP512)]; GluN1/GluN2A and GluN1/GluN2B [9-cyclopropylphenanthrene-3-carboxylic acid (UBP710)]; GluN1/GluN2D [3,5-dihydroxynaphthalene-2-carboxylic acid (UBP551)]; or GluN1/GluN2C and GluN1/GluN2D receptors [6-, 7-, 8-, and 9-nitro isomers of naphth[1,2-c][1,2,5]oxadiazole-5-sulfonic acid (NSC339614)] and have no effect or inhibit responses at the other NMDA receptors. Selective inhibition was also observed; UBP512 inhibits only GluN1/GluN2C and GluN1/GluN2D receptors, whereas 6-bromo-2-oxo-2H-chromene-3-carboxylic acid (UBP608) inhibits GluN1/GluN2A receptors with a 23-fold selectivity compared with GluN1/GluN2D receptors. The actions of these compounds were not competitive with the agonists L-glutamate or glycine and were not voltage-dependent. Whereas the N-terminal regulatory domain was not necessary for activity of either potentiators or inhibitors, segment 2 of the agonist ligand-binding domain was important for potentiating activity, whereas subtype-specific inhibitory activity was dependent upon segment 1. In terms of chemical structure, activity profile, and mechanism of action, these modulators represent a new class of pharmacological agents for the study of NMDA receptor subtype function and provide novel lead compounds for a variety of neurological disorders" http://www.ncbi.nlm.nih.gov/pubmed/20858708 0 1437 L. Pichler and W. Kobinger 1985 Possible function of alpha 1-adrenoceptors in the CNS in anaesthetized and conscious animals Eur.J.Pharmacol. 107 3 305-311 "The influence of St 587 (2-(2-chloro-5-trifluoromethylphenylimino)imidazolidine), a selective alpha 1-adrenoceptor agonist which easily penetrates the blood-brain barrier, was tested on behavior and cardiovascular functions, respectively. The substance (up to 10 mg/kg subcutaneously (s.c.)) did not increase the exploratory activity of naive mice. The hexobarbitone 'sleeping' time in mice was reduced in a dose-dependent manner (St 587 ED50 = 14.4 mg/kg s.c.). Haloperidol 10 mg/kg s.c. induced catalepsy which was antagonized by St 587 in a dose-dependent manner (ED50 = 2.7 mg/kg i.p.). Conversely, the alpha 1-adrenoceptor-blocking agents prazosin and corynanthine elicited catalepsy in mice which had been treated with a subthreshold dose (2 mg/kg s.c.) of haloperidol; the ED50 values of the antagonists were 0.26 and 4.7 mg/kg i.p., respectively. In anaesthetized cats blood pressure and heart rate were not affected by 100 micrograms/kg St 587 injected into the left vertebral artery. In conscious dogs with beta-adrenoceptors blocked, the drug was without effect (100 micrograms/kg intracisternally) on vagally mediated reflex bradycardia, as evoked by intravenous noradrenaline injection. As a positive control the alpha 2-adrenoceptor agonist B-HT 920 which is equipotent to St 587 with respect to peripheral vasopressor effects in rats was injected with 10 micrograms/kg intracisternally and facilitated the reflex bradycardia. It is concluded that alpha 1-adrenoceptors within the brain mediate behavioral activation in states of CNS depression but remain without effect on cardiovascular centers" http://www.ncbi.nlm.nih.gov/pubmed/2984009 0 1438 T. Sonobe and P. Haouzi 2016 Sulfide Intoxication-Induced Circulatory Failure is Mediated by a Depression in Cardiac Contractility Cardiovasc.Toxicol. 16 1 67-78 "Hydrogen sulfide (H2S) intoxication produces a rapid cardio-circulatory failure leading to cardiac arrest. In non-lethal forms of sulfide exposure, the presence of a circulatory shock is associated with long-term neurological sequelae. Our aim was to clarify the mechanisms of H2S-induced circulatory failure. In anesthetized, paralyzed, and mechanically ventilated rats, cardiac output, arterial pressure and ventricular pressures were determined while NaHS was infused to increase arterial concentration of soluble H2S (CgH2S) from undetectable to levels leading to circulatory failure. Compared to control/saline infusion, blood pressure started to decrease significantly along with a modest drop in peripheral vascular resistance (-19 +/- 5%, P < 0.01), when CgH2S reached about 1 muM. As CgH2S exceeded 2-3 muM, parameters of ventricular contractility diminished with no further reduction in peripheral resistance. Whenever H2S exposure was maintained at a higher level (CgH2S over 7 muM), a severe depression of cardiac contractility was observed, leading to asystole within minutes, but with no evidence of peripheral vasoplegia. The immediate and long-term neurological effects of specifically counteracting sulfide-induced cardiac contractility depression following H2S exposure remain to be investigated" http://www.ncbi.nlm.nih.gov/pubmed/25616319 0 1439 "Y. Yamagata, J. N. Jovanovic, A. J. Czernik, P. Greengard and K. Obata" 2002 Bidirectional changes in synapsin I phosphorylation at MAP kinase-dependent sites by acute neuronal excitation in vivo "Journal of Neurochemistry.80 (5) ()(pp 835-842), 2002.Date of Publication: 2002." 5 835-842 "Synapsin I is a synaptic vesicle-associated protein which is phosphorylated at multiple sites by various kinases. It has been proposed to play a role in the regulation of neurotransmitter release and the organization of cytoskeletal architecture in the presynaptic terminal. To better understand the physiological regulation of its phosphorylation in vivo, we induced acute, reversible neuronal excitation by electroconvulsive treatment (ECT) in rats, and studied its effects on synapsin I phosphorylation at sites 3, 4/5 and 6 by immunoblot analyses of homogenates from hippocampus and parietal cortex using phospho-site-specific antibodies. A decrease in phosphorylation at all sites was observed soon after the electrical stimulation, followed by a large increase in phosphorylation at site 4/5 peaking at 5 min and a moderate increase in phosphorylation at site 6 peaking at 20 min. Systemic injection of SL327, a mitogen-activated protein kinase (MAPK) kinase inhibitor, prior to ECT, suppressed the increase in phosphosite 4/5 level, as well as that in MAPK activity, but not that in phospho-site 6 level. Thus, phosphorylation at site 4/5 of synapsin I has been shown to be regulated by MAPK in vivo" DO - http://dx.doi.org/10.1046/j.0022-3042.2001.00753.x 0 1440 "A. H. Watt, D. C. Buss and P. A. Routledge" 1987 Effect of aminophylline on the respiratory depressant action of intravenous adenosine in neonatal rabbits Life Sci. 40 1 29-34 "We administered intravenous adenosine to 11 neonatal rabbits. Adenosine depressed respiration in 10 of 11 rabbits. For the group as a whole the adenosine-induced respiratory depression was highly significant (p less than 0.001). After aminophylline administration to the same animals the respiratory effect of intravenous adenosine was abolished in 3 animals. In 7 animals the effect of adenosine was reversed and respiratory stimulation was observed. After aminophylline adenosine produced a significant (p less than 0.001) increase in respiration in the group studied. The alteration of responses to intravenous adenosine by aminophylline in neonatal rabbits is similar to the effect of aminophylline on respiratory responses to hypoxia in neonates. Such an effect of aminophylline and other methylxanthines on adenosine actions, possibly central in site may explain their beneficial effect in the treatment of apnoea in the human neonate" http://www.ncbi.nlm.nih.gov/pubmed/3796210 0 1441 "J. Hermann, B. Grothe and A. Klug" 2009 Modeling short-term synaptic plasticity at the calyx of Held using in vivo-like stimulation patterns J.Neurophysiol. 101 1 20-30 "We measured synaptic responses to complex stimulus trains in the calyx of Held and used the data to test how well several vesicle-release models could capture the observed dynamics. We tested stimulation protocols consisting of Poisson-distributed activity with periodically changing mean frequencies, trains with constant inter spike intervals, and stimulus trains derived from in vivo responses to natural sounds. All stimuli were embedded in chronic background activity attempting to imitate the naturally occurring spontaneous activity in the auditory brain stem. We found that already the most basic model variant produced very good results, exhibiting very high correlation coefficients between the experimental data and the model predictions. None of the more complex model variants, which incorporated receptor desensitization, synaptic facilitation, and double-exponential recovery from depression, showed improved data-prediction matching accuracy. These findings are in contrast to previous modeling work performed in nonchronically active synapses, where the inclusion of additional physiological parameters into the modeling process tended to result in models with higher accuracy. Our findings suggest that the functional state of chronically active calyces may differ from the functional state of silent calyces and that this functional state of chronically active synapses can be described in relatively simple terms" http://www.ncbi.nlm.nih.gov/pubmed/18971300 0 1442 "N. R. Wray, M. R. James, S. P. Mah, M. Nelson, G. Andrews, P. F. Sullivan, G. W. Montgomery, A. J. Birley, A. Braun and N. G. Martin" 2007 Anxiety and comorbid measures associated with PLXNA2 "Archives of General Psychiatry.64 (3) ()(pp 318-326), 2007.Date of Publication: March 2007." 3 318-326 "Context: Reduction in adult neurogenesis has been proposed as a mechanism for onset of depression. Semaphorins and their coreceptors, plexins, have been implicated in nervous system development and in adult neurogenesis. A recent genomewide association study of schizophrenia identified a variant of the gene encoding plexin A2 (PLXNA2) to be most consistently associated across study samples. Common genetic liabilities have been reported between psychiatric and psychological measures, but few examples exist of common genetic variants. Objective: To perform a genetic association study between 6 single nucleotide polymorphisms from the PLXNA2 gene (rs3736963, rs2767565, rs752016, rs1327175, rs2478813, and rs716461) and anxiety, depression, neuroticism, and psychological distress. Design: Extreme discordant and concordant siblings. Setting: Australia. Participants: Study participants were selected with respect to extreme neuroticism scores from a population cohort of 18 742 twin individuals and their siblings. The participants and their parents (if blood or buccal samples were available) were genotyped, for a total of 2854 genotyped individuals from 990 families. Of these, 624 individuals with a diagnosis of anxiety or depression from 443 families were used in the association analysis. Main Outcome Measures: All the participants completed the Composite International Diagnostic Interview, the 23-item Neuroticism scale of the revised Eysenck Personality Questionnaire, and the 10-item Kessler Psychological Distress Scale. Diagnoses of DSM-IV depression and anxiety were determined from the Composite International Diagnostic Interview. Results: There was evidence of an allelic association between rs2478813 (and other single nucleotide polymorphisms correlated with it) and anxiety, depression, neuroticism, and psychological distress; the association with anxiety is significant after Bonferroni correction for multiple testing (empirical P<.001). The mouse ortholog of PLXNA2 is located in a highly significant linkage region previously reported for anxiety in mice. Conclusion: PLXNA2 is a candidate for causal variation in anxiety and in other psychiatric disorders through its comorbidity with anxiety. ©2007 American Medical Association. All rights reserved" DO - http://dx.doi.org/10.1001/archpsyc.64.3.318 0 1443 P. A. Lambert and G. Venaud 1987 The use of Valpromide in psychiatry "Encephale.13 (6) ()(pp 367-373), 1987.Date of Publication: 1987." 6 367-373 "Valpromide is obtained from amidification of valproic acid. Bio-pharmacological data show several possible mechanisms of action involving an increase in GABA levels in brain as well as changes in membrane conductance on neurons. Valpromide has been shown to decrease aggressivity in stress-induced animals, to regulate anxious induced behaviours, as well as to potentiate central sedative compounds. Psychopathological experiments have shown: a wakening of personality, euphorical effects, an improvement of social behaviour, a stabilization of mood in affective disorders. A potentiation of other CNS drugs (mainly sedative compounds) has been observed. Dosage should be reduced when valpromide is used in combination with these drugs. In manic depression, valpromide has shown a preventive action. Current studies showed that the number of repeated hospitalisations decreased by 60 to 80%. The number and duration of episodes decreased, while there was an increase in the intercritical period. In other indications, valpromide has shown an effect on behavioral and personality disorders, associated to aggressivity and mood elation. It has also shown an effect on sleep disturbances. At the usual dosage of 600 to 1200 mg per day (2 to 4 tablets) valpromide may be easily given on a long term treatment. Treatment should be progressively installed, particularly when combined with other CNS drugs, to prevent cognitive functions disturbances. The only absolute contra-indication is combination to carbamazepine. Controlled studies are currently being performed in manic depression (possible substitutive treatment to lithium) and in behavioural disorders with aggressivity. The existing doubt on the exact mechanism of action of valpromide and on its polymorphic clinical activity does not allow to relate this drug to currently admitted CNS drugs classifications" 0 1444 "P. W. Stacpoole, E. Iwamoto and C. E. Glasgow" 1971 Diisopropylammonium dichloroacetate (DIPA): reversible antagonism towards smooth muscle stimulants and inhibition of acetylcholinesterase in the isolated guinea pig ileum Res.Commun.Chem.Pathol.Pharmacol. 2 4 439-446 http://www.ncbi.nlm.nih.gov/pubmed/5139065 0 1445 M. Saito and S. Watanabe 2008 Differential modulation of lipopolysaccharide- and zymosan-induced hypophagia by dexamethasone treatment Pharmacol.Biochem.Behav. 90 3 428-433 "The treatment of experimental animals with lipopolysaccharide (LPS) induces behavioral depression, in which the central and peripheral inductions of proinflammatory cytokines are proposed to play an important role. We have shown that the intraperitoneal injection of zymosan, composed of insoluble particles prepared from yeast cell walls, can induce behavioral depression assessed as hypophagia in mice, although the role of proinflammatory cytokines in this response has not yet been investigated. We have also shown that the subcutaneous injection of the corticoid, dexamethasone (Dex), a potent inhibitor of cytokine production, is effective in attenuating hypophagia in LPS-treated mice. The attenuated response was associated with the suppression of the gene induction of proinflammatory cytokines (i.e., IL-1beta, IL-6 and TNFalpha) in the brain and liver. In contrast, no significant induction of proinflammatory cytokine genes was observed in the brain or liver during zymosan-induced hypophagia; the subcutaneous injection of Dex did not attenuate zymosan-induced hypophagia but its intraperitoneal injection did. Thus, zymosan-induced hypophagia was less responsive to a subcutaneous injection of dexamethasone than LPS-induced hypophagia, which may be due to the limited role of systemic inflammation in this response. An important role of localized, rather than systemic, inflammation in zymosan-induced hypophagia was suggested, although the role of local proinflammatory cytokines remains to be clarified" http://www.ncbi.nlm.nih.gov/pubmed/18457866 1 1446 B. A. Panaretto and A. L. Wallace 1978 "Dexamethasone concentrations in ovine plasma during its intravenous infusion, its relation to the production of some endogenous hormones, and some of the effects on wool growth" Aust.J.Biol.Sci. 31 3 247-255 "Plasma concentrations of dexamethasone have been measured in sheep during an 8-day infusion of dexamethasone-21 phosphate. The dexamethasone concentration profiles generally revealed a reproducible pattern with three phases--a peak during the first 48 h infusion which was followed by falling concentrations during the next 5 days, and a small increase in dexamethasone concentration during the final 24 h infusion was not uncommon. The pattern of dexamethasone concentrations was retained when dosage was arranged in such a way as to infuse increasing quantities of hormonal analogue as infusion progressed. Aspects of the metabolism of the analogue are discussed. Endogenous thyroxine and cortisol were significantly depressed during infusion. In these experiments wool was completely shed in three out of four animals dosed at a rate of 8.5 mg dexamethasone/kg0.75. The recovery of wool growth to its pretreatment values occurred by about one month after infusion. The consumption of food and body weight increases were satisfactory during the post-infusion period" http://www.ncbi.nlm.nih.gov/pubmed/727993 0 1447 "J. S. Smitha, R. Roopa, B. K. Sagar, B. M. Kutty and C. Andrade" 2014 Images in electroconvulsive therapy: ECS dose-dependently increases cell proliferation in the subgranular region of the rat hippocampus J.ECT. 30 3 193-194 "Stress and depression are associated with impaired neuroplasticity in the hippocampus; there is a decrease in neurogenesis, which is hypothesized to decrease the adaptative competence of the organism. Representative light microscopy images are presented which show that 6 once-daily electroconvulsive shocks (ECS), dose-dependently increased new cell formation in the subgranular region of the hippocampus in healthy adult male Wistar rats (10 sections per rat, 3 rats in each of sham ECS, 10 mC, and 40 mC groups). These neuroplasticity changes, demonstrated 1 month after the last ECS, may explain a part of the mechanism of action of electroconvulsive therapy in conditions such as depression" http://www.ncbi.nlm.nih.gov/pubmed/24901429 0 1448 A. M. Beal 1976 The effect of high rates of vasopressin administration on renal potassium and sodium excretion during potassium loading in the sheep Br.J.Pharmacol. 58 1 81-88 "1 The influence of potassium loading on the renal excretion of sodium, potassium and solute during high rate vasopressin administration has been investigated in sheep. 2 Adrenalectomized sheep were infused with 0.43 M KCl at 2 ml/min for 2-2.5 hours. Coincident with the rise in plasma potassium concentration, the urinary excretion of sodium, potassium, solute and water was increased as was the reabsorption of solute-free water. The rates of urinary excretion of sodium and potassium, osmolal clearance (COsm) and solute-free water reabsorption (TcH2O) for the first 50 min of potassium infusion were each found to be linearly related to the plasma potassium concentration. 3 After 50 min an infusion of vasopressin at 1 or 4 mu/min was superimposed on the potassium infusion for a period of 30 minutes. The administration of vasopressin was consistently associated with further augmentation of potassium excretion and clearance, of osmolal clearance and of solute-free water reabsorption to values above those anticipated from the pre-vasopressin regression lines for these parameters. Urinary sodium showed a coincident depression in the rate of excretion and clearance during the same period. 4 Thirty to fifty minutes after the cessation of vasopressin infusion the potassium and sodium excretions had returnied to values which approximated the pre-vasopressin relations between plasma potassium and the urinary excretions of these ions. 5 Both rates of vasopressin infusion were equally effective in increasing the potassium clearance. Any differences in clearance between the two rates of vasopressin administration were not statistically significant. 6 The large increments in potassium excretion (averaging greater than 40%) were interpreted as indicating that, when vasopressin is present at high concentrations, the distal tubule is one site of action of the hormone in the nephron of sheep" http://www.ncbi.nlm.nih.gov/pubmed/974379 0 1449 "C. K. Farren, A. H. Rezvani, D. Overstreet and S. O'Malley" 2000 Combination pharmacotherapy in alcoholism: a novel treatment approach CNS.Spectr. 5 2 70-76 "Combination pharmacotherapy has proven effective in a number of psychiatric disorders, including depression and schizophrenia. However, compared with other affective disorders, few studies have explored the use of combination therapy in alcoholism, and the majority have been limited to animal models. There is evidence to support a role for combination therapy in alcoholism. For example, several neurochemical systems, including the dopaminergic, serotonergic, and opioidergic, appear to affect alcohol intake. Studies in several different types of alcohol-preferring rats have suggested that coadministration of agents to target more than one of these systems simultaneously may produce beneficial effects on alcohol intake, while avoiding problematic effects, such as alterations in food or water intake. Data from preliminary clinical studies have shown trends toward combination therapy reducing alcohol intake in humans. While such findings are encouraging, they must be explored further in larger, randomized, double-blind trials" http://www.ncbi.nlm.nih.gov/pubmed/18297000 0 1450 L. V. Vinogradova 2010 Interhemispheric difference in susceptibility to epileptogenesis: evidence from the audiogenic kindling model in Wistar rats Brain Res. 1329 175-181 "Audiogenic kindling (AK) represents a model of naturally occurring epileptogenesis in which intensification of repeatedly induced audiogenic seizures results from propagation of epileptic activity from the brainstem to forebrain. Previously it has been shown that unilateral cortical spreading depression (SD) is a reliable earliest manifestation of mild AK produced by repetition of minimal audiogenic seizures (running) in Wistar rats. The unilateral triggering SD suggests the existence of asymmetry in the forebrain recruitment during the kindling and the present study examined whether epileptogenesis produced by this mild AK paradigm is a lateralized process. Twenty five running episodes were induced by brief sound stimulation in Wistar rats susceptible to audiogenic seizures. Behavioral and EEG correlates of AK development were assessed. Running behavior elicited by brief sound stimulation had an asymmetrical pattern with profound preference for one direction. Most rats expressing leftward running displayed full kindling development whereas the majority of rats with rightward running were resistant to AK. The EEG marker of AK, a cortical epileptiform discharge, was recorded only in rats with leftward running and the first discharge appeared in the left cortex. Cortical SD was recorded after repeated running seizures in all rats with reproducible audiogenic response irrespective of the running lateralization and propensity to kindling. Until the late kindling stages, SD was triggered unilaterally in the cortex ipsilateral to the running direction. These findings indicate intrinsically determined lateralization of epileptogenic process in the mild AK model and enhanced vulnerability of the left hemisphere to epileptogenesis" http://www.ncbi.nlm.nih.gov/pubmed/20303340 0 1451 M. C. Koss 2000 Effect of nitric oxide synthesis inhibition on post-occlusive choroidal blood flow in rats J.Ocul.Pharmacol.Ther. 16 1 55-64 "Experiments were designed to study involvement of nitric oxide on vascular responses to ocular ischemia in the anesthetized rat. Anterior choroidal blood flow was measured using laser-Doppler flowmetry. In some experiments, cerebral cortical blood flow also was measured. Ischemia was produced by either occlusion of the cephalic blood supply or more locally via a ligature tightened around the eye stalk. Arterial blood pressure and choroidal blood flow was continuously measured before, during and after a 20 min ischemic challenge. Both methods of ischemia reduced choroidal blood flow (>90%) with no consistent ocular hyperemia seen upon reperfusion. No significant differences in response pattern between the two ischemia techniques were apparent. Treatment with the non-selective inhibitor of nitric oxide (L-NAME 2 mg/kg, i.v.) did not alter either basal choroidal blood flow or the pattern of reperfusion. A larger dose of L-NAME (50 mg/kg, i.v.) reduced both basal choroidal blood flow and the final reperfusion level (most likely due to continued depression of the basal ocular choroidal blood flow). Neither D-NAME nor the neuronal nitric oxide synthase inhibitor, 7-nitroindazole, altered basal anterior choroidal blood flow or the reperfusion pattern seen after reperfusion. The results confirm our previous observations that inhibition of endothelial nitric oxide lowers. basal choroidal blood flow in the rat eye. However, in contrast to the cerebral circulation where L-NAME greatly attenuates initial reperfusion to the cerebral cortex, inhibition of nitric oxide synthase does not appear to notably further influence anterior choroidal reperfusion" http://www.ncbi.nlm.nih.gov/pubmed/10673132 0 1452 "S. Y. Yu, D. C. Wu, L. Liu, Y. Ge and Y. T. Wang" 2008 Role of AMPA receptor trafficking in NMDA receptor-dependent synaptic plasticity in the rat lateral amygdala J.Neurochem. 106 2 889-899 "Stimulated exocytosis and endocytosis of post-synaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid subtype of glutamate receptors (AMPARs) have been proposed as primary mechanisms for the expression of hippocampal CA1 long-term potentiation (LTP) and long-term depression (LTD), respectively. LTP and LTD, the two most well characterized forms of synaptic plasticity, are thought to be important for learning and memory in behaving animals. Both LTP and LTD can also be induced in the lateral amygdala (LA), a critical structure involved in fear conditioning. However, the role of AMPAR trafficking in the expression of either LTP or LTD in this structure remains unclear. In this study, we show that NMDA receptor-dependent LTP and LTD can be reliably induced at the synapses of the auditory thalamic inputs to the LA in brain slices. The expression of LTP was prevented by post-synaptic blockade of vesicle-mediated exocytosis with application of a light chain of Clostridium tetanus neurotoxin and was associated with increased cell-surface AMPAR expression. In contrast, the expression of LTD was prevented by post-synaptic application of a glutamate receptor 2-derived interference peptide, which specifically blocks the stimulated clathrin-dependent endocytosis of AMPARs, and was correlated with a reduction in plasma membrane-surface expression of AMPARs. These results strongly suggest that regulated trafficking of post-synaptic AMPARs is also involved in the expression of LTP and LTD in the LA" http://www.ncbi.nlm.nih.gov/pubmed/18466342 0 1453 C. W. Beattie and A. Corbin 1975 The differential effects of diestrous progestogen administration of proestrous gonadotrophin levels Endocrinology 97 4 885-890 "Progesterone or d-norgestrel, a totally synthetic progestogen, administered subcutaneously at 1330 h on diestrus (Day 2) of 4-day cyclic rats, inhibited ovulation and increased the vaginal cycle length in a dose-related manner. d-norgestrel was at least 5 times as potent as inhibitor of ovulation as progesterone. The dose-related inhibition of ovulation was directly related to suppression of the proestrous serum LH surge. Proestrous serum FSH levels were not depressed at the minimum dose of d-norgestrel that produced both a 100% reduction in ovulation (MED100) and a significant decrease in proestrous serum LH. However, progesterone produced a significant decrease in proestrous serum FSH at its anti-ovulatory MED100. Progesterone and d-norgestrel were equipotent (100 mug/100 g BW) with respect to significant suppression of proestrous serum FSH levels. Follicular growth was retarded, but only at the higher doses of either progestogen which suppressed FSH and LH. These data suggest that a) the increase in acute anti-ovulatory potency of a synthetic non-estrogenic progestogen over progesterone lies in its ability to reduced selectively serum LH levels at low doses, b) the progestational block of ovulation takes place via the hypothalamic-pituitary axis and not the ovary, and c) the retardation of follicular growth that accompanies ovulatory inhibition after diestrous administration of high doses of a progestogen takes place only when both serum FSH and LH are significantly reduced" http://www.ncbi.nlm.nih.gov/pubmed/1238248 0 1454 "N. A. Krupina, I. N. Orlova and G. N. Kryzhanovskii" 1995 "[Effect of melipramine on the development of an experimental depressive syndrome in rats, caused by systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)]" Biull.Eksp.Biol.Med. 120 8 160-163 http://www.ncbi.nlm.nih.gov/pubmed/7579274 1 1455 S. S. Liberman and S. A. Sharova 1975 [A comparison of the effect of the tricyclic antidepressants azaphen and imizin on the gastrointestinal tracts of experimental animals] Farmakol.Toksikol. 38 1 29-32 http://www.ncbi.nlm.nih.gov/pubmed/1112390 0 1456 "B. G. Schreurs, M. M. Oh and D. L. Alkon" 1996 Pairing-specific long-term depression of Purkinje cell excitatory postsynaptic potentials results from a classical conditioning procedure in the rabbit cerebellar slice J.Neurophysiol. 75 3 1051-1060 "1. Using a rabbit cerebellar slice preparation, we stimulated a classical conditioning procedure by stimulating parallel fiber inputs to Purkinje cells with the use of a brief, high-frequency train of eight constant-current pulses 80 ms before climbing fiber inputs to the same Purkinje cell were stimulated with the use of a brief, lower frequency train of three constant-current pulses. In all experiments, we assessed the effects of stimulation by measuring the peak amplitude of Purkinje cell excitatory postsynaptic potentials (EPSPs) to single parallel fiber test pulses. 2. Intradendritically recorded Purkinje cell EPSPs underwent a long-term (> 20 min) reduction in peak amplitude (30%) after paired stimulation of the parallel and climbing fibers but not after unpaired or parallel fiber alone stimulation. We call this phenomenon pairing-specific long-term depression (PSD). 3. Facilitation of the peak amplitude of a second EPSP elicited by a parallel fiber train occurred both before and after paired stimulation suggesting that the locus of depression was not presynaptic. Depression of the peak amplitude of a depolarizing response to focal application of glutamate following pairings of parallel and climbing fiber stimulation added support to a suggested postsynaptic locus of the PSD effect. 4. The application of aniracetam potentiated EPSP peak amplitude by 40%, but these values returned to baseline as a result of pairings. With the removal of aniracetam from the bath 20 min after pairings, normal levels of pairing-specific EPSP depression were observed, indicating that the effect did not result from direct desensitization of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid (AMPA) receptors. 5. Incubation of slices in the protein kinase inhibitor H-7 potentiated EPSP peak amplitudes slightly (9%), but peak amplitudes returned to baseline levels after pairings. The net reduction in EPSP peak amplitude of < 10% after pairings suggested that H-7 partially blocked PSD and that, in turn, PSD involved protein kinases. 6. The means of induction and the specificity of those means suggest that the phenomenology of PSD is fundamentally different from that of long-term depression. PSD only occurs with pairings of trains of parallel fiber and climbing fiber stimulation; it occurs without the need for bicuculline; and it can overcome the blocking effects of aniracetam. 7. Nevertheless, the involvement of protein kinases and the potential role of calcium suggest that the mechanisms involved in the induction of PSD and long-term depression have a number of features in common. 8. Because of the pairing-specific nature of the long-term synaptic depression observed in these experiments, PSD provides a mechanism that may contribute to the role of the cerebellar cortex in classical conditioning" http://www.ncbi.nlm.nih.gov/pubmed/8867117 0 1457 "H. S. Gompf, M. G. Moldavan, R. P. Irwin and C. N. Allen" 2005 Nociceptin/orphanin FQ (N/OFQ) inhibits excitatory and inhibitory synaptic signaling in the suprachiasmatic nucleus (SCN) Neuroscience 132 4 955-965 "Environmental synchronization of the endogenous mammalian circadian rhythm involves glutamatergic and GABAergic neurotransmission within the hypothalamic suprachiasmatic nucleus (SCN). The neuropeptide nociceptin/orphanin FQ (N/OFQ) inhibits light-induced phase shifts, evokes K(+)-currents and reduces the intracellular Ca(2+) concentration in SCN neurons. Since these effects are consistent with a modulatory role for N/OFQ on synaptic transmission in the SCN, we examined the effects of N/OFQ on evoked and spontaneous excitatory and inhibitory currents in the SCN. N/OFQ produced a consistent concentration-dependent inhibition of glutamate-mediated excitatory postsynaptic currents (EPSC) evoked by optic nerve stimulation. N/OFQ did not alter the amplitude of currents induced by application of (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or N-methyl-d-aspartate (NMDA) nor the amplitude of miniature EPSC (mEPSC) consistent with a lack of N/OFQ effect on postsynaptic AMPA or NMDA receptors. N/OFQ significantly reduced the mEPSC frequency. The inhibitory actions of N/OFQ were blocked by omega-conotoxin GVIA, an N-type Ca(2+)channel antagonist and partially blocked by omega-agatoxin TK, a P/Q type Ca(2+) channel blocker. These data indicate that N/OFQ reduces evoked EPSC, in part, by inhibiting the activity of N- and P/Q-type Ca(2+) channels. In addition, N/OFQ produced a consistent reduction in baseline Ca(2+) levels in presynaptic retinohypothalamic tract terminals. N/OFQ also inhibited evoked GABA(A) receptor-mediated inhibitory postsynaptic currents (IPSC) in a concentration dependent manner. However, N/OFQ had no effect on currents activated by muscimol application or on the amplitude of miniature IPSC (mIPSC) and significantly reduced the mIPSC frequency consistent with an inhibition of GABA release downstream from Ca(2+) entry. Finally, N/OFQ inhibited the paired-pulse depression observed in SCN GABAergic synapses consistent with a presynaptic mechanism of action. Together these results suggest a widespread modulatory role for N/OFQ on the synaptic transmission in the SCN" http://www.ncbi.nlm.nih.gov/pubmed/15857701 0 1458 "L. A. Pohorecky, V. Patel and P. Roberts" 1989 Effects of ethanol in an open field apparatus: modification by U50488H and WIN 44441-3 Physiol Behav. 45 2 273-287 "The effects of U50488H, a kappa agonist, and WIN 44441-3, a kappa antagonist, and their modification of the effects of ethanol, on the behavior of rats in a modified open field apparatus, was examined. Crossover activity was increased by U50488H. Headpoke activity was decreased by WIN 44441-3 and increased by U50488H. Rearing activity was increased by WIN 44441-3 but was not affected by U50488H. The effect of both drugs was dose related, with the largest doses having no effect. Ethanol (0.5 g/kg) stimulated crossover activity while it depressed rearing, headpoke and corner activities; except for crossover activity the 2.0 g/kg dose of ethanol depressed these activities. Pretreatment with WIN 44441-3 (0.5 mg/kg) potentiated the stimulant effect of ethanol on crossover activity and partially reversed the depressant effect of ethanol on rearing and headpoke activities. U50488H potentiated the ethanol-induced depression of headpoke and reversed the depression of corner activity. Pretreatment with U50488H had no effect on ethanol's action on crossover and rearing behaviors. Our results indicate that kappa opiate receptors may mediate some behaviors exhibited by rats in a modified open field apparatus. Activation of these receptors increases locomotor and headpoke activity but had no effect on rearing activity. Furthermore, the 0.5 g/kg dose of ethanol has differential effects on different measures of open field behavior, while the 2.0 g/kg dose was largely depressant. Our data suggest that some of these effects of ethanol may be mediated via kappa opioid receptors" http://www.ncbi.nlm.nih.gov/pubmed/2547220 0 1459 M. Muller 2000 Effects of chloride transport inhibition and chloride substitution on neuron function and on hypoxic spreading-depression-like depolarization in rat hippocampal slices Neuroscience 97 1 33-45 "Chloride fluxes play a crucial role in synaptic inhibition, cell pH regulation, as well as in cell volume control. In many neuropathological processes, cell swelling is a pivotal parameter, since cell volume changes and the dimension of the interstitial space critically modulate synchronized neuronal activity as well as the tissue's susceptibility to seizures or spreading depression. This study therefore focuses on the effects of different Cl(-) transport inhibitors and Cl(-) substitution on neuronal function and hypoxia-induced changes in rat hippocampal tissue slices. Orthodromically evoked focal excitatory postsynaptic potentials were depressed by furosemide (2mM), 4,4'-diisothiocyanatostilbene-2, 2'-disulfonic acid (1mM) and Cl(-) substitution by methylsulfate, but were enhanced by 4,4'-dinitrostilbene-2,2'-disulfonic acid (1mM). All four treatments induced multiple population spike firing in response to single orthodromic volleys, suggesting reduced synaptic inhibition. Antidromic population spikes increased following Cl(-) withdrawal, were unaffected in the presence of furosemide and 4, 4'-dinitrostilbene-2,2'-disulfonic acid, but were abolished by 4, 4'-diisothiocyanatostilbene-2,2'-disulfonic acid. The amplitude of the hypoxic spreading-depression-like extracellular potential shift was reduced by furosemide, 4,4'-diisothiocyanatostilbene-2, 2'-disulfonic acid and Cl(-) withdrawal, i.e. by the same treatments that depressed orthodromically evoked postsynaptic potentials. Furosemide prolonged the time to onset and the duration of the spreading-depression-like extracellular potential shift, while 4, 4'-dinitrostilbene-2,2'-disulfonic acid shortened the time to onset. Spreading-depression-related cell swelling was recorded as the shrinkage of relative interstitial space, which was measured as tetramethylammonium-chloride space. Neither the Cl(-) transport inhibitors nor Cl(-) withdrawal had any detectable effect on spreading-depression-related cell swelling. CA1 pyramidal neurons usually hyperpolarized during drug application and their input resistance decreased. Cl(-) withdrawal increased their input resistance and caused spontaneous burst firing. Hypoxia caused the expected spreading-depression-like rapid, near complete depolarization of single pyramidal neurons and drastically reduced their input resistance. The three Cl(-) transport inhibitors and Cl(-) withdrawal delayed the onset of the hypoxic depolarization. In low Cl(-) solutions, the apparent threshold potential at which spreading depression was triggered shifted to more positive membrane potentials. The final voltage of the hypoxic depolarization was, however, not affected. It appears from these results that the reduction in the hypoxic spreading-depression-like extracellular potential shifts by Cl(-) transport inhibitors is at least partially attributable to desynchronization of depolarization, not to decreased depolarization in individual cells. Other contributing factors could be changes in recording conditions, depression of swelling-induced amino acid release from glial cells and unspecific side-effects of the applied drugs. Desynchronization could also account for the delayed spreading-depression onset. It is concluded that Cl(-) fluxes play a role in the triggering of spreading depression, but the spreading-depression-like depolarization itself or its self-regenerative character is not mediated by Cl(-)" http://www.ncbi.nlm.nih.gov/pubmed/10771337 0 1460 "T. L. Nolan, L. M. Geffert, B. J. Kolber, J. D. Madura and C. K. Surratt" 2014 Discovery of Novel-scaffold monoamine transporter ligands via in silico screening with the S1 pocket of the serotonin transporter "ACS Chemical Neuroscience.5 (9) ()(pp 784-792), 2014.Date of Publication: 17 Sep 2014." 9 784-792 "Discovery of new inhibitors of the plasmalemmal monoamine transporters (MATs) continues to provide pharmacotherapeutic options for depression, addiction, attention deficit disorders, psychosis, narcolepsy, and Parkinson's disease. The windfall of high-resolution MAT structural information afforded by X-ray crystallography has enabled the construction of credible computational models. Elucidation of lead compounds, creation of compound structure - activity series, and pharmacologic testing are staggering expenses that could be reduced by using a MAT computational model for virtual screening (VS) of structural libraries containing millions of compounds. Here, VS of the PubChem small molecule structural database using the S1 (primary substrate) ligand pocket of a serotonin transporter homology model yielded 19 prominent ""hit"" compounds. In vitro pharmacology of these VS hits revealed four structurally unique MAT substrate uptake inhibitors with high nanomolar affinity at one or more of the three MATs. In vivo characterization of three of these hits revealed significant activity in a mouse model of acute depression at doses that did not elicit untoward locomotor effects. This constitutes the first report of MAT inhibitor discovery using exclusively the primary substrate pocket as a VS tool. Novel-scaffold MAT inhibitors offer hope of new medications that lack the many classic adverse effects of existing antidepressant drugs" DO - http://dx.doi.org/10.1021/cn500133b 0 1461 M. Boldrini 2015 Molecular regulation of hippocampal neurogenesis in neuropsychiatric disease and treatment "Neuropsychopharmacology.Conference: 54th Annual Meeting of the American College of Neuropsychopharmacology, ACNP 2015 Hollywood, FL United States.Conference Start: 20151206 Conference End: 20151210.Conference Publication: (var.pagings).40 ()(pp S16-S1" var.pagings S16-S17 "Background: Major depressive disorder (MDD) presents with inability to disengage from negatively valenced material and biased memory recall, and depression score is negatively correlated to pattern separation performance. Adult hippocampal neurogenesis is required for pattern separation and adaptations to stress in rodents. Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation in mice. We reported fewer dentate gyrus (DG) mature granule neurons (GNs) in unmedicated MDD, compared with psychiatrically healthy controls. We published that subjects with earlier onset of MDD have fewer GNs in anterior DG vs. subjects with later MDD onset. Although age-related decline of adult neurogenesis is less pronounced in human than in mice, it may still mediate age-related changes in cognitive processing. Selective serotonin repute inhibitors (SSRIs) treatment increase adult neurogenesis in mice and we found that in MDD is associated with more neural progenitor cells (NPCs), GNs, mitotic cells, and angiogenesis. It is unclear if the neurogenesis cascade in MDD is compromised at the level of cell proliferation, maturation or survival, and which are the mechanism by which SSRIs increase adult neurogenesis. Proliferation of NPCs is affected by growth factors, including brain derived neurotrophic factor (BDNF), but fluoxetine-mediated increase in cell survival is BDNFindependent. Vascular endothelial growth factor (VEGF), through the Flk-1 receptor (VEGFR2), is required for fluoxetine-induced cell proliferation. Serotonin receptors and trophic factors act on kinases modulating downstream intracellular molecules that regulate cell maturation and survival. These include cyclic-AMP response element binding (CREB), a leucine zipper transcription factor increased by antidepressants and expressed during cell maturation, and poly [ADP-ribose] polymerase (PARP), a DNA-binding protein activated by DNA strand breaks that protects survival via enzymatic DNA repair. PARP ribosylation also regulates chromatin histone ribosylation in the hippocampus after memory acquisition, regulating the epigenetic mechanism involved in reprogramming neuronal gene expression in memory consolidation. We aimed to assess molecular pathways involved in the regulation of human DG cell proliferation, maturation and survival in MDD, with SSRI treatment, and aging. Methods: We performed immunohistochemistry and stereology to quantify DG neurons and glia expressing VEGFR2, CREB and PARP in 22 psychiatrically healthy controls, 22 unmedicated subjects with MDD and 11 MDD subjects treated with SSRIs for at least 3 months before death. Subject age ranged from 19 to 84 years. All subjects received DSM-IV-validated psychological autopsy for diagnosis, brain and blood toxicology, and neuropathology. All subjects died from sudden death and time between demise and autopsy was within 24 hours. Results: Uncleaved PARP and non-phosphorylated CREB are expressed in more DG cells in untreated MDD than in SSRI-treated MDD and controls. VEGFR2 expression in DG cells correlated with more NPCs and GNs in anterior DG. More lifetime depressive episodes and more severe Global Assessment Scale (GAS) score correlated with fewer GNs in untreated MDD. We did not detect fewer NPCs or GNs with aging, but angiogenesis was decreased. Conclusions: Findings support the hypothesis that PARP and CREB have a role in regulating GN maturation and survival and that VEGF action may result in more adult neurogenesis in human DG. MDD is a major cause of global burden and its severity shows a relationship with GN number. Intracellular pathways that regulate brain structural plasticity may be drug targets for new classes of antidepressants or cognitive-enhancing treatments" DO - http://dx.doi.org/10.1038/npp.2015.324 0 1462 "G. Benzi, F. Berte, E. Arrigoni and L. Sanguinetti" 1970 Action of some antibiotics on the extra-hepatic biliary tract. 8. Gentamicin Arch.Int.Pharmacodyn.Ther. 188 1 137-144 http://www.ncbi.nlm.nih.gov/pubmed/5485094 0 1463 "B. N. Mathur, N. A. Capik, V. A. Alvarez and D. M. Lovinger" 2011 Serotonin induces long-term depression at corticostriatal synapses J.Neurosci. 31 20 7402-7411 "The striatum has important roles in motor control and action learning and, like many brain regions, receives multiple monoaminergic inputs. We have examined serotonergic modulation of rat and mouse corticostriatal neurotransmission and find that serotonin (5-HT) activates 5-HT(1b) receptors resulting in a long-term depression (LTD) of glutamate release and striatal output that we have termed 5-HT-LTD. 5-HT-LTD is presynaptically mediated, cAMP pathway dependent, and inducible by endogenous striatal 5-HT, as revealed by application of a selective 5-HT reuptake inhibitor. 5-HT-LTD is mutually occlusive with dopamine/endocannabinoid-dependent LTD, suggesting that these two forms of LTD act on the same corticostriatal terminals. Thus, serotonergic and dopaminergic mechanisms exist that may interact to persistently sculpt corticostriatal circuits, potentially influencing action learning and striatal-based disorders" http://www.ncbi.nlm.nih.gov/pubmed/21593324 0 1464 "H. Frenk, J. Engel, Jr., R. F. Ackermann, Y. Shavit and J. C. Liebeskind" 1979 Endogenous opioids may mediate post-ictal behavioral depression in amygdaloid-kindled rats Brain Res. 167 2 435-440 http://www.ncbi.nlm.nih.gov/pubmed/221069 1 1465 A. V. Valdman 1982 Psychotropic activity of the natural peptide tuftsin "Annali dell'Istituto Superiore di Sanita.18 (1) ()(pp 9-12), 1982.Date of Publication: 1982." 1 09-Dec "The present study indicates that tuftsin, a tetrapeptide with a phagocytosis-stimulating effect, produces central stimulation, allegedly mediated by the CA brain system. Tuftsin's activating effect on emotional reactivity and behavior is partly similar to the effect of some other small peptides (TRH, MIF) having common or equipotent structural fragments. According to unpublished data, some tuftsin analogs also have a central stimulating effect. This is a promising view of further research for central stimulants among 'small peptides'" 0 1466 "C. H. Gibbons, I. Bonyhay, A. Benson, N. Wang and R. Freeman" 2013 Structural and functional small fiber abnormalities in the neuropathic postural tachycardia syndrome "PLoS ONE.8 (12) (no pagination), 2013.Article Number: e84716.Date of Publication: 27 Dec 2013." 12 "Objective: To define the neuropathology, clinical phenotype, autonomic physiology and differentiating features in individuals with neuropathic and non-neuropathic postural tachycardia syndrome (POTS). Methods: Twenty-four subjects with POTS and 10 healthy control subjects had skin biopsy analysis of intra-epidermal nerve fiber density (IENFD), quantitative sensory testing (QST) and autonomic testing. Subjects completed quality of life, fatigue and disability questionnaires. Subjects were divided into neuropathic and non-neuropathic POTS, defined by abnormal IENFD and abnormal small fiber and sudomotor function. Results: Nine of 24 subjects had neuropathic POTS and had significantly lower resting and tilted heart rates; reduced parasympathetic function; and lower phase 4 valsalva maneuver overshoot compared with those with non-neuropathic POTS (P<0.05). Neuropathic POTS subjects also had less anxiety and depression and greater overall self-perceived health-related quality of life scores than non-neuropathic POTS subjects. A sub-group of POTS patients (cholinergic POTS) had abnormal proximal sudomotor function and symptoms that suggest gastrointestinal and genitourinary parasympathetic nervous system dysfunction. Conclusions and Relevance: POTS subtypes may be distinguished using small fiber and autonomic structural and functional criteria. Patients with non-neuropathic POTS have greater anxiety, greater depression and lower health-related quality of life scores compared to those with neuropathic POTS. These findings suggest different pathophysiological processes underlie the postural tachycardia in neuropathic and non-neuropathic POTS patients. The findings have implications for the therapeutic interventions to treat this disorder. © 2013 Gibbons et al" DO - http://dx.doi.org/10.1371/journal.pone.0084716 0 1467 "H. Taoka, T. Hamamura, S. Endo, S. Miyata, K. Toma, T. Ishihara and S. Kuroda" 2008 Antipsychotics possessing antidepressive efficacy increase Golf protein in rat striatum Psychopharmacology (Berl) 201 2 229-235 "INTRODUCTION: Recently, second-generation antipsychotics (SGAs) have been widely used in the treatment of mood disorders. However, the mechanisms of the antidepressant effect of SGAs remain unclear. We proposed that Golf protein, a stimulant alpha-subunit of G protein coupled with the dopamine D1 receptor, might a play the key role in the antidepressive effect of antidepressants. To clarify the relationship between Golf protein and the antidepressive effects of antipsychotics, we examined the effects of chronic treatment with several antipsychotics on the level of Golf protein in the rat striatum. MATERIALS AND METHODS: Male Wistar rats were treated with one of several antipsychotics for 2 weeks: olanzapine (2, 5, or 10 mg/kg), sulpiride (5, 10, or 50 mg/kg), amisulpride (3, 10, or 20 mg/kg), risperidone (0.2 or 2 mg/kg), haloperidol (0.3 or 3 mg/kg), or clozapine (2 or 10 mg/kg). RESULTS AND DISCUSSION: Olanzapine (5 mg/kg), sulpiride (5, or 10 mg/kg), and amisulpride (10 mg/kg) treatments significantly increased the level of Golf protein, but there was no increase with administration of higher doses of these three antipsychotics. Risperidone, haloperidol, and clozapine treatment did not change the level of Golf protein at any dose. In this study, all antipsychotics that have antidepressive effects increased Golf protein. This suggests that an increase in Golf may play an important role in the antidepressive effect of antipsychotics. CONCLUSION: We postulate that the increase in Golf protein levels result in an increase the proportion of D1 receptors in the high-affinity state and that augmentation of the dopaminergic system exerts the antidepressant effect" http://www.ncbi.nlm.nih.gov/pubmed/18777019 1 1468 "S. O. Ogren, A. C. Holm, H. Hall and U. H. Lindberg" 1984 "Alaproclate, a new selective 5-HT uptake inhibitor with therapeutic potential in depression and senile dementia" J.Neural Transm. 59 4 265-288 "Alaproclate, a new specific 5-HT uptake inhibitor, was examined for its action on several receptors in the brain, for its action on the NA, DA and 5-HT uptake mechanisms in vivo and for its action on brain biogenic amine content. Alaproclate was practically devoid of action on a number of receptors as examined in binding studies in vitro: 5-HT, histamine-H1, alpha 1, -alpha 2-adrenergic and dopamine D2 receptors. Alaproclate had also a weak affinity for 3H-norzimeldine binding sites in contrast to imipramine. Unlike the tricyclic antidepressants alaproclate had a negligible action on muscarinic receptors and failed to block muscarinic induced stimulation in vivo. Contrary to clomipramine alaproclate failed to block NA uptake in vivo. Alaproclate was found to display a regional selectivity in blocking 5-HT uptake in vivo (measured with the H 75/12-method). The compound was most potent in the hippocampus and hypothalamus followed by striatum and cerebral cortex with a low potency in the spinal cord. The results are discussed in relation to a previously presented carrier site model for serotonin reuptake" http://www.ncbi.nlm.nih.gov/pubmed/6205120 0 1469 "T. Mori, L.-Q. Sun, M. Kobayashi, Y. Kiyono, H. Okazawa, T. Furukawa, H. Kawashima, M. J. Welch and Y. Fujibayashi" 2009 Preparation and evaluation of ethylfluoroacetate as a proradiotracer offluoroacetate for the measurement of glial metabolism by PET "Nuclear Medicine and Biology.36 (2) ()(pp 155-162), 2009.Date of Publication: February 2009." 2 155-162 "Introduction: Changes in glial metabolism in brain ischemia, Alzheimer's disease, depression, schizophrenia, epilepsy and manganese neurotoxicity have been reported in recent studies. Therefore, it is very important to measure glial metabolism in vivo for the elucidation and diagnosis of these diseases. Radiolabeled acetate is a good candidate for this purpose, but acetate has little uptake in the brain due to its low lipophilicity. We have designed a new proradiotracer, ethyl [18F]fluoroacetate ([18F]EFA), which is [18F]fluoroacetate ([18F]FA) esterified with ethanol, to increase the lipophilicity of fluoroacetate (FA), allowing the measurement of glial metabolism. Methods: The synthesis of [18F]EFA was achieved using ethyl O-mesyl-glycolate as precursor. The blood-brain barrier permeability of ethyl [1-14C]fluoroacetate ([14C]EFA) was estimated by a brain uptake index (BUI) method. Hydrolysis of [14C]EFA in the brain was calculated by the fraction of radioactivity in lipophilic and water fractions of homogenized brain. Using the plasma of five animal species, the stability of [14C]EFA was measured. Biodistribution studies of [18F]EFA in ddY mice were carried out and compared with [18F]FA. Positron emission tomography (PET) scanning using common marmosets was performed for 90 min postadministration. At 60 min postinjection of [18F]EFA, metabolite studies were performed. Organs were dissected from the marmosets, and extracted metabolites were analyzed with a thin-layer chromatography method. Results: The synthesis of [18F]EFA was accomplished in a short time (29 min) and with a reproducible radiochemical yield of 28.6+/-3.6% (decay corrected) and a high radiochemical purity of more than 95%. In the brain permeability study, the BUI of [14C]EFA was 3.8 times higher than that of sodium [1-14C]fluoroacetate. [14C]EFA was hydrolyzed rapidly in rat brains. In stability studies using the plasma of five animal species, [14C]EFA was stable only in primate plasma. Biodistribution studies in mice showed that the uptake of [18F]EFA in selected organs was higher than that of [18F]FA. From nonprimate PET studies, [18F]EFA was initially taken into the brain after injection. Metabolites related to the tricarboxylic acid (TCA) cycle were detected in common marmoset brain. Conclusion: [18F]EFA rapidly enters the brain and is then converted into TCA cycle metabolites in the brains of common marmosets. [18F]EFA shows promise as a proradiotracer for the measurement of glial metabolism. © 2009 Elsevier Inc. All rights reserved" DO - http://dx.doi.org/10.1016/j.nucmedbio.2008.11.006 0 1470 M. D. Schneider and B. J. Kelman 1979 A proposed mechanism(s) of transitory ischemic injury to myocardium Am.J.Vet.Res. 40 2 170-182 "The main objective of this study was to produce primary acute ischemic injury to myocardium in a live animal. In vitro, guinea pig platelets were sensitive to perturbation and aggregation by a suspension of ultrafine fibrillary collagen material isolated from the aorta of an aged burro (Equus asinus). The platelets responded to the stimulatory action of this material down to 100 to 200 ng (dry weight) added to 0.45 ml of platelet-rich plasma, as determined by aggregometric technique. Aortic fibrillary collagen material injected IV into guinea pigs (350 to 1900 microgram protein/kg of weight) produced a transitory disappearance of virtually all circulating platelets within 5 minutes. In animals in which blood samples were taken 2.5 hours after injection, 50 to 75% of the average base-line platelets in the circulation of controls returned to the circulation. In other experiments, 3 anesthetized animals were injected by jugular vein with an amount of active fibrillary collagen material (300 microgram as protein/kg of animal weight) estimated to produce reversible platelet aggregation in vivo. Two control animals were injected with the same dose of the material that had been inactivated (15 minutes at 100 C) to abolish platelet aggregation. Treated and control animals were maintained under general anesthesia for 2.5 hours. Intraventricular pressures and electrocardiographs (ECG) were monitored continuously for the first 30 minutes. The injection of the active fibrillary collagen material caused a large ventricular pressure elevation (170/10, 180/10, and 150/10 mm of Hg) in approximately 40 s. Preinfusion ventricular pressures in the 3 animals were 65/0, 85/5, and 88/0 mm of Hg, respectively. Within 60 s, there was a reduction in the absolute platelet number in the peripheral circulation. The elevation of ventricular pressure persisted for approximately 5 minutes and was followed within 30 minutes by a set of ECG events suggestive of acute myocardial ischemic injury, which included premature ventricular contractions, transient S-T segment depression concurrent with ventricular hypertension, and S-T segment elevation with reversed tall upright T-waves in association with a decrease to the preinfusion ventricular base line. Other ECG changes included prolongation of the P-R segment, missed ventricular contractions, and arrhythmia. The ECG changes seemed to be subsequent to platelet microthrombus formation in the pulmonary arterial microcirculation. By 2.5 hours after the treatment, platelets ""rebounded"" into the circulation in 2 surviving guinea pigs, and left ventricular pressures and ECG profiles returned to the preinfusion base lines. Guinea pigs IV infused with similar amounts of inactivated (15 minutes at 100 C) fibrillary collagen material did not show changes" http://www.ncbi.nlm.nih.gov/pubmed/464353 0 1471 "R. Moraga-Amaro, H. Gonzalez, V. Ugalde, J. P. Donoso-Ramos, D. Quintana-Donoso, M. Lara, B. Morales, P. Rojas, R. Pacheco and J. Stehberg" 2016 Dopamine receptor D5 deficiency results in a selective reduction of hippocampal NMDA receptor subunit NR2B expression and impaired memory Neuropharmacology 103 222-235 "Pharmacological evidence associates type I dopamine receptors, including subtypes D1 and D5, with learning and memory. Analyses using genetic approaches have determined the relative contribution of dopamine receptor D1 (D1R) in cognitive tasks. However, the lack of drugs that can discriminate between D1R and D5R has made the pharmacological distinction between the two receptors difficult. Here, we aimed to determine the role of D5R in learning and memory. In this study we tested D5R knockout mice and wild-type littermates in a battery of behavioral tests, including memory, attention, locomotion, anxiety and motivational evaluations. Our results show that genetic deficiency of D5R significantly impairs performance in the Morris water maze paradigm, object location and object recognition memory, indicating a relevant role for D5R in spatial memory and recognition memory. Moreover, the lack of D5R resulted in decreased exploration and locomotion. In contrast, D5R deficiency had no impact on working memory, anxiety and depressive-like behavior, measured using the spontaneous alternation, open-field, tail suspension test, and forced swimming test. Electrophysiological analyses performed on hippocampal slices showed impairment in long-term-potentiation in mice lacking D5R. Further analyses at the molecular level showed that genetic deficiency of D5R results in a strong and selective reduction in the expression of the NMDA receptor subunit NR2B in the hippocampus. These findings demonstrate the relevant contribution of D5R in memory and suggest a functional interaction of D5R with hippocampal glutamatergic pathways" http://www.ncbi.nlm.nih.gov/pubmed/26714288 0 1472 "K. Murray, D. L. Ritchie, M. Bruce, C. A. Young, M. Doran, J. W. Ironside and R. G. Will" 2008 Sporadic Creutzfeldt-Jakob disease in two adolescents "Journal of Neurology, Neurosurgery and Psychiatry.79 (1) ()(pp 14-18), 2008.Date of Publication: January 2008." 1 14-18 "Background: Sporadic Creutzfeldt-Jakob disease (CJD) is a condition predominantly affecting older age groups, with cases aged less than 45 years rare and an age at onset or death of less than 20 years exceptional. Methods: Data from the systematic study of sporadic CJD in the UK are available from 1970 onwards. Clinical and pathological data are reviewed in order to identify atypical cases, including those at the extremes of the age range of sporadic CJD. Detailed analysis of atypical cases is undertaken, and in selected cases laboratory transmission studies are carried out in order to provide information on the characteristics of the infectious agent. Results: In the UK, two cases of sporadic CJD in adolescents have been identified, dying at ages 16 and 20 years. The first case predated the epidemic of bovine spongiform encephalopathy and the characteristics of the second case, including laboratory transmission studies, are consistent with a diagnosis of sporadic rather than variant CJD. Conclusion: The cases in this report indicate that sporadic CJD can develop at a very young age, that variant CJD is not the only form of CJD occurring in this age group and that neuropathological examination is essential for accurate diagnosis of human prion disease" DO - http://dx.doi.org/10.1136/jnnp.2006.104570 0 1473 "R. S. Yoon, A. Czaya, H. C. Kwan and M. L. Joy" 1999 Changes in the complex permittivity during spreading depression in rat cortex IEEE Trans.Biomed.Eng 46 11 1330-1338 "With recent developments in current density imaging (CDI), it is feasible to utilize this new technique in brain imaging applications. Since CDI's ability to measure changes in current density depends on a concomitant activity-dependent change in the conductivity of the brain tissue, we have examined the changes in complex conductivity during spreading depression (SD) in rodent neocortex using a coaxial probe. SD was chosen because it is often referred to as an animal model of cerebral ischemia and migraine with aura. The conductivity measurements revealed a change with short latency (30-60 s) followed by a change with a longer latency (200-300 s). This change in conductivity with short latency has not been reported before, and we conjecture that it may be the priming or triggering mechanism prior to the main SD episode. A 20% change in conductivity during SD is sufficiently large to be measured by CDI. Therefore, the ability to measure changes in the conductivity, as opposed to metabolic changes, makes CDI a viable approach to the study of ischemia and migraine with aura" http://www.ncbi.nlm.nih.gov/pubmed/10582418 0 1474 J. N. Eble 1970 The effects of intravenous acetylcholine on the cardiovascular system of the anaesthetized dog Br.J.Pharmacol. 38 2 448P-449P http://www.ncbi.nlm.nih.gov/pubmed/5417876 0 1475 S. Kaukinen 1978 Effects of antihypertensive medication on the cardiovascular response to ketamine in rats Acta Anaesthesiol.Scand. 22 4 437-446 "The effects of hydralazine, clonidine, propranolol and methyldopa medications on the cardiovascular response to ketamine anaesthesia were studied in spontaneously hypertensive (SH) rats. Except in propranolol- and methyldopa-treated animals, blood pressure was increased by ketamine in all groups. The heart rate was increased only in the normotensive control rats, whereas it was reduced in both the unmedicated and all of the medicated SH rats. Plasma renin activity under ketamine anaesthesia was markedly higher in normotensive control rats than in any of the SH groups. The pressor responses to dopamine and metaraminol were not altered by propranolol medication, but hydralazine suppressed these responses, while they were markedly intensified by clonidine and methyldopa treatment. Similarly, small additional doses of ketamine caused a pressor response only in clonidine- and methyldopa-treated animals, whereas in the other groups the response was depressive. The tolerance to haemorrhagic shock during ketamine anaesthesia was notably improved by hydralazine and methyldopa medication, but impaired by propranolol treatment. The results suggest that, with special reference to shock tolerance, hydralazine and methyldopa, and to a lesser extent also clonidine, have a favourable effect on the circulation under ketamine anaesthesia, whereas the action of beta-blockade may be harmful" http://www.ncbi.nlm.nih.gov/pubmed/726860 0 1476 "G. Ramirez-Rodriguez, N. M. Vega-Rivera, J. Oikawa-Sala, A. Gomez-Sanchez, L. Ortiz-Lopez and E. Estrada-Camarena" 2014 Melatonin synergizes with citalopram to induce antidepressant-like behavior and to promote hippocampal neurogenesis in adult mice J.Pineal Res. 56 4 450-461 "Adult hippocampal neurogenesis is affected in some neuropsychiatric disorders such as depression. Numerous evidence indicates that plasma levels of melatonin are decreased in depressed patients. Also, melatonin exerts positive effects on the hippocampal neurogenic process and on depressive-like behavior. In addition, antidepressants revert alterations of hippocampal neurogenesis present in models of depression following a similar time course to the improvement of behavior. In this study, we analyzed the effects of both, citalopram, a widely used antidepressant, and melatonin in the Porsolt forced swim test. In addition, we investigated the potential antidepressant role of the combination of melatonin and citalopram (MLTCITAL), its type of pharmacological interaction on depressive behavior, and its effect on hippocampal neurogenesis. Here, we found decreased immobility behavior in mice treated with melatonin (<14-33%) and citalopram (<17-30%). Additionally, the MLTCITAL combination also decreased immobility (<22-35%) in comparison with control mice, reflecting an antidepressant-like effect after 14 days of treatment. Moreover, MLTCITAL decreased plasma corticosterone levels (29%), survival (>39%), and the absolute number of -associated new neurons (>53%) in the dentate gyrus of the hippocampus. These results indicate that the MLTCITAL combination exerts synergism to induce an antidepressant-like action that could be related to the modulation of adult hippocampal neurogenesis. This outcome opens the opportunity of using melatonin to promote behavioral benefits and hippocampal neurogenesis in depression and also supports the use of the MLTCITAL combination as an alternative to treat depression" http://www.ncbi.nlm.nih.gov/pubmed/24650119 1 1477 "K. S. Hsu, Y. C. Liang and C. C. Huang" 2000 Influence of an extracellular acidosis on excitatory synaptic transmission and long-term potentiation in the CA1 region of rat hippocampal slices J.Neurosci.Res. 62 3 403-415 "The effects of extracellular acidification on the synaptic function and neuronal excitability were investigated on the hippocampal CA1 neurons. A decrease of extracellular pH from 7.4 to 6.7 did not alter either the resting membrane potential or the neuronal membrane input resistance. Extracellularly recorded field excitatory postsynaptic potentials (fEPSPs) and population spikes (PSs) were significantly reduced by acidosis. Additionally, the amplitude of presynaptic fiber volley was also reduced. The sensitivity of postsynaptic neurons to N-methyl-D-aspartate, but not to alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid, was depressed by acidosis. Lowering of extracellular pH did not significantly affect the magnitude of paired-pulse facilitation (PPF) of synaptic transmission. Acidosis also reversibly limited the sustained repetitive firing (RF) of Na(+)-dependent action potentials elicited by injection of depolarizing current pulses into the pyramidal cells. The limitation of RF by extracellular acidification was accompanied by the reduction of the maximal rate of rise (;V(max)) of the action potentials and the amplitude of afterhyperpolarization. Neither the Na (+)/H (+) antiporter blocker 5-(N -ethyl -N -isopropyl)-amiloride nor the selective adenosine A (1) receptor antagonist 1,3-dipropyl -8-cyclopentylxanthine, however, affected the acidosis -induced synaptic depression. It was also found that acidosis did not affect either the induction r maintenance of long -term potentiation (LTP) at Schaffer collateral -CA 1 synapses. These results suggest that the extracellular acidosis -induced synaptic depression is likely to result from an inhibition of presynaptic Na (+) conductance, thereby decreasing the amplitude of action potentials in individual afferent fibers or the number of afferent fiber activation to stimuli and then indirectly affecting the signaling processes contributing to trigger neurotransmitter release" http://www.ncbi.nlm.nih.gov/pubmed/11054810 0 1478 "X. Chen, R. Lin, L. Chang, S. Xu, X. Wei, J. Zhang, C. Wang, R. Anwyl and Q. Wang" 2013 "Enhancement of long-term depression by soluble amyloid beta protein in rat hippocampus is mediated by metabotropic glutamate receptor and involves activation of p38MAPK, STEP and caspase-3" Neuroscience 253 435-443 "It is reported that the amyloid-beta protein (Abeta)-induced impairments in synaptic plasticity coincide with memory decline and dementia. Although Abeta-induced inhibition of hippocampal long-term potentiation has been intensively investigated, the underlying mechanism of Abeta-enhanced long-term depression (LTD) is not clear. Here, we report that acute exposure of rat hippocampal slices to soluble Abeta-enhanced LTD induced by weak low-frequency stimulation (wLFS; 1Hz for 3 min, 180 pulses) in granule cells of the dentate gyrus. Application of LY341495 (a non-selective Group I/II metrabotropic glumate receptor (mGluR) antagonist) completely blocked Abeta-enhanced LTD, whereas D-AP5 (a not selective N-methyl-d-aspartate receptor (NMDAR) antagonist) had no effect on Abeta-enhanced LTD compared with controls. In addition, Abeta-enhanced LTD was occluded by pre-application of 3,5-dihydroxyphenylglycine, a Group1 mGluR (mGluR1/5) agonist, suggesting Abeta-enhanced LTD depends on mGluR1/5 but not NMDAR. We also report here that p38 mitogen-activated protein kinase (p38MAPK) inhibitor SB203580 and postsynaptic protein tyrosine phosphatase inhibitors phenylarsine oxide and sodium orthovanadate prevented the facilitatory effect of Abeta on LTD. Application of striatal-enriched protein tyrosine phosphatase (STEP) activator MG132 facilitated induction of LTD by wLFS, but did not block following Abeta-enhanced LTD induced by another wLFS. On the other hand, Abeta-enhanced LTD blocked following MG132-LTD by wLFS, suggesting Abeta-enhanced hippocampal LTD involves STEP activation. Application of either non-selective caspase inhibitor Z-VAD-FMK or caspase-3 selective inhibitor Z-DEVD-FMK prevented Abeta-enhanced LTD. However, neither the tumor necrosis factor-alpha converting enzyme inhibitor TAPI-2 nor the mammalian target of rapamycin inhibitor rapamycin prevented the enhancement of Abeta on LTD. Therefore, we conclude that soluble Abeta enhances LTD in the hippocampal dentate gyrus region, and the facilitatory effect of Abeta on LTD involves mGluR1/5, p38MAPK, STEP and caspase-3 activation" http://www.ncbi.nlm.nih.gov/pubmed/24012839 0 1479 "J. M. Masserano, G. S. Takimoto and N. Weiner" 1981 Electroconvulsive shock increases tyrosine hydroxylase activity in the brain and adrenal gland of the rat "Science.214 (4521) ()(pp 662-665), 1981.Date of Publication: 1981." 4521 662-665 "A single application of electroconvulsive shock produced a rapid but short-lasting increase in tyrosine hydroxylase activity above control values in the rat adrenal medulla and striatum. After repeated electroconvulsive shock treatment (once per day for 7 days), tyrosine hydroxylase activity increased significantly in the locus ceruleus, nucleus of the tractus solitarius, hippocampus, cerebellum, and frontal cortex and remained elevated for 4 to 8 days. Adrenal tyrosine hydroxylase activity increased 1 day after the termination of repeated electroconvulsive shock treatments and remained elevated for at least 24 days, possibly reflecting the establishment of a new and higher steady state level of catecholamine biosynthesis in the adrenal. These findings suggest that the persistent changes in tyrosine hydroxylase activity produced by repeated electroconvulsive shock may be a factor contributing to the long lasting antidepressant effects of this treatment" 0 1480 "K. H. Ali, T. W. Feeley, M. Bieber, B. McGrath and N. N. Teng" 1987 Cardiovascular effect of intravenous lipid A in rabbits Circ.Shock 23 4 285-293 "The in vivo cardiovascular effect of intravenous administration of monophosphoryl lipid A (mp-lipid A) and diphosphoryl lipid A (dp-lipid A) in awake New Zealand white rabbits was investigated. Observed changes were evaluated in comparison to a control group and an endotoxin-treated group. Rabbits given lipid A showed a significant depression in cardiac index (p less than .025), mean arterial pressure (p less than .025, dp-lipid A only), arterial carbon dioxide tension (p less than .025), and total leukocyte count (p less than .05) compared to controls. Animals receiving lipid A tended to respond overall in a manner closely matching that of the endotoxin group. Dosages of lipid A given were approximately 3.5 times larger than the endotoxin dosages with respect to actual number of molecules administered (1.25-2.0 times larger by mass). These results indicate that lipid A is active in producing the cardiovascular and leukopenic effects characteristic of experimental septic shock" http://www.ncbi.nlm.nih.gov/pubmed/3690820 0 1481 J. W. Phillis 1974 Neomycin and ruthenium red antagonism of monoaminergic depression of cerebral cortical neurones Life Sci. 15 2 213-222 http://www.ncbi.nlm.nih.gov/pubmed/4549912 0 1482 "J. D. Johnson, B. A. Jant, S. Kaufman and L. Sokoloff" 1971 Effects of ionic strength on the RNA polymerase activities of isolated nuclei and nucleoli of rat liver Arch.Biochem.Biophys. 142 2 489-500 http://www.ncbi.nlm.nih.gov/pubmed/5550156 0 1483 "D. Pevni, I. Frolkis, A. Iaina, Y. Wollman, T. Chernichovski, I. Shapira, G. Uretzky and R. Mohr" 2001 Protamine cardiotoxicity and nitric oxide Eur.J.Cardiothorac.Surg. 20 1 147-152 "OBJECTIVES: The purpose of this study is to assess the role of the nitric oxide (NO) pathway in protamine-induced cardiotoxicity and to formulate a possible explanation for this adverse effect. METHODS: Isolated rat hearts were perfused by Krebs--Henseleit (KH) solution using a modified Langendorff model. They were randomized into three groups: A, 40 min perfusion with KH solution; B, 20 min perfusion with KH solution and 20 min with protamine; C, as B but Ng-monomethyl-L-arginine (L-NMMA), a non-selective inhibitor of the NO pathway, was added during 40 min of the perfusion period. Left ventricular (LV) function was measured every 10 min. NO and tumor necrosis factor-alpha (TNF) were detected in the effluent from the coronary sinus (CS) and in the supernatant of the cardiac myocytes culture. Nitric oxide synthases (NOS) mRNA levels were determined in groups A and B from LV samples at baseline and after 40 min of perfusion. RESULTS: We found that protamine at a dose of 12 microg/ml causes significant depression of LV function (decreased peak systolic pressure to 22.5+/-3.2% and dP/dt max to 22.9+/-3.1%). L-NMMA did not prevent protamine cardiotoxicity. NOS mRNA was not detected from LV samples in any group. The NO in the effluent from the CS and from the supernatant of the cardiomyocytes culture was below detectable levels. However, a significant amount of TNF was measured in the effluent from the CS (108+/-17 pg/min for group B and 117+/-13 pg/min for group C) and in the supernatant of the cardiomyocytes culture (65+/-21 pg/ml). CONCLUSIONS: This study suggests that direct protamine-induced cardiotoxicity does not depend on the NO pathway. Our finding that protamine induced TNF release by cardiomyocytes can shed new light on the understanding of protamine cardiotoxicity" http://www.ncbi.nlm.nih.gov/pubmed/11423288 0 1484 M. G. Schwacha and D. J. Loegering 1992 Respiratory burst capacity of activated macrophages is resistant to depression by erythrocyte phagocytosis Inflammation 16 4 285-294 "The present study evaluated whether macrophage activation would reduce the depression in the capacity of macrophages to produce H2O2 following EIgG phagocytosis. Macrophage activation was accomplished by exposing inflammatory rat peritoneal macrophages to 10 units of IFN gamma for 72 h. IFN gamma treatment caused a four to fivefold increase in phorbol myristate acetate (PMA)-triggered H2O2 production, but Fc receptor phagocytic function was unaltered. IFN gamma-activated macrophages were able to phagocytize a greater number of EIgG before a decrease in PMA-triggered H2O2 production was observed and the level of H2O2 production did not fall below that of untreated-inflammatory macrophages that had not received an EIgG phagocytic challenge. The depression in Fc receptor phagocytic function was unaltered with macrophage activation. These results indicate that activated macrophages are resistant to the depression of respiratory burst capacity caused by erythrocyte phagocytosis and suggests that IFN gamma treatment may be effective in preventing the impairment of host defense against bacterial infection that is associated with erythrocyte phagocytosis" http://www.ncbi.nlm.nih.gov/pubmed/1526661 0 1485 "F. McKechnie, S. Lewis and G. Mead" 2010 A pilot observational study of the association between fatigue after stroke and C-reactive protein J.R.Coll.Physicians Edinb. 40 1 09-Dec "BACKGROUND: The aetiology of fatigue after stroke is unknown. We explored the relationship between fatigue and C-reactive protein (CRP) as a marker of inflammation. METHODS: This cross-sectional study recruited inpatients with a stroke (onset within the previous three months) over a five-week period. Those with dysphasia or confusion severe enough to prevent informed consent and those with current infection were excluded. A semi-structured interview determined a) fulfillment of a case definition for fatigue and b) severity of fatigue (fatigue assessment scale, FAS). Venous blood was taken for CRP. A hospital anxiety and depression score (HADS) was used to screen for emotional distress. RESULTS: Of the 28 patients recruited (mean age 72.7 years, proportion men 47%), 15 (53%) fulfilled the case definition for fatigue. C-reactive protein data were logarithmically transformed for analysis. C-reactive protein levels did not differ significantly between those with and without fatigue, according to the case definition (=28, p=0.35). After exclusion of those with pre-stroke fatigue and those with high scores on the HADS (suggestive of emotional distress), the geometric mean CRP of the fatigued group was 16.04 mg/l (95% CI: 7.12-36.14) compared with 5.16 mg/l (95% CI: 2.7-9.85) in the non-fatigued group (n=21, p=0.025, unpaired t test), but the relationship between FAS and CRP was not statistically significant (r=0.37, p=0.098). CONCLUSION: This pilot study is the first to demonstrate an association between fatigue after stroke and higher CRP, after excluding patients with pre-stroke fatigue and those with probable mood disorders. If this finding is confirmed in a larger number of patients, it might provide a target for treating fatigue after stroke" http://www.ncbi.nlm.nih.gov/pubmed/21125032 0 1486 "A. M. Smith, G. K. Dhawan, Z. Zhang, K. B. Siripurapu, P. A. Crooks and L. P. Dwoskin" 2009 "The novel nicotinic receptor antagonist, N,N'-dodecane-1,12-diyl-bis-3-picolinium dibromide (bPiDDB), inhibits nicotine-evoked [(3)H]norepinephrine overflow from rat hippocampal slices" Biochem.Pharmacol. 78 7 889-897 "Smoking is a significant health concern and strongly correlated with clinical depression. Depression is associated with decreased extracellular NE concentrations in brain. Smokers may be self-medicating and alleviating their depression through nicotine stimulated norepinephrine (NE) release. Several antidepressants inhibit NE transporter (NET) function, thereby augmenting extracellular NE concentrations. Antidepressants, such as bupropion, also inhibit nicotinic receptor (nAChR) function. The current study determined if a recently discovered novel nAChR antagonist, N,N'-dodecane-1,12-diyl-bis-3-picolinium dibromide (bPiDDB), inhibits nicotine-evoked NE release from superfused rat hippocampal slices. Previous studies determined that bPiDDB potently (IC(50)=2 nM) inhibits nicotine-evoked striatal [(3)H]dopamine (DA) release in vitro, nicotine-evoked DA release in nucleus accumbens in vivo, and nicotine self-administration in rats. In the current study, nicotine stimulated [(3)H]NE release from rat hippocampal slices (EC(50)=50 microM). bPiDDB inhibited (IC(50)=430 nM; I(max)=90%) [(3)H]NE release evoked by 30 microM nicotine. For comparison, the nonselective nAChR antagonist, mecamylamine, and the alpha7 antagonist, methyllycaconitine, also inhibited nicotine-evoked [(3)H]NE release (IC(50)=31 and 275 nM, respectively; I(max)=91% and 72%, respectively). Inhibition by bPiDDB and mecamylamine was not overcome by increasing nicotine concentrations; Schild regression slope was different from unity, consistent with allosteric inhibition. Thus, bPiDDB was 200-fold more potent inhibiting nAChRs mediating nicotine-evoked [(3)H]DA release from striatum than those mediating nicotine-evoked [(3)H]NE release from hippocampus" http://www.ncbi.nlm.nih.gov/pubmed/19631612 0 1487 "G. E. Wiegand, V. J. Bauer, S. R. Safir, D. A. Blickens and S. J. Riggi" 1972 Quaternary 4- (and 5-) azolylpyridazinium salts. A new class of oral hypoglycemic agents J.Med.Chem. 15 12 1326-1328 http://www.ncbi.nlm.nih.gov/pubmed/4635983 0 1488 "J. T. Brandt, D. A. Pierce and N. Fausto" 1972 Ornithine decarboxylase activity and polyamine synthesis during kidney hypertrophy Biochim.Biophys.Acta 279 1 184-193 http://www.ncbi.nlm.nih.gov/pubmed/4119904 0 1489 "M. Shaked, K. Weissmuller, H. Svoboda, P. Hortschansky, N. Nishino, S. Wolfl and K. L. Tucker" 2008 Histone deacetylases control neurogenesis in embryonic brain by inhibition of BMP2/4 signaling PLoS.One. 3 7 e2668 "BACKGROUND: Histone-modifying enzymes are essential for a wide variety of cellular processes dependent upon changes in gene expression. Histone deacetylases (HDACs) lead to the compaction of chromatin and subsequent silencing of gene transcription, and they have recently been implicated in a diversity of functions and dysfunctions in the postnatal and adult brain including ocular dominance plasticity, memory consolidation, drug addiction, and depression. Here we investigate the role of HDACs in the generation of neurons and astrocytes in the embryonic brain. PRINCIPAL FINDINGS: As a variety of HDACs are expressed in differentiating neural progenitor cells, we have taken a pharmacological approach to inhibit multiple family members. Inhibition of class I and II HDACs in developing mouse embryos with trichostatin A resulted in a dramatic reduction in neurogenesis in the ganglionic eminences and a modest increase in neurogenesis in the cortex. An identical effect was observed upon pharmacological inhibition of HDACs in in vitro-differentiating neural precursors derived from the same brain regions. A reduction in neurogenesis in ganglionic eminence-derived neural precursors was accompanied by an increase in the production of immature astrocytes. We show that HDACs control neurogenesis by inhibition of the bone morphogenetic protein BMP2/4 signaling pathway in radial glial cells. HDACs function at the transcriptional level by inhibiting and promoting, respectively, the expression of Bmp2 and Smad7, an intracellular inhibitor of BMP signaling. Inhibition of the BMP2/4 signaling pathway restored normal levels of neurogenesis and astrogliogenesis to both ganglionic eminence- and cortex-derived cultures in which HDACs were inhibited. CONCLUSIONS: Our results demonstrate a transcriptionally-based regulation of BMP2/4 signaling by HDACs both in vivo and in vitro that is critical for neurogenesis in the ganglionic eminences and that modulates cortical neurogenesis. The results also suggest that HDACs may regulate the developmental switch from neurogenesis to astrogliogenesis that occurs in late gestation" http://www.ncbi.nlm.nih.gov/pubmed/18628975 0 1490 "Y. Akagawa, Y. Masuda, A. Maruyama, T. Shimizu and Y. Hishikawa" 1999 Effects of repeated selective serotonin reuptake inhibitor paroxetine treatments on mouse forced swimming Methods Find.Exp.Clin.Pharmacol. 21 9 599-601 "Studies were performed in the mouse forced swimming model, a well known experimental depression model, in order to detect the mechanism of the antidepressive effects induced by repeated serotonin reuptake inhibitor (SSRI) dosing. Five-day repeat dosing of a typical SSRI, paroxetine, increased climbing, a distinctive antidepressive behavior, 1 h after but not 1 h before treatment. The coinjection of paroxetine and serum in mice treated with four repeated doses of paroxetine distinctively increased the behavior, but the coinjection of paroxetine and serum in mice without paroxetine did not. These results indicate that repeated dosing of paroxetine produces a serum substance related to the antidepressive effects induced by serotonin neuron activities. Furthermore, the behavior induced by 5-day repeated dosing of paroxetine was decreased by 100 and 10 micrograms/kg of ketanserin (5-HT2 antagonist) and 100 micrograms/kg of LY-278584 (5-HT3 antagonist). The present findings strongly suggest that repeated dosing of paroxetine produces a serum substance stimulating the antidepressive neuronal pathway sensitively mediated by 5-HT2 and 5-HT3 receptor activity" http://www.ncbi.nlm.nih.gov/pubmed/10669904 1 1491 J. N. Hingtgen and M. H. Aprison 1975 Behavioral depression in pigeons following l-tryptophan administration Life Sci. 16 9 1471-1476 http://www.ncbi.nlm.nih.gov/pubmed/1134205 1 1492 V. P. Chuang and S. R. Reuter 1975 Experimental diminution fo splenci function by selective embolization of the splenic artery Surg.Gynecol.Obstet. 140 5 715-720 "The splenic artery was occluded by the selective injection of Amicar-mixed clot or Gelfoam in 18 dogs. The dogs were sacrificed at 24 hours, two weeks and two months. Angiography was done before and after embolization, three hours after embolization and prior to sacrifice. White blood counts and hematocrit values were evaluated weekly in the dogs sacrificed at two months. The results of this study reveal differences in the effects of the two embolic materials. Because Amicar-mixed clot was partially lysed in the first several hours and also pushed peripherally, the depression of hematologic function seen with its use was transient and most spleens returned to a relatively normal gross and histologic appearance. With Gelfoam, although the embolic material was also pushed peripherally into the branches of the splenic artery in several of the dogs, the depression of hematologic function was prolonged, and moderate splenic parenchymal fibrosis was seen. The areas between the bands of fibrosis appeared normal. The results indicate that selective embolic occlusion of the splenic artery and its branches may offer a method of depressing splenic function in patients who are not candidates for splenectomy" http://www.ncbi.nlm.nih.gov/pubmed/1145406 0 1493 "Y. K. Narnaware, B. I. Baker and M. G. Tomlinson" 1994 "The effect of various stresses, corticosteroids and adrenergic agents on phagocytosis in the rainbow trout Oncorhynchus mykiss" Fish.Physiol Biochem. 13 1 31-40 "The effect of acute and chronic stress on the phagocytic activity of putative macrophages from the rainbow trout. Oncorhynchus mykiss has been assessed, using an in vitro phagocytic index, in which the average number of engulfed yeast cells in a population of phagocytes is determined. An injection stress given under light anaesthesia, or a longer noise stress combined with confinement, both significantly reduced, within 3 h, the level of phagocytic activity of macrophages from the spleen and pronephros. Daily injection stress over six days had a lesser effect on the proportion of phagocytically active cells even though plasma cortisol levels were equally raised. Daily dexamethasone injection depressed the proportion of phagocytically active cells more than saline injection. In these in vivo experiments, it was not possible to determine whether stress and steroids depressed the phagocytic activity of individual macrophages or caused the active macrophages to migrate out of the spleen and pronephros. Administration of cortisol (200 nM) to trout macrophages in vitro failed to depress phagocytic activity within a 3h period but both alpha- and beta-adrenergic agonists (10 muM) were usually depressive. It is proposed that the autonomic nervous system may be an early regulator of macrophage phagocytosis following stress and that corticosteroids only exert their suppressive effect on macrophage activity in the longer term" http://www.ncbi.nlm.nih.gov/pubmed/24203269 0 1494 A. Rancillac and J. G. Barbara 2005 Frequency-dependent recruitment of inhibition mediated by stellate cells in the rat cerebellar cortex J.Neurosci.Res. 80 3 414-423 "In the cerebellum, dendritic inhibition of Purkinje cells (PCs) is mediated by stellate cells (SCs). These inhibitory interneurons are critically involved in the cerebellar network; they control the timing and firing frequency of PCs, the only output cells of the cerebellar cortex. However, the underlying properties of parallel fiber (PF) to SC excitatory synapses have not been fully determined. To characterize the conditions favoring the recruitment of SCs in the cerebellum, we analyzed evoked and spontaneous excitatory postsynaptic currents (EPSCs) recorded from SCs of rat cerebellar slices. We found that SC EPSCs evoked with single suprathreshold-intensity stimulations were mostly unitary, with a large amplitude and variable latencies, and failed with a high rate. Increasing the frequency of stimulation above 60 Hz significantly reduced failures, whereas mean SC EPSC amplitude was increased by less than 20%. Decreasing failures at PF-SC synapses experimentally enhanced the number of asynchronous SC EPSCs per stimulation but, again, moderately increased the mean SC EPSC amplitude. Finally, brief presynaptic bursts transiently depressed synaptic transmission. This depression resulted from the release of endocannabinoids and might act as a negative-feedback mechanism. Thus, we conclude that SC EPSCs evoked with single suprathreshold-intensity stimulations are mostly unitary and that PF-SC synapse efficacy is highly regulated by the presynaptic temporal pattern of activity and the frequency of afferent inputs. Such synaptic properties may control the responsiveness of SC synapses to the frequency of PF stimulations, which may control the spatial extent and duration of the recruitment of inhibition in the cerebellar cortex" http://www.ncbi.nlm.nih.gov/pubmed/15789412 0 1495 "J. E. Rubin, R. C. Gerkin, G. Q. Bi and C. C. Chow" 2005 Calcium time course as a signal for spike-timing-dependent plasticity J.Neurophysiol. 93 5 2600-2613 "Calcium has been proposed as a postsynaptic signal underlying synaptic spike-timing-dependent plasticity (STDP). We examine this hypothesis with computational modeling based on experimental results from hippocampal cultures, some of which are presented here, in which pairs and triplets of pre- and postsynaptic spikes induce potentiation and depression in a temporally asymmetric way. Specifically, we present a set of model biochemical detectors, based on plausible molecular pathways, which make direct use of the time course of the calcium signal to reproduce these experimental STDP results. Our model features a modular structure, in which long-term potentiation (LTP) and depression (LTD) components compete to determine final plasticity outcomes; one aspect of this competition is a veto through which appropriate calcium time courses suppress LTD. Simulations of our model are also shown to be consistent with classical LTP and LTD induced by several presynaptic stimulation paradigms. Overall, our results provide computational evidence that, while the postsynaptic calcium time course contains sufficient information to distinguish various experimental long-term plasticity paradigms, small changes in the properties of back-propagation of action potentials or in synaptic dynamics can alter the calcium time course in ways that will significantly affect STDP induction by any detector based exclusively on postsynaptic calcium. This may account for the variability of STDP outcomes seen within hippocampal cultures, under repeated application of a single experimental protocol, as well as for that seen in multiple spike experiments across different systems" http://www.ncbi.nlm.nih.gov/pubmed/15625097 0 1496 "M. S. Hazari, J. Callaway, D. W. Winsett, C. Lamb, N. Haykal-Coates, Q. T. Krantz, C. King, D. L. Costa and A. K. Farraj" 2012 "Dobutamine ""stress"" test and latent cardiac susceptibility to inhaled diesel exhaust in normal and hypertensive rats" Environ.Health Perspect. 120 8 1088-1093 "BACKGROUND: Exercise ""stress"" testing is a screening tool used to determine the amount of stress for which the heart can compensate before developing abnormal rhythm or ischemia, particularly in susceptible persons. Although this approach has been used to assess risk in humans exposed to air pollution, it has never been applied to rodent studies. OBJECTIVE: We hypothesized that a single exposure to diesel exhaust (DE) would increase the risk of adverse cardiac events such as arrhythmia and myocardial ischemia in rats undergoing a dobutamine challenge test, which can be used to mimic exercise-like stress. METHODS: Wistar-Kyoto normotensive (WKY) and spontaneously hypertensive (SH) rats implanted with radiotelemeters and a chronic intravenous catheter were whole-body exposed to 150 mug/m3 DE for 4 hr. Increasing doses of dobutamine, a beta1-adrenergic agonist, were administered to conscious unrestrained rats 24 hr later to elicit the cardiac response observed during exercise while heart rate (HR) and electrocardiogram (ECG) were monitored. RESULTS: A single exposure to DE potentiated the HR response of WKY and SH rats during dobutamine challenge and prevented HR recovery at rest. During peak challenge, DE-exposed SH rats had lower overall HR variability when compared with controls, in addition to transient ST depression. All DE-exposed animals also had increased arrhythmias. CONCLUSIONS: These results are the first evidence that rats exhibit stress-induced cardiac dysrhythmia and ischemia sensitivity comparable to humans after a single exposure to a toxic air pollutant, particularly when in the presence of underlying cardiovascular disease. Thus, exposure to low concentrations of air pollution can impair the heart's ability to respond to stress and increase the risk of subsequent triggered dysfunction" http://www.ncbi.nlm.nih.gov/pubmed/22543081 0 1497 "T. Serchov, H. W. Clement, M. K. Schwarz, F. Iasevoli, D. K. Tosh, M. Idzko, K. A. Jacobson, B. A. de, C. Normann, K. Biber and C. D. van" 2015 "Increased Signaling via Adenosine A1 Receptors, Sleep Deprivation, Imipramine, and Ketamine Inhibit Depressive-like Behavior via Induction of Homer1a" Neuron 87 3 549-562 "Major depressive disorder is among the most commonly diagnosed disabling mental diseases. Several non-pharmacological treatments of depression upregulate adenosine concentration and/or adenosine A1 receptors (A1R) in the brain. To test whether enhanced A1R signaling mediates antidepressant effects, we generated a transgenic mouse with enhanced doxycycline-regulated A1R expression, specifically in forebrain neurons. Upregulating A1R led to pronounced acute and chronic resilience toward depressive-like behavior in various tests. Conversely, A1R knockout mice displayed an increased depressive-like behavior and were resistant to the antidepressant effects of sleep deprivation (SD). Various antidepressant treatments increase homer1a expression in medial prefrontal cortex (mPFC). Specific siRNA knockdown of homer1a in mPFC enhanced depressive-like behavior and prevented the antidepressant effects of A1R upregulation, SD, imipramine, and ketamine treatment. In contrast, viral overexpression of homer1a in the mPFC had antidepressant effects. Thus, increased expression of homer1a is a final common pathway mediating the antidepressant effects of different antidepressant treatments" http://www.ncbi.nlm.nih.gov/pubmed/26247862 1 1498 H. Ito 1989 [Cochlear dysfunction induced by arterial obstruction in the cat anterior cerebellar artery] Nihon Jibiinkoka Gakkai Kaiho 92 11 1863-1868 "To determine the effects of circulatory disorder on the cochlear function, compound action potentials (AP) were measured in cats with the anterior cerebellar and the labyrinthine arteries occluded. While transitory AP depression followed the anterior cerebellar artery occlusion in approximately one third of the animals, there were no changes in the others. In contrast to this, AP disappeared rapidly in all cases with labyrinthine artery occlusion and recovered only after release of the occlusion in a period of time proportionate to the duration of occlusion. The different ways of response in the two occlusion sites seem to be attributed mainly to a greater chance of collateral circulations in the proximal. In addition, wide range of variance was observed from cat to cat in the effect of the anterior cerebellar artery occlusion and in the recovery following the release of occlusion in the labyrinthine artery, which may be attributed to anatomical variation inherent in the artery system" http://www.ncbi.nlm.nih.gov/pubmed/2593033 0 1499 "B. Brookshire, T. E. Hill-Smith, D. T. Balu, J. Turner, J. A. Blendy and I. Lucki" 2012 "The tryptophan hydroxylase 2 (TPH2) polymorhism C2432T alters TPH2 expression, contributes to increased serotonin (5-HT) synthesis, and mediates response to SSRIS" "Biological Psychiatry.Conference: 67th Annual Scientific Convention and Meeting of the Society of Biological Psychiatry Philadelphia, PA United States.Conference Start: 20120503 Conference End: 20120505.Conference Publication: (var.pagings).71 (8 Supp" var.pagings 34S-35S "Background: Currently available therapies for treatment of Major Depressive Disorder involve manipulation of brain monoamine systems, but mechanisms behind successful responses to treatment remain unclear. In this study, we examined whether a novel polymorphism C2432T in the Tph2 gene mediates the 5-HT system and differential antidepressant response in a responder MRL/ MpJ (MRL) strain compared to a nonresponder C57Bl/6J (C57) strain (Balu et al. 2009). We then cross-bred C57 and MRL strains for two generations to isolate the Tph2 polymorphism and determine its functionality. Methods: qPCR was used to compare Tph2 mRNA expression levels in the hippocampus of the parent strains. 5-HT synthesis levels were quantified using NSD-1015 in the parent strains. Increased 5-HT levels in response to citalopram were also measured using in vivo microdialysis in the parent strain. Parent and F2 crosses were evaluated for response to citalopram in the tail suspension test. Results: MRL mice showed significant increases in Tph2 mRNA expression compared to C57 animals (p<0.05, n=10/group) and increased 5-HT synthesis in the prefrontal cortex (p=0.05, n=10/group). In addition, MRL mice showed a 3-fold increase in 5-HT response to acute citalopram in the hippocampus (p<0.05, n=5/group). F2 generation animals displayed a sex-specific genotype dependent tail suspension test response to citalopram (p=0.1, n=3-7/group) in females. Conclusions: The C2432T polymorphism may mediate 5-HT system function and antidepressant response in a sex-specific manner. Future studies will examine the mechanism of action and the Tph2 expression and 5-HT synthesis patterns of the F2 generation cross to determine the functionality of C2432T" DO - http://dx.doi.org/10.1016/j.biopsych.2012.02.012 0 1500 X. Wei and K. Messner 1996 The postnatal development of the insertions of the medial collateral ligament in the rat knee Anat.Embryol.(Berl) 193 1 53-59 "Bone soft tissue remodelling at the femoral and tibial insertions of the medial collateral ligament (MCL) of the rat knee was monitored at regular intervals from birth to 120 days of age in 40 Sprague Dawley rats. At birth the femoral insertion originated from the perichondrium of the epiphysis. By day 8 the perichondrium within the insertion had turned into fibrocartilage. Secondary ossification of the femoral epiphysis had progressed in the region near to the insertion site by day 15. The epiphyseal cartilage was entirely replaced by bone by day 40 except for the fibrocartilage within the insertion. After that stage, no qualitative change in zonal insertion characteristics was observed, but only increase in size and decrease in cellularity. At birth, the tibial ligament inserted onto the thin cortical bone of the metaphysis via periosteum. At day 8, osteoclasts started to resorb the thin cortical bone at the ligament insertion, thus forming a metaphyseal depression between days 10 and 20. From days 20 to 120, the insertion remained qualitatively unchanged, showing three zones, the ligament, periosteum, and metaphyseal trabecular bone. The deep periosteal layer showed osteoclastic activity in the proximal part and osteoblastic activity in the distal part. The migration-mechanism of the ligament insertion during growth seems to be caused by this growth-related osteoclastic resorption of the proximal metaphyseal bone and by simultaneous osteogenic activity, which successively cements the distal part of the ligament to bone. The persistence of the periosteal layer and the metaphyseal depression for up to 120 days may be regarded as a sign of continuing growth in this animal model. This is the first investigation showing that the formation of the metaphyseal depression is a purely postnatal event, and suggests that this process might be initiated by the change in mode of growth and joint biomechanics after birth, enabling ligament development and migration in a growing and increasingly loaded weight-bearing joint. The mainly resorptive process, which takes place during development of the tibial MCL insertion, may account for the tensile failure of this ligament that commonly occurs at this site during growth. The pronounced morphological differences between the chondral femoral and the periosteal tibial attachment of the adult MCL are apparently caused by the different postnatal development processes at epiphyses and metaphyses" http://www.ncbi.nlm.nih.gov/pubmed/8838496 0 1501 "B. de la Puente, E. Romero-Alejo, J. M. Vela, M. Merlos, D. Zamanillo and E. Portillo-Salido" 2015 Changes in saccharin preference behavior as a primary outcome to evaluate pain and analgesia in acetic acid-induced visceral pain in micez "Journal of Pain Research.8 ()(pp 663-673), 2015.Date of Publication: 06 Oct 2015." 663-673 "Reflex-based procedures are important measures in preclinical pain studies that evaluate stimulated behaviors. These procedures, however, are insufficient to capture the complexity of the pain experience, which is often associated with the depression of several innate behaviors. While recent studies have made efforts to evidence the suppression of some positively motivated behaviors in certain pain models, they are still far from being routinely used as readouts for analgesic screening. Here, we characterized and compared the effect of the analgesic ibuprofen (Ibu) and the stimulant, caffeine, in assays of acute pain-stimulated and pain-depressed behavior. Intraperitoneal injection of acetic acid (AA) served as a noxious stimulus to stimulate a writhing response or depress saccharin preference and locomotor activity (LMA) in mice. AA injection caused the maximum number of writhes between 5 and 20 minutes after administration, and writhing almost disappeared 1 hour later. AA-treated mice showed signs of depression-like behaviors after writhing resolution, as evidenced by reduced locomotion and saccharin preference for at least 4 and 6 hours, respectively. Depression-like behaviors resolved within 24 hours after AA administration. A dose of Ibu (40 mg/kg) - inactive to reduce AA-induced abdominal writhing - administered before or after AA injection significantly reverted pain-induced saccharin preference deficit. The same dose of Ibu also significantly reverted the AA-depressed LMA, but only when it was administered after AA injection. Caffeine restored locomotion - but not saccharin preference - in AA-treated mice, thus suggesting that the reduction in saccharin preference - but not in locomotion - was specifically sensitive to analgesics. In conclusion, AA-induced acute pain attenuated saccharin preference and LMA beyond the resolution of writhing behavior, and the changes in the expression of hedonic behavior, such as sweet taste preference, can be used as a more sensitive and translational model to evaluate analgesics" DO - http://dx.doi.org/10.2147/JPR.S91230 0 1502 "T. W. Stone, C. Lui and J. I. Addae" 2011 Effects of ethylenediamine--a putative GABA-releasing agent--on rat hippocampal slices and neocortical activity in vivo Eur.J.Pharmacol. 650 02-Mar 568-578 "The simple diamine diaminoethane (ethylenediamine, EDA) has been shown to activate GABA receptors in the central and peripheral nervous systems, partly by a direct action and partly by releasing endogenous GABA. These effects have been shown to be produced by the complexation of EDA with bicarbonate to form a carbamate. The present work has compared EDA, GABA and beta-alanine responses in rat CA1 neurons using extracellular and intracellular recordings, as well as neocortical evoked potentials in vivo. Superfusion of GABA onto hippocampal slices produced depolarisation and a decrease of field epsps, both effects fading rapidly, but showing sensitivity to blockade by bicuculline. EDA produced an initial hyperpolarisation and increase of extracellular field epsp size with no fade and only partial sensitivity to bicuculline, with subsequent depolarisation, while beta-alanine produces a much larger underlying hyperpolarisation and increase in fepsps, followed by depolarisation and inhibition of fepsps. The responses to beta-alanine, but not GABA or EDA, were blocked by strychnine. In vivo experiments, recording somatosensory evoked potentials, confirmed that EDA produced an initial increase followed by depression, and that this effect was not fully blocked by bicuculline. Overall the results indicate that EDA has actions in addition to the activation of GABA receptors. These actions are not attributable to activation of beta-alanine-sensitive glycine receptors, but may involve the activation of sites sensitive to adipic acid, which is structurally equivalent to the dicarbamate of EDA. The results emphasise the complex pharmacology of simple amines in bicarbonate-containing solutions" http://www.ncbi.nlm.nih.gov/pubmed/21050846 0 1503 "R. V. Carsia, N. M. Reisch, M. J. Fennell and H. Weber" 1987 Adrenocortical function of the domestic fowl: effects of orchiectomy and androgen replacement Proc.Soc.Exp.Biol.Med. 185 2 223-232 "The effect of orchiectomy and androgen replacement on cockerel adrenocortical function was investigated. Orchiectomized cockerels (2 weeks old) were implanted with Silastic tubing containing various amounts of one of the following steroids: cholesterol, testosterone (T), androstenedione (A4), and 5 alpha-dihydrotestosterone (DHT). Birds were administered additional implants, containing doses of steroids equivalent to those of the initial implants, at 4 and 8 weeks of treatment (i.e., 6 and 10 weeks of age). Sham-operated cockerels administered empty implants served as intact controls for comparison of data. Animals were killed after 10 weeks of treatment (12 weeks old). Trunk plasma corticosterone (B) and plasma T, and B production by collagenase-isolated adrenocortical cells incubated briefly (2 hr) with or without steroidogenic agents were measured by radioimmunoassay. Orchiectomy with implantation of the inert sterol, cholesterol (hereafter referred to as orchiectomy), did not alter plasma B concentrations and did not affect basal cellular B production or cellular B production induced by a maximal steroidogenic concentration of ACTH or that maximally supported by 25-hydroxycholesterol. However, orchiectomy did lower maximal 8-bromo-cyclic AMP-induced B production by 30%. Low-implant doses of A4 (1-cm implant) and T (0.3-cm implant), that maintained comb growth, lowered plasma B concentrations by 24-42%, whereas a high-implant dose of T (3-cm implant) and all implant doses of DHT had no effect on plasma B concentrations. Thus, androgen replacement had different effects on plasma B depending on the type of androgen and the implant dose. In contrast, androgen replacement consistently suppressed basal and maximal ACTH-induced cellular B production regardless of the type of androgen. Furthermore, the degree of suppression was dose-dependent. These results suggest that the differential effect of androgen replacement on plasma B concentrations was due to differences in the clearance of circulating B and/or differences in blood volume. In addition, the present study suggests that in the absence of the testes, androgens are suppressants of adrenocortical cell function in the domestic fowl" http://www.ncbi.nlm.nih.gov/pubmed/3033685 0 1504 "E. Gomez-Gil, C. Gasto, M. Carretero, M. Diaz-Ricart, M. Salamero, R. Navines and G. Escolar" 2004 Decrease of the platelet 5-HT2A receptor function by long-term imipramine treatment in endogenous depression "Human Psychopharmacology.19 (4) ()(pp 251-258), 2004.Date of Publication: June 2004." 4 251-258 "Background. Animal studies have found that many antidepressants induce decreases in both the density and the functional activity of the serotonin 2A (5-HT2A) receptor subtype. However, the extrapolation of findings to humans has been inconclusive. A physiological platelet response mediated by this receptor, the serotonin-amplified platelet aggregation, was measured to study whether long-term antidepressant treatment induces changes in 5-HT2A receptor functioning in endogenous depressed patients. Method. The percentage of serotonin-amplified platelet aggregation to adenosine diphosphate (ADP) was studied in 15 untreated patients with major depressive disorder (DSM-IV) with endogenous features (Newcastle scale). This index was used as an indirect measurement of the functional status of platelet 5-HT2A receptors. Aggregation studies were repeated once remission of the symptoms was achieved during treatment with imipramine (150-300 mg/day). A group of 15 concurrent normal subjects was used as a control. Results. A statistically significant decrease (p = 0.038) in the percentage of serotonin-amplified platelet aggregation to ADP was observed when remission was achieved (after 145 +/- 27 days). Conclusions. The results showed a decrease in a platelet functional response mediated by 5-HT2A receptors following effective imipramine treatment, suggesting that desensitization or down-regulation of the 5-HT2A receptor function could be linked to the therapeutic effect of some antidepressants. The data also support the use of platelet aggregometry as a surrogate measurement of antidepressant action, particularly in intra-subject designs. Copyright © 2004 John Wiley & Sons, Ltd" DO - http://dx.doi.org/10.1002/hup.583 0 1505 "J. Perez-Tejada, A. Arregi, E. Gomez-Lazaro, O. Vegas, A. Azpiroz and L. Garmendia" 2013 "Coping with chronic social stress in mice: hypothalamic-pituitary-adrenal/ sympathetic-adrenal-medullary axis activity, behavioral changes and effects of antalarmin treatment: implications for the study of stress-related psychopathologies" Neuroendocrinology 98 1 73-88 "The aim of this study was to analyze the individual differences that lead to the development of psychopathological changes in response to chronic social stress. We also assessed the ability of an antagonist of the corticotrophin-releasing hormone (CRH) receptors to reverse the effects of stress. Male adult mice were exposed to repeated defeat experiences for 21 days using a sensorial contact model. After 18 days of defeat, two groups of subjects were established (active and passive), according to their behaviors during social confrontation. Antalarmin treatment was given for 4 and 6 days. The results corroborated previous data indicating that subjects who adopted a passive coping strategy had higher corticosterone levels after 21 days of defeat and decreased resting levels 3 days later. Moreover, they showed higher resting expression levels of hypothalamic CRH than their active counterparts. On day 24, the experimental animals were subjected to another social defeat to determine whether the stress response remained. The increase in corticosterone and hypothalamic CRH levels was similar for all of the stressed subjects, but the passive subjects also had a greater CRH response in the amygdala. Passive subjects had decreased levels of adrenal dopamine beta-hydroxylase, tyrosine hydroxylase and plasma adrenaline compared to the active subjects, and lower plasma noradrenaline levels than manipulated controls. The passive profile of physiological changes in both the hypothalamic-pituitary-adrenal and sympathetic-adrenal-medullary (SAM) axes has been associated with changes related to mood disorders, such as posttraumatic stress disorder and depression. The active coping profile is characterized by similar corticosterone resting levels to controls and increased SAM activity. Both profiles showed alterations in the novel palatable and forced swimming tests, with the passive profile being the most vulnerable to the effects of stress in this last test. Pharmacological treatment with antalarmin failed to reverse the effects of stress" http://www.ncbi.nlm.nih.gov/pubmed/23796983 1 1506 "G. J. Ragland, J. Fuller, J. L. Feder and D. A. Hahn" 2009 Biphasic metabolic rate trajectory of pupal diapause termination and post-diapause development in a tephritid fly J.Insect Physiol 55 4 344-350 "Metabolic depression is a highly conserved feature of insect diapause, and an increase in metabolism is a reliable indicator of diapause termination and the initiation of post-diapause development. The trajectory of metabolic rate following diapause termination can guide the identification of important physiological and developmental landmarks during this developmental transition, yet quantitative descriptions of these trajectories are relatively rare. Here we track changes in metabolic rate from diapause through diapause termination and pharate adult development in Rhagoletis pomonella (Diptera: Tephritidae), a univoltine tephritid fly that diapauses in the pupal stage. Using respirometric monitoring we show that diapause termination and subsequent pharate adult development is characterized by a biphasic increase in metabolic rate. Respiration rate initially increases logistically, reaching a plateau that is followed by a final, exponential increase terminating in adult eclosion. We develop a non-linear model describing this pattern with easily interpretable landmarks, and we map visible landmarks of morphogenesis onto the trajectory. The bulk of visible morphogenesis in pharate adult development occurs relatively late in the trajectory during the final, exponential phase, that matches the U-shaped trajectory of non-diapause individuals. These results mirror a qualitative description of the same trajectories of diapause and non-diapause flesh flies (Sarcophaga). Overall, our results suggest that (1) the course of diapause breakage and post-diapause development may be evolutionarily conserved in higher flies with pupal diapause, and (2) the biphasic trajectory is distinct from a more continuous trajectory observed during direct development" http://www.ncbi.nlm.nih.gov/pubmed/19200436 0 1507 I. Jurna and K. Brune 1990 "Central effect of the non-steroid anti-inflammatory agents, indomethacin, ibuprofen, and diclofenac, determined in C fibre-evoked activity in single neurones of the rat thalamus" Pain 41 1 71-80 "This study aimed to investigate if the non-steroid anti-inflammatory agents, indomethacin, ibuprofen, and diclofenac, are capable of depressing sensory responses of the nociceptive system by a central action. For this purpose, experiments were carried out on rats under urethane anaesthesia in which activity was elicited by electrical stimulation of afferent C fibres in the sural nerve. Recordings were made ipsi- or contralaterally from single neurones in the dorsomedial part of the ventral nucleus (VDM) of the thalamus. The 3 drugs produced a dose-dependent depression of the evoked activity which amounted to about 60% of the controls at the highest doses employed and lasted longer than 60 min. Their potency ranking, according to the ED50 values (in brackets), is: indomethacin (5 mg/kg) greater than diclofenac (10.9 mg/kg) greater than ibuprofen (15.6 mg/kg). The results suggest that a central action might contribute to the analgesia produced by these non-steroid anti-inflammatory agents" http://www.ncbi.nlm.nih.gov/pubmed/2352767 0 1508 "M. Benbouzid, C. Gaveriaux-Ruff, I. Yalcin, E. Waltisperger, L. H. Tessier, A. Muller, B. L. Kieffer, M. J. Freund-Mercier and M. Barrot" 2008 Delta-opioid receptors are critical for tricyclic antidepressant treatment of neuropathic allodynia Biol.Psychiatry 63 6 633-636 "BACKGROUND: The therapeutic effect of antidepressant drugs against depression usually necessitates a chronic treatment. A large body of clinical evidence indicates that antidepressant drugs can also be highly effective against chronic neuropathic pain. However, the mechanism by which these drugs alleviate pain is still unclear. METHODS: We used a murine model of neuropathic pain induced by sciatic nerve constriction to study the antiallodynic properties of a chronic treatment with the tricyclic antidepressants nortriptyline and amitriptyline. Using knockout and pharmacological approaches in mice, we determined the influence of delta-opioid receptors in the therapeutic action of chronic antidepressant treatment. RESULTS: In our model, a chronic treatment by tricyclic antidepressant drugs totally suppresses the mechanical allodynia in neuropathic C57Bl/6J mice. This therapeutic effect can be acutely reversed by an injection of the delta-opioid receptor antagonist naltrindole. Moreover, the antiallodynic property of antidepressant treatment is absent in mice deficient for the delta-opioid receptor gene. CONCLUSIONS: The antiallodynic effect of chronic antidepressant treatment is mediated by a recruitment of the endogenous opioid system acting through delta-opioid receptors" http://www.ncbi.nlm.nih.gov/pubmed/17693391 0 1509 "T. Fu, A. Stellmacher, E. B. Znalesniak, D. C. Dieterich, H. Kalbacher and W. Hoffmann" 2014 Tff3 is expressed in neurons and microglial cells Cell Physiol Biochem. 34 6 1912-1919 "BACKGROUND/AIMS: The trefoil factor family (TFF) peptide TFF3 is typically secreted by mucous epithelia, but is also expressed in the immune system and the brain. It was the aim of this study to determine the cerebral cell types which express Tff3. METHODS: Primary cultures from rat embryonic or neonatal cerebral cortex and hippocampus, respectively, were studied by means of RT-PCR and immunofluorescence. Moreover, Tff3 expression was localized by immunocytochemistry in sections of adult rat cerebellum. RESULTS: Tff3 transcripts were detectable in neural cultures of both the cortex and the hippocampus as well as in glial cell-enriched cultures. Tff3 peptide co-localized with Map2 indicating an expression in neurons in vitro. The neuronal expression was confirmed by immunofluorescence studies of adult rat cerebellum. Furthermore, Tff3 peptide showed also a clear co-localization with Iba-1 in vitro typical of activated microglial cells. CONCLUSION: The neuronal expression of Tff3 is in line with a function of a typical neuropeptide influencing, e.g., fear, memory, depression and motoric skills. The expression in activated microglial cells, which is demonstrated here for the first time, points towards a possible function for Tff3 in immune reactions in the CNS. This opens a plethora of additional possible functions for Tff3 including synaptic plasticity and cognition as well as during neuroinflammatory diseases and psychiatric disorders" http://www.ncbi.nlm.nih.gov/pubmed/25504043 0 1510 "M. K. Leung, J. McLintock and J. Iversen" 1978 Intranasal exposure of the Richardson's ground squirrel to Western equine encephalomyelitis virus Can.J.Comp Med. 42 2 184-191 "Adult Richardson's ground squirrels were infected with western equine encephalomyelitis virus by intranasal instillation. Mortality followed the instillation of a minimum threshold of 4.7 logs of virus while infection was produced by a dosage of 2.3 logs. The incubation period was from four to seven days, being preceded by a viremic phase. Signs were depression, ataxia and paralysis of the limbs. Highest titres of virus were recovered from the brain and histopathological changes involving the central nervous system included meningitis, vasculitis, perivascular cuffing, gliosis, neuronophagia and neuronal degeneration. The virus was also found in a variety of extraneural tissues. Lesions in extraneural tissues included necrosis of brown fat and an apparent increase in number of Kupffer's cells in the liver. The lymphoid tissue was involved indicating a possible source for viremia. The duration and magnitude of viremia were ample enough to provide virus source for arthropods. The potential for transmission of the virus independent of arthropods was discussed in view of the pathogenesis demonstrated in the experimental infections" http://www.ncbi.nlm.nih.gov/pubmed/667706 0 1511 "N. R. Swerdlow, R. Hauger, M. Irwin, G. F. Koob, K. T. Britton and L. Pulvirenti" 1991 "Endocrine, immune, and neurochemical changes in rats during withdrawal from chronic amphetamine intoxication" Neuropsychopharmacology 5 1 23-31 "In humans who chronically abuse amphetamine (AMPH), sudden abstinence often precipitates an organic mood disorder that mimics many symptoms of major depression. We report that AMPH exposure and withdrawal in rats modifies hypothalamic-pituitary-adrenal axis endocrine responses, peripheral immune functions, and regional brain catecholamine levels. Compared to vehicle-treated animals, rats treated with AMPH for 10 days exhibit significantly decreased physostigmine-induced release of adrenocorticotropin hormone (ACTH). During AMPH withdrawal, these animals show a loss of the normal correlation between levels of plasma ACTH and corticosterone. Chronic AMPH treatment in rats causes a significant increase in natural killer cell activity. Brain dopamine levels in these animals are decreased in the caudate nucleus but are increased in the nucleus accumbens. AMPH withdrawal in rats may be a useful model for studying the physiologic and neural substrates of human AMPH withdrawal states" http://www.ncbi.nlm.nih.gov/pubmed/1657016 1 1512 W. Zhang and J. A. Rosenkranz 2013 Repeated restraint stress enhances cue-elicited conditioned freezing and impairs acquisition of extinction in an age-dependent manner Behav.Brain Res. 248 Dec-24 "Affective disorders are believed to involve dysfunction within the amygdala, a key structure for processing emotional information. Chronic stress may contribute to affective disorders such as depression and anxiety via its effects on the amygdala. Previous research has shown that chronic stress increases amygdala neuronal activity in an age-dependent manner. However, whether these distinct changes in amgydala neuronal activity are accompanied by age-dependent changes in amygdala-dependent affective behavior is unclear. In this study, we investigated how chronic stress impacts amgydala-dependent auditory fear conditioning in adolescent and adult rats in a repeated restraint model. We found that repeated restraint enhanced conditioned freezing in both adolescent and adult rats. But repeated restraint led to impaired acquisition of fear extinction only in adolescent rats. Along with previous findings, these results suggest that chronic stress may precipitate affective disorders via differential mechanisms, with different outcomes at different ages" http://www.ncbi.nlm.nih.gov/pubmed/23538069 0 1513 P. Bolme and K. Fuxe 1971 Pharmacological studies on the hypotensive effects of clonidine Eur.J.Pharmacol. 13 2 168-174 http://www.ncbi.nlm.nih.gov/pubmed/5544069 0 1514 "C. G. Reich, M. E. Taylor and M. M. McCarthy" 2009 Differential effects of chronic unpredictable stress on hippocampal CB1 receptors in male and female rats Behav.Brain Res. 203 2 264-269 "Chronic unpredictable mild stress (CMS), an animal model of depression, downregulates hippocampal CB1 receptors in adult male rats. Given that endocannabinoids are implicated in modulating stress and anxiety and that women are vulnerable to stress-related disorders, we tested the effects of CMS on both female and male rats. Gonadectomized (gndx) and gonadally intact male and female rats were exposed to a three-week chronic stress protocol. Following CMS, CB1 receptor and fatty-acid-amide-hydrolase (FAAH) expression levels in the hippocampus were assessed by western blot analysis. CMS reliably produced a downregulation of CB1 receptors ( approximately 50%) in the hippocampus of both gndx and intact males. This effect was more robust in the dorsal than in the ventral hippocampus. Conversely, CMS produced an upregulation of CB1 receptors ( approximately 150%) in the hippocampus of both gndx and intact females. This upregulation was only observed in the dorsal hippocampus of female animals. CMS produced an upregulation of FAAH levels in both male and female animals. In non-stress control animals, males were observed to have higher CB1 levels than females, but no differences in FAAH were found. These findings suggest that the endocannabinoid (eCB) system is preferentially organized in male and female animals to respond differentially to chronic stress. These sex differences in the eCB system may help development of novel treatments for stress and depression that are designed specifically for women and men" http://www.ncbi.nlm.nih.gov/pubmed/19460405 1 1515 "S. Miyata, Y. Koyama, M. Taniguchi and M. Tohyama" 2012 Excessive levels of plasma corticosterone induces morphological changes in oligodendrocytes in corpus callosum Journal of Neurochemistry.Conference: 11th Biennial Meeting of the Asian-Pacific Society for Neurochemistry / 55th Annual Meeting of the Japanese Society for Neurochemistry Kobe Japan.Conference Start: 20120929 Conference End: 20121002.Conference Publi var.pagings 125-126 "Depression is probably the oldest and still one of the most frequently diagnosed psychiatric illnesses. Major depression is one of the leading causes of disturbances in emotional, cognitive, autonomic, and endocrine functions, affecting nearly 7% of the population in Japan. According to the large amount of information on depressive diseases that has been accumulated during recent years, patients with major depression show an enhanced biologic stress-response mechanism, especially a hyperactive hypothalamicpituitary- adrenal (HPA) axis and high levels of circulating cortisol. Although dysregulation of the HPA axis by chronic stress is indicative of major depression, the molecular mechanisms and functional changes in the brain underlying depression are largely unknown. In this study, by using repeated water-immersion and restraint stress (WIRS) as a stressor for mice, we attempted to elucidate the molecular pathway induced by elevated plasma corticosterone levels. We observed the following effects both, in vivo and in vitro: (1) repeated exposure to WIRS activates the 3- phosphoinositide-dependent protein kinase (PDK1)-;serum glucocorticoid regulated kinase (SGK1)-;N-myc downstream-regulated gene 1 (NDRG1)-;adhesion molecule stabilization pathway via an increase in plasma corticosterone levels; (2) the activation of this signaling pathway induces morphological changes in oligodendrocytes; and (3) after recovery from chronic stress, the abnormal arborization of oligodendrocytes and depression-like symptoms return to the control levels. These results indicate that phosphorylation of SGK1 causing changes in the morphology of oligodendrocytes. Moreover, the chronic stress-induced dysregulation the oligodendrocytes is suggested to be closely associated with the development of major depression" DO - http://dx.doi.org/10.1111/j.1471-4159.2012.07906.x 0 1516 C. M. Pennartz 1997 Reinforcement learning by Hebbian synapses with adaptive thresholds Neuroscience 81 2 303-319 "A central problem in learning theory is how the vertebrate brain processes reinforcing stimuli in order to master complex sensorimotor tasks. This problem belongs to the domain of supervised learning, in which errors in the response of a neural network serve as the basis for modification of synaptic connectivity in the network and thereby train it on a computational task. The model presented here shows how a reinforcing feedback can modify synapses in a neuronal network according to the principles of Hebbian learning. The reinforcing feedback steers synapses towards long-term potentiation or depression by critically influencing the rise in postsynaptic calcium, in accordance with findings on synaptic plasticity in mammalian brain. An important feature of the model is the dependence of modification thresholds on the previous history of reinforcing feedback processed by the network. The learning algorithm trained networks successfully on a task in which a population vector in the motor output was required to match a sensory stimulus vector presented shortly before. In another task, networks were trained to compute coordinate transformations by combining different visual inputs. The model continued to behave well when simplified units were replaced by single-compartment neurons equipped with several conductances and operating in continuous time. This novel form of reinforcement learning incorporates essential properties of Hebbian synaptic plasticity and thereby shows that supervised learning can be accomplished by a learning rule similar to those used in physiologically plausible models of unsupervised learning. The model can be crudely correlated to the anatomy and electrophysiology of the amygdala, prefrontal and cingulate cortex and has predictive implications for further experiments on synaptic plasticity and learning processes mediated by these areas" http://www.ncbi.nlm.nih.gov/pubmed/9300423 0 1517 "M. L. Lehmann, T. Mustafa, A. M. Eiden, M. Herkenham and L. E. Eiden" 2013 PACAP-deficient mice show attenuated corticosterone secretion and fail to develop depressive behavior during chronic social defeat stress Psychoneuroendocrinology 38 5 702-715 "The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) regulates activation of the hypothalamic-pituitary-adrenal (HPA) axis and the adrenal gland in response to various stressors. We previously found that in response to acute psychological stress (restraint), elevated corticotrophin-releasing hormone (CRH) mRNA levels in the hypothalamic paraventricular nucleus (PVN) as well as elevated plasma corticosterone (CORT) were profoundly attenuated in PACAP-deficient mice. To determine whether HPA axis responses and stress-induced depressive-like behaviors in a chronic stress paradigm are affected by PACAP deficiency, we subjected mice to 14 days of social defeat stress. Defeat-exposed PACAP-/- mice showed a marked attenuation of stress-induced increases in serum CORT levels, cellular PVN DeltaFosB immunostaining, and depressive-like behaviors (social interaction and forced swim tests) compared to wild-type control mice. The PACAP-/- mice showed reduced PVN FosB-positive cell numbers, but relatively elevated cell counts in several forebrain areas including the medial prefrontal cortex, after social stress. PACAP appears to be specific for mediating HPA activation only in psychological stress because marked elevations in plasma CORT after a systemic stressor (lipopolysaccharide administration) occurred regardless of genotype. We conclude that chronically elevated CORT is a key component of depressive effects of social defeat, and that attenuation of the CORT response at the level of the PVN, as well as extrahypothalamic forebrain regions, in PACAP-deficient mice protects from development of depressive behavior" http://www.ncbi.nlm.nih.gov/pubmed/23062748 1 1518 P. D. Hrdina and T. B. Vu 1993 Chronic fluoxetine treatment upregulates 5-HT uptake sites and 5-HT2 receptors in rat brain: an autoradiographic study Synapse 14 4 324-331 "This study was undertaken to investigate the effect of chronic treatment with fluoxetine, a selective serotonin uptake inhibitor used widely in the treatment of depression, on the distribution and density of 5-HT uptake sites, 5-HT2 receptors, and vesicular amine uptake sites in rat brain. Fluoxetine (10 mg/kg i.p.) was administered daily for 21 days. The density of 5-HT uptake sites labelled by [3H]paroxetine, 5-HT2 receptors labelled by [3H]ketanserin in presence of tetrabenazine and vesicular amine uptake sites labelled by [3H]ketanserin in the presence of mianserin were measured by quantitative autoradiography in 22 areas of rat brain, using coronal tissue sections. Chronic administration of fluoxetine produced significant increases in the density of 5-HT uptake sites in layers of frontoparietal cortex (by 32-43%), of striate cortex (by 55%), in CA1 field of hippocampus (by 111%) and in superior colliculus (by 20%). Fluoxetine treatment also resulted in upregulation of 5-HT2 receptors in layers of frontoparietal cortex (31-38%) and in CA2-3 fields of hippocampus (by 39%). The density of tetrabenazine-sensitive vesicular amine uptake sites in the caudate-putamen was also significantly increased (by 66%). The observed alterations in 5-HT uptake site and 5-HT2 receptor densities are likely a part of adaptive neuronal changes that occur after chronic administration of fluoxetine and may be related to the antidepressant effect of the drug" http://www.ncbi.nlm.nih.gov/pubmed/8248854 0 1519 J. H. Song and D. H. Youn 2014 Theta-burst stimulation induces LTP at excitatory and inhibitory synapses in the spinal trigeminal subnucleus interpolaris Neurosci.Lett. 574 01-May "Long-lasting synaptic modifications of excitatory and inhibitory synaptic transmissions induced by theta-burst stimulation (TBS) were examined in the spinal trigeminal subnucleus interpolaris (Vi). We found that conditioning afferents of another subnucleus caudalis (Vc) to the Vi with TBS produced long-term depression (LTD). However, when GABAA and glycine receptors were blocked, the same stimulation paradigm produced long-term potentiation (LTP). The induction of LTP involved neither NMDA receptors nor a presynaptic change. The expression of LTP was obviously suppressed by the activation of group I mGluRs because its magnitude increased in the presence of antagonists for group I mGluRs. Besides the LTP at excitatory synapses, TBS also induced LTP at inhibitory GABAergic synapses, which required the activation of NMDA receptors and NO-cGMP signaling but was not involved in the increase of postsynaptic Ca(2+) concentration. Therefore, this study shows, for the first time, an activity-dependent plasticity at excitatory and inhibitory synapses in the Vi by the same conditioning stimulation" http://www.ncbi.nlm.nih.gov/pubmed/24852827 0 1520 C. Tsoukas and W. Rosenau 1977 Inhibition of lymphotoxin- and lymphocyte-mediated cytolysis by high molecular-weight dextran Proc.Soc.Exp.Biol.Med. 154 2 215-218 http://www.ncbi.nlm.nih.gov/pubmed/300163 0 1521 "S. Shivaji, D. M. Saxena and M. K. Pillai" 1978 Mode of action of alkylating agents using a ciliate protozoan as a model system: Part V--effect of metepa on protein synthesis in Blepharisma intermedium (Ciliata) Indian J.Exp.Biol. 16 6 632-635 http://www.ncbi.nlm.nih.gov/pubmed/100418 0 1522 E. Gunther 1976 [Animal experimental studies on the effects of noise stress on male fertility] Andrologia 8 2 95-100 "Psychic stress is able to cause male infertility. Stieve found out aspermatogenesis in executed men. Cockett et al. immobilized 5 Macaca-Monkeys 15 to 40 days in capsule module under simulated space flight conditions and detected severe testicular degeneration. Carosi and Calabro reported about workers exposed to industrial noise over a period of years; the number of offspring was found to be much lower than in non exposed families. We examined the effect of noise on the fertility of 21 male guinea pigs. Sounding of 110 dB lasted 3-5 hours daily over a period of 22-31 days. Histological examination of the testicular tissue did not show any disorder of spermatogenesis. We believe that the negative result is attributed to failings in the test arrangement. Sounding only lasted for a maximum of 31 days. However, the duration of spermatogenesis in guinea pigs is about 40 days. Moreover the sounding maximum was only 5 hours per day, yet the time of recovery took 4-5 times longer every day. Consequently the daily short-term depression of the neuroendrocrinium affected the gonadotropine secretion in similarity to the daily biorhythmic variation. Therefore the expected inhibition of fertility by the neuroendrocrinic way could not be demonstrated. Our experiments also revealed another problem. In noise-exposed guinea pigs there was 8.2 per cent tubuli contorti without complete spermatogenesis. Moreover, in the control group even 9.9 per cent of the tubuli was found to be sperm-free. It is not clear why such a contrary reaction occurred. However, it is possible that hormonal stimulation increased temporarily as a result of noise stress. It should be noted that this effect has also been reported by Arguellis" http://www.ncbi.nlm.nih.gov/pubmed/962176 0 1523 "N. E. Anden, H. Corrodi and K. Fuxe" 1972 The effect of psychotomimetic glycolate esters on central monoamine neurons Eur.J.Pharmacol. 17 1 97-102 http://www.ncbi.nlm.nih.gov/pubmed/4401437 0 1524 "L. N. Cornelisse, J. E. van der Harst, J. C. Lodder, P. J. Baarendse, A. J. Timmerman, H. D. Mansvelder, B. M. Spruijt and A. B. Brussaard" 2007 Reduced 5- J.Neurophysiol. 98 1 196-204 "Autoinhibitory serotonin 1A receptors (5-HT(1A)) in dorsal raphe nucleus (DRN) have been implicated in chronic depression and in actions of selective serotonin reuptake inhibitors (SSRI). Due to experimental limitations, it was never studied at single-cell level whether changes in 5-HT(1A) receptor functionality occur in depression and during SSRI treatment. Here we address this question in a social stress paradigm in rats that mimics anhedonia, a core symptom of depression. We used whole cell patch-clamp recordings of 5-HT- and baclophen-induced G-protein-coupled inwardly rectifying potassium (GIRK) currents as a measure of 5-HT(1A)- and GABA(B) receptor functionality. 5-HT(1A)- and GABA(B) receptor-mediated GIRK-currents were not affected in socially stressed rats, suggesting that there was no abnormal (auto)inhibition in the DRN on social stress. However, chronic fluoxetine treatment of socially stressed rats restored anticipatory behavior and reduced the responsiveness of 5-HT(1A) receptor-mediated GIRK currents. Because GABA(B) receptor-induced GIRK responses were also suppressed, fluoxetine does not appear to desensitize 5-HT(1A) receptors but rather one of the downstream components shared with GABA(B) receptors. This fluoxetine effect on GIRK currents was also present in healthy animals and was independent of the animal's ""depressed"" state. Thus our data show that symptoms of depression after social stress are not paralleled by changes in 5-HT(1A) receptor signaling in DRN neurons, but SSRI treatment can alleviate these behavioral symptoms while acting strongly on the 5-HT(1A) receptor signaling pathway" http://www.ncbi.nlm.nih.gov/pubmed/17460100 1 1525 D. C. Klein and R. V. Talmage 1968 Thyrocalcitonin suppression of hydroxyproline rlease from bone Proc.Soc.Exp.Biol.Med. 127 1 95-99 http://www.ncbi.nlm.nih.gov/pubmed/5644673 0 1526 "H. Dodt, M. Eder, A. Frick and W. Zieglgansberger" 1999 Precisely localized LTD in the neocortex revealed by infrared-guided laser stimulation Science 286 5437 110-113 "In a direct approach to elucidate the origin of long-term depression (LTD), glutamate was applied onto dendrites of neurons in rat neocortical slices. An infrared-guided laser stimulation was used to release glutamate from caged glutamate in the focal spot of an ultraviolet laser. A burst of light flashes caused an LTD-like depression of glutamate receptor responses, which was highly confined to the region of ""tetanic"" stimulation (<10 micrometers). A similar depression of glutamate receptor responses was observed during LTD of synaptic transmission. A spatially highly specific postsynaptic mechanism can account for the LTD induced by glutamate release" http://www.ncbi.nlm.nih.gov/pubmed/10506556 0 1527 S. L. Dickinson and P. Slater 1980 "Opiate receptor antagonism by L-prolyl-L-leucyl-glycinamide, MIF-I" Peptides 1 4 293-299 "Chronic administration of 1-prolyl-l-leucyl-glycinamide (MIF-I) to mice slightly reduced morphine's antinociceptive activity in the hot-plate test and modified the biphasic motor activity response to morphine. MIF-I antagonized the initial depression of activity and potentiated the increased motor activity phase. Chronic treatment of rats with MIF-I prevented morphine's antinociceptive activity in the tail flick tests. MIF-I partly antagonized the inhibition by morphine of the coaxially stimulated guinea-pig ileum preparation. The inhibition of the ileum produced by ethylketocyclazocine was weakly antagonized by MIF-I. In contrast, MIF-I had no effect on the inhibition of the stimulated mouse vas deferens produced by Leu-enkephalin. The findings show that MIF-I weakly and selectively inhibits mu-type opiate receptors which suggests that MIF-I could be an endogenous inhibitor of opiate receptors" http://www.ncbi.nlm.nih.gov/pubmed/6117839 0 1528 "A. M. Smith, L. P. Dwoskin and J. R. Pauly" 2010 Early exposure to nicotine during critical periods of brain development: Mechanisms and consequences Journal of Pediatric Biochemistry 1 2 2010 "Tobacco use during pregnancy continues to be a major problem with more than 16% of women in the United States continuing to smoke while pregnant. Tobacco smoke is known to contain more than 4,000 different chemicals, and while many of these compounds have the potential to interfere with proper neurodevelopment, there is direct evidence that nicotine, the major psychoactive substance present in tobacco, acts as a neuroteratogen. Nicotine activates, and subsequently desensitizes, neuronal nicotinic acetylcholine receptor subtypes (AChRs), which are expressed in the developing central nervous system (CNS) prior to the in-growth of cholinergic neurons. Nicotinic AChRs are present by the first trimester of development in both humans and rodents, and activation of these receptors by acetylcholine is thought to play a critical role in CNS development. The purpose of the current review is to provide an overview of the role that nicotinic AChRs play in the developing CNS and to describe the effects of nicotine exposure during early development on neuronal cell biology, nicotinic AChR expression and neurotransmitter system (e.g., dopamine, norepinephrine, serotonin) function. In particular, differences that occur as a result of the timing and duration of nicotine exposure will be discussed. Emphasis will be placed on preclinical studies examining particular periods of time which correspond to periods of prenatal development in humans (i.e., first, second and third trimesters). Finally, the effects of early nicotine exposure on neurobehavioral development as it pertains to specific disorders, i.e., attention deficit hyperactivity disorder (ADHD), depression and addiction, will be discussed. © 2010 - IOS Press and the authors. All rights reserved" 0 1529 "Y. K. Kwon, Y. J. Lee, J. G. Choi, E. K. Lee, W. J. Jeon, O. M. Jeong, M. C. Kim, S. J. Joh, J. H. Kwon and J. H. Kim" 2006 An outbreak of avian influenza subtype H9N8 among chickens in South Korea Avian Pathol. 35 6 443-447 "Low pathogenic avian influenza subtype H9N8 was diagnosed on a Korean native chicken farm in Gyeonggi province, South Korea, in late April 2004. Clinical signs included moderate respiratory distress, depression, mild diarrhoea, loss of appetite and a slightly elevated mortality (1.4% in 5 days). Pathologically, mucopurulent tracheitis and air sacculitis were prominently found with urate renal deposition. The isolated A/chicken/Kr/164/04 (H9N8) had an Ala-Ser-Gly-Arg (A/S/G/R) motif at the cleavage site of haemagglutinin, which has been commonly found in H9N2 isolated from Korean poultry. Phylogenetic analysis of the haemagglutinin and neuraminidase genes of the H9N8 avian influenza virus (AIV) isolate showed that reassortment had occurred. Its haemagglutinin gene was similar to that of Korean H9N2 AIVs, but its neuraminidase gene was closely related to that of A/WBF/Kr/KCA16/03 (H3N8) isolated from the faeces of wild birds in Korea. The pathogenicity of the isolate was tested on 6-week-old specific pathogen free chickens. The inoculated virus (H9N8) was recovered from most tested organs, including the trachea, lung, kidney, spleen, and caecal tonsil. This is the first report of an outbreak of low pathogenic avian influenza in chickens caused by AIV subtype H9N8" http://www.ncbi.nlm.nih.gov/pubmed/17121732 0 1530 R. A. Wiley and J. H. Collins 1969 "Phosphorus analogs of nitrogenous drugs. II. 10H-Dibenzo[1,4]thiaphosphorins as central nervous system depressants" J.Med.Chem. 12 1 146-149 http://www.ncbi.nlm.nih.gov/pubmed/4178726 0 1531 "N. Ravouru, P. Kondreddy, D. Korakanchi and M. Haritha" 2013 Formulation and evaluation of niosomal nasal drug delivery system of folic acid for brain targeting Curr.Drug Discov.Technol. 10 4 270-282 "Nasal mucosa offers advantages to deliver drugs to brain via olfactory route thus provides rapid onset of drug action and hence faster therapeutic effect. Therefore, various strategies have been proposed to improve the delivery of different drugs to brain including liposomes, colloidal drug carriers, micelles, chimeric peptide technology and nanotechnology through nasal route. The low blood level of folates is the primary cause of depression in Alzheimer's disease. Folic acid is a water soluble vitamin showing difficulty in crossing the blood brain barrier and thus was formulated as niosomal nasal drug delivery systems to target the brain. In the present work, folic acid niosomes were prepared using different nonionic surfactants i.e., span 20, span 60, span 80, tween 20, tween 80 and cholesterol by using lipid layer hydration technique. These were evaluated for particle size, viscosity, osmotic shock, entrapment efficiency and in vitro drug release. The influence of different formulation variables such as surfactant type, surfactant concentration, and cholesterol concentration was optimized for required size distribution, viscosity, entrapment efficiency and in vitro release. The prepared niosomes were in the size range of 3.05-5.625 microm. Niosomes prepared with span 60 and cholesterol in the ratio of 1:1 (50 mg: 50 mg) shown higher entrapment efficiency of 69.42% and better in vitro drug release of 64.2% at the end of 12 hrs and therefore considered as optimized formulation. The stability studies were carried out by storing niosomes at 4+/-1 degrees C and 25+/-1 degrees C and showed good stability over the period of storage. The release of drug from niosomes followed anomalous diffusion and obeyed first order release kinetics. Ex-vivo perfusion studies were also performed by using rat model, about 48.15% of drug was found to be absorbed through nasal cavity at the end of 6 hrs" http://www.ncbi.nlm.nih.gov/pubmed/23863098 0 1532 "R. J. Jaeger, H. Plugge and S. Szabo" 1980 Acute urinary bladder toxicity of a polyurethane foam catalyst mixture: a possible new target organ for propionitrile derivative J.Environ.Pathol.Toxicol. 4 02-Mar 555-562 "The toxicity of the mixture NIAX-ESN which contains 95% dimethylaminopropionitrile was evaluated in male rats. Large doses (2.0 ml/kg ip) rapidly produced CNS excitation followed by depression and death. The mixture (given orally as two doses of 0.31 or 0.62 ml/kg respectively) induced acute urinary bladder lesions in 3 days. The changes consisted of massive transmural edema, acute ulcers and inflammation and, occassionally hemorrhagic necrosis of the bladder wall" http://www.ncbi.nlm.nih.gov/pubmed/7462919 0 1533 "J. F. Schmand, A. Ayala and I. H. Chaudry" 1994 "Effects of trauma, duration of hypotension, and resuscitation regimen on cellular immunity after hemorrhagic shock" Crit Care Med. 22 7 1076-1083 "OBJECTIVE: To determine the effects of: a) surgical trauma, b) crystalloid resuscitation, and c) different durations of hypotension on cellular immunity after hemorrhagic shock. DESIGN: Prospective, multiexperimental, randomized, controlled studies. SETTING: University research laboratory. SUBJECTS: Inbred C3H/HeN (endotoxin-sensitive) mice, aged 6 to 7 wks, weighing 18 to 23 g. INTERVENTIONS: Crystalloid resuscitation, with and without blood, after hemorrhage. MEASUREMENTS AND MAIN RESULTS: Mice which did or did not undergo laparotomy were subjected to hypotension of 35 mm Hg for 60 or 90 mins. Crystalloid resuscitation with and without blood was then provided. Animals were killed at 2 hrs after hemorrhage and cytokine concentrations in supernatants of splenocytes, splenic macrophages, and serum were assessed by bioassays. The cellular release of interleukin (IL)-2, IL-3, IL-6, tumor necrosis factor, and the splenocyte proliferative capacity were significantly and similarly depressed in all groups. Conversely, circulating IL-6 concentrations were significantly increased in all groups. CONCLUSIONS: Cellular immunity was depressed at 2 hrs after simple hemorrhage and no further depression occurred if hemorrhage was coupled with trauma, pure crystalloid resuscitation was provided, or the shock period was prolonged. Thus, the early immunodepression after hemorrhage was mainly dependent on the severity rather than the duration of shock, resuscitation regimen, or tissue trauma" http://www.ncbi.nlm.nih.gov/pubmed/8026194 0 1534 P. Lurquin 1967 [Effects of sodium chloride on the esterification of leucine in transfer ribonucleic acids] Arch.Int.Physiol Biochim. 75 5 888-889 http://www.ncbi.nlm.nih.gov/pubmed/4173518 0 1535 E. R. Schertel and D. A. Allen 1993 Continuous pulmonary C-fiber stimulation produces sustained reflex cardiovascular depression Am.J.Physiol 265 6 Pt 2 H1856-H1863 "We used an isolated perfused in situ left lung preparation to evaluate the hemodynamic response to specific pulmonary C-fiber stimulation with capsaicin in two groups of anesthetized dogs. In one group (n = 6), continuous administration of capsaicin at 5 micrograms.kg-1.min-1 into the isolated pulmonary circulation produced sustained (20 min) reflex decreases in mean arterial pressure, cardiac output, maximal left ventricular rate of pressure over time, and heart rate. These effects were abolished by vagotomy. In a second group (n = 5) of atropinized dogs, a mild hemorrhage was first performed in each dog during control conditions (capsaicin vehicle administration). The hemorrhage was performed by removing 10% of blood volume over 3 min and then replacing this blood 3 min later. After reinfusion and stabilization, the mild hemorrhage was repeated during continuous administration of capsaicin (6.0 +/- 1.0 microgram.kg-1.min-1) into the isolated pulmonary circulation. The decrease of mean arterial pressure in response to hemorrhage was significantly greater during capsaicin administration than during control conditions. Lung denervation prevented the effect of capsaicin administration on the response to hemorrhage. We concluded that continuous pulmonary C-fiber stimulation produces sustained cardiovascular depression and compromises the hemodynamic response to mild hemorrhage in dogs. This latter effect may represent a central alteration of baroreflex gain" http://www.ncbi.nlm.nih.gov/pubmed/8285223 0 1536 B. Hald 1991 Porcine nephropathy in Europe IARC Sci.Publ. 115 49-56 "Numerous surveys conducted in North America, Asia and Europe have revealed that ochratoxin A is a natural contaminant of plant products. Contamination frequencies of up to 40% have been encountered, at levels in the range of 5-500 micrograms/kg. Ochratoxin A is a major causal determinant of the disease porcine nephropathy; but other nephrotoxic mycotoxins, such as citrinin and the fungal quinones, may be involved. The disease is characterized clinically by polyuria and growth depression. Renal lesions in pigs include degeneration of the proximal tubules, interstitial fibrosis and hyalinization of the glomeruli. The disease is endemic, outbreaks being associated with bad weather conditions. A positive correlation has been observed between the prevalence rates of porcine nephropathy and the frequency of ochratoxin A in corresponding feed samples. Surveys for residues of ochratoxin A in kidneys from cases of porcine nephropathy in a number of European countries other than Denmark have demonstrated that 21-42% of samples contain ochratoxin A in the range of 1-100 micrograms/kg" http://www.ncbi.nlm.nih.gov/pubmed/1820353 0 1537 "J. A. Bennett, P. N. McWilliam and S. L. Shepheard" 1987 A gamma-aminobutyric-acid-mediated inhibition of neurones in the nucleus tractus solitarius of the cat J.Physiol 392 417-430 1. Extracellular recordings were made from 123 synaptically activated neurones in the nucleus tractus solitarius of the chloralose-anaesthetized cat. 2. Ninety-one neurones were activated by electrical stimulation of cardiac or pulmonary vagal branches and thirty-two by stimulation of the aortic nerve. 3. Ionophoretic application of GABA abolished or markedly reduced the evoked or spontaneous activity of each neurone tested. These inhibitory effects were antagonized by the simultaneous ionophoretic application of bicuculline. 4. Glycine inhibited the evoked activity of 60% of neurones tested. This inhibition could be antagonized by the simultaneous application of strychnine. 5. Application of bicuculline alone increased the evoked or spontaneous activity of a large proportion of the neurones; strychnine alone had no significant effect on the evoked or spontaneous activity of the neurones. 6. These results are consistent with the hypothesis that GABA acts as an inhibitory transmitter substance within the nucleus tractus solitarius http://www.ncbi.nlm.nih.gov/pubmed/3446786 0 1538 N. H. Kalin 2015 Anxious temperament: Results from a translational neuroscience approach "European Neuropsychopharmacology.Conference: 28th European College of Neuropsychopharmacology, ECNP Congress Amsterdam Netherlands.Conference Start: 20150829 Conference End: 20150901.Conference Publication: (var.pagings).25 ()(pp S108-S109), 2015.Dat" var.pagings S108-S109 "Anxiety and depressive disorders commonly present early in life. Therefore, an opportunity exists for early identification and intervention prior to the long-term sequelae of these disorders. Studies demonstrate that childhood anxious temperament (AT) is the phenotype most predictive of the later development of anxiety and depression. We characterized AT in developing rhesus monkeys and discovered the altered neural circuitry that underlies AT. Using lesioning strategies, we established that the central nucleus of the amygdala (Ce), is one region that causally underlies the expression of AT. We also characterized phenotypic variation in relation to AT demonstrating common and selective neural substrates that underlie different symptomatic presentations of AT. Heritability analyses demonstrate that AT is approximately 35% heritable and using genetic covariation analyses we further identified the heritable neural substrate responsible for mediating AT. Our work points to the possibility of selectively targeting different components of the neural circuit some of which are more genetically determined while others are more influenced by environment. To investigate molecular mechanisms underlying AT and its neural substrate, we performed genome wide transcriptome analyses that demonstrate a reduction in Ce neuroplasticity gene expression in individuals with extreme AT. We currently are using viral vector infection strategies in young monkeys to test the mechanistic role of these identified alterations in Ce gene regulation. These data provide the foundation for the development of novel early individualized treatment strategies aimed at the prevention of the later development of severe psychopathology" 0 1539 C. Biemont and J. Bouletreau-Merle 1978 Inbreeding effect: embryonic development and fecundity of Drosophila melanogaster offspring Experientia 34 10 1273-1274 Inbreeding depression observed on fecundity of adult Drosophila depends on the effect observed during development of the eggs laid by their parents. This depression does not then depend on the homozygosity per se of the adult genome. It is mainly due to the deleterious effect observed primarily during embryogenesis http://www.ncbi.nlm.nih.gov/pubmed/104884 0 1540 "R. G. Evans, C. Wheatley, C. Engel, J. Nielsen and L. J. Ciborowski" 1984 Modification of the bone marrow toxicity of cis-diamminedichloroplatinum(II) in mice by diethyldithiocarbamate Cancer Res. 44 9 3686-3690 "It has been shown that cis-platinum-induced nephrotoxicity in rats can be inhibited by diethyldithiocarbamate (DDC). We report here the bone marrow protective properties of DDC in hybrid (C57BL X BALB/c) mice exposed to single and fractionated doses of cis-platinum. Relatively nontoxic doses of DDC afford maximum protection, using that dose of cis-platinum that would result in the death of 50% of the mice within 9 days as an end point (dose-limiting gut toxicity in mice), when injected 0.5 to 2 hr following i.p. cis-platinum treatment. Survivals of colony-forming units in spleen, nucleated bone marrow cells, and peripheral white blood cell were used to assess the bone marrow protective properties of DDC following both single and fractionated doses of cis-platinum. A dose modification factor of 3.2 (based on colony-forming units in spleen survival) was obtained when DDC (1000 mg/kg) was injected into mice 0.5 hr after graded doses of cis-platinum. When fractionated doses of cis-platinum were used (6 mg/kg on Days 0, 10, 20, and 30), the survival of colony-forming units in spleen was markedly enhanced if the animals were rescued with DDC 0.5 hr following each cis-platinum dose. When bone marrow cellularity was measured immediately before and 2 days after each dose of cis-platinum, a similar pattern of depression and recovery was noted whether DDC was present or not; however, the depression was less marked in mice rescued with DDC. When peripheral white blood cell counts were monitored, the nadir and recovery were similar in the presence or absence of DDC; however, recovery occurred sooner in the animals that had received DDC. Our data support the ability of DDC to modify the bone marrow toxicity of cis-platinum in normal mice. Experiments are in progress in tumor-bearing animals exploring the differential protection afforded by DDC between bone marrow and tumor" http://www.ncbi.nlm.nih.gov/pubmed/6331656 0 1541 "M. Boyko, R. Kutz, B. F. Gruenbaum, H. Cohen, N. Kozlovsky, S. E. Gruenbaum, Y. Shapira and A. Zlotnik" 2013 The influence of aging on poststroke depression using a rat model via middle cerebral artery occlusion Cogn Affect.Behav.Neurosci. 13 4 847-859 "Poststroke depression (PSD) is the most frequent psychological sequela following stroke. While previous studies describe the impact of age on brain infarct volume, brain edema, and blood-brain barrier (BBB) breakdown following ischemia, the role of age on PSD has yet to be described. Here, we examine the influence of age on PSD progression in a rat model of PSD by middle cerebral artery occlusion (MCAO). One hundred forty-three rats were divided into three groups. 48 rats 20 weeks of age underwent a sham procedure, 51 rats 20 weeks of age had MCAO, and 44 rats 22-26 months of age had MCAO. Groups were further divided into two subgroups. The first subgroup was used to measure infarct lesion volume, brain edema, and BBB breakdown at 24 h. In the second subgroup at 3 weeks after MCAO, rats were subjected to a sucrose preference test, two-way shuttle avoidance task, forced swimming test, and a brain-derived neurotrophic factor (BDNF) protein level measurement. Total and striatal infarct volume, brain edema, and BBB breakdown in the striatum were increased in older rats, as compared with younger rats. While both old and young rats exhibited depressive-like behaviors on each of the behavioral tests and lower BDNF levels post-MCAO, as compared with control rats, there were no differences between old and young rats. Although older rats suffered from larger infarct volumes, increased brain edema and more BBB disruption following MCAO, the lack of behavioral differences between young and old rats suggests that there was no effect of rat age on the incidence of PSD" http://www.ncbi.nlm.nih.gov/pubmed/23761136 0 1542 "W. Zhu, S. Ma, R. Qu and D. Kang" 2006 Antidepressant-like effect of paeonol "Pharmaceutical Biology.44 (3) ()(pp 229-235), 2006.Date of Publication: 01 May 2006." 3 229-235 "The current study investigated the putative antidepressant-like effect of paeonol, a phenolic component from the root bark of Paeonia suffruticosa Andr. (Ranunculaceae), in mice or rats using the tail suspension test (TST) and forced swimming test (FST), two widely accepted pharmacological models for detecting antidepressant activity in modern medicinal researchers. It was found that paeonol, at doses of 20, 40, and 80 mg/kg (p.o.), reduced immobility time in TST and FST in mice. Paeonol also decreased immobility time at 25 and 50 mg/kg (p.o.) in the FST in rats. Furthermore, paeonol as well as fluoxetine (FLU), at the doses tested, did not produce significant effects on locomotor activity. With 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and lactic dehydrogenase (LDH) assay, 5, 10, and 20 muM paeonol or a classical antidepressant, 10 muM FLU, protected PC12 cells from the lesion induced by 10 muM corticosterone (Cort) treatment for 48 h. In the fura-2/AM (acetoxymethyl ester) labeling assay, 10 and 20 muM paeonol, 10 muM FLU attenuated the intracellular Ca 2+ overloading induced by 200 muM Cort treatment for 48 h in PC12 cells. In summary, we first demonstrated that paeonol possessed an antidepressant-like action through the protection of PC12 cells as well as reversal intracellular Ca 2+ overloading. © 2006 Taylor & Francis Group, LLC" DO - http://dx.doi.org/10.1080/13880200600685576 1 1543 "J. B. Press, C. M. Hofmann, N. H. Eudy, W. J. Fanshawe, I. P. Day, E. N. Greenblatt and S. R. Safir" 1979 "10-(Alkylamino)-4H-thieno[3,4-b][1,5]benzodiazepines. A novel class of potential neuroleptic agents" J.Med.Chem. 22 6 725-731 "An investigation of the structural requirements for CNS activity of the title compounds was undertaken. A synthesis of the precursor dihydro-10H-thieno[3,4-b][1,5]benzodiazepin-10-ones was achieved and three routes for their conversion to the title compounds were developed. The compounds were tested for neuroleptic activity by means of the blockade or d-amphetamine lethality in aggregated mice and/or effects on locomotor activity in rats. Antidepressant activity was examined using inhibition of tetrabenazine-induced depression in mice. Most of the compounds were found to be potent neuroleptic agents with several exhibiting additional antidepressant activity" http://www.ncbi.nlm.nih.gov/pubmed/37338 1 1544 A. S. Pivovarov and D. V. Boguslavskii 2000 "[The Na,K pump regulates a decrease in the cholinosensitivity of the neurons in the snail Helix lucorum taurica Kryn in a cellular analog of habituation: its dependence on intracellular calcium]" Zh.Vyssh.Nerv.Deiat.Im I.P.Pavlova 50 5 855-866 "In Helix lucorum snail we studied the effects of ouabain, inhibitor of Na,K-pump, on the depression of cholinosensitivity in command neurons of withdrawal behavior and the role of the intracellular free Ca2+. The cellular analog of the negative learning (habituation) was used Transmembrane integral inward currents were recorded from the identified LPa2, LPa3, RPa3, and RPa2 neurons in ganglia preparation using two-electrode voltage clamp technique. Acetylcholine (ACh) was locally applied iontophoretically. Reduction of neuronal cholinosensitivity was estimated as a depth of depression of the ACh-induced inward current during rhythmic local application of ACh (interstimulus interval of 1-3 min) onto the somatic membrane. Bath application of ouabain (0.1 mM) produced an increase in depression in one group of neurons and its decrease in another group. After 60-150 min of spontaneous diffusion of a calcium ion chelator BAPTA (1 mM) from the intracellular microelectrode, ouabain produced only the increase in depression. If CaCl2 (100 mM) was added to the solution of the voltage-recording intracellular microelectrode, 60 min later ouabain produced only the reduction of the depression of the ACh current. The conclusion is drawn that the inhibition of the Na,K-pump by ouabain modifies the depression of neuronal cholinosensitivity in the cellular analog of habituation. The direction of the modulatory effect depends on the basal concentration of the intracellular free Ca2+" http://www.ncbi.nlm.nih.gov/pubmed/11085001 0 1545 M. E. McKenzie and P. L. Long 1986 Immunization of chickens against coccidiosis with extracts of Eimeria-infected tissues Poult.Sci. 65 5 892-897 "Immunization of chickens with extracts prepared from Eimeria-infected tissues was attempted. Significant protection against weight depression was conferred when chickens were inoculated intra-abdominally with tissue extracts prepared from ceca infected with two different strains of E. tenella. When extracts were given intravenously, with or without the adjuvant, polyandenylic-polyuridylic acid, weight depression was not ameliorated after challenge. Experiments using extracts from two strains of E. acervulina- and E. maxima- and one strain of E. brunetti-infected tissues failed to protect against weight gain depression after challenge" http://www.ncbi.nlm.nih.gov/pubmed/3725726 0 1546 "G. J. Kant, R. M. Wylie, K. Chu and S. Ghosh" 1998 "Effects of the serotonin agonists 8-OH-DPAT, buspirone, and DOI on water maze performance" "Pharmacology Biochemistry and Behavior.59 (3) ()(pp 729-735), 1998.Date of Publication: March 1998." 3 729-735 "We have previously reported that the serotonin 5-HT(1A) agonist 8-OH- DPAT and the 5-HT(2C) agonist TFMPP impair performance on a water maze. In the present report we extended those studies by examining a second 5-HT(1A) agonist, buspirone, to see whether its effects paralleled those of 8-OH- DPAT, and by testing the effects of the 5-HT2 agonist DOI. Unlike the open pool Morris water maze, the maze used in these experiments has alleys and doorways. The maze can be easily reconfigured to present rats with both previously learned or new maze challenges. Performance is assessed by time to reach the maze exit platform and the number of wrong doorways entered (errors). At doses that did not affect performance in a previously learned maze, the 5-HT(1A) agonists 8-OH-DPAT (0.1 mg/kg) and buspirone (1 mg/kg) slowed acquisition of a new maze configuration as measured by both swim time to the exit platform and errors committed. A higher dose of buspirone (10 mg/kg) completely blocked acquisition of a novel maze. In contrast, DOI slowed performance as assessed by swim time on both a well-learned maze as well as acquisition of a new maze, but did not affect error rate on either task, suggesting that this 5-HT2 agonist impaired performance by depressing motor activity. These experiments demonstrate that serotonin agonists, especially the 5-HT(1A) subtype, can impair learning" DO - http://dx.doi.org/10.1016/S0091-3057%2897%2900553-4 0 1547 "C. Dournes, S. Beeske, C. Belzung and G. Griebel" 2013 "Deep brain stimulation in treatment-resistant depression in mice: comparison with the CRF1 antagonist, SSR125543" Prog.Neuropsychopharmacol.Biol.Psychiatry 40 213-220 "Deep brain stimulation (DBS) has been demonstrated to represent a targeted therapeutic alternative for treatment-resistant depression. In this study, we used the unpredictable chronic mild stress (UCMS) test to validate high-frequency electrical stimulation of the cingulate cortex (CC) as a possible treatment to improve behavioral symptoms associated with a depressive-like state in treatment-resistant mice. The effects of DBS were compared with those of the CRF(1) antagonist, SSR125543. Mice were subjected to UCMS, which consisted of the sequential and unpredictable application of mild stressors for a total of 8 weeks. From week 4 until the end of week 6, mice received either a saline injection or were treated with the antidepressant, fluoxetine (10 mg/kg, i.p.). At the end of week 6, fluoxetine-treated mice were subdivided into two populations, that is one responding to fluoxetine, and one not responding, based on their fur coat state, an index of depressive-like state in this test. Non-responders were subsequently subjected to bilateral DBS (at 80 or 120 Hz, 1-h/day) or were treated with SSR125543 (20 mg/kg, i.p.) for two weeks. Stimulation of the CC at 120 Hz in treatment-resistant mice resulted in a normalization of motivated-like responses, anxiety-related behaviors, hyperactivity and aggressiveness. SSR125543 improved motivated-like and aggressive behaviors. These findings demonstrate that bilateral DBS of the CC and, to a lesser extent, pharmacological blockade of the CRF(1) receptor in treatment-resistant mice can attenuate several aspects of depressive-like behaviors, suggesting further that these approaches may represent valid alternatives for the treatment of drug-resistant depressed and/or anxious patients" http://www.ncbi.nlm.nih.gov/pubmed/23367508 1 1548 "A. Langslet, W. G. Johansen, M. Ryg, T. Skomedal and I. Oye" 1971 Effects of dibenzepine and imipramine on the isolated rat heart Eur.J.Pharmacol. 14 4 333-339 http://www.ncbi.nlm.nih.gov/pubmed/5157764 0 1549 "J. Dine, I. A. Ionescu, C. Avrabos, Y. C. Yen, F. Holsboer, R. Landgraf, U. Schmidt and M. Eder" 2015 "Intranasally applied neuropeptide S shifts a high-anxiety electrophysiological endophenotype in the ventral hippocampus towards a ""normal""-anxiety one" PLoS.One. 10 4 e0120272 "The neurobiological basis of pathological anxiety and the improvement of its pharmacological treatment are a matter of intensive investigation. Here, using electrophysiological techniques in brain slices from animals of the high anxiety-related behavior (HAB) and normal anxiety-related behavior (NAB) mouse model, we show that basal neurotransmission at ventral hippocampal CA3-CA1 synapses is weaker in HAB compared to NAB mice. We further demonstrate that paired-pulse facilitation (PPF) and long-term potentiation (LTP) at these synapses are more pronounced in slices from HAB animals. Based on previous findings, we also examined whether intranasal delivery of neuropeptide S (NPS), which increasingly emerges as a potential novel treatment option for anxiety symptoms occurring in a variety of diseases like anxiety disorders, posttraumatic stress disorder, and major depression, impacts on the high-anxiety electrophysiological endophenotype in HAB mice. Strikingly, we detected enhanced basal neurotransmission and reduced PPF and LTP in slices from NPS-treated HAB animals. Collectively, our study uncovers a multifaceted high-anxiety neurophysiological endophenotype in the murine ventral hippocampus and provides the first evidence that an intranasally applied neuropeptide can shift such an endophenotype in an anxiety-regulating brain structure towards a ""normal""-anxiety one" http://www.ncbi.nlm.nih.gov/pubmed/25830625 0 1550 "R. Vigot, C. Batini, R. T. Kado and T. Yamamori" 2002 Synaptic long-term depression (LTD) in vivo recorded on the rat cerebellar cortex Arch.Ital.Biol. 140 1 01-Dec "Long-Term Depression (LTD) of the parallel fiber synapses of the cerebellar cortex has been intensively studied over the last 20 years and is now considered to be a physiological mechanism underlying learning and memory of the cerebellar cortex. With microelectrode recording in vivo, the induced LTD is recorded reliably up to 2 hours. Using surface electrodes we have recorded parallel fiber responses due to the currents generated by the AMPA type receptors of the dendritic spines in the intact vermal cortex of decerebrated rats. We have found that by conjunctively stimulating the climbing and parallel fiber pathways, an LTD was induced which persisted for as long as the recording conditions permitted. The longest lasting LTD of our present results was for 5 hours" http://www.ncbi.nlm.nih.gov/pubmed/11889918 0 1551 "M. Shimizu-Albergine, S. D. Rybalkin, I. G. Rybalkina, R. Feil, W. Wolfsgruber, F. Hofmann and J. A. Beavo" 2003 Individual cerebellar Purkinje cells express different cGMP phosphodiesterases (PDEs): in vivo phosphorylation of cGMP-specific PDE (PDE5) as an indicator of cGMP-dependent protein kinase (PKG) activation J.Neurosci. 23 16 6452-6459 "The nitric oxide (NO)-cGMP pathway has been implicated as playing a crucial role in the induction of cerebellar long-term depression (LTD). The amplitude and duration of the cGMP signal is controlled by cyclic nucleotide phosphodiesterases (PDEs). Here we identify PDE5 and PDE1B as the two major cGMP-hydrolyzing PDEs specifically and differentially expressed in the Purkinje neurons of mouse cerebellum. PDE5 was found in all Purkinje neurons, whereas PDE1B was detected only in a subset of these cells, suggesting that individual Purkinje cells may differentially regulate cGMP, depending on the PDE isozymes expressed. Although expression of guanylate cyclase and/or cGMP-dependent protein kinase (PKG) in Purkinje cells have been reported, neither cGMP accumulation nor PKG activation in these cells in vivo has been demonstrated. To determine if changes in PKG activation and PDE5 regulation occur in vivo we have examined the phosphorylation of PDE5 in mouse cerebellar Purkinje cells by immunocytochemistry and Western blot analyses using a phosphospecific PDE5 antibody. Injection of sodium nitroprusside or selective PKG activators into the lateral ventricle of mouse brain induced PDE5 phosphorylation in vivo, but was completely missing in Purkinje cell-specific PKG I knock-out mice. In cerebellar slices, treatment with sildenafil or IBMX led to different levels of phospho-PDE5 accumulation and activation of PDE5. These results suggest that phosphorylation of PDE5 in Purkinje neurons after cGMP-PKG activation performs a critical role in the termination of the cGMP signal during LTD progression; moreover, PDE5 phosphorylation may be used as an in vivo indicator for PKG activation" http://www.ncbi.nlm.nih.gov/pubmed/12878685 0 1552 "S. C. Dilsaver, J. A. Peck and D. H. Overstreet" 1992 The Flinders Sensitive Line exhibits enhanced thermic responsiveness to nicotine relative to the Sprague-Dawley rat "Pharmacology Biochemistry and Behavior.41 (1) ()(pp 23-27), 1992.Date of Publication: 1992." 1 23-27 The Flinders Sensitive Line (FSL) was derived from the Sprague-Dawley rat by selectively breeding animals with heightened sensitivity to an anticholinesterase. The FSL now consistently exhibits enhanced behavioral and physiological responses to muscarinic agonists relative to its progenitor. The authors now report the FSL exhibits enhanced thermic responsiveness to nicotine relative to the Sprague-Dawley rat. The possible relevance of this finding to investigators interested in the disorders of mood is briefly discussed 0 1553 "G. Curzon, G. A. Kennett, G. S. Sarna and P. S. Whitton" 1992 The effect of tianeptine and other antidepressants on a rat model of depression "British Journal of Psychiatry.160 (FEB.Suppl 15) ()(pp 51-55), 1992.Date of Publication: 1992." FEB. Suppl 15 51-55 "A model of depression based on measurements made after restraining rats for two hours has been developed. The model is associated with elevation in corticosterone, reflects the higher incidence of depression in women, and shows increased post-synaptic 5-HT function with adaptation. The effects of tianeptine and other antidepressants on the model were studied. Chronic pre-treatment with desipramine, sertraline (amine uptake inhibitors), and chlordiazepoxide normalised open field activity after restraint. Single high doses, post-restraint, of 8-OH-DPAT, gepirone (5-HT agonists), and tianeptine normalised open field activity, whereas desipramine, chlordiazepoxide, and diazepam did not. It is of considerable interest that tianeptine decreased the availability of 5-HT to receptors" 0 1554 "Z. Xia, H. Wei, J. Duan, T. Zhou, Z. Yang and F. Xu" 2016 Chronic unpredicted mild stress-induced depression alter saxagliptin pharmacokinetics and CYP450 activity in GK rats PeerJ. 4 e1611 "Background. This study was to explore the pharmacokinetics of saxagliptin (Sax) in Goto-Kakizaki (GK) rats complicated with depression induced by chronic unpredicted mild stress (CUMS). The comorbidity of diabetic patients with depression is becoming more and more epidemic. Whether depression mental disorder alters the pharmacokinetics of hypoglycemic drugs in diabetes patients is not clear. Methods. Five-week-old male GK rats were kept in the cage for 7 weeks in a specific pathogen free (SPF)-grade lab until the emergence of diabetes and were then divided into two groups: control group and depression model group. Rats in the CUMS-induced depression group were exposed to a series of stressors for 8 weeks. Plasma serotonin and dopamine levels and behavior of open-field test were used to confirm the establishment of the depression model. All rats were given 0.5 mg/kg Sax orally after 8 weeks and blood samples were collected at different time points. The Sax concentration was assayed by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The CYP450 activity of the liver microsomes was determined by using cocktails of probe drugs in which the activities of CYP enzymes were assessed through the determination of the production of the probe drugs. Results. Statistically significant differences in Sax pharmacokinetics were observed for area under curve, clearance, peak concentration, peak time and mean residence time between the depression rats and the control rats, while no statistical differences were observed for half-time and distribution volume by HPLC-MS/MS analysis. The CYP450 activity had different changes in the depression group. Conclusions. These results indicated that CUMS-induced depression alters the drug metabolic process of Sax and CYP450 activity of the liver microsomal enzymes in GK rats" http://www.ncbi.nlm.nih.gov/pubmed/26819853 1 1555 "P. F. Renshaw, N. E. Joseph and J. S. Leigh, Jr." 1986 Chronic dietary lithium induces increased levels of myo-inositol-1-phosphatase activity in rat cerebral cortex homogenates Brain Res. 380 2 401-404 "The monovalent lithium ion inhibits the enzyme myo-inositol-1-phosphatase at concentrations comparable to those which are useful in the treatment of manic depressive illness. However, dialyzed cortical homogenates from rats which have been fed diets containing lithium carbonate demonstrate increased myo-inositol-1-phosphate phosphatase activity. Over a 4-week period, there is an approximate doubling of the lithium-sensitive myo-inositol-1-phosphatase activity in the homogenate" http://www.ncbi.nlm.nih.gov/pubmed/3019470 0 1556 "M. A. Leo, N. Lowe and C. S. Lieber" 1984 Decreased hepatic vitamin A after drug administration in men and in rats Am.J.Clin.Nutr. 40 6 1131-1136 "Eleven patients with moderate drug-induced liver changes were found to have extremely low hepatic vitamin A levels (less than 10% of normal). Their serum vitamin A, retinol-binding protein, and transthyretin were only slightly affected. In rats, two representative drugs (phenobarbital and methylcholanthrene) produced a significant depression of hepatic vitamin A, whereas plasma vitamin A levels remained normal. The livers of drug-treated animals showed no abnormalities except for the expected proliferation of the smooth endoplasmic reticulum and induction of microsomal enzymes and cytochrome P-450 (phenobarbital) and P-448 (methylcholanthrene). These findings suggest that the decrease in hepatic vitamin A may be secondary, at least in part, to enhanced microsomal metabolism" http://www.ncbi.nlm.nih.gov/pubmed/6507338 0 1557 "B. Martinez-Cruz, J. A. Godoy and J. J. Negro" 2004 Population genetics after fragmentation: the case of the endangered Spanish imperial eagle (Aquila adalberti) Mol.Ecol. 13 8 2243-2255 "The highly endangered Spanish imperial eagle, Aquila adalberti, has suffered from both population decline and fragmentation during the last century. Here we describe the current genetic status of the population using an extensive sampling of its current distribution range and both mitochondrial control region sequences and nuclear microsatellite markers. Results were evaluated in comparison to those obtained for the Eastern imperial eagle, Aquila heliaca, its nearest extant relative. Mitochondrial haplotype diversity was lower in the Spanish than in the Eastern species whereas microsatellite allelic richness and expected heterozygosity did not differ. Both allelic richness and expected heterozygosity were lower in the small Parque Nacional de Donana breeding nucleus compared to the remaining nuclei. A signal for a recent genetic bottleneck was not detected in the current Spanish imperial eagle population. We obtained low but significant pairwise FST values that were congruent with a model of isolation by distance. FST and exact tests showed differentiation among the peripheral and small Parque Nacional de Donana population and the remaining breeding subgroups. The centrally located Montes de Toledo population did not differ from the surrounding Centro, Extremadura and Sierra Morena populations whereas the latter were significantly differentiated. On the other hand, a Bayesian approach identified two groups, Parque Nacional de Donana and the rest of breeding nuclei. Recent migration rates into and from Parque Nacional de Donana and the rest of breeding nuclei were detected by assignment methods and estimated as 2.4 and 5.7 individuals per generation, respectively, by a Bayesian approach. We discuss how management strategies should aim at the maintenance of current genetic variability levels and the avoidance of inbreeding depression through the connection of the different nuclei" http://www.ncbi.nlm.nih.gov/pubmed/15245398 0 1558 Y. Z. Xu and K. Krnjevic 2001 "Unlike 2-deoxy-D-glucose, 3-O-methyl-D-glucose does not induce long-term potentiation in rat hippocampal slices" Brain Res. 895 01-Feb 250-252 "Equimolar replacement of 10 mM glucose by 2-deoxy-D-glucose (2-DG) causes substantial depression followed by a sharp and sustained potentiation of CA1 field EPSPs. In the present experiments, similar applications of 3-O-methyl-D-glucose, which is also taken up by cells but is not phosphorylated, had only a weak blocking action and elicited no potentiation. Possible explanations for the marked effects of 2-DG include a more rapid block of glycolysis and the production of phosphorylated derivatives of 2-DG" http://www.ncbi.nlm.nih.gov/pubmed/11259785 0 1559 "K. W. Kohn, V. H. Bono, Jr. and H. E. Kann, Jr." 1968 "Anthramycin, a new type of DNA-inhibiting antibiotic: reaction with DNA and effect on nucleic acid synthesis in mouse leukemia cells" Biochim.Biophys.Acta 155 1 121-129 http://www.ncbi.nlm.nih.gov/pubmed/5647054 0 1560 "D. V. Skarra, T. Cornwell, V. Solodushko, A. Brown and M. S. Taylor" 2011 "CyPPA, a positive modulator of small-conductance Ca(2+)-activated K(+) channels, inhibits phasic uterine contractions and delays preterm birth in mice" Am.J.Physiol Cell Physiol 301 5 C1027-C1035 "Organized uterine contractions, including those necessary for parturition, are dependent on calcium entry through voltage-gated calcium channels in myometrial smooth muscle cells. Recent evidence suggests that small-conductance Ca(2+)-activated potassium channels (K(Ca)2), specifically isoforms K(Ca)2.2 and 2.3, may control these contractions through negative feedback regulation of Ca(2+) entry. We tested whether selective pharmacologic activation of K(Ca)2.2/2.3 channels might depress uterine contractions, providing a new strategy for preterm labor intervention. Western blot analysis and immunofluorescence microscopy revealed expression of both K(Ca)2.2 and K(Ca)2.3 in the myometrium of nonpregnant (NP) and pregnant (gestation day 10 and 16; D10 and D16, respectively) mice. Spontaneous phasic contractions of isolated NP, D10, and D16 uterine strips were all suppressed by the K(Ca)2.2/2.3-selective activator CyPPA in a concentration-dependent manner. This effect was antagonized by the selective K(Ca)2 inhibitor apamin. Whereas CyPPA sensitivity was reduced in D10 and D16 versus NP strips (pIC(50) 5.33 +/- 0.09, 4.64 +/- 0.03, 4.72 +/- 0.10, respectively), all contractions were abolished between 30 and 60 muM. Blunted contractions were associated with CyPPA depression of spontaneous Ca(2+) events in myometrial smooth muscle bundles. Augmentation of uterine contractions with oxytocin or prostaglandin F(2alpha) did not reduce CyPPA sensitivity or efficacy. Finally, in an RU486-induced preterm labor model, CyPPA significantly delayed time to delivery by 3.4 h and caused a 2.5-fold increase in pup retention. These data indicate that pharmacologic stimulation of myometrial K(Ca)2.2/2.3 channels effectively suppresses Ca(2+)-mediated uterine contractions and delays preterm birth in mice, supporting the potential utility of this approach in tocolytic therapies" http://www.ncbi.nlm.nih.gov/pubmed/21795518 0 1561 W. Stazka 1970 "Inhibitory effect of histamine on tissue respiration of the heart muscle ""in vitro""" Acta Physiol Pol. 21 3 271-274 http://www.ncbi.nlm.nih.gov/pubmed/5516394 0 1562 "M. Sasanelli, P. Paradies, D. Otranto, R. P. Lia and C. D. de" 2008 Haemothorax associated with Angiostrongylus vasorum infection in a dog J.Small Anim Pract. 49 8 417-420 "Angiostrongylosis was diagnosed in a dog presenting with haemothorax on the basis of detection of Angiostrongylus vasorum first-stage larvae both in the pleural effusion and in faeces. A one-year-old, male, mixed-breed dog was presented with fever, depression and persistent cough of one month's duration. Clinical examination revealed temperature of 39.5 degrees C, loud bronchovesicular sounds on thoracic auscultation and attenuated cardiac sounds. Thoracic radiographs showed a moderate bilateral pleural effusion and a diffuse interstitial pulmonary pattern, with an alveolar pattern in one lobe. Routine haematology revealed anaemia and leucocytosis with eosinophilia, basophilia and thrombocytopenia. Coagulation assays showed a consumptive coagulopathy resembling disseminated intravascular coagulation. The relationship between haemothorax and the presence of A vasorum larvae in the pleural effusion is discussed. The dog was successfully treated with fenbendazole until negative for larvae on faecal examination. This case report indicates that A vasorum infection should be considered as a possible aetiological cause of haemothorax in dogs" http://www.ncbi.nlm.nih.gov/pubmed/18482330 0 1563 "J. Dabrowska, P. Nowak and R. Brus" 2008 Reactivity of 5-HT1A receptor in adult rats after neonatal noradrenergic neurons' lesion--implications for antidepressant-like action Brain Res. 1239 66-76 "The aim of this study was to assess the 5-HT1A receptor reactivity after neonatal noradrenergic neurons' lesion. DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine), 50 mg/kg, was administered 30 min after a selective serotonin reuptake inhibitor (SSRI)--zimelidine (10 mg/kg) on the 1st and 3rd day of life. Zimelidine was used to prevent serotonin (5-HT) depletion. 5-HT1A autoreceptor is involved in the regulation of 5-HT release as well as the pathogenesis of depression. During a microdialysis study of anaesthetized rats, the 5-HT1A receptor agonist, R-(+)-8-OH-DPAT (0.1 mg/kg), decreased 5-HT release in the medial prefrontal cortex of control rats but this effect was significantly attenuated in DSP-4-treated animals (10-12 weeks old). To further determine which type of receptor, either pre or postsynaptically located, is involved in the attenuated response to the 5-HT1A receptor agonist in lesioned rats, behavioral tests were conducted. In the forced swimming test, DSP-4 treated rats after saline injection, displayed shorter immobility time in comparison to control rats. R-(+)-8-OH-DPAT (0.5 mg/kg) evoked an antidepressant-like effect in control and DSP-4 treated rats in a learned helplessness paradigm as well as the forced swimming test. The results of this study provided further support for the exclusive desensitization of 5-HT1A autoreceptor in adult rats with neonatal lesion of the central noradrenergic system" http://www.ncbi.nlm.nih.gov/pubmed/18789911 1 1564 1976 Urinary oestrogens in heifers treated with prednisolone during the oestrous cycle Acta Vet.Scand. 17 3 376-378 http://www.ncbi.nlm.nih.gov/pubmed/988739 0 1565 "T. Oshima, H. Koike, K. Nakayama and H. Takagi" 1972 [Cardiovascular action of Salbutamol] Nihon Yakurigaku Zasshi 68 1 73-85 http://www.ncbi.nlm.nih.gov/pubmed/5065041 0 1566 "M. Hiraoka, S. Kawano and H. Kinoshita" 1987 Contribution of Ca2+-influx to generation of the transient inward current in guinea-pig ventricular muscles Jpn.J.Physiol 37 3 479-496 "Contribution of Ca2+-influx via the slow channel to generation of the transient inward current in guinea-pig ventricular muscles was studied using a single sucrose gap voltage clamp technique. The transient inward current (TI) was induced from superfusion of the preparations with the low-K+ (0 mM), high-Ca2+ (3.6 mM) solution. Application of 2 mM-CO2+ quickly and reversibly suppressed the TI amplitude to 25% of the control and delayed its peak timing to 153% during 10-20 min. Inhibition developed as quickly as Co2+ suppressed the slow inward current (Is), and its recovery took place without apparent time lag behind its effect on Is. The block of both TI and Is by Co2+ was antagonized by raising external Ca2+ to 7.2 mM. Removal of external Ca2+ caused a prompt suppression of both Is and TI. Application of 2 or 5 mM-procaine HCl produced a complete abolition of TI with a mild depression of Is. While 1 mM-caffeic caused a suppression of TI after a transient augmentation, 10 mM-caffeine completely eliminated it without abolishing Is. These results indicate that the Ca2+-influx through the slow channel acts not only to load the cell with those ions, but also to influence somehow the Ca2+-release from the stores under the Ca2+-overloaded conditions" http://www.ncbi.nlm.nih.gov/pubmed/2446033 0 1567 "J. R. Schmidt, L. Krugner-Higby, T. D. Heath, R. Sullivan and L. J. Smith" 2011 Epidural administration of liposome-encapsulated hydromorphone provides extended analgesia in a rodent model of stifle arthritis J.Am.Assoc.Lab Anim Sci. 50 4 507-512 "Liposome encapsulation of opioids by using an ammonium-sulfate-gradient loading technique significantly slows the release time of the drug. This study evaluated the duration of analgesia in a rodent model of monoarthritis after epidural administration of liposome-encapsulated hydromorphone (LE-hydromorphone; prepared by ammonium-sulfate-gradient loading) compared with standard hydromorphone and a negative control of blank liposomes. Analgesia was assessed by changes in thermal withdrawal latency, relative weight-bearing, and subjective behavioral scoring. Analgesia in arthritic rats was short-lived after epidural hydromorphone; increases in pain threshold were observed only at 2 h after administration. In contrast, thermal pain thresholds after epidural LE-hydromorphone were increased for as long as 72 h, and subjective lameness scores were lower for as long as 96 h after epidural administration. Injection of LE-hydromorphone epidurally was associated with various mild changes in CNS behavior, and 2 rats succumbed to respiratory depression and death. In conclusion, LE-hydromorphone prolonged the duration of epidural analgesia compared with the standard formulation of hydromorphone, but CNS side effects warrant careful administration of this LE-hydromorphone in future studies" http://www.ncbi.nlm.nih.gov/pubmed/21838980 0 1568 "D. T. Stephens, L. M. Critchlow and D. D. Hoskins" 1983 Mechanism of inhibition by gossypol of glycolysis and motility of monkey spermatozoa in vitro J.Reprod.Fertil. 69 2 447-452 "Low levels of gossypol inhibited motility and anaerobic glycolysis of ejaculated rhesus monkey spermatozoa. Inhibition (50%) of both occurred at a gossypol: sperm ratio of 8 nmol/10(8) spermatozoa, and complete inhibition of both occurred at a ratio of 75 nmol/10(8) spermatozoa. Determination and comparison of the levels of glycolytic intermediates in intact spermatozoa, incubated with and without gossypol, indicated that the only site of glycolytic inhibition was lactate dehydrogenase-X (EC 1 X 1 X 1 X 27). At gossypol: sperm ratios above 6 nmol/10(8) spermatozoa, gossypol also decreased the concentrations of the adenine nucleotides, ATP, ADP and AMP, and this is most probably the basis for its toxic effect on spermatozoa" http://www.ncbi.nlm.nih.gov/pubmed/6631812 0 1569 "J. Han, Z. Liu, W. Ren and X. Zhang" 2011 Counteractive effects of cannabinoid and nicotine-addictive behavior Neuroreport 22 4 181-184 "Our recent results suggest that cannabinoid exposure induces conditioned place preference (CPP) through facilitated induction of synaptic long-term depression at dopamine circuitry of the midbrain ventral tegmental area (VTA). Here, we show that chronic nicotine exposure also induces CPP, but facilitates the induction of synaptic long-term potentiation in the VTA. Coadministration of cannabinoid and nicotine leads to a blockade of facilitated long-term depression and long-term potentiation induction in these neurons and elimination of CPP. These findings point to counteractive effects of cannabinoid and nicotine-addictive behavior through opposite changes in synaptic plasticity of dopamine circuitry of the VTA" http://www.ncbi.nlm.nih.gov/pubmed/21304327 0 1570 "K. Fuxe, W. Romero-Fernandez, G. Mudo, M. Perez-Alea, A. O. Tarakanov, M. Narvaez, L. F. Agnati, N. Belluardo and D. O. Borroto-Escuela" 2014 FGFR1-5-HT1A receptor heterocomplexes: Relevance for neuroplasticity and depression "European Neuropsychopharmacology.Conference: 27th European College of Neuropsychopharmacology, ECNP Congress Berlin Germany.Conference Start: 20141018 Conference End: 20141021.Conference Publication: (var.pagings).24 ()(pp S114), 2014.Date of Publica" var.pagings S114 "The hippocampal atrophy consistently found in major depression may be involved in the pathophysiology of this disease in view of its critical role in the emotional networks. Evidence is given for the existence of FGFR1-5-HT1A heteroreceptor complexes which are involved in neuroplasticity in the hippocampus using the proximity ligation assay with a partial interface characterization [1]. The participation of 5-HT1A and FGFR1 homodimers and recruitment of b-arrestin2 was demonstrated in the FGFR1-5-HT1A heteroreceptor complexes upon agonist treatments [2]. Co-activation of the two protomers also resulted in synergistic increases in extensions of PC12 cells and neurite densities and protrusions in primary hippocampal cultures dependent on the receptor interface. We have also found that acute and a 10 day i.c.v. treatment with FGF-2 and the 5-HT1A agonist 8-OHDPAT in the Sprague- Dawley rat can produce synergistic antidepressant effects in the forced swim test. Thus, this cotreatment may result in more rapid and stronger antidepressant-like actions than found with SSRIs. Evidence is also presented for the existence of FGFR1-5-HT1A heteroreceptor complexes in the mesencephalic raphe 5-HT nerve cells [3]. The raphe 5-HT1A autoreceptor when being part of the FGFR1-5-HT1A heteroreceptor complex may therefore have a beneficial role in depression by assisting in the recovery of 5-HT nerve cell trophism from a state of atrophy including increased 5-HT synthesis and storage. The findings indicate that neurotrophic and antidepressant effects of 5-HT may, in part, be mediated by activation of the 5-HT1A receptor protomer in the hippocampal FGFR1-5-HT1A receptor complex enhancing the FGFR1 signaling" 0 1571 "R. Abadie-Guedes, R. C. Guedes and R. S. Bezerra" 2012 The impairing effect of acute ethanol on spreading depression is antagonized by astaxanthin in rats of 2 young-adult ages Alcohol Clin.Exp.Res. 36 9 1563-1567 "BACKGROUND: Ethanol (EtOH) abuse and insufficient ingestion of antioxidants are external factors that can alter brain electrophysiology. Our previous studies have demonstrated that the excitability-related brain electrophysiological phenomenon known as cortical spreading depression (CSD) was facilitated by chronic EtOH intake, and chronic treatment with carotenoids attenuated this effect. Here, we investigated the acute effect of a single EtOH administration on CSD in young and adult rats previously (1 hour) treated with 10 mug/kg of astaxanthin. METHODS: Male Wistar rats (5 young- and 5 adult groups, 60 to 80 and 150 to 180 days of age, respectively) were treated by 2 gavage procedures at 1-hour interval as follows: groups 1 and 2 received astaxanthin in gavage I combined with EtOH (group 1) or water (group 2) in gavage II; groups 3 and 4 received olive oil (the vehicle in which astaxanthin was dissolved) in gavage I combined with EtOH (group 3) or water (group 4) in gavage II; group 5 received water in gavage I combined with EtOH in gavage II. CSD was recorded on the cortical surface for 4 hours. RESULTS: Compared to the respective water and oil controls (groups 2 and 4; CSD velocities: 3.73 +/- 0.09 and 3.78 +/- 0.07 mm/min in the young groups; 2.99 +/- 0.10 and 3.05 +/- 0.19 mm/min in the adult groups), a single dose of EtOH (groups 3 and 5) decreased CSD propagation velocities (3.29 +/- 0.23 and 3.16 +/- 0.10 mm/min in the young groups; 2.71 +/- 0.27 and 2.75 +/- 0.31 mm/min in the adult groups). Astaxanthin antagonized the impairing effect of acute EtOH on CSD (group 1; mean velocity: 3.70 +/- 0.19 and 3.13 +/- 0.16 mm/min for the young and adult groups, respectively). CONCLUSIONS: The results showed an antagonistic effect of acute EtOH treatment on CSD propagation that was reverted by astaxanthin. The EtOH-astaxanthin interaction was not influenced by the age, as it was found in both young and adult animals" http://www.ncbi.nlm.nih.gov/pubmed/22432539 1 1572 "P. Fidzinski, O. Shor and J. Behr" 2008 Target-cell-specific bidirectional synaptic plasticity at hippocampal output synapses Eur.J.Neurosci. 27 5 1111-1118 "It is commonly accepted that the hippocampus is critically involved in the explicit memory formation of mammals. The subiculum is the principal target of CA1 pyramidal cells and thus serves as the major relay station for the outgoing hippocampal information. Pyramidal cells in the subiculum can be classified according to their firing properties into burst-spiking and regular-spiking cells. In the present study we demonstrate that burst-spiking and regular-spiking cells show fundamentally different forms of low frequency-induced synaptic plasticity in rats. In burst-spiking cells, low-frequency stimulation (at 0.5-5 Hz) induces frequency-dependent long-term depression (LTD) with a maximum at 1 Hz. This LTD is dependent on the activation of NMDAR and masks an mGluR-dependent long-term potentiation (LTP). In contrast, in regular-spiking cells low-frequency stimulation induces an mGluR-dependent LTP that masks an NMDAR-dependent LTD. Both processes depend on postsynaptic Ca(2+)-signaling as BAPTA prevents the induction of synaptic plasticity in both cell types. Thus, mGluR-dependent LTP and NMDAR-dependent LTD occur simultaneously at CA1-subiculum synapses and the predominant direction of synaptic plasticity relies on the cell type investigated. Our data indicate a novel mechanism for the sliding-threshold model of synaptic plasticity, in which induction of LTP and LTD seems to be driven by the relative activation state of NMDAR and mGluR. Our observation that the direction of synaptic plasticity correlates with the discharge properties of the postsynaptic cell reveals a novel and intriguing mechanism of target specificity that may serve in tuning the significance of neuronal information by trafficking hippocampal output onto either subicular burst-spiking or regular-spiking cells" http://www.ncbi.nlm.nih.gov/pubmed/18312585 0 1573 "F. B. Sant'Ambrogio, J. W. Anderson, T. Nishino and G. Sant'Ambrogio" 1993 Effects of halothane and isoflurane in the upper airway of dogs during development Respir.Physiol 91 02-Mar 237-246 "It has been previously found that volatile anesthetics significantly affect the activity of laryngeal receptors. In this study we have investigated the respiratory effects of these volatile anesthetics delivered into the upper airway of newborn and adult dogs. Experiments were performed on 17 5-14-day-old, 3 26-28-day-old and 3 adult dogs, anesthetized and breathing spontaneously through a tracheostomy. In the youngest age group, halothane decreased ventilation (VE) to 37.6 +/- 6.8% of control (mean +/- SE; P < 0.01) due to a decrease in both frequency and tidal volume. Peak inspiratory and expiratory flows, and esophageal pressure (Pes) were depressed also (60.8 +/- 6.5%, 51.6 +/- 7.1% and 66.5 +/- 8.1% of control, respectively; P < 0.01). Superior laryngeal nerve (SLN) section abolished the changes in VE, but residual significant decreases in peak flows and Pes were still present and disappeared only after topical anesthetization of the nasal cavities. Isoflurane had similar but weaker effects on VE (74.2 +/- 2.8% of control; P < 0.01), accompanied by a decrease in peak inspiratory and expiratory flows and Pes. SLN section abolished these changes. In the 26-28 day age group there was only a decrease in peak inspiratory airflow with the halothane challenge; isoflurane did not have any effect. In the adult dogs halothane caused only a marginal decrease in inspiratory time. The depressive effects of halothane and isoflurane should be considered when they are used for induction of anesthesia in newborns" http://www.ncbi.nlm.nih.gov/pubmed/8469847 0 1574 "B. Zimmerberg, A. R. Martinez, C. M. Skudder, E. Y. Killien, S. A. Robinson and S. A. Brunelli" 2010 Effects of gestational allopregnanolone administration in rats bred for high affective behavior Physiol Behav. 99 2 212-217 "The anxiolytic neurosteroid allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one or 3alpha,5alpha-THP) has been proposed to play a developmental role in emergent neural regulation of affective behavior. This experiment examined whether allopregnanolone administered during the last week of gestation in rats would alter neonatal and adult offspring behaviors in the selectively-bred High vocalizing line, who have low levels of allopregnanolone and high levels of anxious/depressive behaviors. Dams were injected twice a day with the neurosteroid or vehicle, or handled as controls, and were tested on the elevated plus maze just before parturition. Maternal behavior was assessed throughout the first week of life, and affective behavior in the offspring was tested at one week of age (ultrasonic vocalizations test) and as adults (plus maze and forced swim tests). Offspring prenatally exposed to allopregnanolone were less anxious as neonates and less depressed as adults compared to both control groups. Only male adult offspring, however, revealed less anxious behavior on the plus maze. Neither the dams' anxiety behavior measured in late gestation nor their postnatal maternal behavior was altered compared to controls, suggesting a direct, long-lasting effect of gestational allopregnanolone on the developing fetal brain independent of mediating maternal factors. These results are discussed in light of new evidence about the developmental role of the GABA-A receptor prenatally" http://www.ncbi.nlm.nih.gov/pubmed/19490923 1 1575 "A. Moretti, C. Ciceri and G. K. Suchowsky" 1969 Effect of a combination of B complex vitamins and ascorbic acid on liver lipid content in rats intoxicated with ethyl alcohol Arzneimittelforschung. 19 10 1742-1743 http://www.ncbi.nlm.nih.gov/pubmed/5395376 0 1576 "L. Peng, L. Gu, B. Li and L. Hertz" 2014 Fluoxetine and all other SSRIs are 5-HT2B Agonists - Importance for their Therapeutic Effects Curr.Neuropharmacol. 12 4 365-379 "Fluoxetine and other serotonin-specific re-uptake inhibitors (SSRIs) are generally thought to owe their therapeutic potency to inhibition of the serotonin transporter (SERT). However, research in our laboratory showed that it affects, with relatively high affinity the 5-HT2B receptor in cultured astrocytes; this finding was confirmed by independent observations showing that fluoxetine loses its ability to elicit SSRI-like responses in behavioral assays in mice in which the 5-HT2B receptor was knocked-out genetically or inhibited pharmacologically. All clinically used SSRIs are approximately equipotent towards 5-HT2B receptors and exert their effect on cultured astrocytes at concentrations similar to those used clinically, a substantial difference from their effect on SERT. We have demonstrated up-regulation and editing of astrocytic genes for ADAR2, the kainate receptor GluK2, cPLA2 and the 5-HT2B receptor itself after chronic treatment of cultures, which do not express SERT and after treatment of mice (expressing SERT) for 2 weeks with fluoxetine, followed by isolation of astrocytic and neuronal cell fractionation. Affected genes were identical in both experimental paradigms. Fluoxetine treatment also altered Ca(2+) homeostatic cascades, in a specific way that differs from that seen after treatment with the anti-bipolar drugs carbamazepine, lithium, or valproic acid. All changes occurred after a lag period similar to what is seen for fluoxetine's clinical effects, and some of the genes were altered in the opposite direction by mild chronic inescapable stress, known to cause anhedonia, a component of major depression. In the anhedonic mice these changes were reversed by treatment with SSRIs" http://www.ncbi.nlm.nih.gov/pubmed/25342944 0 1577 "P. R. Lowenstein, M. I. Vacas and D. P. Cardinali" 1982 Effect of pentoxifylline on alpha- and beta-adrenoceptor sites in cerebral cortex medial basal hypothalamus and pineal gland of the rat Neuropharmacology 21 3 243-248 "The intraperitoneal injection of the methylxanthine derivative pentoxifylline (3,7-dimethyl-1-(5-oxo-hexyl)-xanthine] brought about, 3 hr later, a significant depression of alpha- and beta-adrenoceptor sites in the cerebral cortex, and of beta-adrenoceptor sites in medial basal hypothalamus and pineal gland, (assessed from the specific binding of radioactive dihydroergocryptine and dihydroalprenolol respectively). The changes in the density of binding sites were not accompanied by significant modifications of the Kd's. Sympathetic denervation of the pineal gland by superior cervical ganglionectomy (SCGx) abolished the changes of beta-adrenoceptor number in the pineal caused by pentoxifylline. The increase of alpha-adrenoceptor sites in the hypothalamus brought about by ganglionectomy was not affected by injection of pentoxifylline. Pentoxifylline did not compete in vitro for radioligand binding to brain membranes. These results suggest that methylxanthines depress brain adrenoceptor sites acutely, probably by down-regulation of receptors following the increase in catecholamine release caused by injection of the drug" http://www.ncbi.nlm.nih.gov/pubmed/6280095 0 1578 "J. E. Hanson, J. F. Pare, L. Deng, Y. Smith and Q. Zhou" 2015 Altered GluN2B NMDA receptor function and synaptic plasticity during early pathology in the PS2APP mouse model of Alzheimer's disease Neurobiol.Dis. 74 254-262 "GluN2B subunit containing NMDARs (GluN2B-NMDARs) mediate pathophysiological effects of acutely applied amyloid beta (Abeta), including impaired long-term potentiation (LTP). However, in transgenic Alzheimer's disease (AD) mouse models which feature gradual Abeta accumulation, the function of GluN2B-NMDARs and their contribution to synaptic plasticity are unknown. Therefore, we examined the role of GluN2B-NMDARs in synaptic function and plasticity in the hippocampus of PS2APP transgenic mice. Although LTP induced by theta burst stimulation (TBS) was normal in PS2APP mice, it was significantly reduced by the selective GluN2B-NMDAR antagonist Ro25-6981 (Ro25) in PS2APP mice, but not wild type (wt) mice. While NMDARs activated by single synaptic stimuli were not blocked by Ro25, NMDARs recruited during burst stimulation showed larger blockade by Ro25 in PS2APP mice. Thus, the unusual dependence of LTP on GluN2B-NMDARs in PS2APP mice suggests that non-synaptic GluN2B-NMDARs are activated by glutamate that spills out of synaptic cleft during the burst stimulation used to induce LTP. While long-term depression (LTD) was normal in PS2APP mice, and Ro25 had no impact on LTD in wt mice, Ro25 impaired LTD in PS2APP mice, again demonstrating aberrant GluN2B-NMDAR function during plasticity. Together these results demonstrate altered GluN2B-NMDAR function in a model of early AD pathology that has implications for the therapeutic targeting of NMDARs in AD" http://www.ncbi.nlm.nih.gov/pubmed/25484285 0 1579 2008 Phosphatidylserine. Monograph Altern.Med.Rev. 13 3 245-247 http://www.ncbi.nlm.nih.gov/pubmed/18950250 0 1580 "J. Asayama, T. Tatsumi, H. Miyazaki, Y. Yamahara, T. Matsumoto, R. Sakai, M. Inoue, I. Omori, D. Inoue and M. Nakagawa" 1992 Effects of hypoxia and reoxygenation on steady-state and potentiated contractions in papillary muscle of guinea pigs Jpn.Heart J. 33 1 73-81 "We studied the effects of hypoxia and reoxygenation on steady-state contractions and potentiated contractions of papillary muscles of guinea pigs. Isometric tension was measured while 120 min periods of hypoxia and reoxygenation were repeated twice. Reoxygenation after the first period of hypoxia induced a gradual recovery in steady-state contractions and a rapid recovery in potentiated contractions from the first hypoxia-induced contractile depression. After the second period of hypoxia, steady-state and potentiated contractions decreased progressively. During the second period of reoxygenation, the recovery of steady-state and potentiated contractions was very poor and the marked elevation of diastolic tension did not decrease. There were no good correlations between hypoxic depression just before reoxygenation and the recovery of both potentiated contraction and steady-state contraction at 120 min of reoxygenation. The recovery from the hypoxia-induced depression was poor in the preparations with marked elevation in diastolic tension. From these findings, we conclude that hypoxia-induced depression is progressively worsened by an additional episode of hypoxia and that diastolic tension is one of the determinants of the low contractile level achieved by steady-state and potentiated contractions in the severely hypoxic state. The degree of hypoxia-induced depression does not determine redevelopment of force with reoxygenation" http://www.ncbi.nlm.nih.gov/pubmed/1573781 0 1581 "A. Bizzi, E. Veneroni, S. Garattini, L. Puglisi and R. Paoletti" 1967 Hypersensitivity olipid mobilizing agents in essential fatty acid (EFA) deficient rats Eur.J.Pharmacol. 2 1 48-52 http://www.ncbi.nlm.nih.gov/pubmed/4296636 0 1582 "R. N. Willette, B. M. Doorley and H. N. Sapru" 1987 Activation of cholinergic mechanisms in the medulla oblongata reverse intravenous opioid-induced respiratory depression J.Pharmacol.Exp.Ther. 240 1 352-358 "The role of cholinergic mechanisms in opioid-induced respiratory depression was investigated in isoflurane-anesthetized rats. In these animals, the i.v. administration of fentanyl, a clinically useful potent opioid analgesic/anesthetic, induced a prolonged period of apnea and subsequent rise in the end-tidal CO2, hypotension and bradycardia. The centrally acting anticholinesterase, physostigmine, significantly decreased fentanyl-induced respiratory and circulatory depression. The beneficial respiratory and circulatory effects of physostigmine could be abolished by the administration of muscarinic antagonists, e.g., scopolamine hydrobromide or atropine sulfate. Inhibition of inspiratory phrenic nerve activity by fentanyl and restoration of this activity by the subsequent i.v. administration of physostigmine indicates that the origin of this opioid-cholinergic interaction is the central nervous system. Similar effects on phrenic nerve discharge were observed when the systemic administration of fentanyl was followed by microinjection of physostigmine or carbachol in the rostral ventrolateral medulla. In conclusion, opioid-induced respiratory depression after systemic administration is obtunded greatly by facilitation of muscarinic mechanisms in the ventrolateral medulla. Inhibition of a cholinergic link in the central chemosensor may underlie opioid-induced respiratory depression. Manipulation of this cholinergic link could lead to the use and development of analgesics devoid of respiratory depression" http://www.ncbi.nlm.nih.gov/pubmed/3806396 0 1583 "T. Ahmed, D. Blum, S. Burnouf, D. Demeyer, V. Buee-Scherrer, R. D'Hooge, L. Buee and D. Balschun" 2015 Rescue of impaired late-phase long-term depression in a tau transgenic mouse model Neurobiol.Aging 36 2 730-739 "Cognitive decline, the hallmark of Alzheimer's disease, and accompanying neuropsychiatric symptoms share dysfunctions of synaptic processes as a common cellular pathomechanism. Long-term potentiation has proven to be a sensitive tool for the ""diagnosis"" of such synaptic dysfunctions. Much less, however, is known about how long-term depression (LTD), an alternative mechanism for the storage of memory, is affected by Alzheimer's disease progression. Here, we demonstrate that impaired late LTD (>3 hours) in THY-Tau22 mice can be rescued by either inhibition of glycogen synthase kinase-3 (GSK3beta) activity or by application of the protein-phosphatase 2A agonist selenate. In line with these findings, we observed increased phosphorylation of GSK3beta at Y216 and reduced total phosphatase activity in biochemical assays of hippocampal tissue of THY-Tau22 mice. Interestingly, LTD induction and pharmacologic inhibition of GSK3beta appeared to downregulate GSK3ss activity via a marked upregulation of phosphorylation at the inhibitory Ser9 residue. Our results point to alterations in phosphorylation and/or dephosphorylation homeostasis as key mechanisms underlying the deficits in LTD and hippocampus-dependent learning found in THY-Tau22 mice" http://www.ncbi.nlm.nih.gov/pubmed/25443285 0 1584 "B. R. McAuslan, G. N. Hannan and W. Reilly" 1982 "Signals causing change in morphological phenotype, growth mode, and gene expression of vascular endothelial cells" J.Cell Physiol 112 1 96-106 "Comparison of three different lines of bovine aortal endothelial cells provides a clear demonstration of reversible morphologic phenotype coincidental with change in expression and growth mode. These phenotypic forms can be externally controlled so that cells may exist either in an epithelioid contact-inhibitable state or as a fibroblastoid non-contact-inhibitable state. Clonal cell line N (normal) shows a strong tendency to maintain the epithelioid phenotype. Clonal cell line Sp (sprout) can readily and reversibly adopt the epithelioid or fibroblastoid phenotype. A factor in normal serum is responsible for maintaining the cells in the epithelioid phenotype. This factor could be a growth factor since several polypeptide growth factors are shown to drive cells from the fibroblastoid phenotype to the epithelioid phenotype within 11 hours. This growth factor-induced change is not mediated through induced DNA synthesis. Clonal cell line V (variant) normally maintains the fibroblastoid phenotype but can be directed to the epithelioid phenotype provided cells are on an appropriate collagenous matrix. Associated with these changes in morphological phenotype are depression of the expression of the pro alpha 2 chain of collagen type I which may be characteristic of the contact-inhibited state and of an 80,000 mol wt polypeptide synthesized only by cells in the fibroblastoid phenotype. An endothelial cell collagen EC1 (mol wt 177,000) was synthesized by all cell lines regardless of phenotype whereas a suspected breakdown product EC3 (mol wt 100,000) was found only in the epithelioid phenotype. Other differences and similarities between cell lines include expression of a 135,000 mol wt glycoprotein GP (V and N), the procollagen of collagen type III (N) of fibronectin (N, V, Sp), and of the pro alpha 1 chain of collagen type I (Sp, V). The characteristic expression of each line and its response to signals controlling morphologic phenotype impinges on the question of whether there exist several distinct types of vascular endothelial cells with different functional potentials controlled by extracellular signals" http://www.ncbi.nlm.nih.gov/pubmed/7107719 0 1585 D. A. Roff 2002 Inbreeding depression: tests of the overdominance and partial dominance hypotheses Evolution 56 4 768-775 "The two principal theories of the causal mechanism for inbreeding depression are the partial dominance hypothesis and the overdominance hypothesis. According to the first hypothesis, inbreeding increases the frequency of homozygous combinations of deleterious recessive alleles thereby decreasing fitness, whereas the overdominance hypothesis posits that inbreeding increases homozygosity and thus reduces the frequency of the superior heterozygotes. These two hypotheses make different predictions on the effect of crossing inbred lines: the overdominance hypothesis predicts that trait means will be restored to the outbred means, whereas the partial dominance hypothesis predicts that trait means will exceed those of the outbred population. I tested these predictions using seven inbred lines of the sand cricket, Gryllus firmus. Fourteen generations of brother-sister mating resulted in an inbreeding depression of 20-34% in four traits: nymphal weights at ages 14 days, 21 days, 28 days, and early fecundity. An incomplete diallel cross of these lines showed genetic variation among lines and an increase in all trait means above the outbred means, with three being significantly higher. These results provide support for the partial dominance hypothesis and are inconsistent with the overdominance hypothesis" http://www.ncbi.nlm.nih.gov/pubmed/12038534 0 1586 "E. S. Dolgin, B. Charlesworth, S. E. Baird and A. D. Cutter" 2007 Inbreeding and outbreeding depression in Caenorhabditis nematodes Evolution 61 6 1339-1352 "The nematode Caenorhabditis elegans reproduces primarily by self-fertilization of hermaphrodites, yet males are present at low frequencies in natural populations (androdioecy). The ancestral state of C. elegans was probably gonochorism (separate males and females), as in its relative C. remanei. Males may be maintained in C. elegans because outcrossed individuals escape inbreeding depression. The level of inbreeding depression is, however, expected to be low in such a highly selfing species, compared with an outcrosser like C. remanei. To investigate these issues, we measured life-history traits in the progeny of inbred versus outcrossed C. elegans and C. remanei individuals derived from recently isolated natural populations. In addition, we maintained inbred lines of C. remanei through 13 generations of full-sibling mating. Highly inbred C. remanei showed dramatic reductions in brood size and relative fitness compared to outcrossed individuals, with evidence of both direct genetic and maternal-effect inbreeding depression. This decline in fitness accumulated over time, causing extinction of nearly 90% of inbred lines, with no evidence of purging of deleterious mutations from the remaining lines. In contrast, pure strains of C. elegans performed better than crosses between strains, indicating outbreeding depression. The results are discussed in relation to the evolution of androdioecy and the effect of mating system on the level of inbreeding depression" http://www.ncbi.nlm.nih.gov/pubmed/17542844 0 1587 "P. T. McCauley, M. Robinson, F. B. Daniel and G. R. Olson" 1995 "Toxicity studies of 1,3-dichlorobenzene in Sprague-Dawley rats" Drug Chem.Toxicol. 18 02-Mar 201-221 "Male and female Sprague-Dawley rats received 1,3-dichlorobenzene daily by corn oil gavage for 10 or 90 consecutive days. The 10-day study doses were 0, 37, 147, 368 and 735 mg/kg; the 90-day study doses were 0, 9, 37, 147 and 588 mg/kg. In the 10-day study, there was a significant depression of body weight in both sexes at 735 mg/kg. Liver weights were significantly increased in both sexes at 368 and 735 mg/kg. Serum cholesterol levels were significantly elevated in both sexes at 368 and 735 mg/kg. Histopathological evaluation revealed centrolobular hepatocellular degeneration at 368 mg/kg in males and 735 mg/kg in females. In the 90-day study, body weights were significantly depressed in both sexes at 588 mg/kg. Normalization of food and water consumption by final body weight indicated that at 588 mg/kg both sexes had increased food and water consumption relative to controls. Absolute and relative liver weights were significantly increased in both sexes at 147 and 588 mg/kg. Relative kidney weights were significantly higher in both sexes at 588 mg/kg and in males at 147 mg/kg. Serum cholesterol and calcium levels were significantly elevated over controls in females at 37, 147, and 588 mg/kg, and in males at all dose levels. Histopathological evaluation at 147 and/or 588 mg/kg demonstrated liver and thyroid lesions in both sexes, and pituitary and kidney lesions in males. A NOAEL was not firmly established" http://www.ncbi.nlm.nih.gov/pubmed/7497912 0 1588 "D. A. Valentino, A. J. Riccitelli and R. L. Dufresne" 1991 Chronic DMI reduces thresholds for brain stimulation reward in the rat Pharmacol.Biochem.Behav. 39 1 01-Apr "The authors sought a demonstration of the validity of brain stimulation reward (BSR) models of depression. It was predicted that chronic, but not acute antidepressant treatment would enhance BSR responding. Rats with medial forebrain bundle electrodes were separated into 4 groups that received either saline or desmethylimipramine at 5, 10, or 20 mg/kg daily. A rate-free, threshold measure that has not previously been employed in studies of BSR and antidepressants was used. BSR thresholds were monitored every 3rd day over a 9-day baseline period and an 18-day drug treatment period, and after 12 days of drug withdrawal. Groups did not differ from one another till the 15th and 18th day of drug treatment. The greatest effects were seen in the 10 and 20 mg groups. The 20 mg group returned to baseline after drug withdrawal, but the 10 mg group did not. The absolute size of the effect was considered to be small, leading the authors to speculate that antidepressants act on homeostatic mechanisms that stabilize BSR substrates, only indirectly enhancing transmission of the reward signal" http://www.ncbi.nlm.nih.gov/pubmed/1924490 1 1589 "V. Goransson, C. Johnsson, O. Nylander and P. Hansell" 2002 Renomedullary and intestinal hyaluronan content during body water excess: a study in rats and gerbils J.Physiol 542 Pt 1 315-322 "Our previous studies in rats have suggested a role for renomedullary hyaluronan (HA) in water homeostasis. The gerbil is known for its unique ability to conserve water. In the present study renal papillary and intestinal HA were compared between groups of anaesthetized gerbils and rats before and after up to 6 h of I.V. water loading. Baseline papillary HA in gerbils was only 37 % of that in the rat. Water loading in rats increased the papillary HA content. Elevation was maximal (+27 %, P < 0.05) after 2 h of water loading and then declined to control levels after 6 h of water loading (+3 %, n.s.). In contrast, the gerbil responded with a decreased papillary HA content during water loading. The depression was maximal after 2 h (-49 %, P < 0.05) and was still 41 % below the control values after 6 h (P < 0.05). The urine flow rate increased rapidly in the rat and its maximum, 21 times above the control level (P < 0.05), occurred at the HA peak, i.e. after 2 h of water loading while in the gerbil, the urine flow rate increased slowly and slightly and was only six times above control values after 6 h of water loading (P < 0.05). The HA content along the intestine was similar in the two species: lowest in the duodenum and jejunum and highest in the distal colon. To conclude, in the rat, the elevation of papillary interstitial HA during acute water loading would counteract water reabsorption by changing the physico-chemical characteristics of the interstitial matrix favouring rapid water diuresis. This would work as a complement to the powerful regulation by ADH. The gerbil has a diametrically different regulation of papillary HA turnover during water loading. The decreased papillary HA level during water loading and the slow and small diuretic response may represent a genetic difference in adaptation to enhance the ability to conserve water in an arid environment" http://www.ncbi.nlm.nih.gov/pubmed/12096072 0 1590 "S. Lee, K. Sen and N. Kopell" 2009 Cortical gamma rhythms modulate NMDAR-mediated spike timing dependent plasticity in a biophysical model PLoS.Comput.Biol. 5 12 e1000602 "Spike timing dependent plasticity (STDP) has been observed experimentally in vitro and is a widely studied neural algorithm for synaptic modification. While the functional role of STDP has been investigated extensively, the effect of rhythms on the precise timing of STDP has not been characterized as well. We use a simplified biophysical model of a cortical network that generates pyramidal interneuronal gamma rhythms (PING). Plasticity via STDP is investigated at the excitatory pyramidal cell synapse from a gamma frequency (30-90 Hz) input independent of the network gamma rhythm. The input may represent a corticocortical or an information-specific thalamocortical connection. This synapse is mediated by N-methyl-D-aspartate receptor mediated (NMDAR) currents. For distinct network and input frequencies, the model shows robust frequency regimes of potentiation and depression, providing a mechanism by which responses to certain inputs can potentiate while responses to other inputs depress. For potentiating regimes, the model suggests an optimal amount and duration of plasticity that can occur, which depends on the time course for the decay of the postsynaptic NMDAR current. Prolonging the duration of the input beyond this optimal time results in depression. Inserting pauses in the input can increase the total potentiation. The optimal pause length corresponds to the decay time of the NMDAR current. Thus, STDP in this model provides a mechanism for potentiation and depression depending on input frequency and suggests that the slow NMDAR current decay helps to regulate the optimal amplitude and duration of the plasticity. The optimal pause length is comparable to the time scale of the negative phase of a modulatory theta rhythm, which may pause gamma rhythm spiking. Our pause results may suggest a novel role for this theta rhythm in plasticity. Finally, we discuss our results in the context of auditory thalamocortical plasticity" http://www.ncbi.nlm.nih.gov/pubmed/20011119 0 1591 "M. A. Gillingham, F. Cezilly, R. Wattier and A. Bechet" 2013 Evidence for an association between post-fledging dispersal and microsatellite multilocus heterozygosity in a large population of greater flamingos PLoS.One. 8 11 e81118 "Dispersal can be divided into three stages: departure, transience and settlement. Despite the fact that theoretical studies have emphasized the importance of heterozygosity on dispersal strategies, empirical evidence of its effect on different stages of dispersal is lacking. Here, using multi-event capture-mark-recapture models, we show a negative association between microsatellite multilocus heterozygosity (MLH; 10 loci; n = 1023) and post-fledging dispersal propensity for greater flamingos, Phoenicopterus roseus, born in southern France. We propose that the negative effects of inbreeding depression affects competitive ability and therefore more homozygous individuals are more likely to disperse because they are less able to compete within the highly saturated natal site. Finally, a model with the effect of MLH on propensity of post-fledgling dispersers to disperse to the long-distance sites of Africa was equivalent to the null model, suggesting that MLH had low to no effect on dispersal distance. Variations in individual genetic quality thus result in context-dependent heterogeneity in dispersal strategies at each stage of dispersal. Our results have important implications on fitness since sites visited early in life are known to influence site selection later on in life and future survival" http://www.ncbi.nlm.nih.gov/pubmed/24278385 0 1592 W. A. LaFramboise and D. E. Woodrum 1985 Elevated diaphragm electromyogram during neonatal hypoxic ventilatory depression J.Appl.Physiol (1985.) 59 4 1040-1045 "Diaphragmatic electromyogram (EMG) was obtained in eight 48-h-old unanesthetized monkeys while breathing air and then either of two different hypoxic gas mixtures (12 or 8% O2 in N2) for 5 min. Minute ventilation (VI) rose significantly above control levels by 1 min of hypoxemia while animals were breathing either of the hypoxic gas mixtures as tidal volume (VT) and slope and rate moving average EMG increased. The relative gains in VI were associated with comparable increases in diaphragmatic neural activity per minute (EMG/min = peak EMG X frequency) during this early phase of hypoxemia. VI subsequently fell to control levels (inspired O2 fraction = 12%, arterial PO2 = 23 +/- 3 Torr) or significantly below (inspired O2 fraction = 8%, arterial PO2 = 18 +/- 0.4 Torr) by 5 min of hypoxemia, secondary to changes in VT. Despite the decline in VI, slope and rate moving average EMG, and EMG/min remained statistically above control values by 5 min of hypoxemia, although there was a trend for EMG/min to decrease slightly from the 1-min peak response. These findings demonstrate that hypoxic-induced depression of neural input to the diaphragm is not independently responsible for the biphasic nature of the newborn ventilatory response, although it cannot be ruled out as a contributor. The fall in inspiratory volumes despite constant elevated EMG activity suggests the presence of a change in respiratory mechanics and/or an impairment in diaphragmatic contractile function without offsetting neural compensatory activity" http://www.ncbi.nlm.nih.gov/pubmed/2997107 0 1593 B. Heicke 1970 [Inhibition of DNA synthesis and cell multiplication by apurinic acid and apyrimidinic acid] Naunyn Schmiedebergs Arch.Pharmakol. 266 2 161-178 http://www.ncbi.nlm.nih.gov/pubmed/4245725 0 1594 T. Pearson and B. G. Frenguelli 2000 Volume-regulated anion channels do not contribute extracellular adenosine during the hypoxic depression of excitatory synaptic transmission in area CA1 of rat hippocampus Eur.J.Neurosci. 12 8 3064-3066 "We investigated whether volume-regulated anion channels (VRACs) contributed to the accumulation of extracellular adenosine during hypoxia in area CA1. The rapid hypoxic depression of the fEPSP was greatly attenuated by the selective adenosine A1 receptor antagonist DPCPX (50 nM), but not affected by the VRAC blockers tamoxifen (10-30 microM) or DNDS (1 mM). Our data argue against the efflux of adenosine per se or its precursor ATP through VRACs as making a significant contribution to extracellular adenosine during the early stages of hypoxia" http://www.ncbi.nlm.nih.gov/pubmed/10971648 0 1595 "E. Klein, J. Patel, R. McDevitt and J. Zohar" 1987 Chronic lithium treatment increases the phosphorylation of a 64-kDa protein in rat brains Brain Res. 407 2 312-316 "Despite the wide clinical use of lithium in the treatment of manic depressive illness there is no adequate explanation for its mechanism of action. In the light of lithium's suggestive effects on the second messenger system in the brain, we studied the effects of chronic dietary lithium treatment (achieving blood levels in the therapeutic range) on protein phosphorylation in different areas of rat brain. An increase in the phosphorylation of a 64-kDa membrane-associated protein was evident in the lithium-treated rats compared to controls. This increase was observed only under basal phosphorylating conditions and was abolished when the phosphorylation was performed in the presence of Ca2+ or Ca2+ and calmodulin. The possibility that this 64-kDa protein affected by lithium is the beta-subunit of the calmodulin-dependent protein kinase or a different protein which co-migrates with it is discussed" http://www.ncbi.nlm.nih.gov/pubmed/3032364 0 1596 "R.-J. Liu, K. Ota, S. Dutheil and G. Aghajanian" 2014 Rapid antidepressant ketamine strengthens CRF-activated amygdala projections to basilar dendrites of layer V pyramidal neurons in pl and ac but not il subregions of medial prefrontal cortex (MPFC) "Neuropsychopharmacology.Conference: 53rd Annual Meeting of the American College of Neuropsychopharmacology, ACNP 2014 Phoenix, AZ United States.Conference Start: 20141207 Conference End: 20141211.Conference Publication: (var.pagings).39 ()(pp S637-S63" var.pagings S637-S638 "Background: A single sub-anesthetic dose of ketamine, a NMDA receptor blocker, produces a robust, prolonged antidepressant response in treatment-resistant depression. In chronic stress models ketamine reverses depression-like behaviors and associated deficits in apical spine density and serotonin (5-HT)- or hypocretin/orexin (hcrt)-activated EPSCs in layer V pyramidal cells of mPFC (Li et al., 2011). These apical deficits are rapidly reversed by ketamine through activation of the mTORC1 synaptogenic pathway (Li et al., 2010). Little is known, however, about the effects of ketamine on inputs to basilar dendrites of layer V cells. The basilar dendrites of layer V cells receive an excitatory input from glutaminergic pyramidal cells of the basolateral nucleus of the amygdala (BLA) (Gabbott et al., 2012). Pyramidal cells of the BLA express CRF-1 receptors (Van Pett et al., 2000) and are selectively depolarized by the stress-activated peptide corticotrophin releasing factor (CRF) (Giesbrecht et al., 2010). Preliminarily, CRF was found to generate excitatory postsynaptic potentials (EPSCs) in layer V pyramidal cells via CRF1 receptors in rat mPFC brain slices. Accordingly, we investigated: (1) whether CRF-induced EPSCs in mPFC depend upon BLA inputs to the basilar dendrites; (2) whether ketamine enhanced CRF activated EPSCs or increased dendritic spine density in the basilar field; (3) whether the CRF effects were reduced by chronic stress; and (4) whether ketamine effects differed between mPFC subregions. Methods: Whole cell patch clamp recordings were from layer V pyramidal cells in PL, AC, and IL subregions of adult rat mPFC brain slices; EPSC responses to bath applied CRF (200 nM) and 5-HT were recorded. Cells were passively filled with Neurobiotin and later processed and imaged by 2-photon laser scanning for spine density analysis. Excitotoxin lesions were made in the BLA and recordings were performed after a lapse of two weeks to allow for degeneration of BLA-cortical projections. The apical dendritic tuft was severed in some layer V pyramidal cells to evaluate the relative contribution of apical versus basilar dendrites. Rapamycin (i.c.v.) pretreatment was used to determine if CRF-sensitive responses were enhanced by ketamine via the mTORC1 pathway. The effects of ketamine (10 mg/kg) were examined in brain slices 24 hrs following injection (i.p.) of the drug. Results: We found: (1) that the effects of CRF in mPFC were largely dependent on the integrity of BLA inputs; (2) that ketamine pretreatment enhanced CRF-induced EPSCs with an associated increase in basilar dendritic spine density of layer V pyramidal cells of PL and AC but not IL subregions;; (3) that the effects of ketamine were mediated via the mTOR synaptogenic pathway as they were prevented by pretreatment with the mTORC1 blocker rapamycin; and (4) that chronic stress did not reduce CRF-induced EPSCs in basilar dendrites, contrasting with the marked loss of apicallytargeted responses after chronic stress. (5) that ketamine increased apical EPSCs in all subregions including IL, which projects to the amygdaloid inhibitory intercalated neurons (ICN) that can suppress amygdaloid stress/fear responses (Quirk et al., 2003; Cho et al., 2013). Conclusions: The main findings of this study are: (1) that the stress-activated hormone CRF induces EPSCs in basilar dendrites of mPFC layer V pyramidal cells via activation BLA inputs; (2) that ketamine pretreatment enhances CRFinduced EPSCs and increases basilar dendritic spine density in both PL and AC but not IL subregions; (3) that ketamine does increase apical EPSCs in IL, which via its projection to ICN can suppress amygdaloid stress/fear responses; and (4) that CRF responses in the basilar domain are resistant to stress, contrasting with a marked reduction of responses to 5-HT and hcrt in the apical domain (Liu et al, 2008), conforming with the general rule that pyramidal cell basilar dendrites are resistant to chronic stress. The net result of these stress-induced changes is a shift in balance in favor CRF-activated basilar dendritic inputs over weakened apical inputs. These results are consistent with a disproportionate influence of the amygdala in chronic stress and major depression (see Price and Drevets, 2010). We propose that ketamine by restoring the strength of apical inputs to all subregions including IL would ameliorate this imbalance" DO - http://dx.doi.org/10.1038/npp.2014.282 0 1597 "V. V. Mikheev, V. L. Bianki and V. P. Poshivalov" 1988 Influence of unilateral cortical spreading depression on intraspecies aggression and sociability of isolated mice Neurosci.Behav.Physiol 18 5 432-438 http://www.ncbi.nlm.nih.gov/pubmed/3216996 0 1598 C. M. Lathers 1980 Effect of timolol on autonomic neural discharge associated with ouabain-induced arrhythmia Eur.J.Pharmacol. 64 02-Mar 95-106 "The purpose of this study was to determine the effect of the beta-blocking agent timolol on postganglionic cardiac and preganglionic splanchnic sympathetic and vagal neural discharge, ouabain-induced arrhythmia, heart rate and mean arterial blood pressure. Cats were anesthetized with alpha-chloralose, given atropine, and pretreated with timolol (5 mg/kg, i.v. infused at a rate of 0.5 mg/kg/min for 10 min). Bolus injections of ouabain (25 microgram/kg, i.v.) were given every 15 min until the animals died; the first injection was given 15 min after the end of the timolol infusion. When compared with cats (n = 13) receiving only ouabain, timolol (n = 11 cats) increased the time to ouabain-induced arrhythmia and death from 23 +/- 3 to 48 +/- 7 and 46 +/- 3 to 76 +/- 9 min, respectively (p less than 0.05). Both heat rate and mean arterial blood pressure had decreased from 137 +/- 4 to 104 +/- 6 beats/min and 133 +/- 6 to 103 +/- 7 mm Hg, respectively (P less than 0.05); ouabain did not reverse the decreases. Neural activity monitored from the vagus and from the postganglionic cardiac and preganglionic splanchnic sympathetic nerves was not significantly altered by the infusion of timolol. The administration of ouabain after timolol did not alter splanchnic nor vagal discharge. Most important was the observation that postganglionic cardiac sympathetic neural discharge exhibited both increases and decreases, i.e., a nonuniform neural discharge, at the time of ouabain-induced arrhythmia and that the ouabain-induced nonuniformity did not occur in the cats pretreated with timolol. Thus, the protective effect of timolol may be due, in part, to prevention of the nonuniform postganglionic cardiac sympathetic neural discharge and to the prevention of ouabain-induced increases in vagal discharge. The establishment of beta-blockade and a direct negative inotropic action may also have contributed to the antiarrhythmic action of timolol" http://www.ncbi.nlm.nih.gov/pubmed/7398767 0 1599 P. A. Fried 1974 Parameters influencing the effect of DELTA9 THC on activity wheel behavior "Pharmacology Biochemistry and Behavior.2 (3) ()(pp 435-438), 1974.Date of Publication: 1974." 3 435-438 "In 2 studies the effect of DELTA9 THC (tetrahydrocannabinol) on activity wheel behavior in rats was examined. The amount of laboratory acclimation prior to testing was manipulated and either 4 mg/kg or 8 mg/kg DELTA9 THC was given intraperitoneally. Activity counts were taken 15 min, 1, 6, 24, 48 or 72 hr after the injection. Those animals that received 4 mg/kg DELTA9 THC and had little laboratory acclimation were significantly more active than their controls during the first 15 min, but after 1 hr were, like the other 3 experimental groups, less active than the appropriate controls. The time course for the depressant action of the DELTA9 THC at both dose levels was quite similar and lasted for approximately 24 hr" DO - http://dx.doi.org/10.1016/0091-3057%2874%2990094-X 0 1600 2001 "Disability insurance--ADA--benefits for mental disability, alcoholism and drug abuse. Weyer v. Twentieth Century Fox Film Corp., 198 F.3d 1104 (9th Cir. 2000)" "Benefits quarterly.17 (3) ()(pp 64-66), 2001.Date of Publication: 2001." 3 64-66 0 1601 "P. R. Maroko, P. Libby, W. R. Ginks, C. M. Bloor, W. E. Shell, B. E. Sobel and J. Ross, Jr." 1972 Coronary artery reperfusion. I. Early effects on local myocardial function and the extent of myocardial necrosis J.Clin.Invest 51 10 2710-2716 "The effects of coronary artery reperfusion 3 hr after coronary occlusion on contractile function and the development of myocardial damage at 24 hr was studied experimentally. In 14 control and 6 reperfused dogs, relationships between epicardial ST segment elevation 15 min after coronary occlusion and myocardial creatine phosphokinase activity (CPK) and histologic appearance 24 hr later were examined. The electrocardiograms were recorded from 10 to 15 sites on the left ventricular epicardium and transmural samples for CPK and histology were obtained from the same sites where epicardial electrocardiograms had been recorded. An inverse relation existed between ST segment elevation (mv) 15 min after occlusion and log CPK activity (IU/ mg of protein) 24 hr later, log CPK = - 0.06ST + 1.26. In dogs subjected to coronary artery reperfusion, there was significantly less CPK depression (log CPK = - 0.01ST + 1.31, [P < 0.01]) than that expected from the control group. In the control group 97% of specimens showing ST segment elevations over 2 mv at 15 min showed abnormal histology 24 hr later. In contrast, in the reperfused group 43% of sites exhibiting elevated ST segment at 15 min showed abnormal histology 24 hr later. In six additional dogs it was shown that the paradoxical movement of the left ventricular wall could be reversed within 1 hr of perfusion. Therefore, by enzymatic and histologic criteria, as well as by functional assessment, coronary artery reperfusion 3 hr after occlusion resulted in salvage of myocardial tissue" http://www.ncbi.nlm.nih.gov/pubmed/5056663 0 1602 "S. Wei, X. W. Ji, C. L. Wu, Z. F. Li, P. Sun, J. Q. Wang, Q. T. Zhao, J. Gao, Y. H. Guo, S. G. Sun and M. Q. Qiao" 2014 Resident intruder paradigm-induced aggression relieves depressive-like behaviors in male rats subjected to chronic mild stress Med.Sci.Monit. 20 945-952 "BACKGROUND: Accumulating epidemiological evidence shows that life event stressors are major vulnerability factors for psychiatric diseases such as major depression. It is also well known that the resident intruder paradigm (RIP) results in aggressive behavior in male rats. However, it is not known how resident intruder paradigm-induced aggression affects depressive-like behavior in isolated male rats subjected to chronic mild stress (CMS), which is an animal model of depression. MATERIAL AND METHODS: Male Wistar rats were divided into 3 groups: non-stressed controls, isolated rats subjected to the CMS protocol, and resident intruder paradigm-exposed rats subjected to the CMS protocol. RESULTS: In the sucrose intake test, ingestion of a 1% sucrose solution by rats in the CMS group was significantly lower than in control and CMS+RIP rats after 3 weeks of stress. In the open-field test, CMS rats had significantly lower open-field scores compared to control rats. Furthermore, the total scores given the CMS group were significantly lower than in the CMS+RIP rats. In the forced swimming test (FST), the immobility times of CMS rats were significantly longer than those of the control or CMS+RIP rats. However, no differences were observed between controls and CMS+RIP rats. CONCLUSIONS: Our data show that aggressive behavior evoked by the resident intruder paradigm could relieve broad-spectrum depressive-like behaviors in isolated adult male rats subjected to CMS" http://www.ncbi.nlm.nih.gov/pubmed/24911067 1 1603 "M. Kuloglu, M. Atmaca, E. Tezcan, O. Gecici, H. Tunckol and B. Ustundag" 2002 Antioxidant enzyme activities and malondialdehyde levels in patients with obsessive-compulsive disorder "Neuropsychobiology.46 (1) ()(pp 27-32), 2002.Date of Publication: 2002." 1 27-32 "To examine the importance of free radicals in the pathogenesis of obsessive-compulsive disorder (OCD), we aimed to evaluate whether malondialdehyde (MDA), a product of lipid peroxidation, and antioxidant enzyme [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)] activity levels were associated with OCD. The patients were divided into two subgroups according to whether DSM-IV major depressive disorder (MDD) was accompanied (OCD + MDD) or not (OCD - MDD). The MDA and antioxidant enzyme levels both in patients and controls were determined. SOD activity levels were significantly higher in the OCD + MDD group compared with the control and the OCD - MDD group. Although the OCD - MDD group had slightly higher SOD activity levels as compared with the controls, the difference was not statistically significant. GSH-Px activity levels were statistically significantly higher in both groups compared with controls. Likewise, there was a significant difference in GSH-Px activity levels between the OCD + MDD and OCD - MDD group. CAT activity levels were slightly higher in the OCD + MDD group compared with the OCD - MDD and control group. MDA levels in both groups were significantly higher than in controls. In addition, the difference in MDA levels between both groups was statistically significant. In conclusion, our results suggest that OCD is associated with free radicals and that it may be a heterogeneous subtype including some biological indications of anxiety and affective disorders. More comprehensive and detailed studies are needed to decipher the exact role of free radicals in OCD. Copyright © 2002 S. Karger AG, Basel" DO - http://dx.doi.org/10.1159/000063573 0 1604 "E. B. Arushanian, V. A. Baturin and A. V. Popov" 1993 [The reciprocal relationships between the epiphysis and the suprachiasmatic nuclei of the hypothalamus during the restructuring of the circadian mobility in rats under an altered light regimen] Zh.Vyssh.Nerv.Deiat.Im I.P.Pavlova 43 1 69-75 "Pinealectomy and reserpine advanced the reorganization of the circadian rhythm of motor activity of rats following a ten-hour shift in the photoperiod. Bilateral electrolytic lesion of the hypothalamic suprachiasmatic nuclei and administration of the antidepressant drug, imipramine, on the contrary, delayed the rhythm change. The results suggest a possible antagonistic reciprocal relationship between the pineal gland and the main pacemaker, whose balance causes a gradual adaptation of animals to the changing environment. Fast reorganization of motor activity at pineal dysfunction or under the influence of depressogenic drugs could cause desynchronization and psychiatric disorders in a form of depression" http://www.ncbi.nlm.nih.gov/pubmed/8385401 0 1605 "P. Paakkari, I. Paakkari, A. L. Siren and G. Feuerstein" 1990 "Respiratory and locomotor stimulation by low doses of dermorphin, a mu1 receptor-mediated effect" J.Pharmacol.Exp.Ther. 252 1 235-240 "The selective opioid mu receptor agonist dermorphin increased the locomotor activity of rats dose dependently at 10 to 100 pmol/kg i.c.v. Respiratory rate, relative tidal volume and respiratory minute volume also increased unrelated to changes in locomotor activity. Higher doses, on the other hand, produced catalepsy and respiratory depression. Pretreatment of the rats with the mu1-selective antagonist naloxonazine (10 mg/kg i.v.) blocked the stimulant locomotor and respiratory effects of low doses of dermorphin (10-100 pmol/kg), but potentiated the respiratory depressant effect of a high dose (10 nmol/kg) of dermorphin. The selective benzodiazepine antagonist flumazenil (5 mg/kg), which has been shown previously to antagonize catalepsy and respiratory depression produced by relatively high doses of dermorphin, did not antagonize the respiratory or locomotor stimulant effect of dermorphin. The data suggest that mu1-opioid receptors are responsible for the low dose stimulant effects of dermorphin on locomotor activity and respiration whereas mu2 receptors mediate the respiratory depressant effect of dermorphin" http://www.ncbi.nlm.nih.gov/pubmed/1967644 0 1606 "J. Shlik, E. Vasar and J. Bradwejn" 1997 Cholecystokinin and psychiatric disorders : role in aetiology and potential of receptor antagonists in therapy CNS.Drugs 8 2 134-152 "Cholecystokinin (CCK) is one of the most abundant neuropeptides in the brain. It is found in the highest levels in cortical and limbic structures and also in the basal ganglia. Two subtypes of CCK receptors have been described in the brain and gastrointestinal tissues. CCK(A) (alimentary subtype) receptors are mainly located in the gastrointestinal tract, regulating secretion of enzymes from the pancreas and emptying of the gallbladder. However, CCK(A) receptors are also found in several brain regions, with the highest densities in structures poorly protected by the haematoencephalic barrier (the area postrema, nucleus tractus solitarius and hypothalamus). The distribution of CCK(B) (brain subtype) receptors overlaps with the localisation of CCK and its mRNA in different brain areas, with the highest densities in the cerebral cortex, basal ganglia, nucleus accumbens and forebrain limbic structures.Both subtype of CCK receptor belong to the guanine nucleotide-binding protein-(G protein)-linked receptor superfamily containing 7 transmembrane domains. Signal transduction at CCK receptors is mediated via G(q) protein-related activation of phospholipase C and the formation of inositol 1,4,5-triphosphate (IP(3)) and 1,2-diacylglycerol (DAG). Recent cloning of CCK(A) and CCK(B) receptors has shown that mRNA for both receptors is distributed in the same tissues as established in radioligand binding and receptor autoradiography studies, with few exceptions.The existence of multiple CCK receptors has fuelled the development of selective CCK(A) and CCK(B) receptor antagonists. These antagonists belong to distinct chemical groups, including dibutyryl derivatives of cyclic nucleotides, amino acid derivatives, partial sequences and derivatives of the -COOH terminal sequence heptapeptides of CCK, benzodiazepine derivatives, 'peptoids' based on fragments of the CCK molecule, and pyrazolidinones. At the present time, the compounds of choice for blockade of the CCK(A) receptor are lorglumide, devazepide and lintitript (SR27897). L-365,260, CI-988, L-740,093 and LY288513 are the drugs most widely used to block CCK(B) receptors.Studies with CCK antagonists (and agonists) in animals and humans suggest a role for CCK in the regulation of anxiety and panic. The administration of CCK agonists [ceruletide (caerulein), CCK-4, pentagastrin] has an anxiogenic action in various animal models and in different animal species. However, the anxiogenic action of CCK agonists is restricted to nonconditioned (ethological) models of anxiety, with very limited activity in the 'classical' conditioned models. Pharmacological studies have revealed that CCK(B) receptors are the key targets in the anxiogenic action of CCK agonists. Nevertheless, CCK(B) antagonists displayed very little activity, if any at all, in these models, but strongly antagonised the effects of CCK(B) agonists. The anxiogenic/panicogenic action of CCK(B) agonists (CCK-4, pentagastrin) is even more pronounced in human studies, but the effectiveness of CCK(B) antagonists as anxiolytics remains unclear. Clinical trials performed to date have provided inconclusive data about the anxiolytic potential of CCK(B) receptor antagonists, probably because of limiting pharmacokinetic factors.The results of some animal experiments suggest a role for CCK in depression. The administration of CCK(B) antagonists causes antidepressant-like action in mouse models of depression. However, human studies replicating this result have yet to be carried out.A prominent biochemical alteration in schizophrenia is a reduction of CCK levels in the cerebral cortex. This change may be related to the loss of cortical neurons, due to the schizophrenic process itself. In animal studies (mainly in mice), administration of CCK agonists and antagonists has been shown to be effective in several models, reflecting a possible antipsychotic activity of these drugs. However, the data obtained in human studies suggest that CCK agonists and antagonists do not improve the symptoms of schizophrenia. Taking into account the reduced levels of CCK and its receptors found in schizophrenia, treatments increasing, but not blocking, brain CCK activity may be more appropriate" http://www.ncbi.nlm.nih.gov/pubmed/23338219 0 1607 "L. R. Stein, C. F. Zorumski, S. Imai and Y. Izumi" 2015 Nampt is required for long-term depression and the function of GluN2B subunit-containing NMDA receptors Brain Res.Bull. 119 Pt A 41-51 "Nicotinamide adenine dinucleotide (NAD(+)) is an essential coenzyme/cosubstrate for many biological processes in cellular metabolism. The rate-limiting step in the major pathway of mammalian NAD(+) biosynthesis is mediated by nicotinamide phosphoribosyltransferase (Nampt). Previously, we showed that mice lacking Nampt in forebrain excitatory neurons (CamKIIalphaNampt(-/-) mice) exhibited hyperactivity, impaired learning and memory, and reduced anxiety-like behaviors. However, it remained unclear if these functional effects were accompanied by synaptic changes. Here, we show that CamKIIalphaNampt(-/-) mice have impaired induction of long-term depression (LTD) in the Schaffer collateral pathway, but normal induction of long-term potentiation (LTP), at postnatal day 30. Pharmacological assessments demonstrated that CamKIIalphaNampt(-/-) mice also display dysfunction of synaptic GluN2B (NR2B)-containing N-methyl-d-aspartate receptors (NMDARs) prior to changes in NMDAR subunit expression. These results support a novel, important role for Nampt-mediated NAD(+) biosynthesis in LTD and in the function of GluN2B-containing NMDARs" http://www.ncbi.nlm.nih.gov/pubmed/26481044 0 1608 "W. D. Figg, H. Li, T. Sissung, A. Retter, S. Wu, J. L. Gulley, P. Arlen, J. J. Wright, H. Parnes, K. Fedenko, L. Latham, S. M. Steinberg, E. Jones, C. Chen and W. Dahut" 2007 "Pre-clinical and clinical evaluation of estramustine, docetaxel and thalidomide combination in androgen-independent prostate cancer" "BJU International.99 (5) ()(pp 1047-1055), 2007.Date of Publication: May 2007." 5 1047-1055 "OBJECTIVE: To evaluate the combination of docetaxel plus estramustine (which prolongs survival in patients with androgen-independent prostate cancer, AIPC), and thalidomide (that also adds to docetaxel activity), both pre-clinically and clinically in AIPC. PATIENTS, MATERIALS AND METHODS: In the pre-clinical evaluation we injected PC3 cells subcutaneously into severely combined immunodeficient mice and started treatment after the tumour volume reached 50 mm3. We also evaluated the combination using luciferase-labelled PC3M-luc-C6 cells in nude mice. We enrolled 20 patients with metastatic progressive AIPC into a phase II clinical trial to evaluate this combination. Docetaxel (30 mg/m2) was administered every week, for 3 of 4 weeks. The dose of thalidomide was 200 mg/day and estramustine was given three times a day at 1, 2, 3, 8, 9, 10, 15, 16 and 17 days. RESULTS: In the mice, thalidomide with docetaxel plus estramustine reduced tumour volume by 88% at 17 days vs the control treatment (p = 0.001). The combination of docetaxel, estramustine and thalidomide nearly eradicated the signal from the luciferase-expressing PC3M cells in the metastasis model. Clinically, the progression-free time was 7.2 months with this combination; 18 of 20 patients had a decline of half or more in prostate-specific antigen level and two of 10 patients with soft-tissue lesions had a partial response on computed tomography. There were 24 grade 3 and two grade 4 complications associated with this combination. There was a statistically significant association between overall survival and the CYP1B1*3 genotype (P = 0.013). CONCLUSION: Docetaxel-based chemotherapy is now regarded as a standard regimen for metastatic AIPC. The combination of estramustine, docetaxel and thalidomide is an advantageous treatment in pre-clinical models of prostate cancer and is a safe, tolerable and active regimen in patients with AIPC" DO - http://dx.doi.org/10.1111/j.1464-410X.2007.06763.x 0 1609 M. A. Brotto and T. M. Nosek 1996 Hydrogen peroxide disrupts Ca2+ release from the sarcoplasmic reticulum of rat skeletal muscle fibers J.Appl.Physiol (1985.) 81 2 731-737 "Reactive oxygen species such as superoxide (O2-) and H2O2 are produced at low levels in resting muscles and at substantially higher levels in exercising muscles. Increased respiratory activity with exercise leads to O2- production by the NADPH oxidase reaction and the subsequent generation of H2O2 from O2- by spontaneous dismutation or by the superoxide dismutase reaction. The long-lasting (24-h) depression of contractile function after exercise has been linked to damage of one or more proteins important in the excitation-contraction coupling process. We studied mechanically and chemically skinned fibers from the extensor digitorum longus muscle of the rat to evaluate the effects of a 5-min exposure to 1.0 mM H2O2 on muscle function. We found that H2O2 had no effect on the isometric force-producing properties of the contractile apparatus or on Ca2+ uptake by the sarcoplasmic reticulum. It did, however, significantly affect Ca2+ release from the sarcoplasmic reticulum. Maximum depolarization-induced Ca2+ release was inhibited, and the sensitivity to depolarization was decreased. Ca(2+)-induced release was completely blocked. We conclude that elevated levels of H2O2 with exercise are capable of damaging one or more proteins of the excitation-contraction coupling process to produce a disruption in function that can account, at least in part, for the long-lasting effects of fatiguing stimulation" http://www.ncbi.nlm.nih.gov/pubmed/8872640 0 1610 "I. M. Reid, A. M. Dew and L. A. Williams" 1984 Haematology of subclinical fatty liver in dairy cows Res.Vet.Sci. 37 1 63-65 "The relationship between liver fat content and haematology was investigated in 369 cows from eight herds sampled in the second week after calving. High levels of fat in the liver were associated with a depression in total white cell count and in neutrophils, eosinophils and lymphocytes. There was no correlation between liver fat content and the percentage of E rosetting lymphocytes, packed cell volume or haemoglobin concentration. The changes in peripheral white cell counts may be related to the increased incidence of post parturient disease in cows with fatty liver" http://www.ncbi.nlm.nih.gov/pubmed/6473916 0 1611 L. Wolpert 2009 "Diffusible gradients are out - an interview with Lewis Wolpert. Interviewed by Richardson, Michael K" Int.J.Dev.Biol. 53 05-Jun 659-662 "In 1969, Lewis Wolpert published a paper outlining his new concepts of ""pattern formation"" and ""positional information"". He had already published research on the mechanics of cell membranes in amoebae, and a series of classic studies of sea urchin gastrulation with Trygve Gustavson. Wolpert had presented his 1969 paper a year earlier at a Woods Hole conference, where it received a very hostile reception: ""I wasnt asked back to America for many years!"". But with Francis Crick lining up in support of diffusible morphogen gradients, positional information eventually became established as a guiding principle for research into biological pattern formation. It is now clear that pattern formation is much more complex than could possibly have been imagined in 1969. But Wolpert still believes in positional information, and regards intercalation during regeneration as its best supporting evidence. However, he and others doubt that diffusible morphogen gradients are a plausible mechanism: ""Diffusible gradients are too messy"", he says. Since his retirement, Lewis Wolpert has remained active as a theoretical biologist and continues to publish in leading journals. He has also campaigned for a greater public understanding of the stigma of depression. He was interviewed at home in London on July 26th, 2007 by Michael Richardson" http://www.ncbi.nlm.nih.gov/pubmed/19557674 0 1612 "A. Pasipoularides, M. Shu, A. Shah, A. Tucconi and D. D. Glower" 2003 RV instantaneous intraventricular diastolic pressure and velocity distributions in normal and volume overload awake dog disease models Am.J.Physiol Heart Circ.Physiol 285 5 H1956-H1965 "Intraventricular diastolic right ventricular (RV) flow field dynamics were studied by functional imaging using three-dimensional (3D) real-time echocardiography with sonomicrometry and computational fluid dynamics in seven awake dogs at control with normal wall motion (NWM) and RV volume overload with diastolic paradoxical septal motion. Burgeoning flow cross section between inflow anulus and chamber walls induces a convective pressure rise, which represents a ""convective deceleration load"" (CDL). High spatiotemporal resolution dynamic pressure and velocity distributions of the intraventricular RV flow field revealed time-dependent, subtle interactions between intraventricular local acceleration and convective pressure gradients. During the E-wave upstroke, the total pressure gradient along intraventricular flow is the algebraic sum of a pressure decrease contributed by local acceleration and a pressure rise contributed by a convective deceleration that partially counterbalances the local acceleration gradient. This underlies the smallness of early diastolic intraventricular gradients. At peak volumetric inflow, local acceleration vanishes and the total adverse intraventricular gradient is convective. During the E-wave downstroke, the strongly adverse gradient embodies the streamwise pressure augmentations from both local and convective decelerations. It induces flow separation and large-scale vortical motions, stronger in NWM. Their dynamic corollaries on intraventricular pressure and velocity distributions were ascertained. In the NWM pattern, the strong ring-like vortex surrounding the central core encroaches on the area available for flow toward the apex. This results in higher linear velocities later in the downstroke of the E wave than at peak inflow rate. The augmentation of CDL by ventriculoannular disproportion may contribute to E wave and E-to-A ratio depression with chamber dilatation" http://www.ncbi.nlm.nih.gov/pubmed/14561678 0 1613 "G. Kunigiri, P. N. Jayakumar, N. Janakiramaiah and B. N. Gangadhar" 2007 MRI T(2) relaxometry of brain regions and cognitive dysfunction following electroconvulsive therapy Indian J.Psychiatry 49 3 195-199 "BACKGROUND: Although electroconvulsive therapy (ECT) causes no structural brain damage, recent studies reported altered brain perfusion acutely following ECT. This is in keeping with brain edema which was noted in animal experiments following electroconvulsive shock. AIM: This study examined alteration in magnetic resonance imaging (MRI) T(2) relaxation time, a measure of brain edema, and its relation to therapeutic efficacy, orientation and memory impairment with ECT. MATERIALS AND METHODS: Fifteen drug-naive consenting patients of major depressive disorder with melancholia (DSM-IV) received ECT as first-line treatment. MRI scans were done before the first ECT and at 2 hours after the second ECT. T(2) relaxation time was measured bilaterally in thalamus, hippocampus, medial temporal lobes and dorsolateral frontal cortex by a blind rater. RESULTS: Depression scores and memory scores were reduced significantly both after the second and fifth ECT. There was no change in T(2) relaxation time after second ECT. CONCLUSION: The finding suggests that ECT does not produce demonstrable change acutely in brain parenchyma detectable by MRI scans" http://www.ncbi.nlm.nih.gov/pubmed/20661386 0 1614 L. N. Milde 1988 The hypoxic mouse model for screening cerebral protective agents: a re-examination Anesth.Analg. 67 10 917-922 "The hypoxic mouse model, in which mice are subjected to an atmosphere of 5% O2 in nitrogen, has been used to screen anesthetics for possible cerebral protection by measuring their ability to prolong survival in mice exposed to hypoxia. Although prolonged survival time in this model is primarily due to a decreased cerebral metabolic rate produced by a specific anesthetic, results can also be influenced by body temperature, dose of anesthetic, and ventilatory or circulatory depression produced by the anesthetic. Using the hypoxic mouse model, the effects of thiopental in conjunction with changes in ambient temperature, changes in thiopental dose, and the presence or absence of nitrous oxide (N2O) were examined. Survival times were measured in eight groups of animals, either untreated animals or animals pretreated with 100 mg/kg thiopental intraperitoneally; exposed to hypoxia in the presence or absence of N2O; at ambient temperatures of either 25 degrees C or 35.5 degrees C. Survival times of seven additional groups of mice, either untreated or treated with doses of 50, 60, 70, 80, 90 or 120 mg/kg thiopental intraperitoneally, exposed to hypoxia in an ambient temperature of 35.5 degrees C were measured to determine a dose-response curve. At an ambient temperature of 35.5 degrees C in which the rectal temperature of both untreated and thiopental-treated animals was maintained near 36 degrees C, thiopental-treated animals did not survive any longer than the untreated animals. Exposure to N2O shortened survival times of both groups by approximately 20%.(ABSTRACT TRUNCATED AT 250 WORDS)" http://www.ncbi.nlm.nih.gov/pubmed/3421494 0 1615 "I. SHIMA, E. Fifkova and J. Bures" 1963 LIMITS OF SPREADING DEPRESSION IN PIGEON STRIATUM J.Comp Neurol. 121 485-492 http://www.ncbi.nlm.nih.gov/pubmed/14100028 0 1616 "J. S. Lindholm, H. Autio, L. Vesa, H. Antila, L. Lindemann, M. C. Hoener, P. Skolnick, T. Rantamaki and E. Castren" 2012 The antidepressant-like effects of glutamatergic drugs ketamine and AMPA receptor potentiator LY 451646 are preserved in bdnf(+)/(-) heterozygous null mice Neuropharmacology 62 1 391-397 "Accumulating evidence suggests that biogenic amine-based antidepressants act, at least in part, via regulation of brain-derived neurotrophic factor (BDNF) signaling. Biogenic amine-based antidepressants increase BDNF synthesis and activate its signaling pathway through TrkB receptors. Moreover, the antidepressant-like effects of these molecules are abolished in BDNF deficient mice. Glutamate-based drugs, including the NMDA antagonist ketamine, and the AMPA receptor potentiator LY 451646, mimic the effects of antidepressants in preclinical tests with high predictive validity. In humans, a single intravenous dose of ketamine produces an antidepressant effect that is rapid, robust and persistent. In this study, we examined the role of BDNF in expression of the antidepressant-like effects of ketamine and an AMPA receptor potentiator (LY 451646) in the forced swim test (FST). Ketamine and LY 451646 produced antidepressant-like effects in the FST in mice at 45 min after a single injection, but no effects were observed one week after a single ketamine injection. As previously reported, the effects of imipramine in the forced swim test were blunted in heterozygous BDNF knockout (bdnf(+/-)) mice. However ketamine and LY 451646 produced similar antidepressant-like responses in wildtype and bdnf(+/-) mice. Neither ketamine nor LY 451646 significantly influenced the levels BDNF or TrkB phosphorylation in the hippocampus when assessed at 45 min or 7 days after the drug administration. These data demonstrate that under the conditions tested, neither ketamine nor the AMPA-potentiator LY 451656 activate BDNF signaling, but produce a characteristic antidepressant-like response in heterozygous bdnf(+/-) mice. These data indicate that unlike biogenic amine-based agents, BDNF signaling does not play a pivotal role in the antidepressant effects of glutamate-based compounds. This article is part of a Special Issue entitled 'Anxiety and Depression'" http://www.ncbi.nlm.nih.gov/pubmed/21867718 0 1617 "V. Grosso, N. F. De, S. Breda, S. Monti, M. Todoerti, R. Caporali and C. Montecucco" 2015 Anxiety and depression in patients with rheumatoid arthritis treated with biological drugs: Prevalence and relationship with disease activity "Annals of the Rheumatic Diseases.Conference: Annual European Congress of Rheumatology of the European League Against Rheumatism, EULAR 2015 Rome Italy.Conference Start: 20150610 Conference End: 20150613.Conference Publication: (var.pagings).74 ()(pp 1" var.pagings 1027 "Background: Many patients with rheumatoid arthritis (RA) experience anxiety and depression, with higher presence of these disorders in those with poorer outcome [1]. Previous experiences found relationships with psychological status and disease activity in patients with active disease [2,3]. Further evidences are needed to asses the impact on residual RA activity during treatment. Objectives: To register the prevalence of anxious (ANX) and depressive (DEP) disorders in RA patients treated with bDMARDs with stable disease and therapy and to evaluate their connection with disease activity. Methods: We assessed the presence of ANX and DEP disorders with the HADS questionnaire [4] in patients with RA treated according the EULAR 2013 recommendations with bDMARDs [5].We registered disease activity using DAS28 score during the same day of questionnaire compiling. Patients with major changes in their DMARD therapy during the previous six months, with known diagnosis of anxiety-depressive syndrome, fibromyalgia, or treated with antidepressant drugs were excluded. The variables of interest were compared between groups with Kruskall-Wallis test. Results: We assessed 200 patients, female 171 (85%), with an overall median (IQR) age and disease duration of 62,35 (54,09 - 76,03) years and 11,24 (7,29 - 19,46) years respectively. At least one ANX or DEP disorder was present in 93 (46.5%) patients. In patients with ANX, DEP and with ANX*DEP disorders values of pain VAS, DAS28, GH, PGA, number of painful joints on 28 (TND28), HAQ were higher than those in HEALTY group (p<0,01). Prednisone dosage was higher among patients with ANX or DEP disorders. Number of swollen joints on 28 (SWJ28) CRP and ESR were not different among groups. There was a moderate correlation between HADS scores and DAS28, pain VAS, PGA, GH and TND28. Conclusions: There is a high prevalence of ANX and DEP disorders in patients with RA. Patients with those disorders have higher level of residual disease based on higher subjective variables, while objective variables (SWJ28 and laboratory indexes) remain unmodified. The higher steroid doses in patients with ANX or DEP are probably due to higher disease activity measured with DAS28. (Table Presented)" DO - http://dx.doi.org/10.1136/annrheumdis-2015-eular.3290 0 1618 "Y. Kim, H. Y. Cho, Y. J. Ahn, J. Kim and Y. W. Yoon" 2012 Effect of NMDA NR2B antagonist on neuropathic pain in two spinal cord injury models Pain 153 5 1022-1029 "N-Methyl-d-aspartate (NMDA) receptors are thought to play an important role in the processes of central sensitization and pathogenesis of neuropathic pain, particularly after spinal cord injury (SCI). NMDA antagonists effectively reduce neuropathic pain, but serious side effects prevent their use as therapeutic drugs. NMDA NR2B antagonists have been reported to effectively reduce inflammatory and neuropathic pain. In this study, we investigated the effects of NR2B antagonists on neuropathic pain and the expression of NR2B in the spinal cord in 2 SCI models. SCI was induced at T12 by a New York University impactor (contusion) or by sectioning of the lateral half of the spinal cord (hemisection). Ifenprodil (100, 200, 500, 1000nmol) and Ro25-6981 (20, 50, 100, 200nmol) were intrathecally injected and behavioral tests were conducted. Ifenprodil increased the paw withdrawal threshold in both models but also produced mild motor depression at higher doses. Ro25-6981 increased the mechanical nociceptive threshold in a dose-dependent manner without motor depression. NR2B expression was significantly increased on both sides at the spinal segments of L1-2 and L4-5 in the hemisection model but did not change in the contusion model. Increased expression of NR2B in the hemisection model was reduced by intrathecal ifenprodil. These results suggest that intrathecal NMDA NR2B antagonist increased the mechanical nociceptive threshold after SCI without motor depression. A selective subtype of NMDA receptor, such as NR2B, may be a more selective target for pain control because NMDA receptors play a crucial role in the development and maintenance of chronic pain" http://www.ncbi.nlm.nih.gov/pubmed/22424878 0 1619 "C. M. Teaf, R. D. Harbison and J. B. Bishop" 1985 Germ-cell mutagenesis and GSH depression in reproductive tissue of the F-344 rat induced by ethyl methanesulfonate Mutat.Res. 144 2 93-98 "Sensitivity of male F-344 rats to the dominant lethal (DL) mutagenic effect of ethyl methanesulfonate (EMS) was studied in conjunction with an evaluation of EMS-induced depression of glutathione (GSH) in testis, epididymis and vas deferens. At the maximal effect, during week 3 (days 15-19 post-EMS), a dosage of 50 mg/kg caused 13.3% fetal death (FD) vs. 3.3% in controls, while 100 mg/kg caused 56.6% FD in the same interval. EMS maximally depressed GSH to 33%, 54% and 77% of control in vas, epididymis and testis respectively. The slope of the DL dose-response curve for EMS in rats shows a 3-4-fold greater sensitivity than that reported for mice. The steepness of this curve suggests that small perturbations in endogenous protective mechanisms, such as GSH depression, may exert a greater proportional effect on germ-cell mutagenesis in rats which should be more readily observable than in mice. EMS and other electrophilic toxicants may thus influence their own primary reproductive toxicity and/or that of other agents by depression of GSH in male reproductive tissue" http://www.ncbi.nlm.nih.gov/pubmed/4047076 0 1620 E. X. Albuquerque and W. Grampp 1968 Effects of tetrodotoxin on the slowly adapting stretch receptor neurone of lobster J.Physiol 195 1 141-156 "1. A study has been made of the effects of tetrodotoxin on the impulse activity, resting membrane potential, input resistance, and the generator potential and its after-hyperpolarization of the slowly adapting stretch receptor neurone of the lobster.2. Tetrodotoxin was able to abolish completely within about 2 min the impulse activity in most cells, when given in a dose of 2 x 10(-8) g/ml., but in all cells, when administered in a dose of 4 x 10(-8) g/ml. After blockage by the toxin in concentrations as high as 4 x 10(-6) g/ml. for periods of up to 30 min the action potential was restored by washing the preparation in physiological solution for 1 hr.3. In a concentration of 4 x 10(-8) g/ml. tetrodotoxin produced within 1-2 min an average increase of 4.8 mV of the resting membrane potential and a simultaneous 47% reduction of the resting input resistance. These effects were reversed by washing the preparation in physiological solution for 1 hr.4. Tetrodotoxin administered in doses as high as 4 x 10(-6) g/ml. for periods of up to 30 min had no effect on the amplitude of the steady phase of the generator potential.5. In a concentration of 4 x 10(-8) g/ml. tetrodotoxin produced within 5 min a 65% reduction of the amplitude of the hyperpolarization following the generator potential. This effect was reversed by washing the preparation in physiological solution for 1 hr.6. The simultaneous increase in resting membrane potential and decrease in membrane resistance is suggested to be due to an elevated potassium permeability besides a reduced sodium conductance. The constancy in height of the generator potential in the presence of a decreased membrane resistance makes necessary the assumption of an augmented generator current. The decrease in amplitude of the hyperpolarization following the generator potential may be the result of an increase in potassium conductance and/or a reduction in acceleration of an electrogenic pump in consequence of a diminished sodium influx during the generator potential" http://www.ncbi.nlm.nih.gov/pubmed/5639797 0 1621 M. M. Shehata 1980 Interaction of diphenylhydantoin and some oral hypoglycemic drugs related to carbohydrate metabolism in rats Pol.J.Pharmacol.Pharm. 32 1 Nov-14 "Daily treatment of rats with 50 or 100 mg/kg ip of diphenylhydantoin (DPH) for 3 weeks caused a significant elevation of blood glucose level and reduction of hepatic glycogen content. In rats receiving daily oral doses of tolbutamide (100 mg/kg) or phenformin (50 mg/kg) for the last 7 days of DPH treatment, the blood glucose level did not differ from those in the control group; in rats receiving the low doses of DHP, the reduction in hepatic glycogen content was prevented by either hypoglycemic drug; in rats receiving the high dose of DPH in combination with the hypoglycemics the glycogen reduction was smaller than in rats receiving DPH alone. A week's treatment with tolbutamide (100 mg/kg) alone resulted in a significant depression of the blood glucose level and elevation of hepatic glycogen content; phenformin (50 mg/kg) given alone for one week elevated the level of hepatic glycogen, but to a lesser degree than tolbutamide did, and did not affect the blood glucose level" http://www.ncbi.nlm.nih.gov/pubmed/7454606 0 1622 "A. Balazs, J. Mann, L. Takacsi-Nagy, I. Zimonyi, A. Molnar and T. Klupp" 1983 In vitro proliferation of normal and leukaemic human leukocytes controlled by an inhibitory endopeptide Folia Haematol.Int.Mag.Klin.Morphol.Blutforsch. 110 1 24-31 "GI-3, an endogenous inhibitory fraction isolated from leukocytes, selectively inhibits the proliferation of granuloid precursor cells in a non-toxic manner. Its active principle was determined as an acidic chlor-tolidine positive decapeptide [ 3 ]. The in vitro effect on normal and acute leukaemic human bone marrow and blood cells was examined. A dose dependent inhibition by GI-3 of 3H-TdR incorporation into myeloid cells of normal bone marrow was found, the sensitivity of human cells being higher than that of rat cells. The proliferation of the target leukaemic bone marrow and blood cells (AML, AMMoL) was also decreased by the endogenous inhibitor in a dose dependent manner in untreated subjects as well as in patients in remission or relapse. The rate of inhibition of leukaemic of well-known cytostatics (adriamycin hydrochloride, dianhydrogalactitol) applied for comparison. Beyond its direct cytostatic effect, GI-3 could be used in the differential diagnosis of blastic leukaemias, complementing the routine cytochemical methods" http://www.ncbi.nlm.nih.gov/pubmed/6192050 0 1623 Y. Kobayashi and H. Kizuka 1973 Contribution of rat brain monoamine oxidase (MAO) circulating MAO levels "Federation Proceedings.32 (3) ()(pp I), 1973.Date of Publication: 1973." 3 I 0 1624 F. Limosin 2002 Clinical and biological specificities of female alcoholism "Encephale.28 (6 I) ()(pp 503-509), 2002.Date of Publication: November/December 2002." 6 I 503-509 "Even though the number of alcohol-dependent women is only about 1/3 of the number of alcoholic men, the alcoholism in women, by its clinical features and its course, is the source of therapeutic and economic stakes, particularly in young women among whom an increase of alcohol consumption related problems is reported. Another specificity of the female alcoholism is the lack of care seeking, whereas women have tendency globally to solicit more often care structures than men. Women represent only 1/4 of the overall treated alcoholic patients. The main explanation for this phenomenon is the pejorative social and moral connotation of the female alcoholism, with frequent feelings of shame and deep guilt, that also account for the frequency of hidden and lonely alcohol intakes. The female alcoholism is essentially characterized by an increased vulnerability to the toxic effects of the alcohol, whereas the pathological consumption starts later and with smaller daily amounts. Most studies have revealed a higher vulnerability in women to somatic complications directly attributable to the alcohol organs toxicity, such as hepatic cirrhosis and cardiovascular complications (high blood pressure, non obstructive cardiomyopathy). The reported brain morphological abnormalities could also occur more precociously in alcoholic women than in men. A decreased corpus callosum size among alcoholic women, but not in alcoholic men, was thus found in a recent study, compared with healthy controls. Among the different hypothesis proposed to explain this increased alcohol toxicity, the most incriminated is higher alcohol blood rates for the same ingested amount, mainly of the fact of a lower size with a weaker proportion of the bodily total water, but also of weaker concentrations of gastro-intestinal tract ADH, or of a longer metabolism during some menstrual phases. Indeed, some experimental studies on animal showed that the alcohol toxic effects may occur only from a threshold of alcohol blood rate. More recent studies suggest that the explanation to keep is more related to the lower gastric metabolism in women (lower ADH activity), than the difference of gastric volume or alcohol hepatic oxidation. Regarding to comorbidity, in the Epidemiologic Catchment Area survey, 65 % of women, versus 44 % of men, with abuse and/or dependence to alcohol had at least one another life - time psychiatric disorder (mainly depression and anxiety disorders), compared to 36 % of the overall women of the studied sample. On the other hand, the alcoholdependence is, more often than in men, secondary to other psychiatric disorders, essentially depressive episodes, but less associated to antisocial behaviours. Among the different etiopathogenic factors involved in the alcoholdependence occurrence, genetic factors seem to have a determinant impact. According to the previous family, separation/adoption and twins studies performed, genetic factors could explain 50 to 60 % of the alcoholism vulnerability in both men and women. In this context, and whereas we assist to the development of etiopathogenic models with new therapeutic perspectives in alcoholdependence, it seems necessary not to neglect female alcoholism specificities" 0 1625 "A. Der-Avakian, M. S. Mazei-Robison, J. P. Kesby, E. J. Nestler and A. Markou" 2014 "Enduring deficits in brain reward function after chronic social defeat in rats: susceptibility, resilience, and antidepressant response" Biol.Psychiatry 76 7 542-549 "BACKGROUND: Anhedonia, or diminished interest or pleasure in rewarding activities, characterizes depression and reflects deficits in brain reward circuitries. Social stress induces anhedonia and increases risk of depression, although the effect of social stress on brain reward function is incompletely understood. METHODS: This study assessed the following: 1) brain reward function in rats (using the intracranial self-stimulation procedure) and protein levels of brain-derived neurotrophic factor and related signaling molecules in response to chronic social defeat, 2) brain reward function during social defeat and long-term treatment with the antidepressants fluoxetine (5 mg/kg/day) and desipramine (10 mg/kg/day), and 3) forced swim test behavior after social defeat and fluoxetine treatment. RESULTS: Social defeat profoundly and persistently decreased brain reward function, reflecting an enduring anhedonic response, in susceptible rats, whereas resilient rats showed no long-term brain reward deficits. In the ventral tegmental area, social defeat, regardless of susceptibility or resilience, decreased brain-derived neurotrophic factor and increased phosphorylated AKT, whereas only susceptibility was associated with increased phosphorylated mammalian target of rapamycin. Fluoxetine and desipramine reversed lower, but not higher, stress-induced brain reward deficits in susceptible rats. Fluoxetine decreased immobility in the forced swim test, as did social defeat. CONCLUSIONS: These results suggest that the differential persistent anhedonic response to psychosocial stress may be mediated by ventral tegmental area signaling molecules independent of brain-derived neurotrophic factor and indicate that greater stress-induced anhedonia is associated with resistance to antidepressant treatment. Consideration of these behavioral and neurobiological factors associated with resistance to stress and antidepressant action may promote the discovery of novel targets to treat stress-related mood disorders" http://www.ncbi.nlm.nih.gov/pubmed/24576687 1 1626 J. C. Gilbert and M. G. Wyllie 1975 Effects of prostaglandins on the ATPase activities of synaptosomes Biochem.Pharmacol. 24 4 551-556 http://www.ncbi.nlm.nih.gov/pubmed/122896 0 1627 N. A. Shevchuk 2008 Adapted cold shower as a potential treatment for depression "Medical Hypotheses.70 (5) ()(pp 995-1001), 2008.Date of Publication: 2008." 5 995-1001 "Depression is a debilitating mood disorder that is among the top causes of disability worldwide. It can be characterized by a set of somatic, emotional, and behavioral symptoms, one of which is a high risk of suicide. This work presents a hypothesis that depression may be caused by the convergence of two factors: (A) A lifestyle that lacks certain physiological stressors that have been experienced by primates through millions of years of evolution, such as brief changes in body temperature (e.g. cold swim), and this lack of ""thermal exercise"" may cause inadequate functioning of the brain. (B) Genetic makeup that predisposes an individual to be affected by the above condition more seriously than other people. To test the hypothesis, an approach to treating depression is proposed that consists of adapted cold showers (20 degreeC, 2-3 min, preceded by a 5-min gradual adaptation to make the procedure less shocking) performed once or twice daily. The proposed duration of treatment is several weeks to several months. The following evidence appears to support the hypothesis: Exposure to cold is known to activate the sympathetic nervous system and increase the blood level of beta-endorphin and noradrenaline and to increase synaptic release of noradrenaline in the brain as well. Additionally, due to the high density of cold receptors in the skin, a cold shower is expected to send an overwhelming amount of electrical impulses from peripheral nerve endings to the brain, which could result in an anti-depressive effect. Practical testing by a statistically insignificant number of people, who did not have sufficient symptoms to be diagnosed with depression, showed that the cold hydrotherapy can relieve depressive symptoms rather effectively. The therapy was also found to have a significant analgesic effect and it does not appear to have noticeable side effects or cause dependence. In conclusion, wider and more rigorous studies would be needed to test the validity of the hypothesis. © 2007 Elsevier Ltd. All rights reserved" DO - http://dx.doi.org/10.1016/j.mehy.2007.04.052 0 1628 "S. S. Parmar, A. K. Gupta, H. H. Singh and T. K. Gupta" 1972 "Benzimidazolyl-1,2,4(H)-triazoles as central nervous system depressants" J.Med.Chem. 15 9 999-1000 http://www.ncbi.nlm.nih.gov/pubmed/5051021 0 1629 "P. Coy, R. Romar, R. R. Payton, L. McCann, A. M. Saxton and J. L. Edwards" 2005 "Maintenance of meiotic arrest in bovine oocytes using the S-enantiomer of roscovitine: effects on maturation, fertilization and subsequent embryo development in vitro" Reproduction. 129 1 19-26 "The overall objective was to evaluate the effectiveness of the S-enantiomer of roscovitine (inhibitor of p34cdc2/cyclin B kinase) to maintain bovine cumulus-oocyte complexes at the germinal vesicle (GV) stage for extended times after removal from antral follicles without compromising subsequent maturation, fertilization and embryo development. Oocytes were cultured in 0, 12.5, 25 or 50 micromol/l S-roscovitine for 24 h. Hoechst staining showed that 50 micromol/l S-roscovitine maintained >90% of oocytes at the GV stage and inhibited gonadotropin-induced cumulus expansion. Fewer oocytes underwent nuclear maturation after in vitro maturation (Hoechst staining) when cultured in 50 micromol/l S-roscovitine for 66 versus 21 or 42 h. Zona pellucida (ZP) hardening (pronase resistance), cortical granule types (lens culinaris agglutinin-fluorescein isothiocyanate), nuclear maturation and fertilization with frozen-thawed spermatozoa (Hoechst staining) were assessed after culture of oocytes in 50 micromol/l S-roscovitine for 0, 24 or 48 h. Neither ZP hardening, nor nuclear maturation nor fertilization were altered by roscovitine culture for 48 h. A higher proportion of oocytes had a type III cortical granule pattern (premature translocation to the oolemma) after roscovitine culture for 48 h. However, embryo development was not compromised as cleavage, development to 8-16 cell and blastocyst stages were at least comparable in control and roscovitine-treated oocytes. In conclusion, the studies have shown that S-roscovitine reversibly maintained bovine oocytes at the GV stage for 48 h. However, maintenance of oocytes in static culture for 48 h was not sufficient to improve development above non-treated controls" http://www.ncbi.nlm.nih.gov/pubmed/15615895 0 1630 "L. Ding, X. Zhang, H. Guo, J. Yuan, S. Li, W. Hu, T. Golden and N. Wu" 2015 The Functional Study of a Chinese Herbal Compounded Antidepressant Medicine--Jie Yu Chu Fan Capsule on Chronic Unpredictable Mild Stress Mouse Model PLoS.One. 10 7 e0133405 "Jie Yu Chu Fan capsule (JYCF) is a new compounded Chinese herbal medicine for the treatment of depression. The present study was designed to explore the antidepressant effects and the possible mechanisms of JYCF by using chronic unpredictable mild stress (CUMS) mouse model and comparing results to that of fluoxetine. Behavioral tests including an open field test, sucrose preference test and forced swim test were performed to evaluate the antidepressant effects of JYCF. The concentrations of monoamine neurotransmitters and metabolic products including norepinephrine (NE), 5-hydroxytryptamine (5-HT), dopamine (DA), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the cerebral cortex and hippocampus of mice were determined by means of high performance liquid chromatography with electrochemical detection (HPLC-EC). The results show that a successful mouse CUMS model was established through 5 weeks of continuous unpredictable stimulation, as indicated by the significant decrease in sucrose preference and locomotor activity and increase in immobility time in the forced swim test. Chronic treatment of JYCF (1.25, 2.5 and 5 g/kg) and fluoxetine (20 mg/kg) significantly reversed the CUMS-induced behavioral abnormalities. JYCF (1.25, 2.5 and 5 g/kg) significantly increased NE in CUMS mouse prefrontal cortex (P < 0.01, P < 0.01, P < 0.05 respectively) and 5-HT in hippocampus (P < 0.05). In summary, our findings suggest that JYCF exerts comparable antidepressant-like effects to that of fluoxetine in CUMS mice. Besides, the antidepressant-like effect of JYCF is mediated by the increase of monoaminergic transmitters including 5-HT and NE" http://www.ncbi.nlm.nih.gov/pubmed/26186537 0 1631 "W. C. Mustain, P. G. Rychahou and B. M. Evers" 2011 The role of neurotensin in physiologic and pathologic processes "Current Opinion in Endocrinology, Diabetes and Obesity.18 (1) ()(pp 75-82), 2011.Date of Publication: February 2011." 1 75-82 "Purpose of Review: Neurotensin is a 13-amino acid peptide found in the central nervous system central nervous system and the gastrointestinal tract. Since its initial discovery in 1973, neurotensin has been shown to play a role in a wide range of physiologic and pathologic processes throughout the body. Ongoing research efforts continue to clarify the role of neurotensin in various central nervous system and gastrointestinal processes, as well as how disruption of these normal mechanisms may lead to diseases ranging from schizophrenia to colorectal cancer. The goal of this review is to provide an overview of the most recent advances in the field of neurotensin research, in the context of what has been previously published. Recent Findings: Because of the seemingly unrelated functions of neurotensin in the central nervous system and the periphery, the scope of the articles reviewed is rather broad. Contributions continue to be made to our understanding of the downstream effects of neurotensin signaling and the complex feedback loops between neurotensin and other signaling molecules. By selective targeting or blockade of specific neurotensin receptors, investigators have identified potential drugs for use in the treatment of schizophrenia, alcoholism, chronic pain, or cancer. Neurotensin-based pharmacologic agents are being used successfully in animal models for a number of these conditions. Summary: The review highlights the wide array of biological processes in which neurotensin has a role, and summarizes the most recent advances in various fields of neurotensin research. The knowledge gained through this research has led to the development of first-in-class drugs for the treatment of various medical conditions, and it is clear that in the coming years some of these agents will be ready to move from the bench to the bedside in clinical trials. © 2011 Wolters Kluwer Health Lippincott Williams & Wilkins" DO - http://dx.doi.org/10.1097/MED.0b013e3283419052 0 1632 I. Panocka and M. Massi 1992 Long-lasting suppression of alcohol preference in rats following serotonin receptor blockade by ritanserin Brain Res.Bull. 28 3 493-496 "Rats with developed preference for 3% ethanol were injected subcutaneously (SC) with 10 mg/kg of the 5HT2 antagonist ritanserin for 9 days. This resulted in a marked and significant suppression of alcohol preference, as compared to controls. The effect was very long-lasting, as shown by the fact that it was still evident up to 20 days after the end of the treatment. Since ritanserin shows some affinity also for D2-dopaminergic receptors (even though much lower than for 5HT2 receptors), for comparison, other rats were injected SC for 9 days with 0.0625 mg/kg of haloperidol or with its vehicle. The effect of haloperidol treatment was low and short-lasting. Depletion of endogenous serotonin by p-chlorophenylalanine (600 mg/kg x 3 days) completely abolished the suppression of alcohol preference by ritanserin. These results suggest that: 1) the ritanserin-induced reduction of alcohol preference is not due to dopaminergic blockade, 2) that the effect of ritanserin is completely dependent on the endogenous serotoninergic mechanisms" http://www.ncbi.nlm.nih.gov/pubmed/1534269 0 1633 O. Sato 1971 [Studies on cerebral circulation with intracerebral rheography] Nihon Geka Hokan 40 1 45-79 http://www.ncbi.nlm.nih.gov/pubmed/5106425 0 1634 "K. A. Baranova, E. A. Rybnikova, V. I. Mironova and M. O. Samoilov" 2009 "[The hypoxic preconditioning effect upon expression of the NGFI-A transcription factor in the rat brain following an unavoidable stess in the ""learned helpnessness"" model]" Ross.Fiziol.Zh.Im I.M.Sechenova 95 4 405-416 "In this study, by an immunocytochemistry it is established that development of the depression after an inescapable stress in the learned helplessness model in rats is associated with stable induction of the transcription factor NGFI-A in the dorsal hippocampus (CA1 field) and in the paraventricular hypothalamic magnocellular nucleus (PVNm), as well as with rapid and transient stress-induced expression of NGFI-A in the dentate gyrus and, supported on high level till 5 days, in the neocortex. Hypoxic preconditioning using mild repetitive hypobaric hypoxia (360 Torr for 2 hrs each of 3 days) prevented development of the depressive state in rats, and considerably changed the dynamics of the NGFI-A immunoreactivity in the hippocampus: the stable increase of an expression in the dentate gyrus and only transitory and delayed (for 5 day) in the CA1 field was detected. In the neocortex (Layer II) the stress influence was levelled with preconditioning by preventing the prolongation of the first wave of expression NGFI-A untill 5 days, and in PVNm, on the contrary, was stimulated the second (delayed) wave of an expression of this transcription factor. The pattern of NGFI-A expression in the hippocampus, neocortex and hypothalamus of preconditioned rats revealed an obvious pathological response to aversive stress, which results in development of depressive frustration rather than the adaptation. Stress-induced modifications of early gene product NGFI-A expression in the brain caused by hypoxic preconditioning, possibly, play important role in tolerance to hard psychoemotional stresses and may be an important part of antidepressive mechanisms" http://www.ncbi.nlm.nih.gov/pubmed/19505043 1 1635 K. M. Gill and A. A. Grace 2011 Heterogeneous processing of amygdala and hippocampal inputs in the rostral and caudal subregions of the nucleus accumbens Int.J.Neuropsychopharmacol. 14 10 1301-1314 "The nucleus accumbens (NAc) receives converging input from a number of structures proposed to play a role in affective disorders. In particular, the basolateral amygdala (BLA) provides an affective input that overlaps with context-related information derived from the ventral subiculum of the hippocampus (vSub). We examined how stimulation of the BLA is modulated by, and in turn affects, vSub inputs to this region. In-vivo extracellular recordings were performed in the NAc of anaesthetized rats. The effect of high-frequency (theta-burst) stimulation (HFS) of the BLA on both BLA and vSub-evoked responses was tested. In addition, the involvement of dopamine D2 receptors in BLA-induced plasticity in the NAc was examined by pre-treatment with sulpiride (5 mg/kg i.v.). Finally, tetrodotoxin (TTX) was used to inactivate the vSub and the effect on BLA-evoked responses was assessed. We found that HFS of the BLA causes hetereogeneous patterns of plasticity, depression and potentiation, respectively, in the rostral and caudal subregions of the NAc that are disrupted following D2 receptor antagonist treatment. In addition, inactivating the vSub with TTX attenuates the ability of the BLA to drive spike firing in the NAc. Thus, the vSub is required for activation of the NAc by the BLA. These data support a model whereby the amygdala can coordinate reward-seeking and fear-related behaviours via its differential regulation of NAc output. In addition, the hippocampus inappropriately dominates information processing within this circuit, potentially contributing to the overwhelming focus on internal emotional states in disorders such as depression" http://www.ncbi.nlm.nih.gov/pubmed/21211108 0 1636 "Y. Wang, N. Serradell and J. Bolos" 2007 Lorcaserin hydrochloride 5-HT2C receptor agonist antiobesity drug "Drugs of the Future.32 (9) ()(pp 766-770), 2007.Date of Publication: September 2007." 9 766-770 "Obesity affects millions of people worldwide and the socio-economic cost of the condition is substantial. Despite lifestyle changes, pharmacotherapy is needed for the treatment of obesity. Lorcaserin is a highly selective 5-HT 2C receptor agonist developed for the treatment of obesity. In rats, lorcaserin led to dose-dependent weight loss. Lorcaserin proved safe and well tolerated in healthy volunteers and obese patients. In a phase II clinical study, patients administered 20 mg/day lorcaserin achieved an average weight loss of 3.6 kg (7.9 lbs), which was significantly greater than the average weight loss of 0.3 kg (0.7 lbs) in the placebo group. A phase III clinical trial is ongoing to evaluate the long-term safety and efficacy of lorcaserin in patients with obesity. Copyright © 2007 Prous Science" DO - http://dx.doi.org/10.1358/dof.2007.032.09.1135518 0 1637 "D. J. Leddin, M. Ray, P. K. Dinda, I. Prokopiw and I. T. Beck" 1988 "16,16-Dimethyl prostaglandin E2 alleviates jejunal microvascular effects of ethanol but not the ethanol-induced inhibition of water, sodium, and glucose absorption" Gastroenterology 94 3 726-732 "To examine the relation between ethanol-induced microvascular and absorptive changes, we have investigated the effect of 16,16-dimethyl prostaglandin E2 on the jejunal intraluminal plasma albumin loss (which was taken as a measure of microvascular changes) and the inhibition of water, sodium, and glucose transport caused by intraluminal ethanol. A group of 8 dogs received intravenously 16,16-dimethyl prostaglandin E2 at a dose of 0.1 microgram/kg as a bolus followed by 0.05 microgram/kg.hour for 2 h (prostaglandin-treated group). A second group of 8 dogs received no 16,16-dimethyl prostaglandin E2 (untreated group). In each dog of both groups, one jejunal segment was perfused with an ethanol-free solution (control segment) and an adjacent segment was perfused with the same solution containing 6% (wt/vol) ethanol (ethanol-perfused segment). The albumin loss (mg/g dry gut wt.90 min, mean +/- SE) by the control and the ethanol-perfused segments was 0.76 +/- 0.23 and 8.29 +/- 1.27, respectively, in the untreated group, and 0.66 +/- 0.23 and 4.81 +/- 0.67, respectively, in the prostaglandin-treated group. The ethanol-induced increase in albumin loss was significant in both groups, but was significantly lower (p less than 0.05) in the prostaglandin-treated group than in the untreated group. Intraluminal ethanol depressed net water, sodium, and glucose transport by 74%, 52%, and 22%, respectively, in the untreated group, and by 92%, 65%, and 38%, respectively, in the prostaglandin-treated group. The magnitude of this depression did not differ significantly between the two groups. As 16,16-dimethyl prostaglandin E2 attenuated the ethanol-induced plasma albumin loss, but not the inhibition of water, sodium, or glucose transport, we conclude that the microvascular and the absorptive changes produced by ethanol are not mediated by the same mechanism" http://www.ncbi.nlm.nih.gov/pubmed/3338641 0 1638 "P. Cherin, C. Rose, C. De Roux-Serratrice, D. Tardy, D. Dobbelaere, B. Grosbois, E. Hachulla, R. Jaussaud, R.-M. Javier, E. Noel, P. Clerson and A. Hartmann" 2010 The neurological manifestations of Gaucher disease type 1: The French Observatoire on Gaucher disease (FROG) Journal of Inherited Metabolic Disease 33 4 August "Background: Gaucher disease (GD), the most prevalent inherited lysosomal storage disorder, is caused by deficient glucocerebrosidase activity. Type 1 GD (GD1), the most common variant, is classically considered non-neuronopathic. Methods: We performed a national cross-sectional observational survey-the French Observatoire on Gaucher Disease (FROG)-in patients with GD1 between March 2005 and September 2006. The study included all patients over 18 years of age with confirmed GD1 who attended participating centers for regular follow-up. Results: One hundred and five patients were included, in whom we studied the prevalence and characteristics of relevant neurological symptoms associated with the neuraxis. Of these, 51 (49%) GD1 patients presented at least one neurological symptom. Four patients (4%) had Parkinson disease and 22 (21%) presented with at least one parkinsonian sign or at least one sign frequently associated with Parkinson disease. Five patients (5%) had a previous diagnosis of peripheral neuropathy. Other central nervous system symptoms were recorded in 20 (19%) patients and other peripheral nervous system symptoms in 39 (37%) patients. Conclusions: These data challenge the current classification of GD, and suggest that the three forms of GD each involve a different profile of neurological manifestations. © 2010 SSIEM and Springer" 0 1639 "A. J. Van der Zijpp, T. R. Scott, B. Glick and M. B. Kreukniet" 1988 Interference with the humoral immune response in diverse genetic lines of chickens. I. The effect of carrageenan Vet.Immunol.Immunopathol. 20 1 53-60 "Two experiments were conducted in which the effect of carrageenan (CGN) on humoral immune response of chicks selected on either high (H) or low (L) antibody production to sheep red blood cells (SRBC) was determined. H and L line chicks were injected i.p. with different doses of CGN prior to immunization with SRBC or Brucella abortus (BA). Four weeks later chicks were reimmunized with the same antigens. In general, control H and L chicks had significantly higher total anti-SRBC titers than CGN-treated chicks in primary response. Also, total anti-BA titers were significantly higher in control chicks than CGN-treated chicks on days 3 and 5 following primary immunization and on days 0 and 7 of the secondary response. Overall, the 2-mercaptoethanol (2ME)-resistant anti-SRBC titers did not differ significantly among the CGN-treated groups. However, control chicks tended to have higher anti-BA 2ME-resistant titers from day 14 p.i. of primary response on. Regardless of antigen or CGN treatment, the H line chicks had significantly higher titers than L line chicks. However, the CGN treatments did not affect the antibody response to BA nor to SRBC differently between L and H line chicks. It would appear that since CGN is cytotoxic for macrophages, selection for antibody production did not result in different abilities of the macrophages of these chicken lines to respond to an antigenic challenge" http://www.ncbi.nlm.nih.gov/pubmed/3149069 0 1640 "O. M. Jeong, M. C. Kim, M. J. Kim, H. M. Kang, H. R. Kim, Y. J. Kim, S. J. Joh, J. H. Kwon and Y. J. Lee" 2009 "Experimental infection of chickens, ducks and quails with the highly pathogenic H5N1 avian influenza virus" J.Vet.Sci. 10 1 53-60 "Highly pathogenic avian influenza viruses (HPAIV) of the H5N1 subtype have spread since 2003 in poultry and wild birds in Asia, Europe and Africa. In Korea, the highly pathogenic H5N1 avian influenza outbreaks took place in 2003/2004, 2006/2007 and 2008. As the 2006/2007 isolates differ phylogenetically from the 2003/2004 isolates, we assessed the clinical responses of chickens, ducks and quails to intranasal inoculation of the 2006/2007 index case virus, A/chicken/Korea/IS/06. All the chickens and quails died on 3 days and 3-6 days post-inoculation (DPI), respectively, whilst the ducks only showed signs of mild depression. The uninoculated chickens and quails placed soon after with the inoculated flock died on 5.3 and 7.5 DPI, respectively. Both oropharyngeal and cloacal swabs were taken for all three species during various time intervals after inoculation. It was found that oropharyngeal swabs showed higher viral titers than in cloacal swabs applicable to all three avian species. The chickens and quails shed the virus until they died (up to 3 to 6 days after inoculation, respectively) whilst the ducks shed the virus on 2-4 DPI. The postmortem tissues collected from the chickens and quails on day 3 and days 4-5 and from clinically normal ducks that were euthanized on day 4 contained the virus. However, the ducks had significantly lower viral titers than the chickens or quails. Thus, the three avian species varied significantly in their clinical signs, mortality, tissue virus titers, and duration of virus shedding. Our observations suggest that duck and quail farms should be monitored particularly closely for the presence of HPAIV so that further virus transmission to other avian or mammalian hosts can be prevented" http://www.ncbi.nlm.nih.gov/pubmed/19255524 0 1641 "J. E. Coelho, P. Alves, P. M. Canas, J. S. Valadas, T. Shmidt, V. L. Batalha, D. G. Ferreira, J. A. Ribeiro, M. Bader, R. A. Cunha, F. S. do Couto and L. V. Lopes" 2014 "Overexpression of Adenosine A2A Receptors in Rats: Effects on Depression, Locomotion, and Anxiety" Front Psychiatry 5 67 "Adenosine A2A receptors (A2AR) are a sub-type of receptors enriched in basal ganglia, activated by the neuromodulator adenosine, which interact with dopamine D2 receptors. Although this reciprocal antagonistic interaction is well-established in motor function, the outcome in dopamine-related behaviors remains uncertain, in particular in depression and anxiety. We have demonstrated an upsurge of A2AR associated to aging and chronic stress. Furthermore, Alzheimer's disease patients present A2AR accumulation in cortical areas together with depressive signs. We now tested the impact of overexpressing A2AR in forebrain neurons on dopamine-related behavior, namely depression. Adult male rats overexpressing human A2AR under the control of CaMKII promoter [Tg(CaMKII-hA2AR)] and aged-matched wild-types (WT) of the same strain (Sprague-Dawley) were studied. The forced swimming test (FST), sucrose preference test (SPT), and the open-field test (OFT) were performed to evaluate behavioral despair, anhedonia, locomotion, and anxiety. Tg(CaMKII-hA2AR) animals spent more time floating and less time swimming in the FST and presented a decreased sucrose preference at 48 h in the SPT. They also covered higher distances in the OFT and spent more time in the central zone than the WT. The results indicate that Tg(CaMKII-hA2AR) rats exhibit depressive-like behavior, hyperlocomotion, and altered exploratory behavior. This A2AR overexpression may explain the depressive signs found in aging, chronic stress, and Alzheimer's disease" http://www.ncbi.nlm.nih.gov/pubmed/24982640 1 1642 "R. S. Sohal, R. G. Allen, K. J. Farmer, R. K. Newton and P. L. Toy" 1985 "Effects of exogenous antioxidants on the levels of endogenous antioxidants, lipid-soluble fluorescent material and life span in the housefly, Musca domestica" Mech.Ageing Dev. 31 3 329-336 "Effects of exogenous antioxidant administration (0.5% and 2% ascorbate, beta-carotene and alpha-tocopherol in sucrose) on life-span, metabolic rate, activities of superoxide dismutase and catalase, levels of glutathione, inorganic peroxides and chloroform-soluble fluorescent material (lipofuscin) were examined in adult male houseflies. Administration of antioxidants at a level of 0.5% did not affect life-span, whereas, 2% ascorbate and alpha-tocopherol decreased average life-span. Metabolic rate of flies was unaffected, except by 2% ascorbate, which caused a decrease. Superoxide dismutase activity was depressed by 2% ascorbate at all ages, and by beta-carotene and alpha-tocopherol in older flies. Catalase activity was unaffected except by alpha-tocopherol at younger ages. Glutathione concentration was decreased by ascorbate and beta-carotene at both concentrations administered. Inorganic peroxides (H2O2) were increased by 2% beta-carotene and alpha-tocopherol. Only high concentrations of ascorbate and beta-carotene decreased the level of soluble fluorescent material. Results suggest that administration of exogenous antioxidants causes a compensatory depression of endogenous defenses" http://www.ncbi.nlm.nih.gov/pubmed/4068768 0 1643 "A. M. Pereira, F. Baccari, Jr., E. A. Titto and J. A. Almeida" 2008 "Effect of thermal stress on physiological parameters, feed intake and plasma thyroid hormones concentration in Alentejana, Mertolenga, Frisian and Limousine cattle breeds" Int.J.Biometeorol. 52 3 199-208 "The aim of the present study was to assess the heat tolerance of animals of two Portuguese (Alentejana and Mertolenga) and two exotic (Frisian and Limousine) cattle breeds, through the monitoring of physiological acclimatization reactions in different thermal situations characterized by alternate periods of thermoneutrality and heat stress simulated in climatic chambers. In the experiment, six heifers of the Alentejana, Frisian and Mertolenga breeds and four heifers of the Limousine breed were used. The increase in chamber temperatures had different consequences on the animals of each breed. When submitted to heat stress, the Frisian animals developed high thermal polypnea (more than 105 breath movements per minute), which did not prevent an increase in the rectal temperature (from 38.7 degrees C to 40.0 degrees C). However, only a slight depression in food intake and in blood thyroid hormone concentrations was observed under thermal stressful conditions. Under the thermal stressful conditions, Limousine animals decreased food intake by 11.4% and blood triiodothyronine (T3) hormone concentration decreased to 76% of the level observed in thermoneutral conditions. Alentejana animals had similar reactions. The Mertolenga cattle exhibited the highest capacity for maintaining homeothermy: under heat stressful conditions, the mean thermal polypnea increased twofold, but mean rectal temperature did not increase. Mean food intake decreased by only 2% and mean T3 blood concentration was lowered to 85,6% of the concentration observed under thermoneutral conditions. These results lead to the conclusion that the Frisian animals had more difficulty in tolerating high temperatures, the Limousine and Alentejana ones had an intermediate difficulty, and the Mertolenga animals were by far the most heat tolerant" http://www.ncbi.nlm.nih.gov/pubmed/17578605 0 1644 "A. Lockridge, J. Su and L. L. Yuan" 2010 Abnormal 5-HT modulation of stress behaviors in the Kv4.2 knockout mouse Neuroscience 170 4 1086-1097 "The Kv4.2 gene codes for an essential subunit of voltage-gated A-type potassium channels that are involved in dendritic signal integration and synaptic plasticity. Detailed cellular characterization in CA1 pyramidal neurons of the hippocampus has shown that knocking out the Kv4.2 gene increases neuronal excitability and promotes long-term potentiation. However, the overall behavioral consequences of these modifications have not been fully explored. Given the growing connection between neuronal plasticity and affect processing in the hippocampus and other Kv4.2 expressing regions, we proposed to investigate whether the absence of this gene would alter the stress response of mice to the forced swimming and tail suspension tests (TSTs) for depression-like behavior. Kv4.2 knockout (KO) mice, generated in the 129SvEv background, demonstrated elevated immobility and a loss of swimming, as well as antidepressant resistance to the selective 5-HT reuptake inhibitor fluoxetine (FLX). Characterization of a relatively new head movement behavior category, responsive to serotonergic treatment in wildtype (WT) mice, supported conclusions of abnormal 5-HT modulation. Electrophysiology recordings in the prefrontal cortex showed a blunting of postsynaptic response to direct 5-HT application following a single period of swim stress only in the animals without the Kv4.2 subunit. Based on our findings, we hypothesize that Kv4.2 KO mice may have an exaggerated 5-HT response to stress leading to a premature desensitization of postsynaptic receptors and a loss of continued behavior modulation. These results may shed some light on the involvement of A-type potassium channels in the effective action of selective serotonin reuptake inhibitor (SSRI) antidepressants" http://www.ncbi.nlm.nih.gov/pubmed/20801198 1 1645 A. Kreutzberger and I. Schlafer 1988 "[Central depressive substances. 7. Nuclear substituted (diallylamino)-1,3,5-triazines]" Arch.Pharm.(Weinheim) 321 11 827-830 http://www.ncbi.nlm.nih.gov/pubmed/3219052 0 1646 "T. Komori, M. Yamamoto, T. Matsumoto, K. Zhang and Y. Okazaki" 2002 Effects of imipramine on T cell subsets in olfactory bulbectomized mice Neuropsychobiology 46 4 194-196 "To elucidate the immunological outcome in antidepressant therapy, the effects of acute or chronic imipramine (IMP) treatment on T cell subsets were examined in sham-operated (SO) and olfactory bulbectomized (OB) mice. Olfactory bulbectomy decreased the ratio of Lyt2-positive suppressor T cells to L3T4-positive T helper cells. Acute IMP treatment did not exert any effect on the ratio in SO nor in OB mice. Chronic IMP administration was found to significantly increase the ratio in SO and OB mice and, as a result, the ratio was significantly higher in SO mice compared with the control, while the ratio was normalized in OB mice. The present study may be suggestive of the immune activation in depression and of the immunosuppressive effects of antidepressants" http://www.ncbi.nlm.nih.gov/pubmed/12566937 1 1647 "L. R. Reznikov, C. A. Grillo, G. G. Piroli, R. K. Pasumarthi, L. P. Reagan and J. Fadel" 2007 Acute stress-mediated increases in extracellular glutamate levels in the rat amygdala: differential effects of antidepressant treatment Eur.J.Neurosci. 25 10 3109-3114 "Depressive illness is associated with changes in amygdalar volume, and stressful life events are known to precipitate depressive episodes in this patient population. Stress affects amygdalar synaptic plasticity and several neurotransmitter systems have been implicated in stress-mediated changes in the brain, including the glutamatergic system. However, the role of the glutamatergic system in stress-mediated plasticity in the amygdala remains to be determined. Accordingly the current study examined the stress modulation of extracellular glutamate levels in the basolateral nucleus (BLA) and the central nucleus (CeA) of the amygdala by in vivo microdialysis. Acute stress increased extracellular glutamate levels in the BLA and CeA, although the dynamics of these stress-mediated changes were dramatically different in these amygdalar nuclei. Tetrodotoxin administration reduced basal, and completely eliminated stress-mediated increases in glutamate efflux in the amygdala, demonstrating that stress effects are dependent on local axonal depolarization. Moreover, stress-mediated increases in glutamate efflux in the BLA were inhibited by the antidepressant tianeptine but not by the selective serotonin-reuptake inhibitor fluoxetine. Collectively, these data demonstrate that stress-induced modulation of glutamate neurochemistry reflects a fundamental pathological change that may contribute to the aetiology and progression of depressive illness, and suggest that some antidepressants such as tianeptine may elicit their clinical effects by modulation of glutamatergic neurotransmission" http://www.ncbi.nlm.nih.gov/pubmed/17561824 0 1648 "S. N. Deep, I. Baitharu, A. Sharma, A. K. Gurjar, D. Prasad and S. B. Singh" 2016 Neuroprotective Role of L-NG-Nitroarginine Methyl Ester (L-NAME) against Chronic Hypobaric Hypoxia with Crowding Stress (CHC) Induced Depression-Like Behaviour PLoS.One. 11 4 e0153371 "Improper neuroimmune responses following chronic stress exposure have been reported to cause neuronal dysfunctions leading to memory impairment, anxiety and depression like behaviours. Though several factors affecting microglial activation and consequent alteration in neuro-inflammatory responses have been well studied, role of NO and its association with microglia in stress induced depression model is yet to be explored. In the present study, we validated combination of chronic hypobaric hypoxia and crowding (CHC) as a stress model for depression and investigated the role of chronic stress induced elevated nitric oxide (NO) level in microglia activation and its effect on neuro-inflammatory responses in brain. Further, we evaluated the ameliorative effect of L-NG-Nitroarginine Methyl Ester (L-NAME) to reverse the stress induced depressive mood state. Four groups of male Sprague Dawley rat were taken and divided into control and CHC stress exposed group with and without treatment of L-NAME. Depression like behaviour and anhedonia in rats were assessed by Forced Swim Test (FST) and Sucrose Preference Test (SPT). Microglial activation was evaluated using Iba-1 immunohistochemistry and proinflammatory cytokines were assessed in the hippocampal region. Our result showed that exposure to CHC stress increased the number of active microglia with corresponding increase in inflammatory cytokines and altered behavioural responses. The inhibition of NO synthesis by L-NAME during CHC exposure decreased the number of active microglia in hippocampus as evident from decreased Iba-1 positive cells. Further, L-NAME administration decreased pro-inflammatory cytokines in hippocampus and improved behaviour of rats. Our study demonstrate that stress induced elevation of NO plays pivotal role in altered microglial activation and consequent neurodegenerative processes leading to depression like behaviour in rat" http://www.ncbi.nlm.nih.gov/pubmed/27082990 1 1649 "K. W. Hong, B. Y. Rhim, W. S. Lee, B. R. Jeong, C. D. Kim and Y. W. Shin" 1989 Release of superoxide-dependent relaxing factor(s) from endothelial cells Am.J.Physiol 257 5 Pt 2 H1340-H1346 "In the present work, an experimental system was designed to study superoxide anion radical, implicated as the cause of vascular dilatation. To circumvent its direct effect, we employed a two-bath system. When the endothelial cells (EC) were exposed to electrical field stimulation (EFS) or to a hypoxanthine-xanthine oxidase system in bath A plus its physiological buffer solution suffused on a helical strip of cat basilar artery in bath B, the contraction to 5-hydroxytryptamine (5-HT) was depressed to approximately 40-50% of the control value. The reduction was not elicited on EFS in a state of calcium deficiency or in the absence of EC. The depression could be prevented by pretreatment with superoxide dismutase (SOD), but not with an effective dose of catalase, dimethyl sulfoxide (DMSO), mannitol, or indomethacin. The percent depression of contraction was paralleled by an increase in SOD-inhibitable cytochrome c reduction, which was not associated with cyclic guanosine 3',5'-monophosphate formation. These results suggest that superoxide-dependent relaxing factor is released from EC differently than the endothelium-derived relaxing factor mediated by acetylcholine" http://www.ncbi.nlm.nih.gov/pubmed/2556045 0 1650 "Y. L. Han, C. Cheng, H. M. Tan, W. K. Wu, Y. L. Wu, H. L. Sun, J. Sun and J. L. Chen" 2007 [Effect of Tongxinluo superfine on experimental anginal model (contraction of collaterals) in rat with endothelial dysfunction] Zhongguo Zhong.Yao Za Zhi. 32 22 "2404-8, 2426" "OBJECTIVE: To study the effect of Tongxinluo superfine (TXL) on experimental anginal model induced by Arginine Vasopressin in rats with endothelial dysfunction. METHOD: First, the endothelial dysfunction rat model was made by methionine-induced hyperhomocysteinemia (HHcy). The thoracic aorta were excised, and acetylcholine (Ach)-induced endothelium dependent relaxation and sodium nitroprusside (SNP) induced endothelium-independent relaxation were measured. Total plasma homocysteine (Hcy) concentrations were measured with automated fluorescence polarization immunoassay (FPIA). Enzyme-linked immunosorbent assay (ELISA) was used to detect plasma von Willebrand factor (vWF) level. Plasma nitric oxide (NO) contents were assayed by method of nitrate reductase. Then, the rat model of collaterals contraction (model group) was established by AVP intravenous injection in rats with endothelial dysfunction and the S wave change (DeltaS) and T wave depression in Lead II ECG were used as the index of angina severity. The nitric oxide (NO) contents in serum and the expression of myocardium eNOS mRNA were measured. RESULT: Ach (0. 1-1000 nmol L(-1))-induced endothelium dependent relaxation (EDR) of aortic rings was significantly decreased in HHcy group. The endothelium-independent relaxation induced by SNP (0.001-10 micromol L(-1)) was not significantly different between the two groups. Plasma homocysteine concentrations and vWF levels in rats treated with methionine were higher than those of control group, while NO contents were significantly decreased in HHcy group compared with control. The results showed that L-methionine intake induced hyperhomocysteinemia in rats. Impaired EDR, increased vWF and decreased NO suggested the exist of endothelial dysfunction. DeltaS of model group increased from 1 min to 5 min and T wave of model group depressed at 2 min compared with that of control after the administration of vasopressin (0.5 U kg(-1)). The intragastric administration of TXL inhibited vasopressin-induced S wave change at 4 min and 5 min and T wave depression from 30 s to 3 min after AVP injection. The NO contents in serum and the expression of myocardium eNOS mRNA of TXL group were increased compared with model group. CONCLUSION: Experimental angina induced by AVP injection is more severe in rats with endothelial dysfunction. Tongxinluo Superfine can protect against collaterals contraction in rats maybe by increasing the NO contents in serum and the expression of myocardium eNOS mRNA" http://www.ncbi.nlm.nih.gov/pubmed/18257270 0 1651 "V. Wiwanitkit, J. Suwansaksri and P. Nasuan" 2001 "Urine trans,trans-muconic acid as a biomarker for benzene exposure in gas station attendants in Bangkok, Thailand" Ann.Clin.Lab Sci. 31 4 399-401 "The toxicity of benzene, a chemical used in many industrial processes, involves bone marrow depression and leukemogenesis and is associated with damage to multiple classes of hematopoietic cells and hematopoietic functions. Environmental exposure to benzene causes an increased body burden, which is reflected in several biomarkers, eg, urine trans,trans-muconic acid (ttMA). Associated with the industrialization of Thailand, a developing country in Southeast Asia, workers in many occupations have acquired substantial risks of benzene exposure. In this study, benzene exposure was monitored by high-performance liquid chromatography (HPLC) of urine ttMA in 79 persons, including 49 controls and 30 gas station attendants. In controls, urine ttMA concentration averaged 0.12 (SD +/- 0.03) mg/g creatinine; in gas station attendants, urine ttMA concentration averaged 4.00 (SD +/- 12.49) mg/g creatinine (p < 0.05). Based on these findings, wider use of urine ttMA determination is recommended as a biomarker for occupational exposure to benzene" http://www.ncbi.nlm.nih.gov/pubmed/11688852 0 1652 "C. H. Chen, K. S. Lin and S. H. Chan" 1994 Further Elucidation of a Pertussis Toxin-Sensitive Transmembrane Signaling Mechanism Involved in Central alpha(2)-Adrenoceptor Activation in the Rat J.Biomed.Sci. 1 1 13-18 "In adult male Sprague-Dawley rats anesthetized with pentobarbital sodium, we elucidated the molecular consequence of central alpha(2)-adrenoceptor activation. The hypotensive and negative chronotropic and inotropic actions of the alpha(2)-adrenoceptor agonist guanabenz were used as our experimental index. Intracerebroventricular administration of pertussis toxin (2.5 &mgr;g) significantly attenuated the cardiovascular suppressant effects of the aminoguanidine compound (100 &mgr;g/kg i.v.). However, application of N-ethylmaleimide (0.125 or 0.250 &mgr;g), phorbol 12-myristate 13-acetate (1.25 or 2.50 &mgr;g), cholera toxin (1.25 or 2.50 &mgr;g) or forskolin (12.5 or 25.0 &mgr;g) into the lateral cerebral ventricle elicited no appreciable blunting effect on the circulatory depression produced by guanabenz. These results were essentially duplicated when pertussis toxin (0.125 or 0.250 &mgr;g), N-ethylmaleimide (0.0125 or 0.05 &mgr;g), phorbol 12-myristate 13-acetate (0.125 or 0.25 &mgr;g), cholera toxin (0.125 or 0.25 &mgr;g) or forskolin (1.25 or 2.50 &mgr;g) was microinjected bilaterally to the nucleus reticularis gigantocellularis, a medullary site believed to be intimately related to the antihypertensive action of guanabenz. These findings suggest that stimulation of the alpha(2)-adrenoceptors in the medulla oblongata may result in the activation of a pertussis toxin-sensitive GTP-binding regulatory protein. They further suggest that the biologic signals subsequent to this action may not be linked to Gs, Gi or Gp but possibly Go. Copyright 1994 S. Karger AG, Basel" http://www.ncbi.nlm.nih.gov/pubmed/11725002 0 1653 "P. Svensson, G. Hesslow and R. Winton" 1996 Effect of ethanol on the excitability of the inferior olive in decerebrate ferret J.Pharmacol.Exp.Ther. 277 2 761-767 "Climbing fibers, which originate in the inferior olive and project to Purkinje cells and Golgi cells in the cerebral cortex, were activated at low (0.4-Hz) and high (4-Hz) frequencies by periorbital stimulation in decerebrate ferrets. Climbing fiber responses were recorded as field potentials from the c3 zone of the cerebellar surface. When periorbital stimulation was applied at high frequency, the climbing fiber responses became strongly depressed within a few seconds. It has previously been shown that this high frequency depression (HFD) of climbing fiber responses is due to a cerebellar inhibition of the inferior olive, probably via the nucleo-olivary pathway. Acute administration of ethanol had small and variable effects on the amplitude of climbing fiber responses evoked by low-frequency stimulation. In contrast, medium concentrations (0.44-2.90 g/l) of ethanol led to a marked reduction of the HFD. Low ( < 0.44 g/l) systemic concentrations had no measurable effects on the HFD, whereas high concentrations ( > 2.90 g/l) caused either an increased HFD or a nonseptic reduction in olivary excitability. Because HFD has previously been shown to involve cerebello-olivary inhibition, the possibility of an interaction between ethanol and GABA-ergic responses in the interposito-olivary pathway is discussed" http://www.ncbi.nlm.nih.gov/pubmed/8627556 0 1654 "N. Kabli, T. Nguyen, G. Balboni, B. F. O'Dowd and S. R. George" 2012 Activation of the l-d opioid receptor heteromer in the nucleus accumbens produces anti-depressant-like and anxiolytic-like effects "Neuropsychopharmacology.Conference: 51st Annual Meeting of the American College of Neuropsychopharmacology, ACNP 2012 Hollywood, FL United States.Conference Start: 20121202 Conference End: 20121206.Conference Publication: (var.pagings).38 ()(pp S183-S" var.pagings S183-S184 "Background: Treatment-resistant major depression remains inadequately treated with currently available anti-depressants. Opioid Receptors (ORs) are involved in the pathophysilogy of major depression yet remain an untapped pharmacological target. Although mu-opioid agonists such as morphine have been used in the clinic to manage refractory depression, their clinical utility is limited by the development of tolerance and adverse side effects ensuing from mOR activation. In contrast with mu- and d-ORs, the mu-delta OR heteromeric complex has unique pharmacological and signaling properties and displays less functional desensitization, rendering it a promising therapeutic target. Although the pharmacological and molecular profile of the mu-delta heteromer in vitro is being elucidated, its physiological role in vivo is largely unknown. Recently, we demonstrated that d-agonists bind within a novel mu-receptor ligand binding pocket and regulate mu-delta heteromer trafficking in cells. In particular, the d-agonist UFP-512 displayed high affinity at the mu-delta heteromer. Since the d-agonists which possess a unique pharmacology at the mu-delta heteromer also elicit anti-depressant-like and anxiolytic-like effects in animal models, we sought to investigate the role of the mu-delta receptor complex in mood regulation. Methods: Since drugs targeting the dOR homomeric receptors may also have effects at the mu-delta heteromer, we devised a strategy to selectively analyze the effects of the mu-delta receptor complex by dissociating it. To this end, we designed a specific inhibitory peptide derived from the distal carboxyl tail of the dOR, which has been implicated in mu- and delta-OR heteromerization. To validate the use of the interfering peptide as a tool for dissociating the mu-delta heteromer, we examined its effect on mu- and delta-OR co-immunoprecitation and d-agonist UFP-512-induced binding at, and trafficking of, the mu-delta heteromer. To determine the role of the md heteromer in mood modulation, we assessed the effect of intraaccumbens micro-injections of TAT-conjugated interfering or scrambled control peptides on the anti-depressant-like and anxiolytic-like effects of UFP-512 in the rat forced swim test (FST), novelty-induced hypophagia (NIH) and elevated plus maze (EPM) paradigms. The effects of intra-accumbens administration of the interfering and control peptides, and UFP-512 on locomotion were also assessed. Results: In vitro, the interfering peptide abolished mu- and delta-OR co-immunoprecipitation and resulted in a loss of UFP-512-detected high affinity binding to, and trafficking of, the mu-delta heteromer, but had no effect on mu- or delta-OR homomers. Thus, the interfering peptide selectively dissociated the mu-delta receptor complex. Bilateral micro-injections of UFP-512 into the nucleus accumbens (NAc) resulted in reduced duration of immobility in the FST, suggestive of anti-depressant-like action. Intra-accumbens UFP-512 microinjection also resulted in decreased latency to drink milk in the NIH paradigm and increased time spent in open arms of the EPM, suggestive of anxiolytic-like action at the level of the NAc. Bilateral micro-injections of the interfering peptide into the nucleus accumbens reversed the UFP-512-induced anti-depressant-like and anxiolytic-like actions in the FST, and NIH and EPM paradigms, respectively, whereas the control peptide had no effect. Pre-treatment with either the mu-antagonist CTOP or the delta-antagonist naltrindole abolished the anti-depressant-like effects of UFP-512 in the FST, suggesting that activation of both mu- and delta-ORs was required. Neither interfering nor inactive peptides alone affected basal responding in any of the behavioral paradigms. Imipramine and diazepam were used as positive controls in the FST and EPM test, respectively. UFP-512 and the interfering and control peptides did not modulate locomotor behavior. Conclusions: Overall, our findings indicate that the mu-delta heteromer mediates the mood modulatory effects of UFP-512 in the NAc and that activation of the mu-delta heteromer in the NAc produces antidepressant- like and anxiolytic-like actions similar in magnitude to the effects of clinically relevant anti-depressants and anxiolytics in animal models of depression and anxiety. Our data also further solidify the role of the NAc in modulating depressive behavior. By coupling to a distinct signal transduction pathway and resisting the desensitization that is characteristic of mORs, the mu-delta heteromer represents a potential therapeutic target for the management of treatment-resistant major depression" DO - http://dx.doi.org/10.1038/npp.2012.219 0 1655 "H. Dong, Z. Gao, H. Rong, M. Jin and X. Zhang" 2014 beta-asarone reverses chronic unpredictable mild stress-induced depression-like behavior and promotes hippocampal neurogenesis in rats Molecules. 19 5 5634-5649 "In this study, we investigated the influence of beta-asarone, the major ingredient of Acorus tatarinowii Schott, on depressive-like behavior induced by the chronic unpredictable mild stresses (CUMS) paradigm and to clarify the underlying mechanisms. The results show that beta-asarone treatment partially reversed the CUMS-induced depression-like behaviors in both the forced swim and sucrose preference tests. The behavioral effects were associated with increased hippocampal neurogenesis indicated by bromodeoxyuridine (BrdU) immunoreactivity. beta-Asarone treatment significantly increased the expression of brain-derived neurotrophic factor (BDNF) at levels of transcription and translation. Moreover, CUMS caused significant reduction in ERK1/2 and CREB phosphorylation, both of which were partially attenuated by beta-asarone administration. It is important to note that beta-asarone treatment had no effect on total levels or phosphorylation state of any of the proteins examined in ERK1/2-CREB pathway in no stress rats, suggesting that beta-asarone acts in a stress-dependent manner to block ERK1/2-CREB signaling. We did not observe a complete reversal of depression-like behaviors to control levels by beta-asarone. To our knowledge, the present study is the first to demonstrate that adult neurogenesis is involved in the antidepressant-like behavioral effects of beta-asarone, suggesting that beta-asarone is a promising candidate for the treatment of depression" http://www.ncbi.nlm.nih.gov/pubmed/24786848 1 1656 S. L. Dale and J. C. Melby 1974 "Altered adrenal steroidogenesis in ""low renin"" essential hypertension" Trans.Assoc.Am.Physicians 87 248-257 http://www.ncbi.nlm.nih.gov/pubmed/4456734 0 1657 "B. A. Ely, K. A. B. Lapidus, D. L. Rosenthal, K. E. Sip, W. K. Goodman, J. Xu and E. R. Stern" 2015 Functional connectivity of the habenula in relation to subclinical depressive symptoms "Biological Psychiatry.Conference: 70th Annual Scientific Convention and Meeting of the Society of Biological Psychiatry, SOBP 2015 Toronto, ON Canada.Conference Start: 20150514 Conference End: 20150516.Conference Publication: (var.pagings).77 (9 Suppl" var.pagings 114S "Background: Converging evidence suggests the habenula (Hb) suppresses midbrain monoaminergic reward signaling and may be important in major depression (MDD). The Hb responds strongly to punishment and negative-reward predictors across species, while Hb stimulation in rodents impacts depression-like behaviors. Furthermore, deep brain stimulation of the Hb in two MDD cases was associated with improved symptoms. However, the small size of the human Hb has limited in vivo investigations. Using high-resolution BOLD fMRI data from the Human Connectome Project (HCP), we examined relationships between resting-state functional connectivity of Hb circuitry and subclinical depressive symptoms Methods: Thirty subjects were chosen from the HCP 500 Subject Release dataset with the 15 highest and 15 lowest NIH Toolbox Sadness ratings. Functional connectivity of the bilateral Hb was assessed via the SPM CONN toolbox at the p<0.005 significance threshold using preprocessed 3T resting-state fMRI data (4x15 minutes concatenated). Results: We found robust Hb connectivity with the contralateral Hb and bilateral insula. This pattern was stronger in the high-Sadness group, which also demonstrated midbrain Hb connectivity. In contrast, the low-Sadness group exhibited significantly stronger Hb connectivity with posterior cingulate, medial prefrontal cortex, and posterior hippocampus. Conclusions: High-resolution fMRI revealed expected patterns of Hb connectivity with the contralateral Hb and midbrain. Stronger connectivity within this network in the high-Sadness group supports the model of greater Hb influence in depression. Stronger connectivity between the Hb and default mode network in the low-Sadness group suggests that interactions between Hb circuitry and regions involved in internally-directed cognition may protect against depressed mood" 0 1658 S. B. Sparber and H. A. Tilson 1971 Environmental influences upon drug-induced suppression of operant behavior J.Pharmacol.Exp.Ther. 179 1 01-Sep http://www.ncbi.nlm.nih.gov/pubmed/5096565 0 1659 "K. Uvnas-Moberg, E. Bjokstrand, V. Hillegaart and S. Ahlenius" 1999 Oxytocin as a possible mediator of SSRI-induced antidepressant effects Psychopharmacology (Berl) 142 1 95-101 "The nonapeptide oxytocin is released into systemic circulation in situations of psychosocial interaction, and has been shown to be involved in mechanisms of social bonding and social recognition in laboratory studies. In view of disturbances in psychosocial relationships being a triggering factor for depression and anxiety, it is interesting to note that experimental studies have shown oxytocin to possess antidepressant- and anxiolytic-like actions. Thus. in the present study we examined effects of the SSRI citalopram (20 mg/kg i.p.) on plasma oxytocin, acutely and upon repeated administration, in adult male Sprague-Dawley rats. Plasma oxytocin, and some functionally related peptides (CCK, gastrin, somatostatin and insulin), were measured by standard radioimmunoassay techniques. Acute citalopram administration produced a statistically significant increase in plasma oxytocin and CCK levels. Administration of citalopram for 14 days did not attenuate the oxytocin-releasing effect to a challenge dose of the SSRI zimeldine (20 mg/kg s.c.), whereas CCK levels were not increased after the subchronic citalopram treatment. Thus, the SSRI citalopram produces increased plasma oxytocin levels acutely, and there appears to be no or little tolerance to this effect upon repeated administration. There were no, or variable, effects on plasma levels of gastrin, somatostatin or insulin. It is suggested that oxytocin release is an important aspect of the pharmacological actions of SSRIs, and this could be an important contributory factor for the clinical profile of this group of antidepressants with particular efficacy in disorders of psychosocial origin" http://www.ncbi.nlm.nih.gov/pubmed/10102788 0 1660 "F. P. Di, F. Pica, C. Croce, C. Favalli, E. Tubaro and E. Garaci" 1990 Effect of acute or daily cocaine administration on cellular immune response and virus infection in mice Nat.Immun.Cell Growth Regul. 9 6 397-405 "The effects of in vivo cocaine administrations on cellular cytotoxicity were studied. Cocaine induced a dose-related immunosuppression of natural killer cell activity, with maximal depression at 1-5 mg/kg. In addition, the degree of inhibition following a single intraperitoneal (i.p.) or intravenous cocaine dose (acute treatment, 1 mg/kg) was similar to that after repeated administration (subchronic treatment: 1 mg/kg/day i.p. for 7 consecutive days or subcutaneous administration by Alzet 2001 osmotic minipumps). T cells from cocaine-treated mice failed to generate cytotoxic T lymphocytes (CTL) in mixed lymphocyte cultures and acute or subchronic cocaine treatment also inhibited CTL generation in vivo. On the other hand, acute administration induced a very rapid (24-hour) inhibition of natural cytotoxicity, with a return to normal within 72 h after treatment. By contrast, repeated doses led to more protracted immunologic consequences and a delayed recovery (144 h). The effect of cocaine on susceptibility to influenza virus (PR8) infection was also investigated. Both acute and subchronic treatment significantly decreased resistance to PR8 infection. The results clearly indicate that cocaine has a potent suppressive effect on cellular immunity and that abuse can adversely affect the outcome of infectious diseases" http://www.ncbi.nlm.nih.gov/pubmed/1965012 0 1661 "Y. F. Wang, X. Y. Cui, Y. B. Hao, X. R. Mei, G. R. Yu, X. Z. Huang, X. M. Kang and X. Q. Zhou" 2011 "The fluxes of CO2 from grazed and fenced temperate steppe during two drought years on the Inner Mongolia Plateau, China" Sci.Total Environ. 410-411 182-190 "The CO(2) flux was measured by the eddy covariance method on a temperate Leymus chinensis steppe over a period of 17 months spanning two consecutive growing seasons. The amount of precipitation was nearly normal, but it was low in the early and high in the late growing period in 2006. In the 2007 growing season, the amount of precipitation was about 45% less than the multi-year average and more evenly distributed. Comparisons were made between a moderately grazed site and a 28-year-old fenced site. The maximum instantaneous CO(2) release and uptake rates were 0.12 (May) and -0.11mg CO(2)m(-2)s(-1) (July) at the fenced site, and 0.11 and -0.16mg CO(2)m(-2)s(-1) (both in July) at the grazed site. In both growing seasons, the grazed site always had a higher daily uptake rate or lower release rate than the fenced site. The grazed site was a CO(2) sink during the growing season of 2007 and a CO(2) source in the growing season of 2006, whereas the fenced site was a CO(2) source in both seasons. Lower precipitation decreased CO(2) loss during the growing season more in the grazed site than in the fenced site, mainly because of depression of total ecosystem respiration (R(e)) in the former and stimulation in the latter. During the dormant season (from October to April), the fenced and grazed sites released 60.0 and 32.4g of C per m(2), respectively. Path analysis showed that temperature had the greatest effect on daily variation of ecosystem CO(2) exchange during the growing seasons at the two study sites. The results suggest that decrease of precipitation and/or increase of temperature will likely promote C loss from L. chinensis steppes, whether fenced or grazed, and that a grazed site is more sensitive" http://www.ncbi.nlm.nih.gov/pubmed/22024234 1 1662 "A. Serefko, A. Szopa, A. Wlaz, S. Wosko, P. Wlaz and E. Poleszak" 2016 Synergistic antidepressant-like effect of the joint administration of caffeine and NMDA receptor ligands in the forced swim test in mice J.Neural Transm.(Vienna.) 123 4 463-472 "The optimal treatment of depressed patients remains one of the most important challenges concerning depression. The identification of the best treatment strategies and development of new, safer, and more effective agents are crucial. The glutamatergic system seems to be a promising drug target, and consequently the use of the NMDA receptor ligands, particularly in co-administration with other substances exerting the antidepressant activity, has emerged among the new ideas. The objective of this study was to examine the effect of caffeine on the performance of mice treated with various NMDA modulators in the forced swim test. We demonstrated a significant interaction between caffeine (5 mg/kg) and the following NMDA receptor ligands: MK-801 (an antagonist binding in the ion channel, 0.05 mg/kg), CGP 37849 (an antagonist of the glutamate site, 0.312 mg/kg), L-701,324 (an antagonist of the glycine site, 1 mg/kg), and D-cycloserine (a high-efficacy partial agonist of the glycine site, 2.5 mg/kg), while the interaction between caffeine and the inorganic modulators, i.e., Zn(2+) (2.5 mg/kg) and Mg(2+) (10 mg/kg), was not considered as significant. Based on the obtained results, the simultaneous blockage of the adenosine and NMDA receptors may be a promising target in the development of new antidepressants" http://www.ncbi.nlm.nih.gov/pubmed/26510772 1 1663 K. Shibuki and D. Okada 1991 Endogenous nitric oxide release required for long-term synaptic depression in the cerebellum Nature 349 6307 326-328 "Conjunctive stimulation of climbing and parallel fibres in the cerebellum evokes a long-term depression of parallel-fibre Purkinje-cell transmission, a phenomenon implicated as the cellular mechanism for cerebellar motor learning. It is suspected that the increase in cyclic GMP concentration that occurs after activation of climbing fibres is required to evoke long-term depression. Excitatory amino acids are known to cause the release of nitric oxide (NO), resulting in elevation of the cGMP level in the cerebellum. Here we report that endogenous NO is released after stimulation of climbing fibres, that long-term depression evoked by conjunctive stimulation of parallel and climbing fibres is blocked by haemoglobin (which strongly binds NO) or L-NG-monomethyl-arginine (an inhibitor of NO synthase), and that exogenous NO or cGMP can substitute for the stimulation of climbing fibres to cause long-term depression in rat cerebellar slices. These results demonstrate that the release of endogenous NO is essential for the induction of synaptic plasticity in the cerebellum" http://www.ncbi.nlm.nih.gov/pubmed/1702879 0 1664 A. K. Rawat 1976 Effect of maternal ethanol consumption on foetal and neonatal rat hepatic protein synthesis Biochem.J. 160 3 653-661 "Effects of maternal ethanol consumption were investigated on the rates of protein synthehsis by livers of foetal and neonatal rats both in vivo and in vitro, and on the activities of enzymes involved in protein synthesis and degradation. The rates of general protein synthesis by ribosomes in vitro studied by measuring the incorporation of [14C]leucine into ribosomal protein showed that maternal ethanol consumption resulted in an inhibition of the rates of protein synthesis by both foetal and neonatal livers from the ethanol-fed group. The rates of incorporation of intravenously injected [14C]leucine into hepatic proteins were also significantly lower in the foetal, neonatal and adult livers from the ethanol-fed group. Incubation of adult-rat liver slices with ethanol resulted in an inhibition of the incorporation of [14C]leucine into hepatic proteins; however, this effect was not observed in the foetal liver slices. This effect of externally added ethanol was at least partially prevented by the addition of pyrazole to the adult liver slices. Pyrazole addition to foetal liver slices was without significant effect on the rates of protein synthesis. Cross-mixing experiments showed that the capacity of both hepatic ribosomes and pH5 enzyme fractions to synthesize proteins was decreased in the foetal liver from the ethanol-fed group. Maternal ethanol consumption resulted in a decrease in hepatic total RNA content, RNA/DNA ratio and ribosomal protein content in the foetal liver. Foetal hepatic DNA content was not significantly affected. Ethanol consumption resulted in a significant decrease in proteolytic activity and the activity of tryptophan oxygenase in the foetal, neonatal and adult livers. It is possible that the mechanisms of inhibition of protein synthesis observed here in the foetal liver after maternal ethanol consumption may be responsible for at least some of the changes observed in 'foetal alcohol syndrome'" http://www.ncbi.nlm.nih.gov/pubmed/1016246 0 1665 "R. Taurines, C. Schwenck, B. Lyttwin, M. Schecklmann, T. Jans, L. Reefschlager, J. Geissler, M. Gerlach and M. Romanos" 2014 Oxytocin plasma concentrations in children and adolescents with autism spectrum disorder: Correlation with autistic symptomatology "ADHD Attention Deficit and Hyperactivity Disorders.6 (3) ()(pp 231-239), 2014.Date of Publication: September 2014." 3 231-239 "Findings from research in animal models and humans have shown a clear role for the neuropeptide oxytocin (OT) on complex social behaviors. This is also true in the context of autism spectrum disorder (ASD). Previous studies on peripheral OT concentrations in children and young adults have reported conflicting results with the initial studies presenting mainly decreased OT plasma levels in ASD compared to healthy controls. Our study therefore aimed to further investigate changes in peripheral OT concentrations as a potential surrogate for the effects observed in the central nervous system (CNS) in ASD. OT plasma concentrations were assessed in 19 male children and adolescents with ASD, all with an IQ > 70 (age 10.7 +/- 3.8 years), 17 healthy male children (age 13.6 +/- 2.1 years) and 19 young male patients with attention deficit hyperactivity disorder (ADHD) as a clinical control group (age 10.4 +/- 1.9 years) using a validated radioimmunoassay. Analysis of covariance revealed significant group differences in OT plasma concentrations (F(2, 48) = 9.574, p < 0.001, eta 2 = 0.285; plasma concentrations ASD 19.61 +/- 7.12 pg/ml, ADHD 8.05 +/- 5.49 pg/ml, healthy controls 14.43 +/- 9.64 pg/ml). Post hoc analyses showed significantly higher concentrations in children with ASD compared to ADHD (p < 0.001). After Bonferroni correction, there was no significant difference in ASD in comparison with healthy controls (p = 0.132). A significant strong correlation between plasma OT and autistic symptomatology, assessed by the Autism Diagnostic Observation Schedule, was observed in the ASD group (p = 0.013, r = 0.603). Patients with ADHD differed from healthy control children by significantly decreased OT concentrations (p = 0.014). No significant influences of the covariates age, IQ, medication and comorbidity could be seen. Our preliminary results point to a correlation of OT plasma concentrations with autistic symptom load in children with ASD and a modulation of the OT system also in the etiologically and phenotypically overlapping disorder ADHD. Further studies in humans and animal models are warranted to clarify the complex association of the OT system with social impairments as well as stress-related and depressive behavior and whether peripheral findings reflect primary changes of OT synthesis and/or release in relevant areas of the CNS. © 2014 Springer-Verlag Wien" DO - http://dx.doi.org/10.1007/s12402-014-0145-y 0 1666 "F. R. Walker, M. H. James, I. B. Hickie and P. D. McGorry" 2014 Clinical staging: a necessary step in the development of improved animal models of mood disturbance? Int.J.Neuropsychopharmacol. 17 3 491-495 "Recently, it has been suggested that the clinical staging approach be considered a serious alternative framework for conceptualising mood related psychopathology. The fundamental difference between clinical staging and the now dominant categorical diagnostic framework is that the entire illness trajectory becomes relevant, as opposed to simply the end-stage. The concept of disease trajectory has significant implications for animal models of psychopathology, and particularly for animal models of depression. This article will introduce and discuss the implications of the clinical staging approach for those undertaking research using animal models of mood disturbance" http://www.ncbi.nlm.nih.gov/pubmed/24128407 0 1667 "Z. X. Pan, H. X. Zhang, Y. X. Wang, L. D. Zhai and W. Du" 2014 Effect of recombinant human bone morphogenetic protein 2/poly-lactide-co-glycolic acid (rhBMP-2/PLGA) with core decompression on repair of rabbit femoral head necrosis Asian Pac.J.Trop.Med. 7 11 895-899 "OBJECTIVE: To observe the effect of recombinant human bone morphogenetic protein 2/poly-lactide-co-glycolic acid (rhBMP-2/PLGA) with core decompression on repair of rabbit femoral head necrosis. METHOD: Bilateral femoral head necrosis models of rabbit were established by steroid injection. A total of 48 rabbits (96 femoral head necrosis) were randomly divided into 4 groups: Group A, control group with12 rabbits, 24 femoral head necrosis; Group B, treated with rhBMP-2/PLGA implantation after core depression, with 12 rabbits, 24 femoral head necrosis; Group C, treated with rhBMP-2 implantation after core depression, with 12 rabbits, 24 femoral head necrosis; Group D treated with core depression group without implantation, with 12 rabbits, 24 femoral head necrosis. All animals were sacrificed after 12 weeks. The ability of repairing bone defect was evaluated by X-ray radiograph. Bone mineral density analysis of the defect regions were used to evaluate the level of ossification. The morphologic change and bone formation was assessed by HE staining. The angiogenesis was evaluated by VEGF immunohistochemistry. RESULTS: The osteogenetic ability and quality of femoral head necrosis in group B were better than those of other groups after 12 weeks by X-ray radiograph and morphologic investigation. And the angiogenesis in group B was better than other groups. Group C had similar osteogenetic quality of femoral head necrosis and angiogenesis with group D. CONCLUSION: The treatment of rhBMP-2/PLGA implantation after core depression can promote the repair of rabbit femoral head necrosis. It is a promising and efficient synthetic bone material to treat the femoral head necrosis" http://www.ncbi.nlm.nih.gov/pubmed/25441990 0 1668 R. A. Chahine and A. E. Raizner 1976 The mechanism of hypotension following angiography Invest Radiol. 11 5 472-478 "The hypotension observed following the intracardiac injection of contrast media is believed to be the result of myocardial depression, peripheral vasodilatation, or both. It is unclear which of these factors is primarily involved in different types of angiography. To assess this problem, Renografin-76 was injected into the aortic root of 15 anesthetized dogs (1 ml/kg) and into the left coronary artery (3-5 ml) in 18 dogs. The heart rate, the systolic and diastolic arterial pressures, left ventricular pressure, peak dp/dt and dp/dt-40 were monitored continuously until return to baseline. Following selective left coronary artery injection, both systolic and diastolic pressures decreased maximally at 5 seconds with parallel changes in peak dp/dt and dp/dt-40. Following the aortic root injection, the blood pressure response was biphasic, increasing at 5 seconds and decreasing maximally at 20 seconds. The corresponding changes in peak dp/dt and dp/dt-40 were initial depression at 5 seconds with quick return to baseline and increase above control at the time of maximal hypotension. The left ventricular end diastolic pressure rose maximally at 5 to 10 seconds for both coronary and aortic injections. The mechanism of hypotension, therefore, varies with the type of angiography. Myocardial depression appears to be a primary factor with selective coronary angiography. However, with aortic root injection, myocardial contractility, although initially depressed, is already improved at the time of maximal hypotension, and thus peripheral vasocilatation is probably the prime mechanism of the hypotension" http://www.ncbi.nlm.nih.gov/pubmed/977264 0 1669 A. Kjellgren and J. Westman 2014 Beneficial effects of treatment with sensory isolation in flotation-tank as a preventive health-care intervention - a randomized controlled pilot trial BMC.Complement Altern.Med. 14 417 "BACKGROUND: Sensory isolation in a flotation tank is a method known for inducing deep relaxation and subsequent positive health effects for patients suffering from e.g. stress or muscle tensions pains. Very few studies have investigated this method as a preventive health-care intervention. The purpose of this study was to evaluate the effects in healthy participants after receiving a series of flotation tank treatment. METHODS: Sixty-five participants (14 men and 51 women) who were all part of a cooperative-health project initiated by their individual companies, were randomized to either a wait-list control group or a flotation tank treatment group where they participated in a seven weeks flotation program with a total of twelve flotation sessions. Questionnaires measuring psychological and physiological variables such as stress and energy, depression and anxiety, optimism, pain, stress, sleep quality, mindfulness, and degree of altered states of consciousness were used. Data were analysed by two-way mixed MANOVA and repeated measures ANOVA. RESULTS: Stress, depression, anxiety, and worst pain were significantly decreased whereas optimism and sleep quality significantly increased for the flotation-REST group. No significant results for the control group were seen. There was also a significant correlation between mindfulness in daily life and degree of altered states of consciousness during the relaxation in the flotation tank. CONCLUSIONS: It was concluded that flotation-REST has beneficial effects on relatively healthy participants. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12613000483752" http://www.ncbi.nlm.nih.gov/pubmed/25344737 0 1670 "J. L. Franco, T. Posser, P. S. Brocardo, R. Trevisan, M. Uliano-Silva, N. H. Gabilan, A. R. S. Santos, R. B. Leal, A. L. S. Rodrigues, M. Farina and A. L. Dafre" 2008 "Involvement of glutathione, ERK1/2 phosphorylation and BDNF expression in the antidepressant-like effect of zinc in rats" "Behavioural Brain Research.188 (2) ()(pp 316-323), 2008.Date of Publication: 09 Apr 2008." 2 316-323 "We investigated the antidepressant-like effect of zinc chloride (zinc) administered acutely during 7 days (i.p. route), or chronically during 30 days (oral route) in the forced swimming test (FST) in rats. It was also investigated whether the antidepressant-like effect of zinc is associated with changes in the glutathione antioxidant system in the Wistar rat brain. Animals receiving a single zinc dose (5, 15 and 30 mg/kg, i.p.) 24 h prior to analysis showed no changes in the FST, but glutathione reductase and glutathione S-transferase activity were reduced in the hippocampus and cerebral cortex. This treatment did not, however, affect the glutathione status (GSH and GSSG) in both brain structures. The 7-day zinc treatment (1, 5 and 15 mg/kg, i.p.) caused a mild though significant antidepressant-like effect in the FST at the highest dosing, without affecting the glutathione antioxidant system. Finally, a consistent antidepressant-like effect was achieved in the FST after chronic (30 days) zinc treatment (300 mg/L, p.o.). This was accompanied by a significant increase in total glutathione levels in the hippocampus and cerebral cortex. The good response to oral treatment in the FST led us to investigate other variables, such as ERK phosphorylation and BDNF expression. Similar to therapeutic antidepressants, zinc in chronic oral treatment produced an increase in ERK phosphorylation and BDNF expression in the cerebral cortex. It is our hypothesis that up-regulation of neuroprotective effectors (GSH, ERK and BDNF) may be related to the antidepressant properties of zinc, but this will require additional work to be confirmed. © 2007 Elsevier B.V. All rights reserved" DO - http://dx.doi.org/10.1016/j.bbr.2007.11.012 1 1671 "L. H. Lee, C. H. Tan, G. Shui, M. R. Wenk and W. Y. Ong" 2012 Role of prefrontal cortical calcium independent phospholipase A(2) in antidepressant-like effect of maprotiline Int.J.Neuropsychopharmacol. 15 8 1087-1098 "There is increasing interest in the pathophysiology and neurochemistry of the prefrontal cortex (PFC) in depression. Blood flow and metabolism are decreased in the PFC of patients with depression compared to controls. Changes in long-chain polyunsaturated fatty acids (PUFAs) are also associated with depression. This study was conducted to elucidate a possible role of PFC activity of an enzyme involved in the release of docosahexaenoic acid (DHA), i.e. calcium-independent phospholipase A2 (iPLA(2)), in the effects of the norepinephrine reuptake inhibitor (NRI) antidepressant, maprotiline, in mice. Treatment of Balb/C mice with maprotiline for 4 wk resulted in reduction in the level of behavioural despair, as determined by decreased immobility and increased climbing during the forced swim test. In contrast, mice treated with maprotiline plus bilateral prefrontal cortical injections of antisense oligonucleotide to iPLA(2), showed significantly increased immobility and decreased climbing, to levels comparable to saline-treated controls, indicating abolishment of the antidepressant-like effect of maprotiline. Lipidomic analyses showed significant decreases in phosphatidylcholine species containing long-chain PUFAs and increases in lysophosphatidylcholine after maprotiline treatment, indicating increased PLA(2) activity and endogenous release of eicosapentaenoic acid (EPA) or DHA after maprotiline treatment. These changes in lipid profiles were absent in mice that received maprotiline and PFC injections of antisense oligonucleotide to iPLA(2). Together, the results indicate that PFC iPLA(2) activity plays an important role in the antidepressant-like effect of maprotiline, possibly through endogenous release of long-chain PUFAs" http://www.ncbi.nlm.nih.gov/pubmed/21835087 1 1672 "A. Sartorius, R. Hellweg, J. Litzke, M. Vogt, C. Dormann, B. Vollmayr, H. Danker-Hopfe and P. Gass" 2009 Correlations and discrepancies between serum and brain tissue levels of neurotrophins after electroconvulsive treatment in rats Pharmacopsychiatry 42 6 270-276 "INTRODUCTION: The neurotrophin brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are a central part of the molecular concepts on neuroplastic changes associated with stress, anxiety and depression. An increasing number of studies uses serum BDNF levels as a potential indicator for central nervous system alterations. METHODS: To analyze the relationship between brain tissue and serum BDNF and NGF levels, we used electroconvulsive shocks (ECS), an animal model of electroconvulsive therapy, and studied the temporal profile of neurotrophin expression in the hippocampus, prefrontal cortex and serum. 88 male Sprague-Dawley rats received single or serial ECS treatments and were killed between 3 hours and 14 days after the last treatment. RESULTS: We found a 2.8-fold rise for BDNF (1.3-fold for NGF) in the prefrontal cortex, and a 2.2-fold rise (1.2-fold for NGF) in the hippocampus after 5 ECS sessions. The temporal expression profile and correlation analyses between tissue and serum BDNF indicate that BDNF crosses the blood-brain barrier. No such correlation was found for NGF. DISCUSSION: The time course of central and peripheral BDNF changes may significantly differ. However, we demonstrate substantial evidence that it can be justified to measure serum BDNF levels with a time delay to monitor brain tissue neurotrophin alterations" http://www.ncbi.nlm.nih.gov/pubmed/19924587 0 1673 "J. M. Roux, T. Jahchan and M. C. Fulchignoni" 1975 Desoxyribonucleic acid and pyrimidine synthesis in the rat during intra-uterine growth retardation: responsiveness of several organs Biol.Neonate 27 03-Apr 129-140 "The response of DNA synthesis, thymidine incorporation and the activities of uridine kinase, carbamyl phosphate synthetase and aspartate transcarbamylase were studied in the rat, following intra-uterine growth retardation. A good correlation was found between the falls of DNA production and thymidine incorporation and the decrease of the activity of the three enzymes during the fetal period. After birth, cell proliferation remained depressed but no further changes occurred in the enzymatic activities" http://www.ncbi.nlm.nih.gov/pubmed/171006 0 1674 "D. L. Moreira, P. O. Souza, M. A. Kaplan, N. A. Pereira, G. L. Cardoso and E. F. Guimaraes" 2001 Effect of leaf essential oil from Piper solmsianum C.DC. in mice behaviour An.Acad.Bras.Cienc. 73 1 33-37 "The essential oil from Piper solmsianum leaves and its major compound (sarisan) were tested to verify their influences upon mice behaviour. The essential oil was obtained by hydrodistillation in a modified Clevenger extractor and analysed by GC/ MS. This analysis revealed in the oil the presence of monoterpenes, sesquiterpenes and of arylpropanoids. The compound sarisan, a myristicin analogue, was isolated from the oil to perform the pharmacological tests. Emulsions of the oil and of sarisan (5.0 and 10.0% v/v) were used in the tests. Pentobarbital (30 mg/ kg s.c.) or diazepam (2.5 mg/ kg s.c.) were tested as standard drugs to verify depressant or anxiolytic effects, respectively. Both essential oil and sarisan showed to have exciting and depressant effects in the tested animals" http://www.ncbi.nlm.nih.gov/pubmed/11246267 1 1675 L. Choudhury and D. K. Ganguly 1978 Some cardiovascular effects of crude scorpion venom Indian J.Med.Res. 68 515-518 http://www.ncbi.nlm.nih.gov/pubmed/744641 0 1676 "O. I. Skiteva, V. I. Lapteva and O. P. Balezina" 2010 Effect of fast and slow calcium buffers on induced secretion of neurotransmitter Bull.Exp.Biol.Med. 149 3 276-279 "Loading of mouse motor nerve terminals with EGTA-AM, but not with BAPTA-AM, inhibited the release of the neurotransmitter in response to stimulation of the nerve with rare (0.3 Hz) ""single"" pulses. During rhythmic stimulation with short (50 EPP) high-frequency (20 Hz) series, BAPTA-AM buffer modified burst pattern in a dose-dependent manner: it replaced the phase of initial facilitation by persistent depression of secretion and decreased its plateau level at the end of the burst. In contrast, loading of the nerve terminals with EGTA-AM buffer produced no effect on the phase of initial facilitation, but decreased the plateau level to the same degree as BAPTA-AM did. Probably, the different effects of both buffers on secretion of neurotransmitter reflect peculiarities of involvement of fast and slow Ca(2+)signals of motor terminals in single and rhythmic release of the neurotransmitter" http://www.ncbi.nlm.nih.gov/pubmed/21246081 0 1677 "M. Xu, C. J. Kim, M. J. Neubert and M. M. Heinricher" 2007 NMDA receptor-mediated activation of medullary pro-nociceptive neurons is required for secondary thermal hyperalgesia Pain 127 3 253-262 "There is now direct evidence that a class of neurons in the rostral ventromedial medulla (RVM) exerts a net facilitatory influence on spinal nociception. The present experiments were designed to test whether activation of these neurons, referred to as ""on-cells"", is required as part of a positive feedback loop leading to secondary hyperalgesia in acute inflammation produced by topical application of mustard oil. Activity of a characterized RVM neuron and paw withdrawals to heat (plantar surface) were recorded in barbiturate-anesthetized rats. Following three baseline trials, mustard oil was applied to the skin above the knee. Cell activity and paw withdrawal latencies were monitored for an additional 45min. Application of mustard oil produced an increase in on-cell discharge that was associated with a substantial decrease in withdrawal latency of the ipsilateral paw. Blocking on-cell activation using local infusion of the NMDA-receptor antagonist AP5 into the RVM prevented hyperalgesia. Secondary thermal hyperalgesia following mustard oil was also associated with a significant decrease in the firing of ""off-cells"", a cell population thought to exert a net inhibitory influence on nociception. Depression of off-cell firing was unaffected by AP5 microinjection. The firing of ""neutral cells"", which have no documented role in nociceptive modulation, was unchanged following mustard oil and also unaffected by AP5 infusion in the RVM. Brainstem descending controls are receiving increasing attention in efforts to understand hyperalgesia and persistent pain states. The present experiments demonstrate that a novel, NMDA-mediated activation of on-cells is required for secondary thermal hyperalgesia in acute inflammation" http://www.ncbi.nlm.nih.gov/pubmed/16997469 0 1678 L. A. Abraham and R. F. Slocombe 2003 Asymptomatic anomalous pulmonary veins in a Siberian Husky Aust.Vet.J. 81 7 406-408 "A 2-year-old, neutered male Siberian Husky presented with depression, weight loss and an inability to prehend food and water. Cerebrospinal fluid was collected under general anaesthesia prior to euthanasia. The elevated white cell count comprised mostly mononuclear cells. Histological changes within the brain were variable and multifocal. Non-suppurative meningitis secondary to lymphoma was diagnosed. At necropsy, abnormal venous drainage of the right cranial and middle lung lobes was found. A dilated major pulmonary vein from these lobes passed across the lateral aspect of the right caudal lung lobe prior to entering the heart, and subpleural veins from the affected lobes were enlarged and tortuous. These vascular abnormalities were considered incidental. There were no apparent congenital abnormalities of the heart and the animal's clinical signs were related to lymphoma of the brain" http://www.ncbi.nlm.nih.gov/pubmed/15084052 0 1679 J. C. Chang and C. S. Barrow 1984 Sensory irritation tolerance and cross-tolerance in F-344 rats exposed to chlorine or formaldehyde gas Toxicol.Appl.Pharmacol. 76 2 319-327 "Inhalation of chlorine (Cl2) or formaldehyde (HCHO) stimulates the trigeminal nerve endings in the nasal mucosa and results in respiratory rate depression in a concentration-dependent manner. To determine tolerance and cross-tolerance, the concentration-response curves of respiratory depression were compared between naive rats and rats pre-exposed to Cl2 or HCHO. Chlorine tolerance development was time and concentration dependent, being significant following a 1-day (6 hr/day), 10 ppm exposure, and reaching the maximum in 4 days. At 2.5 ppm of Cl2, tolerance was significant only after 10 days of exposure. Rats tolerant to Cl2 also showed cross-tolerance to HCHO. Tolerance to HCHO was observed in rats exposed to 28 ppm for 4 days, but not in groups exposed to 15 ppm for 1, 4, or 10 days. However, significant cross-tolerance to Cl2 was evident following a 1-day exposure to 15 ppm HCHO, with greatest effect seen in the group exposed for 10 days. Tolerance was reduced after a 7-day recovery following a 4-day exposure. Cross-tolerance was reduced also, but to a much lesser extent. These results suggest a common mechanism for tolerance and cross-tolerance development, but different reactive sites may exist for Cl2 and HCHO at the trigeminal nerve endings" http://www.ncbi.nlm.nih.gov/pubmed/6495337 0 1680 "D. Lyu, W. Yu, N. Tang, R. Wang, Z. Zhao, F. Xie, Y. He, H. Du and J. Chen" 2013 The mTOR signaling pathway regulates pain-related synaptic plasticity in rat entorhinal-hippocampal pathways Mol.Pain 9 64 "BACKGROUND: Our previous work demonstrated that persistent peripheral nociception (PPN) leads to synaptic plasticity and functional changes in the rat hippocampus. The protein kinase mTOR is a critical regulator of protein synthesis-dependent synaptic plasticity in the hippocampus as well as synaptic plasticity associated with central and peripheral pain sensitization. We examined the role of mTOR signaling in pain-associated entorhinal cortex (EC) - hippocampal synaptic plasticity to reveal possible cellular mechanisms underlying the effects of chronic pain on cognition and emotion. RESULTS: Subcutaneous injection of bee venom (BV) into one hind paw to induce PPN resulted in sustained (> 8 h) mTOR phospho-activation and enhanced phosphorylation of the mTOR target p70 S6 kinase (S6K) in the hippocampus. The magnitude and duration of long-term potentiation (LTP) in both EC - dentate gyrus (DG) and EC - CA1 synaptic pathways were elevated in BV-treated rats as measured by microelectrode array recording. Moreover, the number of potentiated synapses in the hippocampus was markedly upregulated by BV-induced PPN. Both elevated mTOR-S6K signaling and enhanced LTP induced by BV injection were reversed by systemic injection of the mTOR inhibitor rapamycin (RAPA). Rats injected with BV exhibited markedly reduced ambulation and exploratory activity in the open field (signs of depression and anxiety) compared to controls, and these effects were also reversed by RAPA. CONCLUSION: We suggest that PPN-induced enhancement of synaptic plasticity in EC - hippocampal pathways and the behavioral effects of PPN are dependent on mTOR-S6K signaling" http://www.ncbi.nlm.nih.gov/pubmed/24313960 0 1681 "T. Matsuda, K. Maekawa, K. Asano and T. Hisamitsu" 2011 Suppressive effect of juzen-taiho-to on lung metastasis of b16 melanoma cells in vivo Evid.Based.Complement Alternat.Med. 2011 743153 "Juzen-Taiho-To (JTT) is well known to be one of Kampo (Japanese herbal) medicine consisted of 10 component herbs and used for the supplemental therapy of cancer patients with remarkably success. However, the precise mechanisms by which JTT could favorably modify the clinical conditions of cancer patients are not well defined. The present study, therefore, was undertaken to examine the possible mechanisms of JTT on prevention of cancer metastasis using experimental mouse model. JTT was well mixed with rodent chow at concentrations of either 0.2 or 1.0%, and administered orally ad libitum, which was started 1 week before tumor cell injection and continue throughout the experiment. Oral administration of JTT at concentration 0.2 and 1.0% into C57BL/6 male mice significantly inhibited tumor metastasis in lungs, which was induced by the intravenous injection of 2 x 10(5) B16 melanoma cell. JTT at a concentration of 1.0% also significantly suppressed lung metastasis of B16 melanoma cell from hind footpad in C57BL/6 mice. In the second part of experiments, the influence of the depression of natural killer (NK) cell, natural killer T (NKT) cell and several types of cytokines on JTT-mediated inhibition of tumor cell metastasis. Intraperitoneal injection of anti asialo-GM1 antibody against NK cells and anti NK-1.1 monoclonal antibody (mAb) to NKT cells abrogated the inhibitory action of JTT on lung metastasis of B16 melanoma cells. Although intraperitoneal administration of anti-IFN-gamma mAb scarcely affected the inhibitory action of JTT on tumor cell metastasis, injection of amrinone, which used for IL-12 suppression, significantly decreased the ability of JTT to prevent tumor cell metastasis. These results strongly suggest that oral administration of JTT caused increase in the production of IL-12, which is responsible for the activation of both NK cell and NKT cell, in the lungs and results in inhibition of B16 melanoma cell metastasis in the lungs" http://www.ncbi.nlm.nih.gov/pubmed/19131394 0 1682 V. A. Ado 1969 [Suppression of allergic reaction of immediate type by spirazidine] Farmakol.Toksikol. 32 5 592-593 http://www.ncbi.nlm.nih.gov/pubmed/5364679 0 1683 T. Hata and T. Kita 1978 "A newly designed method for removal of the pineal body, and depression of convulsions and enhancement of exploratory movements by pinealectomy in mice" Endocrinol.Jpn. 25 5 407-413 "We designed a simple technique for surgical excision of the pineal body in mice. Such can be accomplished in 10 min by a skilled worker and there are no lesions whatever. In pinealectomized El-strain mice the appearance of convulsions was inhibited up to 30 days, while intact El-mice were all fallen into convulsions by being shaken up and down on a flat carton. Pentazole-induced convulsions propagate from one dd-mouse to another in an aggregated state, but such propagation did not occur in pinealectomized animals. Exploratory movements of pinealectomized dd-mice increased as compared to intact animals and the increase was always more extensively observed in El-mice in which, even in the intact animals, the exploratory movements were much more than those of dd-mice. From the above-mentioned experiment, it is considered that the pineal body plays a role not only in initiating but also in propagating convulsions, and that it may have a depressive action on motor activities in mice" http://www.ncbi.nlm.nih.gov/pubmed/744166 0 1684 "F. B. Le, J. Soo, A. M. Millar, M. Daigle, A. M. Le Guisquet, S. Leman, F. Minier, C. Belzung and P. R. Albert" 2015 Chronic mild stress and antidepressant treatment alter 5-HT1A receptor expression by modifying DNA methylation of a conserved Sp4 site Neurobiol.Dis. 82 332-341 "The serotonin 1A receptor (5-HT1A), a critical regulator of the brain serotonergic tone, is implicated in major depressive disorder (MDD) where it is often found to be dys-regulated. However, the extent to which stress and antidepressant treatment impact 5-HT1A expression in adults remains unclear. To address this issue, we subjected adult male BALB/c mice to unpredictable chronic mild stress (UCMS) to induce a depression-like phenotype that was reversed by chronic treatment with the antidepressant imipramine. In prefrontal cortex (PFC) and midbrain tissue, UCMS increased 5-HT1A RNA and protein levels, changes that are expected to decrease the brain serotonergic activity. The stress-induced increase in 5-HT1A expression was paralleled by a specific increase in DNA methylation of the conserved -681 CpG promoter site, located within a Sp1-like element. We show that the -681 CpG site is recognized and repressed by Sp4, the predominant neuronal Sp1-like factor and that Sp4-induced repression is attenuated by DNA methylation, despite a stress-induced increase in PFC Sp4 levels. These results indicate that adult life stress induces DNA methylation of a conserved promoter site, antagonizing Sp4 repression to increase 5-HT1A expression. Chronic imipramine treatment fully reversed the UCMS-induced increase in methylation of the -681 CpG site in the PFC but not midbrain of stressed animals and also increased 5-HT1A expression in the PFC of control animals. Incomplete reversal by imipramine of stress-induced changes in 5-HT1A methylation and expression indicates a persistence of stress vulnerability, and that sustained reversal of behavioral impairments may require additional pathways" http://www.ncbi.nlm.nih.gov/pubmed/26188176 1 1685 J. Fedotova 2012 Effects of stimulation and blockade of d(2) receptor on depression-like behavior in ovariectomized female rats ISRN.Pharmacol. 2012 305645 "The aim of the present study was to explore the hedonic effects of D(2) receptor agonist, quinpirole and D(2) receptor antagonist, and sulpiride alone or in combination with a low dose of 17beta-E(2)-estradiol (17beta-E(2)) in the adult ovariectomized female rats (OVX). OVX rats of Wistar strain were used in all experiments. Two weeks after surgery rats were chronically treated with vehicle, a low dose of 17beta-E(2) (5.0 mug/rat), quinpirole (0.1 mg/kg), sulpiride (10.0 mg/kg), quinpirole plus 17beta-E(2), or sulpiride plus 17beta-E(2) for 14 days before the forced swimming test. We found that sulpiride significantly decreased immobility time in the OVX females. A combination of sulpiride with a low dose of 17beta-E(2) induced more profound decrease of immobility time in the OVX rats compared to the rats treated with sulpiride alone. On the contrary, quinpirole failed to modify depression-like behavior in the OVX rats. In addition, quinpirole significantly blocked the antidepressant-like effect of 17beta-E(2) in OVX rats. Thus, the D(2) receptor antagonist sulpiride alone or in combination with a low dose of 17beta-E(2) exerted antidepressant-like effect in OVX female rats, while the D(2) receptor agonist quinpirole produced depressant-like profile on OVX rats" http://www.ncbi.nlm.nih.gov/pubmed/22530139 1 1686 "J. K. Lee, J. H. Choi, D. W. Lee, S. J. Kim, S. D. Fitzgerald, Y. S. Lee and D. Y. Kim" 2001 Marble spleen disease in pheasants in Korea J.Vet.Med.Sci. 63 6 699-701 "Two pheasants maintained in outdoor closed pen died within several days after having a history of depression. On necropsy, the spleens from both pheasants were enlarged about 3 times of their normal size and appeared mottled in color varying white to red. Histopathologically, there were diffuse severe follicular necrosis in the spleen and congestion and edema in the lung. Intranuclear basophilic inclusion bodies, which are strongly positive to group II avian adenovirus with immunohistochemistry, were noted in the spleen" http://www.ncbi.nlm.nih.gov/pubmed/11459022 0 1687 "K. Momma, K. Toyoshima, F. Sun and T. Nakanishi" 2009 In vivo dilatation of the ductus arteriosus by Rho kinase inhibition in the rat Neonatology. 95 4 324-331 "BACKGROUND: Fasudil hydrochloride, a Rho kinase inhibitor, was reported to dilate the constricted ductus arteriosus in vitro, and was suggested as a neonatal bridge to heart surgery. OBJECTIVES: To clarify the in vivo effectiveness of fasudil to dilate the neonatal ductus arteriosus, and its usefulness as a bridge to heart surgery. METHODS: We studied the dose and timing of administration of fasudil in the neonatal rat. Postnatal ductal closure was studied on the 21st gestational day following cesarean section and incubation for 30-480 min in room air at 33 degrees C, with a rapid whole-body freezing method. In control rats, the ductus closed rapidly after birth, and the ductal diameter was 0.80 and 0.12 mm at 0 and 30 min after birth. Fasudil was injected peritoneally into the neonate, and the ductus was studied 30 min after injection and 60 min after birth. RESULTS: Fasudil, 10 mg/kg, injected within 5 min after birth, dilated the ductus completely to 0.8 mm, and the dose used clinically, 1 mg/kg, dilated the ductus to 0.4 mm. The ductus-dilating effect of fasudil decreased rapidly as the neonatal ductus constricted. Fasudil, 100 mg/kg, dilated the ductus completely, but induced severe respiratory depression and frequent death in 1-hour-old rats. CONCLUSIONS: Fasudil dilates the neonatal ductus arteriosus dose-dependently in the rat. Fasudil in large doses dilates the neonatal ductus completely, but is associated with fatal side effects, including respiratory depression" http://www.ncbi.nlm.nih.gov/pubmed/19077393 0 1688 L. L. Shanbour and D. Parker 1972 Effects of dopamine and other catecholamines on the splanchnic circulation Can.J.Physiol Pharmacol. 50 6 594-602 http://www.ncbi.nlm.nih.gov/pubmed/5047745 0 1689 "J. Y. Chuang, W. T. Chang, C. G. Cherng, G. S. Kao and L. Yu" 2011 Repeated co-administrations of alcohol- and methamphetamine-produced anxiogenic effect could be associated with the neurotoxicity in the dentate gyrus J.Neural Transm.(Vienna.) 118 11 1559-1569 "To date, joint use of alcohol (EtOH) and methamphetamine (MA) represents a specific combination of polydrug abuse. Repeated administrations of EtOH, MA, and combined EtOH and MA were assessed for their effects on brain cell toxicity, cell mitosis and anxiety/depression-like behavior. We found that repeated co-administrations of EtOH and MA produced profound anxiogenic effects. Specifically, combined EtOH and MA decreased open arm exploratory responses in the elevated plus maze test. Moreover, combined EtOH and MA significantly decreased immobile responses in the tail suspension test. MA, EtOH, and their combination all reduced the number of NeuN-positive cells in amygdala (Amg), while neither of them altered the number of NeuN-positive cells in striatum (St) or prefrontal cortex (PFC). Combined EtOH and MA decreased the number of NeuN-positive cells in dentate gyrus (DG). EtOH, MA, and combined EtOH and MA all diminished comparable number of GFAP-positive cells in Amg, DG, and St. Neither of these treatment affected the number of GFAP-positive cells in PFC. EtOH, MA, and combined EtOH and MA generated comparable inhibiting effects on cell proliferation in the subventricular zone (SVZ) and DG. These results, taken together, suggest that repeated co-administrations of MA and EtOH may produce an observable anxiogenic effect. This combination-produced anxiogenic effect could be associated with neuronal loss in the dentate gurus. In contrast, such an anxiogenic effect is less likely related to this combination-caused glial toxicity in limbic regions or cell proliferation-inhibiting effect in the SVZ or DG" http://www.ncbi.nlm.nih.gov/pubmed/21499940 1 1690 "E. Schwarzer, F. Turrini, D. Ulliers, G. Giribaldi, H. Ginsburg and P. Arese" 1992 Impairment of macrophage functions after ingestion of Plasmodium falciparum-infected erythrocytes or isolated malarial pigment J.Exp.Med. 176 4 1033-1041 "Human monocyte-derived macrophages ingest diamide-treated red blood cells (RBC), anti-D immunoglobulin (Ig)G-opsonized RBC, or Plasmodium falciparum ring-stage parasitized RBC (RPRBC), degrade ingested hemoglobin rapidly, and can repeat the phagocytic cycle. Monocytes fed with trophozoite-parasitized RBC (TPRBC), which contain malarial pigment, or fed with isolated pigment are virtually unable to degrade the ingested material and to repeat the phagocytic cycle. Monocytes fed with pigment display a long-lasting oxidative burst that does not occur when they phagocytose diamide-treated RBC or RPRBC. The phorbol myristate acetate-elicited oxidative burst is irreversibly suppressed in monocytes fed with TPRBC or pigment, but not in monocytes fed with diamide-treated or IgG-opsonized RBC. This pattern of inhibition of phagocytosis and oxidative burst suggests that malarial pigment is responsible for the toxic effects. Pigment iron released in the monocyte phagolysosome may be the responsible element. 3% of total pigment iron is labile and easily detached under conditions simulating the internal environment of the phagolysosome, i.e., pH 5.5 and 10 microM H2O2. Iron liberated from pigment could account for the lipid peroxidation and increased production of malondialdehyde observed in monocytes fed with pigment or in RBC ghosts and liposomes incubated at pH 6.5 in presence of pigment and low amounts of H2O2. Removal of the labile iron fraction from pigment by repeated treatments with 0.1 mM H2O2 at pH 5.5 reduces pigment toxicity. It is suggested that iron released from ingested pigment is responsible for the intoxication of monocytes. In acute and chronic falciparum infections, circulating and tissue-resident phagocytes are seen filled with TPRBC and pigment particles over long periods of time. Moreover, human monocytes previously fed with TPRBC are unable to neutralize pathogenic bacteria, fungi, and tumor cells, and macrophage responses decline during the course of human and animal malaria. The present results may offer a mechanistic explanation for depression of cellular immunity in malaria" http://www.ncbi.nlm.nih.gov/pubmed/1402649 0 1691 N. C. Rawlings and I. J. Churchill 1990 Effect of naloxone on gonadotrophin secretion at various stages of development in the ewe lamb J.Reprod.Fertil. 89 2 503-509 "Spring-born crossbred ewe lambs were raised in a natural photoperiod and saline (N = 6) or naloxone (1 mg/kg) in saline (N = 6) was injected (i.m.) every 2 h for 6 h at 5, 10 and 15 weeks of age and for 8 h at 20, 25 and 30 weeks of age. Blood samples were taken every 12 min during treatment periods. Naloxone had no effect on time to first oestrus (controls 235 +/- 6 days, naloxone 242 +/- 7 days). Mean serum LH concentrations and LH pulse frequency were elevated by naloxone in ewe lambs at 20, 25, and 30 weeks of age (P less than 0.05). The only FSH response to naloxone was a depression of mean serum concentrations at 30 weeks of age (P less than 0.05). LH pulse amplitude was elevated at 5 weeks of age in all ewe lambs and declined thereafter to a nadir at 30 weeks of age in control, but not in naloxone-treated animals (P less than 0.05). LH pulse frequency was elevated at 10 weeks of age in control ewe lambs and in all animals at 30 weeks of age (P less than 0.05). FSH pulse frequency declined from 5 weeks of age in control ewe lambs (P less than 0.05), with very few pulses noted in 25- and 30-week-old animals. We conclude that (1) opioidergic suppression of LH, but not FSH, secretion developed at 20 weeks of age in the growing ewe lambs used in the present study, with no obvious change in suppression before the onset of first oestrus: (2) pulsatile FSH secretion occurred in the young ewe lamb but was lost as the lamb matured: (3) attainment of sexual maturity was preceded by an elevation in LH pulse frequency" http://www.ncbi.nlm.nih.gov/pubmed/2119430 0 1692 T. Aoki and Y. Fujita 1991 [Long-lasting changes in motoneuron discharges following 50 Hz tetanization of afferent nerves in cats] Nihon Ika Daigaku Zasshi 58 3 329-341 "The effects of 50 Hz tetanization on motoneuron discharges were studied in non-immobilized, non-anesthetized, decerebrate cats. Motoneuron discharges were monitored by recording either muscle (hamstring muscles or foot extensors) action potentials or ventral root (L7 or S1) discharges. In the latter case both ventral and dorsal roots were cut and corresponding dorsal roots were stimulated. It was found that in 13 out of 32 cases the tetanization of the sciatic nerve at 4.0T for 5 s produced enhancement of monosynaptically evoked muscle action potentials (H-wave) for 20-25 min. Three categories of potentials were distinguished in ventral root discharge according to latencies and thresholds: monosynaptic, polysynaptic and late potentials. When the dorsal root was tetanized at 2.5-5.0T for 5 s, all of these 3 categories of potentials exhibited an enhancement of the potential lasting for more than 30 min. The late potential, which was the longest-latency polysynaptic potential (4.7-6.5 ms), was the most sensitive to the tetanization. Its enhancement could develop slowly, yet the degree of the enhancement was the greatest, as compared with other two categories of potentials. In contrast, the enhancement of these potentials were always immediate. In 15 out of 46 cases at least one of the 3 categories of potentials exhibited the enhancement. Since the long-lasting changes were induced only with the strength enough to activate polysynaptic pathways, interneurons were considered to be responsible for these plastic changes. The monosynaptic potential could show a long-lasting depression following the tetanization" http://www.ncbi.nlm.nih.gov/pubmed/1880200 0 1693 "C. C. Lim, W. L. Lee, Y. S. Leo, K. E. Lee, K. P. Chan, A. E. Ling, H. Oh, A. P. Auchus, N. I. Paton, F. Hui and P. A. Tambyah" 2003 Late clinical and magnetic resonance imaging follow up of Nipah virus infection J.Neurol.Neurosurg.Psychiatry 74 1 131-133 "The Nipah virus is a newly identified paramyxovirus responsible for an outbreak of fatal encephalitis in Malaysia and Singapore. This paper reports the follow up clinical and magnetic resonance imaging findings in 22 affected subjects. Of 13 patients with encephalitis, one died, one was lost to follow up, and seven recovered. Among the four remaining patients, one had residual sixth nerve palsy, another suffered from severe clinical depression, and a third patient had evidence of retinal artery occlusion. One patient with delayed onset Horner syndrome had a single lesion in the cervical spinal cord. The brain magnetic resonance findings were stable or improved in nine patients over 18 months of follow up. Among a second group of nine asymptomatic seropositive abattoir workers, magnetic resonance examination in seven subjects revealed discrete small lesions in the brain; similar to those detected in encephalitis patients. These findings suggest that in addition to encephalitis, the newly discovered Nipah virus affects the spinal cord and the retina. Late clinical and radiological findings can occur in Nipah virus infections as with other paramyxoviruses" http://www.ncbi.nlm.nih.gov/pubmed/12486285 0 1694 "R. D. Kline, M. A. Corzo, V. W. Hays and G. L. Cromwell" 1973 "Related effects of copper, molybdenum and sulfide on performance, hematology and copper stores of growing pigs" J.Anim Sci. 37 4 936-941 http://www.ncbi.nlm.nih.gov/pubmed/4747186 0 1695 "J. C. Salinas, R. Cabezali, J. Torcal, L. Larrad, R. Sousa, M. Navarro and R. Lozano" 1998 Immune response and cytokines in septic rats undergoing blood transfusion J.Surg.Res. 80 2 295-299 "BACKGROUND: Intrabdominal sepsis and allogeneic blood transfusion have been associated with a depression of the immune response in patients undergoing surgery. Some authors have considered that an already immunocompromised host is probably primed for a potential detrimental effect of allogeneic blood. The aim of this paper is to ascertain the effects of allogeneic blood transfusion on the lymphocyte subsets and cytokines in septic rats. MATERIALS AND METHODS: Thirty rats were allotted into three groups: Sham-CLP, anesthesia and laparotomy; CLP, cecal ligation and puncture; CLP+BT, CLP and allogeneic blood transfusion. Preoperatively and on the 1st, 3rd, and 7th postoperative days, the cell percentages of lymphocyte subpopulations, the IL-2 receptor expression, and the IL-1, IL-2, TNF-alpha and IFN-gamma were measured in blood by flow cytometry and ELISA: RESULTS: CLP+BT rats showed on Day 3 a decrease of the CD4+%, an increase of the IL-2R expression directly correlated to the increase of the CD8+% phenotype, a steady increase of IL-1 levels, a decrease of the TNF-alpha levels on the 1st and 3rd days, and a decrease of the IL-2 and IFN-gamma on Day 1. CONCLUSIONS: An accumulative effect of the immunodepression induced by sepsis was observed when allogeneic blood transfusion is added. Blood transfusion + sepsis induces an extensive impairment on cellular immune response and an initial cytokine downregulation, except for IL-1" http://www.ncbi.nlm.nih.gov/pubmed/9878327 0 1696 "C. Ineichen, H. Sigrist, S. Spinelli, K. P. Lesch, E. Sautter, E. Seifritz and C. R. Pryce" 2012 Establishing a probabilistic reversal learning test in mice: evidence for the processes mediating reward-stay and punishment-shift behaviour and for their modulation by serotonin Neuropharmacology 63 6 1012-1021 "Valid animal models of psychopathology need to include behavioural readouts informed by human findings. In the probabilistic reversal learning (PRL) task, human subjects are confronted with serial reversal of the contingency between two operant stimuli and reward/punishment and, superimposed on this, a low probability (0.2) of punished correct responses/rewarded incorrect responses. In depression, reward-stay and reversals completed are unaffected but response-shift following punished correct response trials, referred to as negative feedback sensitivity (NFS), is increased. The aims of this study were to: establish an operant spatial PRL test appropriate for mice; obtain evidence for the processes mediating reward-stay and punishment-shift responding; and assess effects thereon of genetically- and pharmacologically-altered serotonin (5-HT) function. The study was conducted with wildtype (WT) and heterozygous mutant (HET) mice from a 5-HT transporter (5-HTT) null mutant strain. Mice were mildly food deprived and reward was sugar pellet and punishment was 5-s time out. Mice exhibited high motivation and adaptive reversal performance. Increased probability of punished correct response (PCR) trials per session (p = 0.1, 0.2 or 0.3) led to monotonic decrease in reward-stay and reversals completed, suggesting accurate reward prediction. NFS differed from chance-level at p PCR = 0.1, suggesting accurate punishment prediction, whereas NFS was at chance-level at p = 0.2-0.3. At p PCR = 0.1, HET mice exhibited lower NFS than WT mice. The 5-HTT blocker escitalopram was studied acutely at p PCR = 0.2: a low dose (0.5-1.5 mg/kg) resulted in decreased NFS, increased reward-stay and increased reversals completed, and similarly in WT and HET mice. This study demonstrates that testing PRL in mice can provide evidence on the regulation of reward and punishment processing that is, albeit within certain limits, of relevance to human emotional-cognitive processing, its dysfunction and treatment" http://www.ncbi.nlm.nih.gov/pubmed/22824190 0 1697 "J. M. Kirkwood, R. A. Mascari, H. D. Edington, M. S. Rabkin, R. S. Day, T. L. Whiteside, D. R. Vlock and J. M. Shipe-Spotloe" 2000 Analysis of therapeutic and immunologic effects of R(24) anti-GD3 monoclonal antibody in 37 patients with metastatic melanoma Cancer 88 12 2693-2702 "BACKGROUND: Antitumor effects of antibodies against ganglioside antigens of melanoma have been reported, but neither optimal doses nor mechanisms have been established. METHODS: This Phase IB trial of the murine immunoglobulin IgG(3) monoclonal antibody R(24) against disialoganglioside GD3 was conducted with 37 patients to define better the dose-response relation and mechanism of action of R(24) in patients with metastatic melanoma. RESULTS: Dose-limiting toxicity consisted of a pulmonary capillary leak syndrome in 3 of 5 patients in the 80 mg/M(2)/day dosage tier. Serial blood and tumor biopsy samples were obtained prior to therapy and on Days 5, 9, and 22 following R(24) infusion. Tumor biopsy-infiltrating lymphocytes were enumerated in peritumoral, endotumoral, and perivascular compartments: endotumoral CD4(+) and CD8(+) T cells and HLA-DR(+) T cells increased over time on R(24) antibody. Endotumoral CD4 lymphoid infiltrate activation (DR expression) and antibody-dependent cytotoxicity were the greatest in the one patient who achieved a complete response. CONCLUSIONS: Clinical response was associated with depression in natural killer (CD56(+) and CD56(+)DR(+)) blood cells (P = 0.03) and was associated with R(24) dosage (P = 0.01). A complete response that lasted 2 years and a partial response that lasted 2 months occurred at a dose of 1 mg/M(2)/day. The limited number of clinical responses observed in this trial hampered the correlation of antitumor and immune parameters but provided a rational foundation for the future evaluation of antiganglioside antibodies" http://www.ncbi.nlm.nih.gov/pubmed/10870051 0 1698 "N. Hosoi, T. Sakaba and E. Neher" 2007 Quantitative analysis of calcium-dependent vesicle recruitment and its functional role at the calyx of Held synapse J.Neurosci. 27 52 14286-14298 "Recruitment of release-ready vesicles at synapses is one of the important factors, which determine dynamic properties of signaling between neurons in the brain. It has been shown that the rate of vesicle recruitment is accelerated by strong synaptic activity. An elevated concentration of calcium ions in the presynaptic terminal ([Ca2+]i) has been proposed to be responsible for this effect. However, the precise relationship between [Ca2+]i and recruitment has not been established yet, and the functional consequences of accelerated recruitment during synaptic activity have not been quantified experimentally. To probe the intracellular Ca2+ dependence of vesicle recruitment and to examine its functional role during trains of action potential (AP)-like stimuli, we monitored [Ca2+]i and synaptic responses simultaneously with paired recordings at the calyx of Held synapse. We found that a distinct, rapidly releasing vesicle pool is replenished with a rate that increases linearly with [Ca2+]i, without any apparent cooperativity. The slope factor for this increase is approximately 1 pool/(microM x s). Blocking Ca2+-dependent recruitment specifically with a calmodulin binding peptide revealed that the steady-state EPSCs during 100 Hz AP-like trains were maintained through this Ca2+-dependent recruitment mechanism. Using a simple model of vesicle dynamics, we estimated that the recruitment rate accelerated 10-fold during the steady-state compared with the rate at resting [Ca2+]i. We could also demonstrate an approximate sixfold increase in release probability (facilitation) during the initial 5-15 AP-like stimuli of such trains in our experimental condition, regardless of EPSC depression" http://www.ncbi.nlm.nih.gov/pubmed/18160636 0 1699 "T. Mori, H. Kohda, Y. Kinoshita, Y. Ezaki, N. Morimoto and T. Nishimura" 1980 Inhibition by indomethacin of ovulation induced by human chorionic gonadotrophin in immature rats primed with pregnant mare serum gonadotrophin J.Endocrinol. 84 3 333-341 "Treatment of immature rats with pregnant mare serum gonadotrophin followed by human chorionic gonadotrophin (HCG) caused an acute and temporary increase in concentrations of progesterone, testosterone and oestradiol in plasma with maximum levels 3 h after the administration of HCG. Concurrent injection of indomethacin and HCG reduced, in a dose-dependent manner, the mean number of ova shed and this was accompanied by a dose-dependent decrease in concentrations of plasma progesterone and testosterone but not of oestradiol when they were measured 3 h after the injection of HCG. The minimum effective dose that blocked ovulation completely at 0 h abolished the acute increase of progesterone and testosterone, suggesting that prostaglandins act on ovulation by stimulating steroidogenesis at an early stage in the preovulatory process. The anti-ovulatory action of the minimum effective dose at 0 h became progressively less potent as the time between injection of HCG and administration of indomethacin was increased, although plasma concentrations of progesterone and testosterone measured at autopsy 18 h after treatment with HCG had not changed appreciably. When indomethacin was administered 10 h after HCG, the relationship between the dose of indomethacin and the mean number of ova differed from that observed when simultaneous injections of indomethacin and HCG were given, and the minimum effective dose that prevented ovulation was much higher than that at 0 h, suggesting that prostaglandins act differently on ovulation in the later stage of the preovulatory process. It was concluded that prostaglandins may mediate the action of HCG on ovulation through two mechanisms which operate at different stages of the preovulatory process" http://www.ncbi.nlm.nih.gov/pubmed/7391712 0 1700 "Z. P. HOROVITZ, A. R. FURGIUELE, L. J. BRANNICK, J. C. BURKE and B. N. CRAVER" 1963 A new chemical structure with specific depressant effects on the "Nature.200 ()(pp 369-370), 1963.Date of Publication: 1963." 369-370 1 1701 "J. Knoll, B. Knoll and I. Miklya" 1996 High performing rats are more sensitive toward catecholaminergic activity enhancer (CAE) compounds than their low performing peers Life Sci. 58 11 945-952 "Two breeds of rats, Charles River Wistar [Crl(Wi)Br.] and HSD Wistar [Wistar per LATI (Budapest) Br.], with remarkable difference in learning performance were selected. The rats were trained in the shuttle box with 100 trials per day and the number of conditioned avoidance responses (CARs), the escape failures (EFs) to the unconditioned stimulus and the intersignal reactions (IRs) were counted and evaluated by multi-way analysis of variance (ANOVA). Rats of the Crl (Wi) breed proved to be the 'low performing' (LP) animals and rats of the Wistar per LATI (Budapest) breed the 'high performing' (HP) ones. The HP rats produced higher number of CARs (p<0.001), lower number of EFs (P<0.05) and higher number of IRs (P<0.01) than their LP peers. Significantly higher amounts of noradrenaline from the locus coeruleus and serotonin from the raphe were released in the HP than in the LP rats (p<0.01). There was no difference between HP and LP rats in the amount of dopamine released from the striatum, the substantia nigra and the tuberculum olfactorium. The catecholaminergic activity enhancer (CAE) substance, 1-phenyl-2-propylaminopentane HCl, [(-)PPAP], which enhances action potential-transmitter release coupling in the catecholaminergic neurons, fully antagonized in a dose of 1 mg/kg, tetrabenazine-induced learning depression in HP rats and this dose was ineffective in LP rats. The findings were regarded as further support for the view that endogenous CAE substances regulate catecholaminergic activity in the brain and (-)PPAP acts via this regulation" http://www.ncbi.nlm.nih.gov/pubmed/8786700 0 1702 "G. L. Kennedy, A. J. O'Neill and R. Valentine" 2001 Inhalation toxicity of Dioxole and Dioxolane compounds in the rat Drug Chem.Toxicol. 24 1 Jan-17 "Four chemicals (Dioxole 418, Dioxolane 418, Dioxolane 416 and Dioxolane 456) which are used as stabilizers in highresolution image were tested or both their acute and repeated inhalation toxicity in the rat using nose-only exposures. Acute studies determined the lethal concentrations following a single 4-hour exposure; repeated exposure inhalation studies determined the potency and target tissue(s) following 6-hour/day exposures, 5 days/week for 2 weeks. Each of the chemicals was at least mildly toxic acutely with approximate lethal concentrations of > 1,500 ppm for Dioxole 418, 1,300 ppm for Dioxolane 418, 1,700 ppm for Dioxolane 416, and 4,300 ppm for Dioxolane 456. No specific unusual clinical signs of response were seen in the rats exposed acutely. Repeated exposures with Dioxole 418 and Dioxolane 418 resulted in no evidence of toxicity with NOAEL's being 440 and 500 ppm respectively (the highest concentrations tested). Repeated exposures to 250 ppm Dioxolane 456 were not tolerated with mortalities observed after exposure. Severe bone marrow hypoplasia along with reductions in platelet and neutrophil counts were observed at this concentration with less severe hemopoietic changes seen also at 10 and 51 ppm. The no-effect level for Dioxolane 456 was determined to be 10 ppm in female rats and I ppm in males. The same hemopoietic effects were seen with Dioxolane 416 at exposures of 53 ppm or greater in males but not in females exposed to 53 ppm Dioxolane 416. Hepatocellular hypertrophy and depression of serum alkaline phosphatase activity were seen in male rats exposed to 500 but not 53 ppm Dioxolane 416. Testicular degeneration was also seen in rats exposed to 500 ppm Dioxolane 416. The NOAEL was 5 ppm for the chemical" http://www.ncbi.nlm.nih.gov/pubmed/11307631 0 1703 "S. Mitra, G. S. Sameer Kumar, V. Tiwari, L. B. Jyothi, S. Thakur and S. Kumar" 2014 Wdr13 knockout mice shows marginally better memory but impaired ability to withstand social isolation stress "FEBS Journal.Conference: FEBS EMBO 2014 Conference Paris France.Conference Start: 20140830 Conference End: 20140904.Conference Publication: (var.pagings).281 ()(pp 216), 2014.Date of Publication: September 2014." var.pagings 216 "Wdr13 is a novel WD repeat protein containing gene, knockout of which in mice results in age dependant mild obesity and pancreatic beta cell hyper-proliferation leading to increased insulin secretion (Singh et al, 2012). Our lab also found that this protein interacts in a co-repressor complex with several nuclear receptors and phosphorylation at 70 S of this protein is important for its function. Function of this gene in brain and behavior haven't been studied extensively though literature survey shows association of this gene with memory. RISH localizes wdr13 expression in hippocampal formation, cerebral cortex, cerebellum and striatum. An age window of 2-3.5 months has been chosen for brain and behavior studies in these knockout mice. Using NMR it was found that metabolic changes in brain are not prominent in this interval. Wdr13 -/0 mice in CD1 background show increased anxiety and impaired ability of novel object recognition. In C57BL6/J background also, the knockout mice showed higher anxiety than that in wild types proving that the phenotype was strain-independent. The Wdr13 knockout mice, however, fared marginally better than the wild type mice in memory tests. There was no significant change in the brain morphology of the adult and hippocampal adult neurogenesis (at 2 months) in these mice was not significantly affected under normal conditions. Deep proteomics using iTRAQ revealed increased levels of synapsin1 and down-regulated levels of neurogranin in hippocampus and prefrontal cortex may be causative for this phenotype. Interestingly, upon social isolation for 3 weeks, the anxiety and depression-like symptoms in the knockout mice are aggravated with loss in dendritic branches in hippocampus and significant decrease in synaptic genes like syn1, rab3a, nrxn2 at transcript and protein levels. This was also accompanied with increase in GATA1, a common negative Transcription Factor for the above-mentioned and known to be marker of MDD (Major Depressive Disorder). We are led to believe that Wdr13 regulates GATA1 expression and absence of it leads to de-regulation of the gene and its downstream targets" DO - http://dx.doi.org/10.1111/febs.12919 0 1704 "C. L. Swenson, G. J. Kociba and P. Arnold" 1988 Chronic idiopathic neutropenia in a cat J.Vet.Intern.Med. 2 2 100-102 "Persistent neutropenia (0-0.6 X 10(9) neutrophils/l) was documented during a 10-month period in a 4-year-old spayed female domestic shorthair cat that was presented for anorexia and depression. Salient abnormalities detected on physical examination were fever (40.3 degrees C), dehydration, and gingivitis. The cat was neutropenic (0.5 X 10(9) neutrophils/l) and enzyme-linked immunosorbent assay (ELISA) test for feline leukemia virus was negative. A bone marrow aspirate showed decreased numbers of mature granulocytic cells. In vitro bone marrow cultures for colony-forming units-granulocyte/macrophage (CFU-GM) were performed comparing bone marrow from the patient with that of a normal cat. The patient had fewer CFU-GM than the control. The number of CFU-GM increased when bone marrow mononuclear cells were cultured in the presence of 10(-5) and 10(-6) mol/l of hydrocortisone, but the cat did not respond to oral prednisolone therapy. The pathogenesis of the neutropenia in this cat remains obscure, but resembles the chronic idiopathic neutropenia syndrome of man" http://www.ncbi.nlm.nih.gov/pubmed/3221355 0 1705 "Y. Eto, K. Suzuki and K. Suzuki" 1971 Lipid composition of rat brain myelin in triethyl tin-induced edema J.Lipid Res. 12 5 570-579 "Chronic triethyl tin intoxication was induced in young adult rats by oral feeding of triethyl tin sulfate. Progressively severe brain edema developed during the 3-month experimental period. The yield of myelin from the brains of the experimental animals decreased to almost half normal per brain, but the isolated myelin appeared morphologically normal. The analysis of whole brain showed corresponding decreases in proteolipid protein and total lipid, particularly galactolipids. The proportions of the major constituents of isolated myelin (chloroform-methanol-insoluble residue, proteolipid protein, and total lipid) were unchanged despite the low yield. However, the proportion of cholesterol increased from 16 to 21% dry weight, and that of total galactolipid decreased from 21 to 15%, as the yield of myelin decreased. This decrease of total galactolipid was mainly due to the decrease in cerebroside. Total phospholipid remained constant initially but showed a slight decrease toward the end of the experiment, due mostly to decreased ethanolamine phospholipid. There was no preferential loss or preservation of phosphatidalethanolamine. The fatty acid composition of sulfatide showed statistically significant shifts to less long-chain fatty acids and less monoenoic acids, but cerebroside and sphingomyelin did not show significant changes in the fatty acid composition. There was no increase in esterified cholesterol. These findings generally support our hypothesis of nonspecific chemical abnormalities of the myelin sheath undergoing secondary degeneration. In an acute experiment, a single intraperitoneal injection of triethyl tin sulfate produced acute and transient brain edema. There were slight decreases in the yield of myelin, but no detectable changes in the chemical composition" http://www.ncbi.nlm.nih.gov/pubmed/5098393 0 1706 "J. S. Richardson, D. L. Keegan, R. C. Bowen, S. L. Blackshaw, S. Cebrian-Perez, N. Dayal, S. Saleh and S. Shrikhande" 1994 Verbal learning by major depressive disorder patients during treatment with fluoxetine or amitriptyline Int.Clin.Psychopharmacol. 9 1 35-40 "After 1 week of a single-blind placebo period, and prior to being randomly assigned to receive treatment with either fluoxetine or amitriptyline, patients meeting strict criteria for a diagnosis of major depressive disorder were given an auditory verbal learning test of working memory, and a blood sample was drawn. After 3 weeks of drug treatment with either amitriptyline or fluoxetine, the patients' symptoms were evaluated, the verbal learning test was repeated, and a second blood sample was taken. The clinical evaluation, the verbal learning test and the blood drawing were repeated a third time 3 weeks after the second assessment. The amount of anticholinergic activity in the blood samples was measured by a competitive radioligand binding assay and expressed in atropine equivalents. Analyses of variance indicated that there were no significant differences at the predrug Assessment 1 between patients subsequently assigned to the fluoxetine group compared with those assigned to the amitriptyline group. At Assessments 2 and 3, the fluoxetine and the amitriptyline groups showed equal clinical improvement but patients receiving amitriptyline did not perform as well on the verbal learning task. Serum anticholinergic activity at Assessments 2 and 3 was considerably higher in the amitriptyline group. This supports the hypothesis that blockade of muscarinic receptors impairs working memory formation. Equally effective antidepressant drugs with little or no anticholinergic action, such as fluoxetine, may be preferable in patients with pre-existing mild cognitive impairment or in patients where a slight reduction in cognitive performance is not acceptable" http://www.ncbi.nlm.nih.gov/pubmed/8195581 0 1707 "Z. Z. Zhao, X. Q. Chen, D. Q. Li, X. X. Gao, M. J. Wang, M. Ai, N. Chen, J. M. Chen, X. M. Li and L. Kuang" 2009 Significant associations between five AKT1 SNP markers and major depressive disorder in the Chinese population "Behavior Genetics.Conference: Behavior Genetics Association 39th Annual Meeting Minneapolis, MN United States.Conference Start: 20090617 Conference End: 20090620.Conference Publication: (var.pagings).39 (6) ()(pp 694), 2009.Date of Publication: Novem" var.pagings 694 "Background: V-akt murine thymoma viral oncogene homologue 1 (AKT1) is a serine/threonine kinase. Abnormality of AKT1 is involved in various diseases, including mental disorder. Recent evidence suggests that the Variation in AKT1 gene has been associated with schizophrenia, Parkinson's disease and type II diabetes. But the relationship of AKT1 gene variation in depression is unknown. The aim of the present study was to investigate the potential role of variability within AKT1 gene polymorphisms as a risk factor for major depressive disorder (MDD). Method: We performed a case-control association analysis of AKT1. Five single nucleotide polymorphisms (SNPs) according to the original study were genotyped among 205 MDD (DSM-IV criteria) and 173 healthy controls from the Chinese population. Samples were investigated by using PCR-RFLP. Results: There were a positive association of allele T of the marker SNP3 with MDD (rs3730358, p =.022). Haplotype analysis showed that the frequency of a four-AKT1 SNP1/2/3/4 haplotype (AGTG) was significantly higher in MDD patients (0.054) than that of controls (0.011) (p =.011). Conclusion: Our research indicate that AKT1 gene May be a potential susceptibility gene for Major Depressive Disorder" DO - http://dx.doi.org/10.1007/s10519-009-9307-7 0 1708 "J. Andersen, N. Stuhr-Hansen, L. Zachariassen, S. Toubro, S. M. Hansen, J. N. Eildal, A. D. Bond, K. P. Bogeso, B. Bang-Andersen, A. S. Kristensen and K. Stromgaard" 2011 Molecular determinants for selective recognition of antidepressants in the human serotonin and norepinephrine transporters Proc.Natl.Acad.Sci.U.S.A 108 29 12137-12142 "Inhibitors of the serotonin transporter (SERT) and norepinephrine transporter (NET) are widely used in the treatment of major depressive disorder. Although SERT/NET selectivity is a key determinant for the therapeutic properties of these drugs, the molecular determinants defining SERT/NET selectivity are poorly understood. In this study, the structural basis for selectivity of the SERT selective inhibitor citalopram and the structurally closely related NET selective inhibitor talopram is delineated. A systematic structure-activity relationship study allowed identification of the substituents that control activity and selectivity toward SERT and NET and revealed a common pattern showing that SERT and NET have opposite preference for the stereochemical configuration of these inhibitors. Mutational analysis of nonconserved SERT/NET residues within the central substrate binding site was performed to determine the molecular basis for inhibitor selectivity. Changing only five residues in NET to the complementary residues in SERT transferred a SERT-like affinity profile for R- and S-citalopram into NET, showing that the selectivity of these compounds is determined by amino acid differences in the central binding site of the transporters. In contrast, the activity of R- and S-talopram was largely unaffected by any mutations within the central substrate binding site of SERT and NET and in the outer vestibule of NET, suggesting that citalopram and talopram bind to distinct sites on SERT and NET. Together, these findings provide important insight into the molecular basis for SERT/NET selectivity of antidepressants, which can be used to guide rational development of unique transporter inhibitors with fine-tuned transporter selectivity" http://www.ncbi.nlm.nih.gov/pubmed/21730142 0 1709 "D. W. Costain, A. R. Green and D. G. Grahame-Smith" 1979 Enhanced 5-hydroxytryptamine-mediated behavioural responses in rats following repeated electroconvulsive shock: relevance to the mechanism of the antidepressive effect of electroconvulsive therapy Psychopharmacology (Berl) 61 2 167-170 "Treatment of rats with one electroconvulsive shock (ECS) per day for 10 days enhanced the hyperactivity syndrome produced by administration of tranylcypromine (10 mg kg-1) and L-tryptophan (50 mg kg-1) given 24 h after the final shock. Similar enhancement was seen whether the shock was alternating sinusoidal or direct current (fractionated), whether it was given through unilaterally or bilaterally placed electrodes and whether or not a neuromuscular blocking agent (fazadinium) was used. Five shocks spread over 10 days or 8 shocks spread over 17 days were similarly effective, whilst 8 shocks in 1 day were ineffective. Therefore when ECS are given to rats in ways similar to those in which electroconvulsive therapy is given to patients with depression, enhancement of behavioural responses to increased 5-HT function is produced" http://www.ncbi.nlm.nih.gov/pubmed/108733 1 1710 A. Beetz 2013 Socio-emotional correlates of a schooldog-teacher-team in the classroom Front Psychol. 4 886 "A growing number of teachers in Europe regularly take their dogs with them into the classroom. Limited research points at positive socio-emotional effects of this practice. In this study the effects of a schooldog-teacher-team on socioemotional experiences in school, depression and emotion regulation strategies were investigated in a classroom of third-graders (male n = 12, female n = 13), which had a schooldog present for 1 day per week in comparison with a control class (male n = 11, female n = 10). In contrast to the control class, the dog-class students reported a stronger improvement with regard to positive attitude toward school (repeated measures ANOVA; F = 10.769, df = 1, p = 0.002) and positive emotions related to learning (F = 4.479, df = 1, p = 0.042) over the course of the year. Since a prerequisite of all kinds of effective learning is a positive attitude and mood toward school and learning, the presence of a schooldog-teacher team thus has the potential to support learning" http://www.ncbi.nlm.nih.gov/pubmed/24348440 0 1711 A. Sato 1990 [Sympathetic regulation of adrenal medullary function during aging] Fiziol.Zh. 36 5 94-99 "Our recent studies on changes in sympathoadrenal medullary function with age in anesthetized Wistar rats were reviewed. Although secretion rates of adrenaline and noradrenaline from the adrenal gland under resting conditions varied among animals, they gradually increased after 300 days and reached a level 2-4 times higher at 800-900 days compared with that of 100 days. Spontaneous activity of a single sympathetic nerve fiber under resting conditions also increased during aging in a manner similar to the catecholamine secretion rates. Reflex responses of mass activity of adrenal sympathetic nerve fibers to stimulation of baroreceptor and cutaneous mechanoreceptors were compared in young adult (4 months old) and aged (26 months old) Wistar rats under strictly controlled conditions for anesthesia, respiration and body temperature. Under these conditions the reflex depression in response to baroreceptor stimulation and cutaneous brushing as well as reflex excitation in response to cutaneous pinching were quite well maintained in the aged rats" http://www.ncbi.nlm.nih.gov/pubmed/2272396 0 1712 "D. S. Shaw, M. Schonberg, J. Sherrill, D. Huffman, J. Lukon, D. Obrosky and M. Kovacs" 2006 Responsivity to offspring's expression of emotion among childhood-onset depressed mothers "Journal of Clinical Child and Adolescent Psychology.35 (4) ()(pp 490-503), 2006.Date of Publication: December 2006." 4 490-503 "This study examined responsivity of mothers with childhood-onset depression (COD) in relation to children's overt expression of positive and negative emotion. It was hypothesized that COD and control mothers would differ in contingent responsivity to their children's expression of both positivity and different types of negative emotionality. Using observations and maternal reports of their own emotional reactions, COD mothers were found to be less responsive to children's expression of distress. A Gender x Group interaction was also found with respect to observed maternal responsiveness to child positivity, such that COD mothers were more responsive to girls ' than boys' expression of positivity. The results are discussed in reference to transactional models of early child psychopathology. Copyright © 2006 by Lawrence Erlbaum Associates, Inc" DO - http://dx.doi.org/10.1207/s15374424jccp3504_1 0 1713 "S. Wachholz, M. Esslinger, J. Plumper, M. P. Manitz, G. Juckel and A. Friebe" 2015 Microglia activation is associated with IFN-alpha induced depressive-like behavior Brain Behav.Immun. "Inflammatory immune activation has been frequently associated with the development of major depression. This association was confirmed in patients receiving long-term treatment with pro-inflammatory interferon-alpha (IFN-alpha). Microglia, the resident immune cells in the brain, might serve as an important interface in this immune system-to-brain communication. The aim of the present study was to investigate the role of microglia in an IFN-alpha mouse model of immune-mediated depression. Male BALB/c mice were treated with daily injections of IFN-alpha for two weeks. Depressive-like behavior was analyzed in the forced swim and tail suspension test. Activation of microglia was measured by flow cytometry. Pro-inflammatory M1 type (MHC-II, CD40, CD54, CD80, CD86, CCR7), anti-inflammatory M2 type (CD206, CD200R), and maturation markers (CD11c, CCR7) were tested, as well as the chemokine receptor CCR2. IFN-alpha led to a significant increase in depressive-like behavior and expression of the pro-inflammatory surface markers MHC-II, CD86, and CD54, indicating M1 polarization. Because IFN-alpha-treated mice showed great individual variance in the behavioral response to IFN-alpha, they were further divided into vulnerable and non-vulnerable subgroups. Only IFN-alpha vulnerable mice (characterized by their development of depressive-like behavior in response to IFN-alpha) showed an increased expression of MHC-II and CD86, while CD54 was similarly enhanced in both subgroups. Thus, IFN-alpha-induced activation of microglia was specifically associated with depressive-like behavior" http://www.ncbi.nlm.nih.gov/pubmed/26408795 1 1714 "L. S. Gotzsche, E. M. Pedersen and P. K. Paulsen" 1993 Lowered threshold for ventricular fibrillation in amiodarone-treated pigs undergoing cardiopulmonary bypass and cardioplegic arrest with St. Thomas' cardioplegic solution Eur.J.Cardiothorac.Surg. 7 4 186-192 "The antiarrhythmic agent amiodarone has been suspected of causing reduced cardiac performance after extracorporeal circulation and cardioplegic arrest in patients. This has recently been confirmed in an experimental model where pigs were exposed to cardiopulmonary bypass and cold cardioplegic arrest with Bretschneider's solution. Due to the high concentration of the cardio-depressant agent procain in Bretschneider's solution, it could be speculated whether it is the combination of amiodarone and this solution that may be potentially deleterious, rather than amiodarone alone. To investigate this, adult pigs (75 +/- 2 kg at surgery) were treated with amiodarone for 30 +/- 2 days (1400 mg/day: n = 8, untreated controls: n = 4, blind experiment), followed by exposure to cardiopulmonary bypass with universal cooling to 28 degrees C and topical cold cardioplegic arrest with St. Thomas' solution for 60 min. Apart from 1 g of calcium (Ca2+) at the end of bypass, no inotropic drugs were administered. Cardiac reserve was tested by right ventricular pacing (200 beats/min until death or up to 30 min). The two groups did not differ concerning preload or afterload, heart rate, cardiac output, left ventricular pressure, arterial pressure or rate of change in left ventricular relaxation (-dP/dt) before or after bypass was terminated, while the rate of change in left ventricular contraction (+dP/dt) was lower in the amiodarone-treated pigs. The time on bypass, before stable hemodynamics had recovered, was prolonged in amiodarone-treated animals, 46 +/- 4 min versus 31 +/- 3 min in the controls (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)" http://www.ncbi.nlm.nih.gov/pubmed/8481255 0 1715 M. Stopfer and T. J. Carew 1996 Heterosynaptic facilitation of tail sensory neuron synaptic transmission during habituation in tail-induced tail and siphon withdrawal reflexes of Aplysia J.Neurosci. 16 16 4933-4948 "In cellular studies of habituation, such as in the gill and siphon withdrawal reflex to tactile stimulation of the siphon of Aplysia, a mechanism that has emerged as an explanation for response decrement during habituation is homosynaptic depression at sensory neurons mediating the behavioral response. We have examined the contribution of homosynaptic depression to habituation in sensory neurons that contribute to two reflex behaviors in Aplysia, tail withdrawal and siphon withdrawal, both elicited by threshold-level tail stimulation. In a companion paper (this issue), we reported that repeated tail stimulation, identical to that producing habituation in siphon withdrawal in freely moving animals, also produces habituation in reduced preparations. In this paper, we extend these behavioral findings by showing that in reduced preparations, identical tail stimulation also produces habituation of the tail withdrawal reflex. In addition, our cellular experiments show that (1) identified sensory and motor neurons in both reflex systems respond to identical repeated tail stimulation; in sensory neurons it produces a progressive decrease in spike number and increase in spike latency, and in motor neurons it produces progressive decrement in complex EPSPs and spike output. (2) Homosynaptic depression of the tail sensory neuron to tail motor neuron synapse does occur when the sensory neurons are activated repetitively by intracellular current. (3) Homosynaptic depression at this synapse does not occur when the sensory neurons are activated repetitively by threshold-level tail stimuli that elicit the behavioral reflex and cause habituation; rather, the sensory neurons exhibit significant heterosynaptic facilitation. Thus, in these reflexes, habituation is not accompanied by homosynaptic depression at the sensory neurons, suggesting that the plasticity underlying habituation occurs primarily at interneuronal sites" http://www.ncbi.nlm.nih.gov/pubmed/8756425 0 1716 D. E. Blandford and D. D. Smyth 1988 Renal alpha 2-adrenoceptor blockade decreases sodium and water excretion in the anesthetized rat Eur.J.Pharmacol. 154 2 117-124 "The reported effects of renal alpha 2-adrenoceptor blockade on sodium and water excretion have been inconsistent. We therefore studied the effect of an intrarenal infusion of an alpha 2-adrenoceptor antagonist in rats undergoing two distinct levels of diuresis and natriuresis. Renal excretion of sodium and water was studied in anesthetized rats that had been unilaterally nephrectomized (right kidney) 10 days prior to the experimental day. In the presence of the lower rate of saline infusion an intrarenal infusion of the alpha 2-adrenoceptor antagonist, yohimbine, (25.6 nmol/kg per min) resulted in no change in urine volume or sodium and potassium excretion. In the presence of the modest diuresis, due to the higher level of saline infusion, intrarenal yohimbine resulted in a decrease in urine volume, sodium excretion and free water clearance. These effects of yohimbine were not found in adrenalectomized rats. The ability to demonstrate an effect of renal alpha 2-adrenoceptor blockade was dependent on the baseline level of sodium and water excretion. These results suggest that renal alpha 2-adrenoceptors may mediate the inhibition of the renal action of vasopressin by adrenal catecholamines" http://www.ncbi.nlm.nih.gov/pubmed/2906609 0 1717 "S. Y. Yau, A. Li, E. D. Zhang, B. R. Christie, A. Xu, T. M. Lee and K. F. So" 2014 Sustained running in rats administered corticosterone prevents the development of depressive behaviors and enhances hippocampal neurogenesis and synaptic plasticity without increasing neurotrophic factor levels Cell Transplant. 23 04-May 481-492 "We have previously shown that voluntary running acts as an anxiolytic and ameliorates deficits in hippocampal neurogenesis and spatial learning. It also reduces depression-like behaviors that are normally observed in rats that were administered either low (30 mg/kg) or moderate (40 mg/kg) doses of corticosterone (CORT). However, the protective effects of running were absent in rats treated with a high (50 mg/kg) dose of CORT. We examined whether allowing animals to exercise for 2 weeks prior and/or concurrently with the administration of 50 mg/kg CORT treatment could have similar protective effects. We examined hippocampal neurogenesis using immunohistochemical staining of proliferative and survival cells with the thymidine analogs (BrdU, CIdU, and IdU). In addition, we monitored synaptic protein expression and quantified the levels of neurotrophic factors in these animals as well as performing behavioral analyses (forced swim test and sucrose preference test). Our results indicate that the depressive phenotype and reductions in neurogenesis that normally accompany high CORT administration could only be prevented by allowing animals to exercise both prior to and concurrently with the CORT administration period. These animals also showed increases in both synaptophysin and PSD-95 protein levels, but surprisingly, neither brain-derived neurotrophic factor (BDNF) nor insulin-like growth factor 1 (IGF-1) levels were increased in these animals. The results suggest that persistent exercise can strengthen resilience to stress by promoting hippocampal neurogenesis and increasing synaptic protein levels, thereby reducing the deleterious effects of stress" http://www.ncbi.nlm.nih.gov/pubmed/24816445 1 1718 "C. D. Derby, B. W. Ache and W. E. Carr" 1987 Purinergic modulation in the brain of the spiny lobster Brain Res. 421 01-Feb 57-64 "Earlier studies identified purinergic chemoreceptors in the olfactory organ of the spiny lobster, Panulirus argus. In this study, electrophysiological experiments demonstrate that purinergic substances can modulate both the spontaneous activity and the evoked responses of neurons within the brain of this animal. Perfusion of the brain with 100 microM adenosine 5'-monophosphate (AMP) modulated the spontaneous activity of 71% of the brain interneurons that were monitored. AMP also modulated the electrically or chemically evoked activity of 25% of the monitored interneurons. The effects were dose-dependent (down to 1 microM) and reversible. The modulatory effects of adenosine were similar to those of AMP, and were antagonized by the adenosine receptor antagonist 1,3-dipropyl-8-p-sulfophenylxanthine. The modulation by AMP or adenosine was depressive in most but not all neurons, as is the case with purinergic effects in the brain of vertebrates. We believe this is the first demonstration of modulatory effects of purinergic substances in the nervous system of any invertebrate" http://www.ncbi.nlm.nih.gov/pubmed/3690285 0 1719 "R. Misslin, C. Belzung and E. Vogel" 1988 Interaction of RO 15-4513 and ethanol on the behaviour of mice: antagonistic or additive effects? Psychopharmacology (Berl) 94 3 392-396 "Opposite effects were observed of ethanol on the behaviour of mice in the two chambered light/dark test. At a low dose, it had anxiogenic effects, while it produced anxiolytic effects at a higher dose. Selective antagonistic actions of RO 15-4513 against the behavioural effects of ethanol have been reported by others without intrinsic actions. In contrast, we found intrinsic depressive properties of RO 15-4513. This drug reduced locomotion in a running wheel test. We suggest that RO 15-4513 reversed certain effects of ethanol in an additive, rather than interactive, manner. In addition, RO 15-4513 did not block the sedation produced by a high dose of ethanol. Since RO 15-4513 revealed proconvulsant properties, it is proposed that the depressive effects of this drug could be related to its proconvulsive activity" http://www.ncbi.nlm.nih.gov/pubmed/3128816 0 1720 J. T. Pento 1988 Fezolamine fumarate "Drugs of the Future.13 (10) ()(pp 913-914), 1988.Date of Publication: 1988." 10 913-914 1 1721 K. R. Drasbek and K. Jensen 2006 "THIP, a hypnotic and antinociceptive drug, enhances an extrasynaptic GABAA receptor-mediated conductance in mouse neocortex" Cereb.Cortex 16 8 1134-1141 "THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) is a selective GABA(A) receptor agonist with a preference for delta-subunit containing GABA(A) receptors. THIP is currently being tested in human trials for its hypnotic effects, displaying advantageous tolerance and addiction properties. Since its cellular actions in the neocortex are uncertain, we studied the effects of THIP on neurons in slices of frontoparietal neocortex of 13- to 19-day-old (P13-19) mice. Using whole-cell patch-clamp recordings, we found that the clinically relevant THIP concentration of 1 muM induced a robust tonic GABA(A)-mediated current in layer 2/3 neurons. In comparison, only a minute tonic current was induced by mimicking in vivo endogenous GABA levels. Miniature IPSCs were not affected by 1 muM THIP suggesting an extrasynaptic site of action. The EC(50) for THIP was 44 muM. In accordance with the stronger expression of delta-containing receptors in superficial neocortical layers, THIP induced a 44% larger tonic current in layer 2/3 than in layer 5 neurons. Finally, monitoring spontaneously active neocortical neurons, THIP caused an overall depression of inhibitory activity, while enhancing excitatory activity prominently. Our studies suggest that THIP activates an extrasynaptic GABA(A) receptor-mediated conductance in the neocortex, which may alter the cortical network activity" http://www.ncbi.nlm.nih.gov/pubmed/16221925 0 1722 "D. M. Brochet, P. Martin, P. Soubrie and P. Simon" 1987 Triiodothyronine potentiation of antidepressant-induced reversal of learned helplessness in rats Psychiatry Res. 21 3 267-275 "Several clinical investigations have suggested that a special relationship exists between thyroid function and affective disorders and/or therapeutic response to antidepressants. The present report describes that the reversal by antidepressants (imipramine, desipramine, and nomifensine) of depressive-like behavior in rats (escape deficits produced by previous exposure to uncontrollable stress) was significantly hastened in animals given daily triiodothyronine (T3). The learned helplessness paradigm might be a useful model for approaching in animals the neurohormonal correlates of affective disorders and the neurobiochemical bases of the reported T3 enhancement of antidepressants" http://www.ncbi.nlm.nih.gov/pubmed/3628611 1 1723 "R. G. Worth, R. M. Esper, N. S. Warra, A. L. Kindzelskii, A. L. Rosenspire, R. F. Todd, III and H. R. Petty" 2001 Mercury inhibition of neutrophil activity: evidence of aberrant cellular signalling and incoherent cellular metabolism Scand.J.Immunol. 53 1 49-55 "Exposure to environmental heavy metals has been reported to affect the immune system. Here, we tested the hypothesis that Hg(+2), acting through membrane proteins, disrupts metabolic dynamics and downstream cell functions in human neutrophils. We found that HgCl(2) inhibited: (1) polarization and (2) immunoglobulin (Ig)G-mediated phagocytosis of sheep erythrocytes in a dose-dependent manner from 2.5 to 10 microM. Because these activities have been linked with pro-inflammatory signalling, we also studied the effects of HgCl(2) on intracellular signalling by measuring protein tyrosine phosphorylation. HgCl(2) at doses = 1 microM increased tyrosine phosphorylation. We also studied the effect of HgCl(2) on neutrophil metabolism by measuring NAD(P)H autofluorescence as an indicator of intracellular NAD(P)H concentration. After HgCl(2) treatment, we found that normal sinusoidal NAD(P)H oscillations became incoherent. We recently reported that the NAD(P)H oscillation frequency is affected by cell migration and activation, which can in turn be regulated by integrin-mediated signalling. Therefore, we examined the effects of HgCl(2) on cell surface distribution of membrane proteins. After exposure to environmentally relevant concentrations of HgCl(2) we found that CR3, but not other membrane proteins (e.g. uPAR, Fc gamma RIIA and the formyl peptide receptor), became clustered on cell surfaces. We suggest that HgCl2 disrupts integrin signalling/functional pathways in neutrophils" http://www.ncbi.nlm.nih.gov/pubmed/11169206 0 1724 R. Yegnanarayan and G. V. Joglekar 1978 Anti-fertility effect of non-steroidal anti-inflammatory drugs Jpn.J.Pharmacol. 28 6 909-917 "The anti-fertility activity of prostaglandin synthesis inhibitors namely the non-steroidal anti-inflammatory drugs: acetyl salicylic acid, indomethacin and oxyphenbutazone were investigated in male and female albino rats and female albino rabbits. Oxyphenbutazone and indomethacin affected the reproductive process in male rats. Indomethacin 3 mg/kg. and acetyl salicylic acid 300 mg/kg produced significant anti-ovulatory activity in the rabbit. In female rats, all three drugs given in high doses over a period of two oestrous cycles reduced mating significantly, while only indomethacin given in a low dose of 0.8 mg/kg over a period of six oestrous cycles could reduce mating significantly. Anti-implantation activity was seen with indomethacin 4 mg/kg. alone, and though post-implantation activity was seen with all three drugs, it was associated with maternal deaths. It appears that non-steroidal anti-inflammatory drugs affect reproduction in female animals" http://www.ncbi.nlm.nih.gov/pubmed/745313 0 1725 "G. J. Nohynek, J. P. Plard, M. Y. Wells, A. Zerial and F. Roquet" 1997 Comparison of the potency of glycosylated and nonglycosylated recombinant human granulocyte colony-stimulating factors in neutropenic and nonneutropenic CD rats Cancer Chemother.Pharmacol. 39 3 259-266 "Recent studies in human bone-marrow culture and healthy human volunteers suggest that lenograstim [glycosylated, recombinant human granulocyte colony-stimulating factor (rHuG-CSF) produced in Chinese hamster ovary (CHO) cells] has greater in vivo potency than filgrastim [nonglycosylated, methionine-extended recombinant human granulocyte colony-stimulating factor (rmetHuG-CSF) produced in Escherichia coli]. To confirm and extend these results we investigated the in vivo potency of both products in normal rats and neutropenic CD rats as an animal model of chemotherapy-induced neutropenia. In normal rats, groups of eight normal male CD rats received four subcutaneous doses of 10, 30, or 100 micrograms/kg filgrastim or lenograstim on days 1-4 of the study, whereas a control group received the vehicle. Blood samples were collected from each animal before treatment (day -5) and on days 2, 3, 5, 8, and 12 of the study for determination of red blood cell (RBC), platelet, white blood cell (WBC), and differential counts. rHuG-CSF and r-metHuG-CSF produced increased WBC counts, principally due to elevated absolute neutrophil counts (ANCs); on days 2, 3, and 5, all groups receiving rG-CSF had ANCs that increased in a progressive and dose-related manner. With the exception of a single value, mean ANCs obtained on days 2, 3, and 5 in lenograstim-treated groups were higher (statistically significant on day 3 at 30 and 100 micrograms/kg and on day 5 at 10, 30, and 100 micrograms/kg) than the respective values obtained in filgrastim-treated groups. No compound-related effect was noted in RBC or platelet parameters. Neutropenia was induced in male CD rats (12 animals/group) with a single intraperitoneal dose of 50 mg/kg cyclophosphamide (CPA) on day 0. On days 1-4, CPA-treated groups were treated with the vehicle (control) or with filgrastim or lenograstim at 30 or 100 micrograms/kg per day. An additional group was not treated with CPA and served as the absolute control group. Blood was collected from alternating subgroups on study day -5 (pretest) and on days 2, 3, 4, 5, 6, 8, 9, and 12 for determination of RBC, platelet, WBC, and differential counts. No major adverse in-life effect was noted in neutropenic rats. Maximal depression of WBCs and ANCs occurred on day 5, followed by recovery to normal values by days 9 (ANC) and 12 (WBC). On day 3 and days 5-9, rHuG-CSF- and metHuG-CSF-treated groups had marked and dose-related increases in WBCs as compared with CPA-treated controls, principally due to elevated ANCs. With the exception of a few values, mean ANC values obtained in lenograstim-treated groups were consistently higher than the respective values obtained in filgrastim-treated groups; the difference was statistically significant on day 3 (30-microgram/kg groups) and on days 6 and 8 (100-microgram/kg groups). In conclusion, treatment of normal and neutropenic CD rats with lenograstim resulted in a dose-related elevation of ANCs that was consistently and significantly higher than the response to identical doses of filgrastim. These results suggest that lenograstim, the glycosylated form of rG-CSF, has superior in vivo potency in normal and neutropenic animals as compared with filgrastim, the nonglycosylated form of rG-CSF" http://www.ncbi.nlm.nih.gov/pubmed/8996530 0 1726 "J. C. Lemos, Y.-Z. Pan, X. Ma, C. Lamy, A. C. Akanwa and S. G. Beck" 2006 Selective 5-HT1B receptor inhibition of glutamatergic and GABAergic synaptic activity in the rat dorsal and median raphe "European Journal of Neuroscience.24 (12) ()(pp 3415-3430), 2006.Date of Publication: December 2006." 12 3415-3430 "The dorsal (DR) and median (MR) raphe nuclei contain 5-hydroxytryptamine (5-HT) cell bodies that give rise to the majority of the ascending 5-HT projections to the forebrain. The DR and MR have differential roles in mediating stress, anxiety and depression. Glutamate and GABA activity sculpt putative 5-HT neuronal firing and 5-HT release in a seemingly differential manner in the MR and DR, yet isolated glutamate and GABA activity within the DR and MR has not been systematically characterized. Visualized whole-cell voltage-clamp techniques were used to record excitatory and inhibitory postsynaptic currents (EPSC and IPSC) in 5-HT-containing neurons. There was a regional variation in action potential-dependent (spontaneous) and basal [miniature (m)] glutamate and GABAergic activity. mEPSC activity was greater than mIPSC activity in the DR, whereas in the MR the mIPSC activity was greater. These differences in EPSC and IPSC frequency indicate that glutamatergic and GABAergic input have distinct cytoarchitectures in the DR and MR. 5-HT1B receptor activation decreased mEPSC frequency in the DR and the MR, but selectively inhibited mIPSC activity only in the MR. This finding, in concert with its previously described function as an autoreceptor, suggests that 5-HT1B receptors influence the ascending 5-HT system through multiple mechanisms. The disparity in organization and integration of glutamatergic and GABAergic input to DR and MR neurons and their regulation by 5-HT1B receptors may contribute to the distinction in MR and DR regulation of forebrain regions and their differential function in the aetiology and pharmacological treatment of psychiatric disease states. © The Authors (2006)" DO - http://dx.doi.org/10.1111/j.1460-9568.2006.05222.x 0 1727 C. W. Hughes and H. J. Pottinger 1986 Chronic CNS recording with in vivo electrochemistry in rats: Monitoring biogenic amine release in behavioral and pharmacological models of depression "Annals of the New York Academy of Sciences.Vol.473 ()(pp 530-534), 1986.Date of Publication: 1986." 530-534 1 1728 "H. S. Xu, J. A. Pilcher and R. S. Jones" 1993 Physiologic study of bile salt and lipid secretion in rats after liver transplantation Ann.Surg. 217 4 404-412 "OBJECTIVE: This experiment determined the effects of liver transplantation on bile salt kinetics and biliary lipid secretion. SUMMARY BACKGROUND DATA: Depression of bile secretion in the three main components and bile cholesterol supersaturation with a high incidence of cholesterol stone formation have been documented in patients with end stage liver diseases after transplantation. However, physiologic changes of bile salt and lipid secretion in recipients remain unclear. METHODS: The study was done using a rat liver transplant model with 1 and 6 hours of donor liver cold preservation in saline. A chronic common bile duct fistula and a duodenal cannula were established for bile collection and the sample biochemical study for 6 days. RESULTS: Altered bile salt kinetics in liver grafted rats included depressed bile flow for 1-3 hours after the revascularization, decreased bile salt concentration and outputs, reduced bile salt basal synthesis rate, and reduced bile salt pool size during the early postoperative period. Phospholipid concentration and secretion rate depressed for 1-3 days without altered cholesterol level. The uncoupling change of the cholesterol and the other bile components resulted in an increased lithogenic indices in bile on days 2 and 3. CONCLUSION: Alterations of bile composition and bile salt kinetics occur in liver transplanted rats. The changes may result from injuries of the liver microcirculation and parenchymal cells caused by cold preservation. The study of bile secretion is helpful for evaluation of the initial graft function. The changed ratio of three bile components may be important for cholesterol stone formation in the liver transplant recipient" http://www.ncbi.nlm.nih.gov/pubmed/8466312 0 1729 "C. E. Marx, L. J. Shampine, G. E. Duncan, M. J. VanDoren, A. C. Grobin, M. W. Massing, R. D. Madison, D. W. Bradford, M. I. Butterfield, J. A. Lieberman and A. L. Morrow" 2006 "Clozapine markedly elevates pregnenolone in rat hippocampus, cerebral cortex, and serum: candidate mechanism for superior efficacy?" Pharmacol.Biochem.Behav. 84 4 598-608 "Clozapine demonstrates superior efficacy in patients with schizophrenia, but the precise mechanisms contributing to this clinical advantage are not clear. Clozapine and olanzapine increase the GABAergic neuroactive steroid (NS) allopregnanolone, and it has been hypothesized that NS induction may contribute to the therapeutic actions of these agents. Pregnenolone administration improves learning and memory in rodent models, and decreases in this NS have been associated with depressive symptoms in humans. These pregnenolone characteristics may be relevant to the actions of antipsychotics. We therefore investigated potential pregnenolone alterations in rat hippocampus and cerebral cortex following clozapine, olanzapine, and other second generation agents as a candidate NS mechanism contributing to antipsychotic efficacy. In the first set of experiments, intact, adrenalectomized, and sham-operated male rats received vehicle or clozapine (20 mg/kg) IP. In the second set, male rats received vehicle, olanzapine (5 mg/kg), quetiapine (20 mg/kg), ziprasidone (10 mg/kg) or aripiprazole (5 mg/kg) IP. Pregnenolone levels were determined by gas chromatography/mass spectrometry. Clozapine markedly elevates pregnenolone in rat hippocampus, cerebral cortex, and serum; hippocampal levels were strongly correlated with serum levels (r=0.987). Olanzapine also elevates pregnenolone levels, but to a lesser degree than clozapine. Pregnenolone induction may contribute to the clinical actions of clozapine and olanzapine" http://www.ncbi.nlm.nih.gov/pubmed/16962649 0 1730 "Z. Y. Ye, Y. G. Lu, H. Sun, X. P. Cheng, T. L. Xu and J. N. Zhou" 2008 Fluoxetine inhibition of glycine receptor activity in rat hippocampal neurons Brain Res. 1239 77-84 "Fluoxetine is a selective serotonin reuptake inhibitor widely used for treating depression. However, fluoxetine treatment may lead to seizures at higher doses, which underlying mechanism remains largely unknown. In this study, we examined the effects of fluoxetine on glycine receptor (GlyR) activity. Using the whole-cell patch-clamp recording method, we found that fluoxetine and its metabolite norfluoxetine inhibited glycine-induced currents in cultured rat hippocampal neurons. This inhibition was dose-dependent, and voltage-independent. Fluoxetine shifted the glycine concentration-response curve to the right without altering the maximal current. Both Lineweaver-Burk and Schild plots suggest competitive inhibition. The amount of fluoxetine inhibition significantly increased when homomeric GlyRs were selectively inhibited with picrotoxin. Moreover, fluoxetine inhibited the current mediated by heteromeric alpha2beta- but not homomeric alpha2-GlyRs transiently expressed in HEK293T cells. These results suggest that fluoxetine is a competitive and subtype-selective GlyR inhibitor, which may explain its capacity to induce seizures" http://www.ncbi.nlm.nih.gov/pubmed/18786514 0 1731 "M. K. Das, A. Bhattacharya and S. K. Ghosal" 2006 Effect of penetration enhancers on skin permeation of trazodone hydrochloride from matrix type transdermal formulation through mouse and human cadaver epidermis Acta Pol.Pharm. 63 6 535-541 "A transdermal dosage form of trazodone hydrochloride (TZN) may be useful in the treatment of moderate to severe depression in schizophrenic patients by providing prolonged duration of action. It will also improve patient compliance and bioavailability. Controlled input of TZN would attenuate fluctuating plasma level of TZN resulting from oral therapy. The aim of the current investigation was to evaluate its flux and the effects of various penetration enhancers, viz., isopropyl myristate (IPM), isopropyl palmitate (IPP), butanol and octanol on transdermal permeation from matrix-based formulations through the skin. The enhancing effect on the permeation of TZN was determined using the mouse and human cadaver epidermis. In vitro permeation data were collected at 37 degrees C using Keshary-Chien diffusion cells. The skin permeation was then evaluated by measuring the steady state permeation flux of TZN, enhancement ratio and the diffusion parameter. The highest enhancing effect was obtained with IPM followed by butanol, octanol and IPP. In general, higher fluxes were observed through mouse epidermis as compared with the human cadaver epidermis. The skin retention of TZN for both the species in the presence of different enhancers was nearly 3 times higher than for the control formulation. Based on the observed results, a transdermal patch of about 70 cm2 consisting of 10 % IPM should be able to attain and maintain therapeutic plasma concentration of TZN at 0.75 mg/mL over a period of 24 h" http://www.ncbi.nlm.nih.gov/pubmed/17438871 0 1732 S. Meltzer-Brody 2011 New insights into perinatal depression: Pathogenesis and treatment during pregnancy and postpartum "Dialogues in Clinical Neuroscience.13 (1) ()(pp 89-100), 2011.Date of Publication: 2011." 1 89-100 "Maternal perinatal mental health has enormous consequences for the well-being of the mother, her baby, and the family. Although it is well documented that perinatal depression is both common and morbid, with a prevalence of 10% to 15% in the general population, there remain many critically important unanswered questions about the pathogenesis of perinatal depression and most effective treatment regimens. Current lines of evidence from both human and animal models implicate hormonal dysregulation, abnormalities in hypothalamic-pituitary-adrenal axis activity, and the contributions of genetics and epigenetics as playing key roles in the development of perinatal reproductive mood disorders. Investigations into both human and animal models of perinatal depression offer much promise for the future identification of the underlying pathophysiology and subsequent early identification and/or prevention and appropriate treatment for women at risk for postpartum depression. Lastly, although it is generally accepted that pregnancy is not protective with regard to new onset or relapse of depression, the way to best treat maternal depression during pregnancy and lactation remains hotly debated. Future research in this area will more clearly elucidate the underlying pathogenesis, the potential long-term impact of perinatal depression on the developing fetus, and how best to counsel pregnant women about the risks of untreated major depressive disorder versus the risks of psychopharmacologic treatment during pregnancy and lactation. © 2011, LLS SAS" 0 1733 L. C. Faria and I. Mody 2004 Protective effect of ifenprodil against spreading depression in the mouse entorhinal cortex J.Neurophysiol. 92 4 2610-2614 "In the brain, spreading depression (SD) is characterized by a large extracellular DC shift, a massive failure of ion homeostasis and a transient cessation of neuronal function. Clinically, SD is believed to be involved in various neurological disorders including migraine and cerebrovascular diseases. The propagation of cortical SD requires the release of glutamate, and N-methyl-D-aspartate (NMDA) receptors play a crucial role in this process. Here, we have isolated the NMDA receptor-mediated component of extracellularly recorded field excitatory postsynaptic potentials (fEPSPs) in layers 2-3 of the entorhinal cortex of murine brain slices. In the absence of GABAA and AMPA receptor-mediated synaptic transmission, stimulation of layer 6 afferents every 15-90 s elicited spontaneous SD on average within 18.5 min after the start of the stimulation. In the presence of ifenprodil, an NR2B receptor subunit-selective NMDA receptor antagonist, the occurrence of SD was nearly abolished. Our results are consistent with an important role of NR2B subunits in triggering SD in the entorhinal cortex" http://www.ncbi.nlm.nih.gov/pubmed/15201313 0 1734 H. C. Tuckwell and N. J. Penington 2014 Computational modeling of spike generation in serotonergic neurons of the dorsal raphe nucleus Prog.Neurobiol. 118 59-101 "Serotonergic neurons of the dorsal raphe nucleus, with their extensive innervation of limbic and higher brain regions and interactions with the endocrine system have important modulatory or regulatory effects on many cognitive, emotional and physiological processes. They have been strongly implicated in responses to stress and in the occurrence of major depressive disorder and other psychiatric disorders. In order to quantify some of these effects, detailed mathematical models of the activity of such cells are required which describe their complex neurochemistry and neurophysiology. We consider here a single-compartment model of these neurons which is capable of describing many of the known features of spike generation, particularly the slow rhythmic pacemaking activity often observed in these cells in a variety of species. Included in the model are 11 kinds of ion channels: a fast sodium current INa, a delayed rectifier potassium current IKDR, a transient potassium current IA, a slow non-inactivating potassium current IM, a low-threshold calcium current IT, two high threshold calcium currents IL and IN, small and large conductance potassium currents ISK and IBK, a hyperpolarization-activated cation current IH and a leak current ILeak. In Sections 3-8, each current type is considered in detail and parameters estimated from voltage clamp data where possible. Three kinds of model are considered for the BK current and two for the leak current. Intracellular calcium ion concentration Cai is an additional component and calcium dynamics along with buffering and pumping is discussed in Section 9. The remainder of the article contains descriptions of computed solutions which reveal both spontaneous and driven spiking with several parameter sets. Attention is focused on the properties usually associated with these neurons, particularly long duration of action potential, steep upslope on the leading edge of spikes, pacemaker-like spiking, long-lasting afterhyperpolarization and the ramp-like return to threshold after a spike. In some cases the membrane potential trajectories display doublets or have humps or notches as have been reported in some experimental studies. The computed time courses of IA and IT during the interspike interval support the generally held view of a competition between them in influencing the frequency of spiking. Spontaneous activity was facilitated by the presence of IH which has been found in these neurons by some investigators. For reasonable sets of parameters spike frequencies between about 0.6Hz and 1.2Hz are obtained, but frequencies as high as 6Hz could be obtained with special parameter choices. Topics investigated and compared with experiment include shoulders, notches, anodal break phenomena, the effects of noradrenergic input, frequency versus current curves, depolarization block, effects of cell size and the effects of IM. The inhibitory effects of activating 5-HT1A autoreceptors are also investigated. There is a considerable discussion of in vitro versus in vivo firing behavior, with focus on the roles of noradrenergic input, corticotropin-releasing factor and orexinergic inputs. Location of cells within the nucleus is probably a major factor, along with the state of the animal" http://www.ncbi.nlm.nih.gov/pubmed/24784445 0 1735 M. Wielosz 1983 Effects of electroconvulsive shock on monoaminergic systems in the rat brain: Thesis "Polish Journal of Pharmacology and Pharmacy.35 (2) ()(pp 127-130), 1983.Date of Publication: 1983." 2 127-130 "The effects of single or repeated electroconvulsive shock (ECS) (once daily for 7 days) on rat behavior and on the level, utilization and uptake of biogenic amines in rat brain were studied between one and ten days after the last ECS. It has been found that a single ECS caused catalepsy and analgesia, depressed locomotor activity and locomotor hypermotility produced by amphetamine and nomifensine (but not by apomorphine) and decreased the frequency of head twitch response evoked by LiCl. Repeated ECS also induced catalepsy and analgesia but enhanced both the spontaneous locomotor activity and amphetamine, nomifensine and apomorphine-induced hypermotility, and increased the frequency of head twitch response produced by LiCl, 5-HTP and 5-methoxytryptamine. Single and repeated ECS did not change exploratory motility or stereotyped behavior induced by apomorphine, but enhanced haloperidol-induced catalepsy and altered dopamine and serotonin levels in the rat brain. The utilization of NA and DA was not changed by repeated ECS, whereas the uptake of these amines was slightly reduced. The present results provide evidence that a single ECS depresses but repeated ECS augments some behavioral responses to dopaminergic and serotonergic agonists. The possible biochemical mechanisms involved in these effects of ECS are discussed" 0 1736 "P. M. Lledo, P. Legendre, J. M. Israel and J. D. Vincent" 1990 Dopamine inhibits two characterized voltage-dependent calcium currents in identified rat lactotroph cells Endocrinology 127 3 990-1001 "The effects of dopamine (DA) on voltage-dependent Ca2+ currents were investigated in cultured rat lactotroph cells using the patch clamp recording technique. Each recorded cell was identified by the reverse hemolytic plaque assay. In the whole-cell configuration, two types of Ca2+ currents, L and T, were characterized on the basis of their kinetics, voltage sensitivity, and pharmacology. The L component had a threshold of -25 mV, showed little inactivation during a 150-msec voltage step, and was maximal at +10 mV. Cadmium ions (100 microM) significantly reduced its amplitude (75%). The T component was activated at a membrane potential close to -50 mV, was maximal at -10 mV, and showed a voltage-dependent inactivation between -90 and -30 mV. It was quickly inactivated during a maintained depolarization (time constant, 27 ms at -30 mV) and was strongly reduced (80%) by nickel ions (100 microM). Bath application of DA (10 nM) caused a markedly general depression of inward Ca2+ currents, acting differently on the T- and L-type currents. DA application shifted the voltage-dependence of the L-type current activation toward depolarization values (8 mV) without modifying its time- and voltage-dependent inactivation. In contrast, DA enhanced the inactivation of the T-type current by accelerating its time-dependent inactivation (25% decrease in the time constant of inactivation) and by shifting the voltage-dependence of the T-type current inactivation toward hyperpolarizing values (-63 mV in control vs. -77 mV in the presence of DA). These effects of DA were dose-dependent and involved the activation of a D2 receptor type. They were mimicked by bromocriptine application (10 nM), whereas sulpiride (100 nM) blocked the DA-evoked response. The D1 antagonist SCH 23390 was ineffective up to 100 microM. All of these DA-induced modifications in Ca2+ currents were abolished using a GTP-free pipette solution or after pretreatment of cells with pertussis toxin, suggesting that DA can regulate the function of Ca2+ channels through GTP-binding proteins (G-proteins). Our results show that DA acts simultaneously by reducing both voltage-dependent Ca2+ currents on lactotroph cells. Thus, DA reduces the entry of Ca2+ ions across the surface membrane and thereby influences electrical activity and the cytosolic free Ca2+ concentration involved in both basal and evoked PRL release" http://www.ncbi.nlm.nih.gov/pubmed/2167220 0 1737 "P. Charlesworth, I. Jacobson and C. D. Richards" 1995 Pentobarbitone modulation of NMDA receptors in neurones isolated from the rat olfactory brain Br.J.Pharmacol. 116 7 3005-3013 1. The action of pentobarbitone on the N-methyl-D-aspartate (NMDA) receptors of neurones freshly dissociated from the olfactory bulb and olfactory tubercle has been studied using patch-clamp techniques. 2. Pentobarbitone produced a concentration-dependent depression of the currents evoked by NMDA with an IC50 value of c. 250 microM. 3. Analysis of the NMDA-evoked noise produced power spectra that could be fitted by the sum of two Lorentzians with corner frequencies of 17 and 82 Hz. Pentobarbitone increased the corner frequency of the high frequency component but did not alter the apparent single channel conductance estimated from the noise. 4. Single channel recordings in either the cell-attached or outside-out patch configurations revealed that NMDA (20 or 50 microM) opened channels with a main conductance level around 55 pS and a principal subconductance around 44 pS. The uncorrected mean open time of the channels was 3.4 ms and mean burst length was 6.0 ms. Mean cluster length was about 12 ms. 5. Pentobarbitone produced a concentration-dependent reduction in both mean open time and burst length. Mean cluster length was much less affected. Pentobarbitone did not decrease unitary current amplitude or bias the open-state current amplitude distribution in favour of a particular substate. 6. From these data it appears that pentobarbitone depresses the inward current evoked by NMDA by reducing the probability of channel opening and this results from a shortening of the lifetime of the channel open state and by decreasing burst length http://www.ncbi.nlm.nih.gov/pubmed/8680736 0 1738 C. J. Dix and B. A. Cooke 1981 Effect of lutropin and cycloheximide on lutropin receptors and cyclic AMP production in Leydig tumour cells in vitro Biochem.J. 196 3 713-719 "A system to study lutropin-induced desensitization of tumour Leydig cells in vitro has been investigated. Tumour Leydig cells were purified on a Percoll gradient and then incubated for 30 min with lutropin (0-1000ng/ml). The cells were then washed and incubated in suspension media at 32 degrees C. 125I-labelled human choriogonadotropin binding and basal and lutropin-stimulated cyclic AMP production were determined at various times. Initially the cells showed a dose-dependent decrease in human choriogonadotropin binding (1.18 and 0.13fmol/10(6) cells respectively) followed by an increase at 1 h (2.32 and 0.87fmol/10(6) cells respectively). Human choriogonadotropin binding remained elevated in the cells pre-incubated without lutropin, whereas the cells pre-incubated with lutropin showed a dose-dependent decrease over the next 10 h (2.20-0.18fmol/10(6) cells respectively). Basal production of cyclic AMP initially reflected the pre-incubation conditions (1.17-21.19ng/10(6) cells per h for 0-1000ng of lutropin/ml respectively). However, by 1 h there was a marked rise in basal cyclic AMP production which returned to the initial lower values by 4 h. At all time intervals studied, lutropin-induced cyclic AMP production showed a decrease that was proportional to lutropin concentration in the pre-incubated media. The decreases in human choriogonadotropin binding produced by pre-incubations with lutropin (100ng/ml) was partially inhibited by the presence of cycloheximide in the pre-incubation media and totally prevented by the continuous presence of cycloheximide. These results demonstrate that desensitization of tumour Leydig cells occurs after exposure to lutropin in vitro. This desensitization involves both a loss of plasma membrane receptors for lutropin and lutropin-stimulated adenylate cyclase. These events can be prevented by cycloheximide and are therefore probably dependent on protein synthesis" http://www.ncbi.nlm.nih.gov/pubmed/6274319 0 1739 "M. Vasileva, R. Renden, H. Horstmann, D. Gitler and T. Kuner" 2013 Overexpression of synapsin Ia in the rat calyx of Held accelerates short-term plasticity and decreases synaptic vesicle volume and active zone area Front Cell Neurosci. 7 270 "Synapsins are synaptic vesicle (SV) proteins organizing a component of the reserve pool of vesicles at most central nervous system synapses. Alternative splicing of the three mammalian genes results in multiple isoforms that may differentially contribute to the organization and maintenance of the SV pools. To address this, we first characterized the expression pattern of synapsin isoforms in the rat calyx of Held. At postnatal day 16, synapsins Ia, Ib, IIb and IIIa were present, while IIa-known to sustain repetitive transmission in glutamatergic terminals-was not detectable. To test if the synapsin I isoforms could mediate IIa-like effect, and if this depends on the presence of the E-domain, we overexpressed either synapsin Ia or synapsin Ib in the rat calyx of Held via recombinant adeno-associated virus-mediated gene transfer. Although the size and overall structure of the perturbed calyces remained unchanged, short-term depression and recovery from depression were accelerated upon overexpression of synapsin I isoforms. Using electron microscopic three-dimensional reconstructions we found a redistribution of SV clusters proximal to the active zones (AZ) alongside with a decrease of both AZ area and SV volume. The number of SVs at individual AZs was strongly reduced. Hence, our data indicate that the amount of synapsin Ia expressed in the calyx regulates the rate and extent of short-term synaptic plasticity by affecting vesicle recruitment to the AZ. Finally, our study reveals a novel contribution of synapsin Ia to define the surface area of AZs" http://www.ncbi.nlm.nih.gov/pubmed/24391547 0 1740 P. Liedholm 1975 On fibrinolysis in reproduction Acta Obstet.Gynecol.Scand.Suppl 41 Jan-47 http://www.ncbi.nlm.nih.gov/pubmed/1059309 0 1741 "O. J. Cassol-Jr, C. M. Comim, F. Petronilho, L. S. Constantino, E. L. Streck, J. Quevedo and F. Dal-Pizzol" 2010 Low dose dexamethasone reverses depressive-like parameters and memory impairment in rats submitted to sepsis Neurosci.Lett. 473 2 126-130 "Sepsis is characterized by a systemic inflammatory response of the immune system against an infection, presenting with hypothalamic-pituitary-adrenal (HPA) axis dysfunction, behavior alterations, and high mortality. In this study, we aimed to evaluate the effects of dexamethasone on mortality, anhedonia, circulating corticosterone and adrenocorticotropin hormone (ACTH) levels, body and adrenal gland weight, and aversive memory in sepsis survivor rats. Male Wistar rats underwent sham operation or cecal ligation and perforation (CLP) procedure. Rats subjected to CLP were treated with ""basic support"" and dexamethasone (at 0.2 and 2mg/kg daily for 7 days after CLP, intraperitonially) or saline. After 10 days of sepsis procedure, it was evaluated aversive memory, sweet food consumption, and body and adrenal gland weight. Serum and plasma were also obtained. It was observed that low dose dexamethasone reverted anhedonia, normalized adrenal gland and body weight, corticosterone and ACTH levels, and decreased mortality and avoidance memory impairment, demonstrating that low doses of dexamethasone for moderate periods may be beneficial for sepsis treatment and its sequelae-depressive-like parameters and memory impairment" http://www.ncbi.nlm.nih.gov/pubmed/20184944 1 1742 "H. Korner, C. Newman, L. Mao, M. R. Kidd, D. Saltman and S. Kippax" 2011 'The black dog just came and sat on my face and built a kennel': Gay men making sense of 'depression' "Health.15 (4) ()(pp 417-436), 2011.Date of Publication: July 2011." 4 417-436 "This article reports on in-depth interviews with gay men about their experiences and understanding of depression. It is a key outcome of the collaboration between social researchers, general practitioners and community partners to investigate the management of depression in gay men in primary care settings. As part of the qualitative arm of the project in-depth interviews were conducted with 40 gay men in Sydney and Adelaide (Australia). The approach to discourse analysis is informed by Hallidayan systemic functional linguistics. Six constructions of depression were identified: (1) depression as a constellation of symptoms; (2) symptoms constructed as experience; (3) depression as agent; (4) depression as mental processes; (5) not meeting social expectations; and (6) engaging with psychiatric discourse: constructing alternative positions. Gay men draw on the biomedical model of depression as low mood and loss of pleasure as well as on constructions of depression in terms of social experience. The biomedical model of depression is, however, not positioned as unproblematic. Rather, gay men align or disalign with this discourse according to their own experience, thereby enacting diverse masculinities. Gay men's discourses of depression are inextricably linked to the community activism of gay men and their community organizations in the context of the HIV epidemic, as well as a synergy between gay men and their doctors. © The Author(s) 2010" DO - http://dx.doi.org/10.1177/1363459310372511 0 1743 "L. Kopper, A. Jeney, K. Lapis and M. Torok" 1978 Studies of the growth of an ascitic tumour. II. A system to study the tumour-age dependent effect of antitumour agents Eur.J.Cancer 14 1 75-82 http://www.ncbi.nlm.nih.gov/pubmed/624305 0 1744 "I. Filipovic, M. Rutemoller and P. Helten" 1975 Triglyceride lipase activity in bovine aorta Blood Vessels 12 4 236-247 "The cell-free supernatant from homogenized bovine aorta hydrolyzed triglycerides, beta-naphthylesters of lauric and stearic acid and Tween 20, 40 and 60. The rate of hydrolysis decreases as the acyl chain length of the substrates increases. The activity against triglycerides of short-chain fatty acids and monoacylesters could be partially separated from that of glycerol-trioleate lipase by ammonium sulfate fractionation. The activity of glycerol-trioleate lipase remained unaffected by heating for 5 min at 60 degrees C or by addition of bile acids, whereas the activity causing hydrolysis of triglycerides with short-chain fatty acids and monoacylesters decreases up to 60% by analogous treatment" http://www.ncbi.nlm.nih.gov/pubmed/1174713 0 1745 "W. Theilmann, W. Loscher, K. Socala, H. Frieling, S. Bleich and C. Brandt" 2014 A new method to model electroconvulsive therapy in rats with increased construct validity and enhanced translational value J.Psychiatr.Res. 53 94-98 "Electroconvulsive therapy is the most effective therapy for major depressive disorder (MDD). The remission rate is above 50% in previously pharmacoresistant patients but the mechanisms of action are not fully understood. Electroconvulsive stimulation (ECS) in rodents mimics antidepressant electroconvulsive therapy (ECT) in humans and is widely used to investigate the underlying mechanisms of ECT. For the translational value of findings in animal models it is essential to establish models with the highest construct, face and predictive validity possible. The commonly used model for ECT in rodents does not meet the demand for high construct validity. For ECT, cortical surface electrodes are used to induce therapeutic seizures whereas ECS in rodents is exclusively performed by auricular or corneal electrodes. However, the stimulation site has a major impact on the type and spread of the induced seizure activity and its antidepressant effect. We propose a method in which ECS is performed by screw electrodes placed above the motor cortex of rats to closely simulate the clinical situation and thereby increase the construct validity of the model. Cortical ECS in rats induced reliably seizures comparable to human ECT. Cortical ECS was more effective than auricular ECS to reduce immobility in the forced swim test. Importantly, auricular stimulation had a negative influence on the general health condition of the rats with signs of fear during the stimulation sessions. These results suggest that auricular ECS in rats is not a suitable ECT model. Cortical ECS in rats promises to be a valid method to mimic ECT" http://www.ncbi.nlm.nih.gov/pubmed/24607291 1 1746 E. S. Vesell and G. T. Passananti 1975 "Anomalous results of studies on drug interaction in man. II. Halofenate (mk-185) and antipyrine, bishydroxycoumarin, and warfarin" Pharmacology 13 2 112-127 "Three highly reproducible experiments on drug interaction in normal human volunteers provided anomalous results: chronic halofenate administration shortened plasma antipyrine and bishydroxycoumarin half-lives but prolonged plasma warfarin half-lives. This dissociation in the effect produced by a chronically administered drug on the metabolism of test drugs has not previously been reported in man. Chronic halofenate administration to rats, mice and dogs stimulated several hepatic microsomal drug-metabolizing systems, including those responsible for bishydroxycoumarin warfarin hydroxylation" http://www.ncbi.nlm.nih.gov/pubmed/49900 0 1747 I. H. Chaudry and M. K. Gould 1970 Effect of externally added ATP on glucose uptake by isolated rat soleus muscle Biochim.Biophys.Acta 196 2 327-335 http://www.ncbi.nlm.nih.gov/pubmed/4984212 0 1748 "A. M. Basso, K. B. Gallagher, N. A. Bratcher, J. D. Brioni, R. B. Moreland, G. C. Hsieh, K. Drescher, G. B. Fox, M. W. Decker and L. E. Rueter" 2005 "Antidepressant-like effect of D(2/3) receptor-, but not D(4) receptor-activation in the rat forced swim test" Neuropsychopharmacology 30 7 1257-1268 "Dopamine plays a role in the pathophysiology of depression and therapeutic effects of antidepressants but the contribution of individual D(2)-like receptor subtypes (D(2), D(3), D(4)) to depression is not known. We present evidence that activation of D(2)/D(3), but not D(4) receptors, can affect the outcome in the rat forced swim test (FST). Nomifensine, a dopamine uptake inhibitor (7, 14, and 28 micromol/kg); quinpirole, a D(2)-like receptor and agonist (0.4, 1.0, and 2.0 micromol/kg); PD 12,8907, a preferential D(3) receptor agonist (0.17, 0.35, and 0.7 micromol/kg); PD 168077 (0.1, 0.3, and 1.0 micromol/kg) and CP 226269 (0.3, 1.0, and 3.0 micromol/kg), both selective D(4) receptor agonists, were administered s.c. 24, 5, and 0.5/1 h before testing. Nomifensine, quinpirole at all doses and PD 128907 at the highest dose decreased immobility time in FST. PD 168077 and CP 226269 had no effect on the model. To further clarify what type of dopamine receptors were involved in the anti-immobility effect of quinpirole, we tested different antagonists. Haloperidol, a D(2)-like receptor antagonist (0.27 micromol/kg), completely blocked the effect of quinpirole; A-437203 (LU-201640), a selective D(3) receptor antagonist (17.46 micromol/kg), showed a nonsignificant trend to attenuate the effect of the low dose of quinpirole, and L-745,870, a selective D(4) receptor antagonist (1.15 micromol/kg), had no effect. The pharmacological selectivity of the compounds tested suggests that the antidepressant-like effects of quinpirole are most likely mediated mainly by D(2) and to a lesser extent by D(3) but not D(4) receptors" http://www.ncbi.nlm.nih.gov/pubmed/15688083 1 1749 "J. Hill, T. J. Ee, L. Thirumangalakudi, J. Coplan and T. Perera" 2011 Effects of ziprasidone on neurogenesis and depressive behavior in adult monkeys "Biological Psychiatry.Conference: 66th Annual Meeting of the Society of Biological Psychiatry San Francisco, CA United States.Conference Start: 20110512 Conference End: 20110514.Conference Publication: (var.pagings).69 (9 Suppl 1) ()(pp 126S), 2011.D" var.pagings 126S "Background: Antidepressant medication treatment has been associated with decreased depressive behavior and increased hippocampal neurogenesis rates in rodents and non-human-primates (NHPs). In this study we examine whether the atypical antipsychotic drug ziprasidone has similar effects in adult NHPs. Methods: Socially-housed, adult bonnets macaque females were exposed to control conditions (N=6) or (weekly) repeated separation stress (N=12) for 15 weeks. Half the subjects in each group received either saline placebo or intramuscular (IM) ziprasidone each week during this 15-week period. The subjects were then euthanized. Dependent measures were weekly behavioral observations and postmortem neurogenesis levels. Results: Exposing NHPs to repeated separation stress resulted in depressionlike behaviors (anhedonia and subordinance) accompanied by reduced hippocampal neurogenesis rates and reductions in dentate gyrus volume. However, IM ziprasidone did not reduce depression-related or increase neurogenesis rates. Across all groups, depression-like behaviors were associated with decreased rates of neurogenesis but this inverse correlation was only significant for new neurons in the anterior dentate gyrus that were at the threshold of completing maturation. Conclusions: Our data confirms an inverse relationship between depressive symptoms and hippocampal neurogenesis rates and additionally demonstrates that psychotropic medications, which lack an antidepressant effect fail to induce neurogenesis in NHPs" DO - http://dx.doi.org/10.1016/j.biopsych.2011.03.031 0 1750 "M. Stepanichev, I. Zdobnova, I. Zarubenko, N. Lazareva and N. V. Gulyaeva" 2006 Differential effects of tumor necrosis factor-alpha co-administered with amyloid beta-peptide (25-35) on memory function and hippocampal damage in rat Behav.Brain Res. 175 2 352-361 "Effects of concurrent intracerebroventricular administration of amyloid-beta peptide 25-35 (Abeta(25-35)) and the proinflammatory cytokine tumor necrosis factor-alpha (TNFalpha) to rats were investigated. A battery of behavioral tests including radial arm maze, passive avoidance, elevated plus-maze and forced swim test as well as histological methods were used. A single administration of Abeta(25-35) induced delayed behavioral deficits manifested in reference and working memory disturbances in the radial maze task involving spatial memory. However, no effects of Abeta(25-35) on learning or retention in a passive avoidance test could be revealed. Abeta(25-35) appeared to decrease anxiety without affecting depression-like behavior in the rats. Abeta(25-35)-induced cognitive deficits could be related to the moderate neuronal cell loss found in the hippocampal CA1 field. Though administration of TNFalpha did not impair learning and memory of rats in the radial maze, it induced gross changes in their behavior during passive avoidance training. Though TNFalpha did not protect against Abeta(25-35)-induced neuronal cell loss in the CA1 field of hippocampus, co-administration of TNFalpha with Abeta(25-35) resulted in an improvement of reference memory impaired by the amyloid peptide, but not of working memory" http://www.ncbi.nlm.nih.gov/pubmed/17070605 0 1751 "H. L. Eley, S. T. Russell and M. J. Tisdale" 2008 Role of the dsRNA-dependent protein kinase (PKR) in the attenuation of protein loss from muscle by insulin and insulin-like growth factor-I (IGF-I) Mol.Cell Biochem. 313 01-Feb 63-69 "Proteolysis-inducing factor (PIF), a tumour-produced cachectic factor, induced a dose-dependent decrease in protein synthesis in murine myotubes, together with an increase in phosphorylation of eucaryotic initiation factor 2 (eIF2) on the alpha-subunit. Both insulin (1 nM) and insulin-like growth factor I (IGF-I) (13.2 nM) attenuated the depression of protein synthesis by PIF and the increased phosphorylation of eIF2alpha, by inhibiting the activation (autophosphorylation) of the dsRNA-dependent protein kinase (PKR) by induction of protein phosphatase 1. A low-molecular weight inhibitor of PKR also reversed the depression of protein synthesis by PIF to the same extent, as did insulin and IGF-I. Both insulin and IGF-I-stimulated protein synthesis in the presence of PIF, and this was attenuated by Salubrinal, an inhibitor of phospho eIF2alpha phosphatase, suggesting that at least part of this action was due to their ability to inhibit phosphorylation of eIF2alpha. Both insulin and IGF-I also attenuated the induction of protein degradation in myotubes induced by PIF, this effect was also attenuated by Salubrinal. These results suggest an alternative mechanism involving PKR to explain the effect of insulin and IGF-I on protein synthesis and degradation in skeletal muscle in the presence of catabolic factors" http://www.ncbi.nlm.nih.gov/pubmed/18360789 0 1752 M. Urabe 1989 [The study of direct effect of methimazole on thymidine incorporation in FRTL-5 cells] Nihon Naibunpi Gakkai Zasshi 65 1 32-41 "During the course of treatment of Graves' disease with the anti-thyroid drug, methimazole (MMI), a decrease in a patient's goiter size is sometimes observed. Using rat thyroid cell strain, FRTL-5, the direct effect of MMI on thyroid cell growth was investigated. FRTL-5 cells (2 X 10(5)) were cultured for 48 hours with TSH, (Bu)2 cAMP or forskolin in the presence of [3H]-thymidine. All three stimulators increased cell growth, expressed as [3H]-thymidine incorporation into DNA in a dose-dependent fashion. When FRTL-5 cells were cultured for 48 hours in the presence of MMI at 10(-6)-10(-3) M with these stimulators (TSH 250 microU/ml, (Bu)2 cAMP 10(-3) M, forskolin 10(-5) M), [3H]-thymidine incorporation was suppressed in dose-dependent fashions (MMI 10(-5) M-10(-3) M). From the present study, it is suggested that methimazole directly modulates thyroid cell growth induced by thyroid growth stimulators which are involved in adenylate cyclase-cyclic AMP system and that the site of its action exists beyond cAMP production" http://www.ncbi.nlm.nih.gov/pubmed/2542105 0 1753 "A. B. Tsypin, V. A. Nasonova, L. A. Vedernikova, S. K. Solov'ev, M. V. Velikaia, A. S. Chiklikchi and E. G. Sazhina" 1993 [Splenic perfusion in the combined treatment of patients with systemic lupus erythematosus] Ter.Arkh. 65 5 61-65 "Twenty patients suffering from severe systemic lupus erythematosus (SLE) underwent 52 sessions of splenoperfusion (SP) by means of extracorporeal perfusion of the patient's blood through isolated porcine spleen. It got prepared directly before the perfusion. The organ was obtained from a healthy animal in sterile conditions, washed from the blood after cannulation of the artery and vein. The patient's blood was pumped from the peripheral vein to the spleen artery. After passing through the splenic vascular bed the blood outflew from the spleen vein into the opposite peripheral vein of the patient. SP was followed by positive clinical changes: normalization of body temperature, regression of skin symptoms and articular syndrome, reduction of lymphadenopathy, hepato- and splenomegaly. The tests indicated inhibition of SLE activity. Sp-related immunocorrective effect was also present as shown by depression of B-cell hyperreactivity and T-cell immunity stimulation. 1-4-year follow-up of 19 patients showed them to be in remission. The data obtained favour SP inclusion into intensive therapy of severe SLE" http://www.ncbi.nlm.nih.gov/pubmed/8036600 0 1754 "Y. Zheng, L. Stiles, Y. T. Chien, C. L. Darlington and P. F. Smith" 2014 The effects of acute stress-induced sleep disturbance on acoustic trauma-induced tinnitus in rats Biomed.Res.Int. 2014 724195 "Chronic tinnitus is a debilitating condition and often accompanied by anxiety, depression, and sleep disturbance. It has been suggested that sleep disturbance, such as insomnia, may be a risk factor/predictor for tinnitus-related distress and the two conditions may share common neurobiological mechanisms. This study investigated whether acute stress-induced sleep disturbance could increase the susceptibility to acoustic trauma-induced tinnitus in rats. The animals were exposed to unilateral acoustic trauma 24 h before sleep disturbance being induced using the cage exchange method. Tinnitus perception was assessed behaviourally using a conditioned lick suppression paradigm 3 weeks after the acoustic trauma. Changes in the orexin system in the hypothalamus, which plays an important role in maintaining long-lasting arousal, were also examined using immunohistochemistry. Cage exchange resulted in a significant reduction in the number of sleep episodes and acoustic trauma-induced tinnitus with acoustic features similar to a 32 kHz tone at 100 dB. However, sleep disturbance did not exacerbate the perception of tinnitus in rats. Neither tinnitus alone nor tinnitus plus sleep disturbance altered the number of orexin-expressing neurons. The results suggest that acute sleep disturbance does not cause long-term changes in the number of orexin neurons and does not change the perception of tinnitus induced by acoustic trauma in rats" http://www.ncbi.nlm.nih.gov/pubmed/25162023 0 1755 J. B. Malick 1981 Clonidine: antidepressant potential? Prog.Clin.Biol.Res. 71 165-175 http://www.ncbi.nlm.nih.gov/pubmed/6276893 1 1756 "S. Chen, X. Zhao, F. Lu, Y. Wang, S. Li, B. Yan and H. Zhou" 2014 Effects of chaiyuwendan decoction on endocannabinoids levels in adipose tissue of rats with chronic stress-induced depression J.Tradit.Chin Med. 34 1 96-99 "OBJECTIVE: To investigate how Chaiyuwendan decoction (CWD) affects endocannabinoid levels in the adipose tissue of depressed rats. METHODS: Twenty-four male Sprague-Dawley rats were randomly divided into four groups with six rats in each. One group was randomly selected as the control group. The remaining three groups were subjected to chronic stress to induce depression. Groups were randomly assigned as a model group, CWD group, and amitriptyline group. CWD was given to the CWD group once a day from the second day of modeling. The amitriptyline group was administered amitriptyline intragastrically (10 mg/kg) once a day. After treatment for 21 days, body weight and fat weight were measured and the levels of N-arachidonoylethanolamine (AEA), 2-arachidonoylglycerol (2-AG), and N-palmitoylethanolamine (PEA) in adipose tissue were determined with liquid chromatography-mass spectrometry. RESULTS: Compared with the control group, body weight, fat weight, AEA, and PEA were significantly lower, and 2-AG was higher, in the model group (P < 0.05, P < 0.01). Compared with the model group, body weight, fat weight, the AEA, and PEA levels were significantly higher, and 2-AG level was significantly lower in the CWD group (P < 0.05). However, the levels did not differ significantly between the CWD group and the amitriptyline group. CONCLUSION: CWD could regulate the levels of AEA, 2-AG, and PEA in rats with depression induced by chronic stress" http://www.ncbi.nlm.nih.gov/pubmed/25102698 1 1757 "D. A. van, O. Mason, A. A. Klompmakers, M. G. Feenstra and D. Denys" 2011 Unilateral deep brain stimulation in the nucleus accumbens core does not affect local monoamine release J.Neurosci.Methods 202 2 113-118 "Recent publications have shown promising results of deep brain stimulation (DBS) in the nucleus accumbens for patients with obsessive compulsive disorder and major depressive disorder. Despite its increasing application in the clinical setting, the neurobiological mechanism of action of DBS is still uncertain. One of the possible effects of DBS might be phasic or tonic changes in monoamine release either locally in the target area or in a distant, connected region. In the present study we investigate whether unilateral DBS of the Nucleus Accumbens Core (NAc core) has a local effect on in vivo monoamine release. Freely moving animals were unilaterally stimulated with 300 muA or 400 muA (120 Hz, pulse width 80 mus) in the NAc core for 5 h. 1h before and during stimulation we measured dopamine, serotonin, their metabolites and noradrenaline using in vivo microdialysis. We found no significant effect of stimulation on extracellular concentrations of monoaminergic neurotransmitters or their metabolites in the NAc core during stimulation. Our results suggest that the rapid effects of DBS in the NAc are not a result of changes in local monoamine release in the NAc core. For future directions it is interesting to note that several microdialysis and electrophysiology studies have shown effects of DBS in areas distant from the stimulation target" http://www.ncbi.nlm.nih.gov/pubmed/21565219 0 1758 "M. Razin, M. Borosh and M. Weinstock" 1993 Rabbits with a genetic impairment in baroreceptor reflex sensitivity show abnormal renal haemodynamics and proximal tubular sodium reabsorption in response to a saline infusion J.Hypertens. 11 8 799-804 "OBJECTIVE: To compare renal haemodynamics and proximal tubular sodium reabsorption (PTSR) in response to an acute intravenous saline infusion in rabbits bred for genetic differences in cardiac baroreflex sensitivity (BRS). Rabbits with low BRS increase their blood pressure significantly on a high-salt diet, in association with an initial delay in sodium excretion. It was hypothesized that this could occur through an impaired baroreflex regulation of renal sympathetic nerve activity. This, in turn, would alter renal blood flow and PTSR. DESIGN: Experiments were performed in two groups of normotensive male rabbits (n = 10 per group), one of which had high BRS (> 5 beats/min per mmHg; group I) and one of which had low BRS (< 4 beats/min per mmHg; group II). Effective renal plasma flow (ERPF) was measured by para-aminohippuric acid clearance, and PTSR by the lithium clearance technique. Sodium, lithium, para-aminohippuric acid and glomerular filtration rate were measured from urine samples collected every 30 min (for 90 min) via an indwelling bladder catheter, during a control infusion of glucose (30 mg/ml) NaCl (1.8 mg/ml), and for 2 h after a threefold increase in NaCl. RESULTS: Group I rabbits increased their ERPF by approximately 40%, in response to saline, and doubled their sodium and lithium clearances within the 2 h, but those in group II did not change their cation excretion or their ERPF significantly during this period. Blood pressure did not increase in either group. CONCLUSIONS: A genetic impairment in BRS may be responsible for the inadequate depression of renal sympathetic nerve activity, which results in a failure to increase ERPF and suppress sodium reabsorption in the proximal tubule in response to salt loading" http://www.ncbi.nlm.nih.gov/pubmed/8228203 0 1759 L. E. Perkins and D. E. Swayne 2001 Pathobiology of A/chicken/Hong Kong/220/97 (H5N1) avian influenza virus in seven gallinaceous species Vet.Pathol. 38 2 149-164 "Direct bird-to-human transmission, with the production of severe respiratory disease and human mortality, is unique to the Hong Kong-origin H5N1 highly pathogenic avian influenza (HPAI) virus, which was originally isolated from a disease outbreak in chickens. The pathobiology of the A/chicken/Hong Kong/220/97 (H5N1) (HK/220) HPAI virus was investigated in chickens, turkeys, Japanese and Bobwhite quail, guinea fowl, pheasants, and partridges, where it produced 75-100% mortality within 10 days. Depression, mucoid diarrhea, and neurologic dysfunction were common clinical manifestations of disease. Grossly, the most severe and consistent lesions included splenomegaly, pulmonary edema and congestion, and hemorrhages in enteric lymphoid areas, on serosal surfaces, and in skeletal muscle. Histologic lesions were observed in multiple organs and were characterized by exudation, hemorrhage, necrosis, inflammation, or a combination of these features. The lung, heart, brain, spleen, and adrenal glands were the most consistently affected, and viral antigen was most often detected by immunohistochemistry in the parenchyma of these organs. The pathogenesis of infection with the HK/220 HPAI virus in these species was twofold. Early mortality occurring at 1-2 days postinoculation (DPI) corresponded to severe pulmonary edema and congestion and virus localization within the vascular endothelium. Mortality occurring after 2 DPI was related to systemic biochemical imbalance, multiorgan failure, or a combination of these factors. The pathobiologic features were analogous to those experimentally induced with other HPAI viruses in domestic poultry" http://www.ncbi.nlm.nih.gov/pubmed/11280371 0 1760 "B. W. Badran, C. E. Glusman, A. W. Badran, C. W. Austelle, W. H. De Vries, J. J. Borckhardt and M. S. George" 2016 "Development, safety, and tolerability of a novel form of noninvasive vagus nerve stimulation: Transcutaneous auricular vagus nerve stimulation (taVNS)" "Biological Psychiatry.Conference: 71st Annual Scientific Convention and Meeting of the Society of Biological Psychiatry, SOBP 2016 Atlanta, GA United States.Conference Start: 20160512 Conference End: 20160514.Conference Publication: (var.pagings).79 (var.pagings " 399S "Background: Cervically implanted vagus nerve stimulation (VNS) is FDA-approved for treating epilepsy or major depression. Additionally, VNS is a reemerging area of interest, showing promise in animal studies with significant translatable applications. We have developed a noninvasive device that electrically stimulates the auricular branch of the vagus called transcutaneous auricular vagus nerve stimulation (taVNS). Methods: This single-blind, sham controlled, crossover study consisted of 2 separate visits during which custom electrodes were used to deliver electrical stimulation to either the left tragus or earlobe (active v sham) in 15 healthy participants. Participants received nine different randomized 60s stimulation sessions of varying pulse width and frequency. Heart rate, skin temperature, and skin conductance were recorded during each session. Participants rated painfulness on a visual analog scale (VAS) and were monitored for adverse events. Results: No adverse events were observed and active stimulation was not more painful than sham. Mean pain VAS scores ranged from 0.2 to 1.94. With respect to heart rate changes, there was no significant decrease in heart rate between all active and all sham stimulations in an overall group analysis (n=135 sessions, mean HR decrease active= 1.86BPM, Sham=1.47BPM; p=0.521). When analyzed based on parameters, two of nine parameters had significant decreases in heart rate (500mus,25Hz; 200mus,25Hz; p<0.05). Conclusions: Short doses of taVNS in a sample of healthy young adults is feasible, tolerable, and reasonably safe. Like all forms of brain stimulation, the parameters of stimulation are important in modulating vagal tone (current (mA), pulse width (us), and frequency (Hz))" DO - http://dx.doi.org/10.1016/j.biopsych.2016.03.1410 0 1761 "S. R. Whittemore, L. A. White and H. R. Sanon" 1991 Acidic and basic fibroblast growth factor levels in spinal cord cultures are not regulated by alterations in heparan sulfate proteoglycan expression Int.J.Dev.Neurosci. 9 6 521-535 "The present study was undertaken to assess both the levels of acidic and basic fibroblast growth factors in spinal cord cultures and to determine how they were presented to responsive cells. Western blots detected a single acidic fibroblast growth factor-like protein (17 kDa) and two (18 kDa, 24 kDa) basic fibroblast growth factor-immunoreactive proteins, the levels of which varied with the antibody used. Levels of all three proteins were unaltered in cultures grown in the presence of a mitotic inhibitor, which greatly reduced the number of astrocytes. Cell blots showed increased survival of spinal cord neurons at Mr that corresponded with the three proteins detected immunologically. Solubilized cultures separated on a P100 column showed mitogenic activity for NIH3T3 cells from 17-18 and 24 kDa fractions. Treatment of the cultures with heparitinase did not decrease the levels of acidic and basic fibroblast growth factors detected by Western blots, suggesting that these proteins were not associated with extracellular membrane heparan sulfate proteoglycans. The major fraction of both proteins appeared to be intracellular with a minor amount complexed with extracellular matrix proteins. An inhibitor of xylose-linked proteoglycan synthesis significantly altered heparan sulfate proteoglycan deposition into extracellular matrix, but did not alter the levels of acidic or basic fibroblast growth factors detected by Western blots, or the levels of choline acetyltransferase, glutamic acid decarboxylase, or aspartate aminotransferase activities. These results indicate that both acidic and basic fibroblast growth factors are stored predominantly intracellularly, with only a minor fraction complexed with extracellular proteins. We suggest that these intracellular proteins may be released following injury in the CNS and mediate a cascade of neuroprotective events" http://www.ncbi.nlm.nih.gov/pubmed/1725084 0 1762 L. A. Vasil'eva and L. A. Samoilova 1968 [Cortical influences on the auditory analyzer system] Nerv.Sist. 9 93-98 http://www.ncbi.nlm.nih.gov/pubmed/5760020 0 1763 "V. Eybl, J. Sykora and F. Mertl" 1969 "[Effect of sodium selenite, sodium tellurite and sodium sulfite on retention and distribution of mercury in mice]" Arch.Toxikol. 24 3 296-305 http://www.ncbi.nlm.nih.gov/pubmed/5360665 0 1764 "S. R. Hulme, O. D. Jones, D. R. Ireland and W. C. Abraham" 2012 Calcium-dependent but action potential-independent BCM-like metaplasticity in the hippocampus J.Neurosci. 32 20 6785-6794 "The Bienenstock, Cooper and Munro (BCM) computational model, which incorporates a metaplastic sliding threshold for LTP induction, accounts well for experience-dependent changes in synaptic plasticity in the visual cortex. BCM-like metaplasticity over a shorter timescale has also been observed in the hippocampus, thus providing a tractable experimental preparation for testing specific predictions of the model. Here, using extracellular and intracellular electrophysiological recordings from acute rat hippocampal slices, we tested the critical BCM predictions (1) that high levels of synaptic activation will induce a metaplastic state that spreads across dendritic compartments, and (2) that postsynaptic cell-firing is the critical trigger for inducing that state. In support of the first premise, high-frequency priming stimulation inhibited subsequent long-term potentiation and facilitated subsequent long-term depression at synapses quiescent during priming, including those located in a dendritic compartment different to that of the primed pathway. These effects were not dependent on changes in synaptic inhibition or NMDA/metabotropic glutamate receptor function. However, in contrast to the BCM prediction, somatic action potentials during priming were neither necessary nor sufficient to induce the metaplasticity effect. Instead, in broad agreement with derivatives of the BCM model, calcium as released from intracellular stores and triggered by M1 muscarinic acetylcholine receptor activation was critical for altering subsequent synaptic plasticity. These results indicate that synaptic plasticity in stratum radiatum of CA1 can be homeostatically regulated by the cell-wide history of synaptic activity through a calcium-dependent but action potential-independent mechanism" http://www.ncbi.nlm.nih.gov/pubmed/22593048 0 1765 "C. Arkenau, A. J. Bosse and E. Schaum" 1969 [Comparative studies on the effect of propranolol and oxyfedrine on body temperature in hypothermia] Arzneimittelforschung. 19 11 1828-1829 http://www.ncbi.nlm.nih.gov/pubmed/4391789 0 1766 D. Kummer 1970 "[Effects of cytostatics and x-rays on nucleic acid metabolism of solid, malignant tumors in vitro]" Z.Krebsforsch. 74 1 76-90 http://www.ncbi.nlm.nih.gov/pubmed/4254297 0 1767 D. Gabel and V. Kasche 1973 Autolysis of beta-trypsin. Influence of calcium ions and heat Acta Chem.Scand. 27 6 1971-1981 http://www.ncbi.nlm.nih.gov/pubmed/4796159 0 1768 J. Hoie 1973 Hemodynamic effects of adenosine di-phosphate (ADP) J.Oslo.City Hosp. 23 6 111-118 http://www.ncbi.nlm.nih.gov/pubmed/4771836 0 1769 R. Turcotte 1985 Opposite effects of cyclophosphamide pretreatment on tuberculin hypersensitivity during the course of sensitization of mice with Mycobacterium bovis BCG Int.J.Immunopharmacol. 7 5 687-695 "The influence of cyclophosphamide (CY) pretreatment upon the development of tuberculin hypersensitivity has been studied during the course of infection of mice with BCG. An enhancement of the DTH response to BCG antigens occurred during the induction phase, whereas a depression of this response occurred at the peak and during the decay phase of sensitization. The development of the early DTH-promoting and of the late DTH-depressing effect of CY was favoured by the use of a supra-optimal dose of BCG. Both these effects were cell-dependent since they could be transferred adoptively to syngeneic recipient mice with sensitized lymphoid cells but not with specific immune sera. Pretreatment with CY favoured the emergence of cells capable of responding in vitro to BCG antigens in the draining lymph nodes of BCG-infected mice. No simple association however, exists between this in vitro lymphocyte transformation response and the DTH response" http://www.ncbi.nlm.nih.gov/pubmed/4044094 0 1770 G. N. Callahan 2002 Madness Emerg.Infect.Dis. 8 9 998-1002 http://www.ncbi.nlm.nih.gov/pubmed/12219740 0 1771 R. L. Macdonald and J. L. Barker 1978 Specific antagonism of GABA-mediated postsynaptic inhibition in cultured mammalian spinal cord neurons: a common mode of convulsant action Neurology 28 4 325-330 "Mammalian spinal neurons grown in tissue culture were used to study the effects of the four convulsants-penicillin, pentylenetetrazol, picrotoxin, and bicuculline-on these neurons' responses to amino acids. Bath application of all four convulsants produced paroxysmal depolarizing events in the neurons; iontophoresis of the four convulsants selectively depressed responses produced by iontophoresis of the putative inhibitory transmitter GABA, and effected this depression without altering either inhibitory responses to beta-alanine or glycine, or excitation mediated by glutamate. These results support the hypothesis that the convulsant activity of these agents comes in part from selective antagonism of GABA-mediated postsynaptic inhibition" http://www.ncbi.nlm.nih.gov/pubmed/565020 0 1772 "D. F. Papolos, E. Edwards, R. Marmur, H. M. Lachman and F. A. Henn" 1993 Effects of the antiglucocorticoid RU 38486 on the induction of learned helpless behavior in Sprague-Dawley rats Brain Res. 615 2 304-309 "Learned helplessness (LH) is induced by exposure to an inescapable or uncontrollable stressor which results in an inability to escape or avoid the same stressor when subsequently presented in a different context. In order to understand which central mechanisms may influence the expression of the learned helpless phenotype, we have pursued an experimental approach that seeks to elucidate the behavioral effects of glucocorticoid (GC) hormones in this animal model of depression. We have previously shown that the induction of LH behavior is enhanced by adrenalectomy, an effect that is reversed by corticosterone. In this study, our aim was to attempt to locate CNS sites responsible for the observed effects of glucocorticoids on learned helpless behavior by introducing the type II GC receptor antagonist, RU 38486 to discrete brain regions. We did not observe a significant effect in LH with acute systemic, acute dentate gyrus or intracerebroventricular injection of RU 38486 in contrast to previous studies using the Porsolt swim test, another animal model of depression. However, we were able to observe a significant change upon chronic administration to the dentate gyrus. These findings suggest that glucocorticoids exert a long-term influence on stress-induced behavior, presumably by affecting glucocorticoid responsive genes in the dentate gyrus" http://www.ncbi.nlm.nih.gov/pubmed/8364739 1 1773 "S. Rana, H. Nam, M. E. Glover, H. Akil, S. J. Watson, S. M. Clinton and I. A. Kerman" 2016 Protective effects of chronic mild stress during adolescence in the low-novelty responder rat Stress. 19 1 133-138 "Stress-elicited behavioral and physiologic responses vary widely across individuals and depend on a combination of environmental and genetic factors. Adolescence is an important developmental period when neural circuits that guide emotional behavior and stress reactivity are still maturing. A critical question is whether stress exposure elicits contrasting effects when it occurs during adolescence versus adulthood. We previously found that Sprague-Dawley rats selectively bred for low-behavioral response to novelty (bred Low Responders; bLRs) are particularly sensitive to chronic unpredictable mild stress (CMS) exposure in adulthood, which exacerbates their typically high levels of spontaneous depressive- and anxiety-like behavior. Given developmental processes known to occur during adolescence, we sought to determine whether the impact of CMS on bLR rats is equivalent when they are exposed to it during adolescence as compared with adulthood. Young bLR rats were either exposed to CMS or control condition from postnatal days 35-60. As adults, we found that CMS-exposed bLRs maintained high levels of sucrose preference and exhibited increased social exploration along with decreased immobility on the forced swim test compared with bLR controls. These data indicate a protective effect of CMS exposure during adolescence in bLR rats" http://www.ncbi.nlm.nih.gov/pubmed/26473581 1 1774 "J. Sederberg, T. H. Stanley, P. Reddy, W. S. Liu, D. Port and S. Gillmor" 1981 Hemodynamic effects of butorphanol-oxygen anesthesia in dogs Anesth.Analg. 60 10 715-719 "The cardiovascular effects of two intravenous rates of butorphanol infusion (0.1 and 0.2 mg/kg/min) were measured in 32 dogs breathing oxygen and nitrous oxide in oxygen. Sixteen dogs were premedicated with atropine and the other 16 were unpremedicated. Of the dogs receiving the higher dose infusion rate, 25% moved with a tail-clamp stimulus whereas 75% moved with the lower doses. Butorphanol produced significant but similar cardiovascular depression with the two rates of infusion irrespective of the presence or absence of atropine medication. Addition of nitrous oxide resulted in further cardiac depression in all groups studied. The data suggest that butorphanol is not an attractive alternative to morphine or fentanyl as a narcotic anesthetic" http://www.ncbi.nlm.nih.gov/pubmed/7197474 0 1775 "F. Laezza, J. J. Doherty and R. Dingledine" 1999 Long-term depression in hippocampal interneurons: joint requirement for pre- and postsynaptic events Science 285 5432 1411-1414 Long-term depression (LTD) is a well-known form of synaptic plasticity of principal neurons in the mammalian brain. Whether such changes occur in interneurons is still controversial. CA3 hippocampal interneurons expressing Ca2+-permeable AMPA receptors exhibited LTD after tetanic stimulation of CA3 excitatory inputs. LTD was independent of NMDA receptors and required both Ca2+ influx through postsynaptic AMPA receptors and activation of presynaptic mGluR7-like receptors. These results point to the capability of interneurons to undergo plastic changes of synaptic strength through joint activation of pre- and postsynaptic glutamate receptors http://www.ncbi.nlm.nih.gov/pubmed/10464102 0 1776 "P. Huang, J. Tunis, C. Parry, R. Tallarida and L. Y. Liu-Chen" 2016 Synergistic antidepressant-like effects between a kappa opioid antagonist (LY2444296) and a delta opioid agonist (ADL5859) in the mouse forced swim test Eur.J.Pharmacol. 781 53-59 "Kappa opioid (KOP) receptor antagonists and delta opioid (DOP) receptor agonists have antidepressant-like effects in animal tests and may be useful for treatment-resistant depression in humans. In this study, we examined whether the combination of a KOP receptor antagonist and a DOP receptor agonist would produce a better than additive effect (i.e. synergy). LY2444296 is a short-acting selective nonpeptide KOP receptor antagonist. ADL5859 is a selective nonpeptide DOP receptor agonist which does not produce seizures and EEG disturbances. Each compound and combinations of the two were examined in the forced swim test (FST) one h post injection, a screening test for antidepressant-like effect, in male adult C57BL/6J mice (Jackson Lab). LY2444296 [subcutaneous (s.c.) injection] at 10 and 30mg/kg, but not 3mg/kg, significantly decreased immobility time in a dose-dependent manner. Intraperitoneal (i.p.) injections of ADL5859 also reduced immobility time dose-dependently at doses of 3 and 10mg/kg, but not at 1mg/kg. An analysis was conducted using the method of Tallarida and Raffa (2010), which employed dose equivalence. The relative potency of the drugs was determined to be LY2444296: ADL5859=1:0.28, which was the dose ratio for combination studies. Six combinations of the two compounds were tested in mice at a fixed dose ratio. We found that LY2444296 and ADL5859 yielded significant synergistic effects for the antidepressant-like effect at the combined dose ranging from 3.84mg/kg to 9.0mg/kg. ADL5859 (10mg/kg), LY2444296 (30mg/kg) and their combined dose (3.84mg/kg) had no effects on locomotor activities. Since the two drugs have distinct pharmacological profiles, such a synergism will allow use of lower doses of both drugs to achieve desired antidepressant effects with fewer side effects" http://www.ncbi.nlm.nih.gov/pubmed/27044434 1 1777 "S. E. Hampson, J. A. Andrews, M. Barckley, M. Gerrard and F. X. Gibbons" 2016 "Harsh Environments, Life History Strategies, and Adjustment: A Longitudinal Study of Oregon Youth" Pers.Individ.Dif. 88 120-124 "We modeled the effects of harsh environments in childhood on adjustment in early emerging adulthood, through parenting style and the development of fast Life History Strategies (LHS; risky beliefs and behaviors) in adolescence. Participants were from the Oregon Youth Substance Use Project (N = 988; 85.7% White). Five cohorts of children in Grades 1-5 at recruitment were assessed through one-year post high school. Greater environmental harshness (neighborhood quality and family poverty) in Grades 1-6 predicted less parental investment at Grade 8. This parenting style was related to the development of fast LHS (favorable beliefs about substance users and willingness to use substances at Grade 9, and engagement in substance use and risky sexual behavior assessed across Grades 10-12). The indirect path from harsh environment through parenting and LHS to (less) psychological adjustment (indicated by lower life satisfaction, self-rated health, trait sociability, and higher depression) was significant (indirect effect -.024, p = .011, 95% CI = -.043, -.006.). This chain of development was comparable to that found by Gibbons et al. (2012) for an African-American sample that, unlike the present study, included perceived racial discrimination in the assessment of harsh environment" http://www.ncbi.nlm.nih.gov/pubmed/26451065 0 1778 "M. Nakazato, K. Hashimoto, U. Schmidt, K. Tchanturia, I. C. Campbell, D. A. Collier, M. Iyo and J. Treasure" 2010 "Serum glutamine, set-shifting ability and anorexia nervosa" Ann.Gen.Psychiatry 9 29 "BACKGROUND: Set-shifting is impaired in people with anorexia nervosa (AN), but the underlying physiological and biochemical processes are unclear. Animal studies have established that glutamatergic pathways in the prefrontal cortex play an important role in set-shifting ability. However, it is not yet understood whether levels of serum glutamatergic amino acids are associated with set-shifting performance in humans. The aim of this study was to determine whether serum concentrations of amino acids related to glutamatergic neurotransmission (glutamine, glutamate, glycine, l-serine, d-serine) are associated with set-shifting ability in people with acute AN and those after recovery. METHODS: Serum concentrations of glutamatergic amino acids were measured in 27 women with current AN (AN group), 18 women recovered from AN (ANRec group) and 28 age-matched healthy controls (HC group). Set-shifting was measured using the Wisconsin Card Sorting Test (WCST) and the Trail Making Task (TMT). Dimensional measures of psychopathology were used, including the Eating Disorder Examination Questionnaire (EDEQ), the Maudsley Obsessive-Compulsive Inventory (MOCI) and the Hospital Anxiety and Depression Scale (HADS). RESULTS: Serum glutamine concentrations in the AN group (1,310.2 +/- 265.6 muM, mean +/- SD) were significantly higher (by approximately 20%) than those in the HC group (1,102.9 +/- 152.7 muM, mean +/- SD) (F(2, 70) = 6.3, P = 0.003, 95% CI 61.2 to 353.4). Concentrations of serum glutamine were positively associated with markers of the illness severity: a negative correlation was present between serum glutamine concentrations and body mass index (BMI) and lowest BMI and a positive correlation was found between duration of illness and EDEQ. The AN group showed significantly impaired set shifting in the WCST, both total errors, and perseverative errors. In the AN group, there were no correlations between serum glutamine concentrations and set shifting. CONCLUSIONS: Serum concentrations of glutamine may be a biomarker of illness severity in people with AN. It does not appear to be directly associated with changes in executive function" http://www.ncbi.nlm.nih.gov/pubmed/20576166 0 1779 P. Barath 1974 New aspects of the role of serotonin in the insulin release mechanism Acta Diabetol.Lat. 11 4 315-329 http://www.ncbi.nlm.nih.gov/pubmed/4619282 0 1780 R. W. Turkington and O. T. Ward 1969 Hormonal stimulation of RNA polymerase in mammary gland in vitro Biochim.Biophys.Acta 174 1 291-301 http://www.ncbi.nlm.nih.gov/pubmed/5766297 0 1781 "H. Karunajeewa, D. A. Barr and M. Fox" 1986 Effect of dietary phosphorus concentration and electrolyte balance on the growth performance of broiler chickens Br.Poult.Sci. 27 4 601-612 "The performance of 1680 male and female broiler chickens given diets with either a low (4.7-4.3 g/kg) or high (8.9-8.2 g/kg) content of inorganic phosphorus and four (150, 200, 250 and 300 mEq/kg) electrolyte balances (Na+K-Cl) was measured from 1-d-old to 49 d of age. Diets with the higher concentration of inorganic phosphorus reduced body weight gains in the starter (P less than 0.01) and finisher (P less than 0.05) phases but the efficiency of food utilisation was reduced only in the starter phase (P less than 0.05). The reduction in body weight gain was greater in males than in females. The growth depression caused by the higher concentration of inorganic phosphorus in the finisher diets was partially alleviated by increasing the electrolyte balance to either 250 or 300 mEq/kg diet. The higher concentration of inorganic phosphorus significantly reduced the dressing percentage and increased the abdominal fat pad weight and litter moisture content. Electrolyte balance had no significant effects on efficiency of food utilisation, abdominal fat pad weights or litter moisture content. Neither the dietary concentration of phosphorus nor the electrolyte balance had a significant effect on mortality or ash content of the tibia" http://www.ncbi.nlm.nih.gov/pubmed/3815128 0 1782 "J. T. Kim, K. Y. Rhee, J. H. Bahk, S. H. Do, Y. J. Lim, H. Ko and K. H. Lee" 2003 "Continuous mixed venous oxygen saturation, not mean blood pressure, is associated with early bupivacaine cardiotoxicity in dogs" Can.J.Anaesth. 50 4 376-381 "PURPOSE: To investigate changes of continuous mixed venous oxygen saturation (cSvO(2)) and mean arterial blood pressure (MBP) in dogs with bupivacaine-induced cardiac depression. METHODS: Bupivacaine was infused into pentobarbital-anesthetized mongrel dogs (n = 8) at a rate of 0.5 mg.kg(-1).min(-1) until the MBP was 40 mmHg or less (end of bupivacaine infusion; BIE). The infusion time was divided into the early period, first 30 min of bupivacaine infusion and the late period, which was from 30 min of bupivacaine infusion until BIE. cSvO(2) was monitored using a fibreoptic pulmonary artery catheter, and MBP and cardiac output (CO) were measured every ten minutes after the initiation of bupivacaine infusion. Arterial blood gas, serum electrolyte and bupivacaine concentration were measured simultaneously. The relationships between CO and cSvO(2), and of CO vs MBP were compared by regression analysis in the early and late periods. RESULTS: The Pearson's correlation coefficients between CO and cSvO(2) were 0.782 (P = 2.1 x 10(-7)) in the early period and 0.824 (P = 1.3 x 10(-6)) in the late period. The correlation coefficients between CO and MBP were 0.019 (P = 0.921) in the early period and 0.799 (P = 4.8 x 10(-6)) in the late period. CONCLUSIONS: cSvO(2), but not MBP, is associated with CO changes in bupivacaine-induced cardiac depression during the early period of bupivacaine intoxication. Decrease of MBP with low cSvO(2) observed during the late period might imply severe cardiac depression induced by bupivacaine infusion" http://www.ncbi.nlm.nih.gov/pubmed/12670815 0 1783 B. I. Gustafsson and D. S. Delbro 1993 Tonic inhibition of small intestinal motility by nitric oxide J.Auton.Nerv.Syst. 44 02-Mar 179-187 "The effects of blocking nitric oxide synthase with the arginine analog N omega-nitro-L-arginine (L-NNA) were investigated in anaesthetized cats, vagotomized and pretreated with guanethidine and atropine. Spontaneous NANC jejunal motility (recorded as the volume changes of an intraluminal balloon) was markedly increased in a dose-dependent and stereospecific manner. The effect of L-NNA was partly reversed by L-arginine, the substrate for nitric oxide (NO) synthesis. Thus, this study presents evidence for a tonic inhibitory influence, via the release of NO, on small intestinal motility in vivo. Furthermore, relaxations upon the L-NNA-induced hypermotility could be elicited by vagal nerve stimulation, which may suggest the existence of another NANC inhibitory transmitter. Hexamethonium abolished such relaxations but did not affect the tone or phasic activity after L-NNA" http://www.ncbi.nlm.nih.gov/pubmed/7693788 0 1784 "C. K. Burton, I. K. Ho and B. Hoskins" 1990 Evidence for involvement of cyclic GMP phosphodiesterase in morphine tolerance J.Pharmacol.Exp.Ther. 252 1 104-111 "Preliminary evidence had suggested that changes in cyclic GMP (cGMP) hydrolysis via cyclic nucleotide phosphodiesterase(s) occurred during development of tolerance to morphine. To examine this finding further and its possible role in development of tolerance to morphine, rats (150-175 g) were injected with 1 ml of a sustained-release morphine preparation (40 mg/ml). Control rats received 1 ml of the oily vehicle. Antinociception, decreased locomotor activity, respiratory depression and mydriasis were measured at various times from 0.5 through 96 hr of exposure to the drug. Particulate and soluble cGMP hydrolysis were measured for the same time periods from periaqueductal gray (PAG), striatum, medulla and oculomotor nucleus, the brain areas believed to mediate the respective behaviors. Each of the behaviors except mydriasis showed development of complete tolerance (no difference from control behaviors) during the 96 hr of continuous exposure. During development of tolerance, particulate cGMP hydrolysis decreased in PAG and increased in striatum and medulla. Particulate cGMP hydrolysis was not altered in oculomotor nucleus, the brain area mediating mydriasis to which tolerance development was partial or incomplete. Significant changes in soluble cGMP hydrolysis occurred only in PAG before decline in the behavioral effect and did not appear to be involved in tolerance phenomena. Modulation of cyclic nucleotide levels by changes in particulate cGMP hydrolysis may produce or allow for development of complete tolerance to various morphine-induced behaviors" http://www.ncbi.nlm.nih.gov/pubmed/2153795 0 1785 P. S. Lacy and A. M. Earle 1986 A correlation between multiple unit activity in the hypothalamus and electrocardiographic changes during a subarachnoid hemorrhage Brain Res. 373 01-Feb 146-152 "A sudden onset and short latency of cardiovascular responses that may follow a subarachnoid hemorrhage (SAH) in the vicinity of the circle of Willis implicate neural mechanisms. To investigate this, multi unit activity (MUA) was recorded from the posterolateral hypothalamus and electrocardiogram was recorded from lead II before and during SAH in rats. A temporal correlation between MUA, heart rate and rhythm changes was observed. Following SAH, transient depression of MUA (approximately 5 s or less) did not affect heart rate; a more sustained suppression preceded bradycardia and arrhythmias. Bradycardia, premature atrial contractions and premature ventricular contractions occurred under two conditions: when MUA was suppressed; and during bursts in MUA when interburst phases were suppressed. Further evidence that bradycardia may be the result of suppression of brain potentials was obtained by failure of bilateral vagotomy, atropine and isoproterenol to reverse bradycardia generated after SAH under the ventral aspect of the brain in the vicinity of circle of Willis. However, bilateral vagotomy reversed bradycardia after SAH in the cisterna magna indicating an activation of central parasympathetic neurons. The results indicate that different neural mechanisms underlie bradycardia generated from the above mentioned two sites, namely, ventral brain and cisterna magna" http://www.ncbi.nlm.nih.gov/pubmed/2424550 0 1786 "T. Nakamura, Y. Matuo, K. Nishikawa, T. Horio and K. Okunuki" 1968 Effects on various types of liver catalase by growth of rhodamine sarcoma and by administration of in vivo catalase-depressing substance prepared from the tumor Gan 59 4 317-325 http://www.ncbi.nlm.nih.gov/pubmed/5707406 0 1787 "M. Komorowski, J. P. Huston, I. Klingenhegel, J. Paulat, J. Sackers and B. Topic" 2012 "Distance from source of reward as a marker for extinction-induced ""despair"": modulation by the antidepressants clomipramine and citalopram" Neuroscience 223 152-162 "Despair-related withdrawal behaviors are common symptoms of major depression (MD) and can be ascribed to a loss or absence of former rewarding events. Extinction of negatively reinforced escape behavior in the Morris Water Maze has been shown to induce despair-like behavior. A new animal model of depressive-like behavior is based on the extinction of positively reinforced behavior, which was shown to induce spatial avoidance of the former source of reward and biting of the operandum. Treatment with antidepressants attenuated these extinction-induced behaviors, suggesting that they reflect a depressive-like state. Here we present a methodological variation of this depression model. We employed an elongated operant chamber rather than a two-compartment procedure with the intent to establish a flowing gradient of withdrawal from the source of reward, rather than an all-or-none binary measure. Furthermore, instead of employing extinction of lever-pressing behavior, we applied a cued fixed-time food-delivery schedule. Sixty adult male Wistar rats (n=12/group) were trained to receive a food reward after appearance of a cue-light (fixed interval 90s) in an elongated Skinner-box of 72 cm length. Prior to extinction, the animals were treated for 9 days with either 7.5 or 10mg/kg of the tricyclic antidepressant clomipramine, 7.5 or 10mg/kg of the selective serotonin reuptake inhibitor (SSRI) citalopram or vehicle. Subsequent testing in an open field was carried out to investigate potential effects of the antidepressants on locomotor- and anxiety-like behavior. An overall increase in distance from the feeder and biting behavior was found over the course of the extinction trials. Both, citalopram and clomipramine decreased the distance from the pellet feeder during the initial extinction trials compared to the vehicle-treated group. The attenuation of withdrawal behavior by the antidepressants supports the hypothesis that avoidance/withdrawal behavior during extinction trials can serve as a marker for extinction-induced depression and suggests the utility of this paradigm as a rodent model of depression" http://www.ncbi.nlm.nih.gov/pubmed/22871517 1 1788 "M. Svensson, T. Hallin, J. Broms, J. Ekstrand and A. Tingstrom" 2016 Spatial memory impairment in Morris water maze after electroconvulsive seizures Acta Neuropsychiatr. 01-Oct "OBJECTIVE: Electroconvulsive therapy (ECT) is one of the most efficient treatments for severe major depression, but some patients suffer from retrograde memory loss after treatment. Electroconvulsive seizures (ECS), an animal model of ECT, have repeatedly been shown to increase hippocampal neurogenesis, and multiple ECS treatments cause retrograde amnesia in hippocampus-dependent memory tasks. Since recent studies propose that addition of newborn hippocampal neurons might degrade existing memories, we investigated whether the memory impairment after multiple ECS treatments is a cumulative effect of repeated treatments, or if it is the result of a delayed effect after a single ECS. METHODS: We used the hippocampus-dependent memory task Morris water maze (MWM) to evaluate spatial memory. Rats were exposed to an 8-day training paradigm before receiving either a single ECS or sham treatment and tested in the MWM 24 h, 72 h, or 7 days after this treatment, or multiple (four) ECS or sham treatments and tested 7 days after the first treatment. RESULTS: A single ECS treatment was not sufficient to cause retrograde amnesia whereas multiple ECS treatments strongly disrupted spatial memory in the MWM. CONCLUSION: The retrograde amnesia after multiple ECS is a cumulative effect of repeated treatments rather than a delayed effect after a single ECS" http://www.ncbi.nlm.nih.gov/pubmed/27139778 0 1789 J. Herbert 1998 "Neurosteroids, brain damage, and mental illness" "Experimental Gerontology.33 (7-8) ()(pp 713-727), 1998.Date of Publication: November/December 1998." 07-Aug 713-727 "The steroidal environment of the brain has marked consequences for both its structure and function. Social or physical stress has deleterious results on hippocampal function. This can be replicated by raising corticoids, which are also highly responsive to stress. Corticosterone, the major glucocorticoid in the rat, induces neuronal death in primary hippocampal cultures. Elevated corticoids also induce mood changes, and these are well known to be associated with stress, particularly chronic stress such as social adversity accentuated by intercurrent aversive life events. DHEA, a second adrenal steroid, has a very different developmental history, increasing rapidly during childhood, reaching a peak in youth, and declining thereafter in both blood and CSF. DHEA, in contrast to corticoids, has brain protective actions. It reduces the neurotoxic actions of glutamate analogues (such as NMDA) as well as those of corticoids. Evidence from several sources suggests that DHEA can act as an antiglucocorticoid. DHEA levels are reduced in major depressive disorders in both adolescents and adults, and a raised cortisol/DHEA ratio (together with intercurrent life events) predicts delayed recovery. DHEA may have a role in the treatment of depression. Together, these findings suggest that altered steroidal environment, whether induced by stress or aging, can have appreciable results on the cellular structure of the brain as well as on its function, although links between the two sets of findings are still tentative" DO - http://dx.doi.org/10.1016/S0531-5565%2898%2900039-4 0 1790 "Z. Zeier, A. Kumar, K. Bodhinathan, J. A. Feller, T. C. Foster and D. C. Bloom" 2009 Fragile X mental retardation protein replacement restores hippocampal synaptic function in a mouse model of fragile X syndrome Gene Ther. 16 9 1122-1129 "Fragile X syndrome (FXS) is caused by a mutation that silences the fragile X mental retardation gene (FMR1), which encodes the fragile X mental retardation protein (FMRP). To determine whether FMRP replacement can rescue phenotypic deficits in a fmr1-knockout (KO) mouse model of FXS, we constructed an adeno-associated virus-based viral vector that expresses the major central nervous system (CNS) isoform of FMRP. Using this vector, we tested whether FMRP replacement could rescue the fmr1-KO phenotype of enhanced long-term depression (LTD), a form of synaptic plasticity that may be linked to cognitive impairments associated with FXS. Extracellular excitatory postsynaptic field potentials were recorded from CA3-CA1 synaptic contacts in hippocampal slices from wild-type (WT) and fmr1-KO mice in the presence of AP-5 and anisomycin. Paired-pulse low-frequency stimulation (PP-LFS)-induced LTD is enhanced in slices obtained from fmr1 KO compared with WT mice. Analyses of hippocampal synaptic function in fmr1-KO mice that received hippocampal injections of vector showed that the PP-LFS-induced LTD was restored to WT levels. These results indicate that expression of the major CNS isoform of FMRP alone is sufficient to rescue this phenotype and suggest that post-developmental protein replacement may have the potential to improve cognitive function in FXS" http://www.ncbi.nlm.nih.gov/pubmed/19571888 0 1791 D. Stellwagen and R. C. Malenka 2006 Synaptic scaling mediated by glial TNF-alpha Nature 440 7087 1054-1059 "Two general forms of synaptic plasticity that operate on different timescales are thought to contribute to the activity-dependent refinement of neural circuitry during development: (1) long-term potentiation (LTP) and long-term depression (LTD), which involve rapid adjustments in the strengths of individual synapses in response to specific patterns of correlated synaptic activity, and (2) homeostatic synaptic scaling, which entails uniform adjustments in the strength of all synapses on a cell in response to prolonged changes in the cell's electrical activity. Without homeostatic synaptic scaling, neural networks can become unstable and perform suboptimally. Although much is known about the mechanisms underlying LTP and LTD, little is known about the mechanisms responsible for synaptic scaling except that such scaling is due, at least in part, to alterations in receptor content at synapses. Here we show that synaptic scaling in response to prolonged blockade of activity is mediated by the pro-inflammatory cytokine tumour-necrosis factor-alpha (TNF-alpha). Using mixtures of wild-type and TNF-alpha-deficient neurons and glia, we also show that glia are the source of the TNF-alpha that is required for this form of synaptic scaling. We suggest that by modulating TNF-alpha levels, glia actively participate in the homeostatic activity-dependent regulation of synaptic connectivity" http://www.ncbi.nlm.nih.gov/pubmed/16547515 0 1792 E. D. Schomburg and H. Steffens 1988 The effect of DOPA and clonidine on reflex pathways from group II muscle afferents to alpha-motoneurones in the cat Exp.Brain Res. 71 2 442-446 In high spinal cats the transmission in both disynaptic and polysynaptic reflex pathways from group II muscle afferents to motoneurones was effectively depressed by DOPA and clonidine together with an often less pronounced depression of transmission in other FRA reflex pathways. The inhibitory effect of both drugs on the inhibitory group II and FRA pathways was generally less distinct than that on the excitatory ones. The results are in agreement with former observations which suggested that the excitatory and the inhibitory FRA pathways are independently controlled by descending pathways from the brain stem (Holmqvist and Lundberg 1961) http://www.ncbi.nlm.nih.gov/pubmed/2844579 0 1793 "M. Ito, W. E. Connor, E. J. Blanchette, C. R. Treadwell and G. V. Vahouny" 1969 "Inhibition of lymphatic absorption of cholesterol by cholestane-3 beta, 5 alpha, 6 beta-triol" J.Lipid Res. 10 6 694-702 "The effect of cholestane-3,5alpha,6-triol (CT) on the intestinal absorption of cholesterol and oleic acid, as well as the absorption of labeled CT, was studied in lymph ductcannulated rats. Intragastric administration of 50 mg of CT in an emulsion with cholesterol-7alpha-(3)H and oleic acid-1-(14)C resulted in 50% inhibition of sterol transfer into lymph but only 8% depression of fatty acid absorption over an 8 hr period. The absorption of labeled CT into lymph was only 2-3% compared with 50% absorption of cholesterol when each was fed alone. 10% of the fed CT was recovered in the intestinal mucosa, and of this, one-half was associated with the brush border fraction. In rats fed CT 6 days prior to cholesterol and fatty acid administration, there was no effect on fatty acid absorption, while cholesterol absorption was reduced by almost 30%. When the intestinal mucosa from these animals were investigated by electron microscopy, it appeared that CT feeding resulted in numerous enlarged mitochondria and a marked increase in length of the microvilli. If animals were allowed to recover for 6 days from the CT prefeeding regime, the intestinal mucosa appeared normal, and the absorption of cholesterol approached that in controls. A possible mechanism for CT inhibition of cholesterol absorption was shown to be competition for the enzyme cholesterol esterase which esterifies cholesterol prior to entrance into the lymphatic system. CT itself is poorly esterified and poorly absorbed, but it is effective in inhibiting esterification of cholesterol in vitro" http://www.ncbi.nlm.nih.gov/pubmed/5356754 0 1794 "S. H. Lockhart, Y. Cohen, N. Yasuda, F. Kim, L. Litt, E. I. Eger, L. H. Chang and T. James" 1990 Absence of abundant binding sites for anesthetics in rabbit brain: an in vivo NMR study Anesthesiology 73 3 455-460 "Using magnetic resonance spectroscopy, the authors tested whether cerebral concentrations of inhaled anesthetics do not increase proportionately at inspired concentrations exceeding 3% 1) because anesthetics bind to and saturate specific sites in the brain or 2) because anesthetic-induced depression of ventilation limits the increase in alveolar anesthetic partial pressure. New Zealand White rabbits were anesthetized with methohexital, 70% nitrous oxide, and local infiltration of 1% lidocaine. Cerebral concentrations of anesthetic were determined from 19F spectra acquired with nuclear magnetic resonance (NMR). Inspired, end-tidal, and arterial anesthetic concentrations, and end-tidal and arterial partial pressure of carbon dioxide were measured. Blood/gas partition coefficients were determined and used to convert arterial anesthetic concentration to partial pressures. In seven spontaneously breathing animals, halothane (1%; n = 5) or isoflurane (0.8%; n = 2) was administered at a constant inspired concentration for 20 min; NMR spectra were acquired between 10 and 20 min. Thereafter, the inspired concentration was increased and the process repeated until apnea occurred. Two additional rabbits were anesthetized with isoflurane and studied similarly but with higher inspired concentrations during mechanical ventilation. In spontaneously breathing animals, ventilatory depression occurred, documented by marked increases in PaCO2, and cerebral concentrations of anesthetic did not increase proportionately at inspired concentrations exceeding 3%. In contrast to an absence of a correlation of inspired and cerebral concentrations during spontaneous ventilation, arterial and cerebral concentrations correlated linearly during both spontaneous and mechanical ventilation (R2 greater than 0.969). These results are consistent with depression of ventilation, rather than binding to specific cerebral sites as an explanation for the nonlinear relationship between cerebral and inspired anesthetic concentrations" http://www.ncbi.nlm.nih.gov/pubmed/2393130 0 1795 "I. Kitayama, T. Yaga, T. Kayahara, K. Nakano, S. Murase, M. Otani and J. Nomura" 1997 "Long-term stress degenerates, but imipramine regenerates, noradrenergic axons in the rat cerebral cortex" Biol.Psychiatry 42 8 687-696 "Exposed to a forced walking stress for 2 weeks, some rats became persistently inactive (depression-model rats), whereas others gradually recovered from exhaustion (spontaneous recovery rats). We also studied rats exposed to short-term stress, rats without stress, and the model rats treated with imipramine or saline. We examined the density of noradrenergic axons in the frontal cortex using retrograde labeling of the locus coeruleus with horseradish peroxidase injected into the cortex and immunohistochemical staining of cortical axons with dopamine beta-hydroxylase antiserum. The density was significantly lower in the depression-model rats, but tended to be higher in the recovery rats and short-term stressed rats. Chronic treatment with imipramine significantly increased the density in the model rats. There was also a correlation between the density of noradrenergic axons and the recovery rate of activity. Our results suggest that cortical noradrenergic degeneration is involved in the pathogenesis of depression" http://www.ncbi.nlm.nih.gov/pubmed/9325562 1 1796 "A. Buras, L. Battle, E. Landers, T. Nguyen and N. Vasudevan" 2014 Thyroid hormones regulate anxiety in the male mouse Horm.Behav. 65 2 88-96 "Thyroid hormone levels are implicated in mood disorders in the adult human but the mechanisms remain unclear partly because, in rodent models, more attention has been paid to the consequences of perinatal hypo and hyperthyroidism. Thyroid hormones act via the thyroid hormone receptor (TR) alpha and beta isoforms, both of which are expressed in the limbic system. TR's modulate gene expression via both unliganded and liganded actions. Though the thyroid hormone receptor (TR) knockouts and a transgenic TRalpha1 knock-in mouse have provided us valuable insight into behavioral phenotypes such as anxiety and depression, it is not clear if this is because of the loss of unliganded actions or liganded actions of the receptor or due to locomotor deficits. We used a hypothyroid mouse model and supplementation with tri-iodothyronine (T3) or thyroxine (T4) to investigate the consequences of dysthyroid hormone levels on behaviors that denote anxiety. Our data from the open field and the light-dark transition tests suggest that adult onset hypothyroidism in male mice produces a mild anxiogenic effect that is possibly due to unliganded receptor actions. T3 or T4 supplementation reverses this phenotype and euthyroid animals show anxiety that is intermediate between the hypothyroid and thyroid hormone supplemented groups. In addition, T3 but not T4 supplemented animals have lower spine density in the CA1 region of the hippocampus and in the central amygdala suggesting that T3-mediated rescue of the hypothyroid state might be due to lower neuronal excitability in the limbic circuit" http://www.ncbi.nlm.nih.gov/pubmed/24333846 0 1797 "J. Marquez-Montes, F. O'Connor, R. Burgos, C. Hernandez, C. Montero and J. L. Castillo-Olivares" 1983 Comparative electrophysiological evaluation of atrial activation and sinoatrial node function following Senning and Mustard procedures: an experimental study Ann.Thorac.Surg. 36 6 692-699 "We compared several electrophysiological variables before and after Mustard and Senning procedures in 14 mongrel dogs and made the following three observations. First, after the Senning operation, the atrial activation in the areas of the anterior and middle internodal tracts is undamaged. After the Mustard procedure, however, conduction through the interatrial septum is practically abolished. Both techniques damage the area of the posterior internodal tract. On the whole, there is greater dispersion of atrial epicardial mapping with the Senning operation. Second, several degrees of depression in the sinus node automatism and intraatrial conduction were observed with both techniques. Third, atrioventricular block in various degrees was observed only after the Mustard procedure. The atrioventricular dissociation observed after the Senning operation was dependent on sinus pacemaker dysfunction only. We think that from the electrophysiological point of view, the Senning procedure is a valid alternative for repair of transposition of the great arteries" http://www.ncbi.nlm.nih.gov/pubmed/6651380 0 1798 "C. Muguruza, F. Rodriguez, J. E. Ortega, L. Uriguen, J. J. Meana, I. Rozas and L. F. Callado" 2009 Evaluation of the antidepressant effect of new synthesized alpha2-adrenoceptor antagonists European Neuropsychopharmacology.Conference: 22 ECNP Congress Istanbul Turkey.Conference Start: 20090912 Conference End: 20090916.Conference Publication: (var.pagings) 19 pp S437-S438 2009 "Depression is associated with a selective increase in the highaffinity conformation of the alpha2-adrenoceptors (alpha2-AR) in the human brain. This enhanced alpha2-AR activity could be implicated in the deficit in noradrenergic transmission described in the aetiology of depression. The administration of different alpha2-AR antagonists increases the release of noradrenaline (NA) in the brain. Thus, the development of new selective alpha2-adrenoceptor antagonists can be considered as an effective therapeutic approach for the treatment of depressive disorders. The aim of the present study was to evaluate the antidepressant effect of three new synthesized guanidine and 2-aminoimidazoline derivatives with alpha2-AR antagonist properties. Initially, we tested the potential effects of these new compounds on noradrenergic transmission in vivo by microdialysis experiments in freely awake rats. Male Sprague-Dawley rats were anaesthetised and placed for stereotaxic surgery with the incisor bar lowered to a 15degree angle. One microdialysis probe was implanted in the prefrontal cortex (AP+2.8; L+1.0; V-5.0, taken in mm from bregma. Local administration in the rat brain cortex of 8b, 17b and 20b (1-100 microM) induced a concentration-dependent increase in extracellular NA levels compared with control rats (Emax=304+/-54%, p < 0.001, n=9; Emax=326+/-113%, p<0.01, n=10; Emax=255+/-76%, p<0.001, n=7; respectively). In all the experiments control rats were administered with artificial cerebrospinal fluid. Systemic administration of 17b (10mg/kg i.p.) increased NA extracellular concentration by 373+/-73% and stayed high over the end of the experiment (F[1,33]= 95.70, P<0.0001, n=6). Following administration (10 mg/kg i.p.) of 8b and 20b a weaker increase of rat cortical NA basal values was observed, reaching a maximal effect of 161+/-30% and 156+/-35%, respectively. Both increases were statistically significant when each group was compared with its respective control (saline 0.2 ml/kg i.p.). The tail suspension test was used in mice to assess the antidepressant activity of the compounds. The 8b compound significantly reduced the immobility time at 10 and 20 mg/kg doses (p < 0.005 vs controls). The 17b compound only reduced the immobility time at 40 mg/kg (p<0.01 vs controls), whereas the 20b showed a significant effect at 20 mg/kg (p < 0.01 vs controls). The well-known antidepressant fluoxetine induced a significant effect at 40 mg/kg (p<0.01 vs controls). The control groups received all saline. All the compounds were administered intraperitoneally. The present results demonstrate that the three alpha2-ARs antagonists tested are able to increase NA levels in the rat brain. Moreover, these compounds showed also antidepressant activity in the tail suspension test. These results support that these new synthesized alpha2-ARs antagonists may be useful antidepressant drugs in the future" 0 1799 "W. Kostowski, W. Dyr and O. Pucilowski" 1990 Activty of diltiazem and nifedipine in some animal models of depression "Polish Journal of Pharmacology and Pharmacy.42 (2) ()(pp 121-127), 1990.Date of Publication: 1990." 2 121-127 1 1800 M. Ognjenovic and L. Perry 2005 "American Chemical Society 230th National Meeting. Pain, anxiety and depression" IDrugs. 8 11 880-883 http://www.ncbi.nlm.nih.gov/pubmed/16254775 0 1801 "K. Li, K. J. Anderson, Q. Peng, A. Noble, B. Lu, A. P. Kelly, N. Wang, S. H. Sacks and W. Zhou" 2008 Cyclic AMP plays a critical role in C3a-receptor-mediated regulation of dendritic cells in antigen uptake and T-cell stimulation Blood 112 13 5084-5094 "The biochemical basis for complement acting directly on antigen-presenting cells to enhance their function in T-cell stimulation has been unclear. Here we present evidence that engagement of C3a receptor (C3aR) on the surface of dendritic cells (DCs) leads to alterations in the level of intracellular cyclic adenosine monophosphate (cAMP), a potent negative regulator of inflammatory cytokines. C3aR activation-induced depression of cAMP was associated with enhanced capacity of DCs for antigen uptake and T-cell stimulation. Conversely, C3aR-deficient DCs showed elevation of cAMP and impaired properties for antigen uptake and immune stimulation. Similarities in the phenotype of C3-deficient and C3aR-deficient DCs suggest that local production of C3 with extracellular metabolism to C3a is an important driver of DC alterations in cAMP. The finding of a link between complement and adaptive immune stimulation through cAMP offers new insight into how innate and adaptive immunity combine to generate efficient effector and memory responses" http://www.ncbi.nlm.nih.gov/pubmed/18812470 0 1802 "W. G. Son, M. Jang, S. M. Jo, J. Yoon and I. Lee" 2015 The volume effect of lidocaine on thoracic epidural anesthesia in conscious Beagle dogs Vet.Anaesth.Analg. 42 4 414-424 "OBJECTIVE: To evaluate the volume effect of local anesthetic solution on thoracic epidural analgesia in dogs. STUDY DESIGN: Prospective, experimental trial. ANIMALS: Five healthy adult Beagle dogs weighing 9.7 +/- 1.3 kg. METHODS: A catheter was inserted into the seventh thoracic epidural space using a lumbosacral approach, and secured with suture under total intravenous (IV) anesthesia with propofol. Each dog was administered four volume treatments (0.05, 0.10, 0.15 and 0.20 mL kg(-1)) of 2% lidocaine via the catheter at 12 hour intervals. In every treatment, dogs were re-anesthetized with propofol (6 mg kg(-1), IV) and isoflurane, and received iohexol at each volume to visualize the epidural distribution (ED) through computed tomography. Three hours after epidurography, when dogs had recovered from anesthesia, the appropriate volume of lidocaine was injected through the catheter, and sensory blockade (SB) in dermatomes was evaluated by pinching with a mosquito forceps. Results were presented as median (range), and the volume effect on ED and SB was analyzed with one-way Kruskal-Wallis anova. RESULTS: In proportion to volumes (0.05, 0.10, 0.15 and 0.20 mL kg(-1)), there were significant increases in the extent of ED from 7.4 (5.5-9.0) to 10.4 (8.0-12.0), 13.2 (12.5-13.0), and 15.2 (13.0-18.0) vertebrae, respectively, p < 0.001, and in SB from 2.7 (1.0-5.0) to 6.8 (4.5-10.5), 9.9 (6.5-13.0), and 13.1 (11.0-15.0) dermatomes, respectively, p < 0.001. Unilateral ED and SB were observed in all treatments with various grades, and this distribution was more frequent in the low volume treatments. In the high volume treatments, temporary complications including Horner's syndrome, ataxia, paraplegia, depression, stupor, and intermittent cough occurred often. CONCLUSIONS AND CLINICAL RELEVANCE: The increase in volume of local anesthetic solution improved SB by resulting in more consistent bilateral dermatome blockade as well as an extended blockade. However, caution should be exerted, as higher volume injections of lidocaine caused side effects in all dogs" http://www.ncbi.nlm.nih.gov/pubmed/25327756 0 1803 "A. Ferrer, F. Formiga, O. Cunillera, M. J. Megido, X. Corbella, J. Almeda and O. S. Group" 2015 Predicting factors of health-related quality of life in octogenarians: a 3-year follow-up longitudinal study "Quality of Life Research.24 (11) ()(pp 2701-2711), 2015.Date of Publication: 01 Nov 2015." 11 2701-2711 "Purpose: The proportion of very old people is rising, and so, describing their health-related quality of life (HRQoL) is an important point of interest. The aim of this study was to analyse the predictive factors on HRQoL throughout a 3-year follow-up period, in a community-based cohort of octogenarian people. Methods: From 290 subjects aged 85 and over, sociodemographic and geriatric data, including levels of frailty phenotype assessment, and HRQoL using the EuroQol 5D3L (EQ-5D) instrument were collected. A longitudinal analysis was performed by generalized estimating equations (jointly testing the bivariate effect of variables and its time dependence) and regression mixed models to evaluate the adjusted effect of variables on HRQoL after a 3-year follow-up. Results: In the EQ-5D baseline assessment, the average visual analogue self-rating scale value was 63.82 (SD +/- 19.45), the EQ-5D index was 0.67 (0.34) and the most significant issues were pain/discomfort (61.2 %), depression (45.3 %) and mobility (44.6 %). The third year index was 0.55 (0.38). Independent predictive factors of a lower HRQoL identified by the regression mixed models were female gender (marginal effect ME = -0.101; p = 0.003), being pre-frail (ME = -0.142; p = 0.011) or frail (ME = -0.071; p = 0.030), having heart failure (ME = -0.081; p = 0.037) and having a high social risk score (ME = -0.020; p = 0.015). In contrast, higher functional status (ME = 0.050; p < 0.001) and nutritional score (ME = 0.013; p = 0.011) appeared to be predictive factors of an enhanced HRQoL. The adjusted effect of ""time of follow-up"" had no statistical significance. Conclusion: Frail individuals at baseline have a significant lower HRQoL, whereas a higher functional status and nutritional status are independent predicting factors of an enhanced HRQoL after 3 years of follow-up. These findings may encourage clinicians in order to asses HRQoL" DO - http://dx.doi.org/10.1007/s11136-015-1004-9 0 1804 "B. Baldo, R. Y. Cheong and A. Petersen" 2014 Effects of deletion of mutant huntingtin in steroidogenic factor 1 neurons on the psychiatric and metabolic phenotype in the BACHD mouse model of Huntington disease PLoS.One. 9 10 e107691 "Psychiatric and metabolic features appear several years before motor disturbances in the neurodegenerative Huntington's disease (HD), caused by an expanded CAG repeat in the huntingtin (HTT) gene. Although the mechanisms leading to these aspects are unknown, dysfunction in the hypothalamus, a brain region controlling emotion and metabolism, has been suggested. A direct link between the expression of the disease causing protein, huntingtin (HTT), in the hypothalamus and the development of metabolic and psychiatric-like features have been shown in the BACHD mouse model of HD. However, precisely which circuitry in the hypothalamus is critical for these features is not known. We hypothesized that expression of mutant HTT in the ventromedial hypothalamus, an area involved in the regulation of metabolism and emotion would be important for the development of these non-motor aspects. Therefore, we inactivated mutant HTT in a specific neuronal population of the ventromedial hypothalamus expressing the transcription factor steroidogenic factor 1 (SF1) in the BACHD mouse using cross-breeding based on a Cre-loxP system. Effects on anxiety-like behavior were assessed using the elevated plus maze and novelty-induced suppressed feeding test. Depressive-like behavior was assessed using the Porsolt forced swim test. Effects on the metabolic phenotype were analyzed using measurements of body weight and body fat, as well as serum insulin and leptin levels. Interestingly, the inactivation of mutant HTT in SF1-expressing neurons exerted a partial positive effect on the depressive-like behavior in female BACHD mice at 4 months of age. In this cohort of mice, no anxiety-like behavior was detected. The deletion of mutant HTT in SF1 neurons did not have any effect on the development of metabolic features in BACHD mice. Taken together, our results indicate that mutant HTT regulates metabolic networks by affecting hypothalamic circuitries that do not involve the SF1 neurons of the ventromedial hypothalamus" http://www.ncbi.nlm.nih.gov/pubmed/25271967 1 1805 "A. A. Pokrovskii, B. V. Morozov, L. V. Kravchenko and V. A. Tutel'ian" 1975 [The effect of sporofusarin on the cell membranes of isolated perfused liver] Biull.Eksp.Biol.Med. 79 5 49-53 "A study was made of the effect of sporofusarin (mycotoxin produced by Fusarium Sporotrichiella v. Sporotrichoides) on the functional activity and permeability of cell membranes of the isolated perfused rat liver. Sporofusarin (in the end concentration of 5.9 . 10(-5) M) produced a marked depressive effect on the rate of bile, formation, urea synthesis and oxygen consumption, and also caused an early and marked disturbance of permeability of the lysosomal and plasma membranes of hepatocytes (an increase in the activity of the enzymes--beta-acetylglucosaminidase, beta-glucuronidase, arylsulfatases A and B, beta-galactosidase in the supernatant fluid of liver homogenate and in the perfusata). It is supposed that depression of the functional activity of the liver under the effect of sporofusarin resulted from damage of the membrane structures of the cell, and, primarily, of lysosomes" http://www.ncbi.nlm.nih.gov/pubmed/1227593 0 1806 "J. M. Dilling, T. Nakashima and J. B. Snow, Jr." 1973 Effect of ethacrynic acid on endolymphatic DC potential Arch.Otolaryngol. 98 3 183-186 http://www.ncbi.nlm.nih.gov/pubmed/4742425 0 1807 "H. Nagayama, J. N. Hingtgen and M. H. Aprison" 1980 Pre- and postsynaptic serotonergic manipulations in an animal model of depression Pharmacol.Biochem.Behav. 13 4 575-579 "Rats working on a food-reinforced operant schedule and exhibiting behavioral depression following administration of D,L-5-hydroxytryptophan (5-HTP) were pretreated with one of three drugs: methysergide, fluoxetine, or amitriptyline. The former two drugs were used to establish a basis for distinguishing between pre- and postsynaptic events. We found that methysergide, a known postsynaptic blocker of serotonin, almost completely abolished the depressive effect of 5-HTP, whereas fluoxetine, a known specific uptake blocker of serotonin, potentiated the depressive effect of the 5-hydroxytryptamine (5-HT) precursor. Amitriptyline, one of the commonly prescribed antidepressive drugs, reduced the behavioral depression following 5-HTP by approximately 50%. These data indicate that amitriptyline can act as an antagonist of 5-HT at the postsynaptic receptor. The results of this study, as well as those recently reported from CNS membrane binding studies, suggest that the therapeutic effects of some antidepressive drugs may be explained by their postsynaptic rather than presynaptic properties at central serotonergic receptors. Thus, these studies support the hypothesis that some types of human depression may be primarily due to an excess of free 5-HT acting at postsynaptic receptors" http://www.ncbi.nlm.nih.gov/pubmed/6968915 1 1808 "D. Zhang, A. Saraf, T. Kolasa, P. Bhatia, G. Z. Zheng, M. Patel, G. S. Lannoye, P. Richardson, A. Stewart, J. C. Rogers, J. D. Brioni and C. S. Surowy" 2007 Fatty acid amide hydrolase inhibitors display broad selectivity and inhibit multiple carboxylesterases as off-targets Neuropharmacology 52 4 1095-1105 "Fatty acid amide hydrolase (FAAH) is the primary regulator of several bioactive lipid amides including anandamide. Inhibitors of FAAH are potentially useful for the treatment of pain, anxiety, depression, and other nervous system disorders. However, FAAH inhibitors must display selectivity for this enzyme relative to the numerous other serine hydrolases present in the human proteome in order to be therapeutically acceptable. Here we employed activity-based protein profiling (ABPP) to assess the selectivity of FAAH inhibitors in multiple rat and human tissues. We discovered that some inhibitors, including carbamate compounds SA-47 and SA-72, and AM404 are exceptionally selective while others, like URB597, BMS-1, OL-135, and LY2077855 are less selective, displaying multiple off-targets. Since proteins around 60kDa constitute the major off-targets for URB597 and several other FAAH inhibitors with different chemical structures, we employed the multi-dimensional protein identification technology (MudPIT) approach to analyze their identities. We identified multiple carboxylesterase isozymes as bona fide off-targets of FAAH inhibitors. Consistently, enzymatic assay confirmed inhibition of carboxylesterase activities in rat liver by FAAH inhibitors. Since carboxylesterases hydrolyze a variety of ester-containing drugs and prodrugs, we speculate that certain FAAH inhibitors, by inhibiting carboxylesterases, might have drug-drug interactions with other medicines if developed as therapeutic agents" http://www.ncbi.nlm.nih.gov/pubmed/17217969 0 1809 G. G. Allwood and G. L. Asherson 1972 Depression of delayed hypersensitivity by pretreatment with Freund-type adjuvants. 3. Depressed arrival of lymphoid cells at recently immunized lymph nodes in mice pretreated with adjuvants Clin.Exp.Immunol. 11 4 579-584 http://www.ncbi.nlm.nih.gov/pubmed/4343615 0 1810 "J. Yu, S. Roh, J. S. Lee, B. H. Yang, M. R. Choi, Y. G. Chai and S. H. Kim" 2010 The Effects of Venlafaxine and Dexamethasone on the Expression of HSP70 in Rat C6 Glioma Cells Psychiatry Investig. 7 1 43-48 "OBJECTIVE: The present study aimed to determine the intracellular action of the antidepressant, venlafaxine, in C6 glioma cells using heat shock protein 70 (HSP70) immunocytochemistry and HSP70 Western blots; HSP70 is known to be associated with stress and depression. METHODS: The extent of HSP70 expression was measured after rat C6 glioma cells were treated with 1) dexamethasone only, 2) venlafaxine only, 3) simultaneous venlafaxine and dexamethasone, or 4) dexamethasone after venlafaxine pretreatment. Dexamethasone (10 microM, 6 hours) did not affect the level of HSP70 expression relative to control. RESULTS: Short-term (1 hour) venlafaxine treatment significantly increased the level of HSP 70 expression. Simultaneous long-term (72 hours) venlafaxine and dexamethasone treatment significantly reduced the level of HSP70 expression. Dexamethasone treatment administered following long-term (24 and 72 hours) pretreatment with venlafaxine also significantly reduced the level of HSP70 expression. CONCLUSION: Short-term treatment with venlafaxine increases the expression of HSP70, but prolonged treatment with dexamethasone suppresses the venlafaxine-induced expression of HSP70. These findings suggest that HSP70 and dexamethasone play a significant role in the pathophysiology of depression" http://www.ncbi.nlm.nih.gov/pubmed/20396432 0 1811 L. Jakobartl and J. P. Huston 1977 Circling and consumatory behavior induced by striatal and neocortical spreading depression Physiol Behav. 19 5 673-677 "Single waves of spreading depression (SD) were induced in freely moving Sprague Dawley rats by microinjection of KCl solution into either neocortex or caudate nucleus. DC recordings of slow potential changes (SPC) revealed that a wave of SD propagates from the neocortex to the caudate nucleus in only a very few cases (12.5% of trials, involving 4.3% of the SPC waves). This result contrasts with earlier reported higher incidences of neocortical-striatal transmission of SD, and suggests that such transmission may vary across rat strains. Invasion of the caudate nucleus by a wave of neocortical SD was accompanied by contralateral circling in 50% of the cases. Similarly, SD induced by injection of KCl into the striatum was accompanied by circling in 43% of trials. It was also found that neocortical SD-induced feeding generally occurred only upon recovery of neocortex from the slow potential negativity, and that invasion of the caudate nucleus by SD is not involved in the elicited feeding phenomenon" http://www.ncbi.nlm.nih.gov/pubmed/605176 0 1812 "Y. B. Lu, Z. Chen, X. Y. Lai and Y. Gao" 2005 [Inhibition of acetamide-45 on airway smooth muscle contraction induced by electric field stimulation and methacholine in vitro] Zhejiang.Da.Xue.Xue.Bao.Yi.Xue.Ban. 34 2 137-140 "OBJECTIVE: To investigate the effects of the new antiallergic agent N-(pyridin-4-yl)-(indol-3-yl) acetamide-45 (acetamide-45) on electric field stimulation (EFS)-and methacholine-induced contraction of airway smooth muscle in vitro. METHODS: Contractions were induced by EFS in isolated trachea and bronchus of rats or by cumulative methacholine concentrations in isolated trachea of guinea pigs. Changes in isometric force of isolated airway smooth muscle were measured by force transducers and recorded on a multi-channel polygraph recorder. RESULTS: Acetamide-45 inhibited the contraction induced by EFS in isolated rat airway. The IC50 was 10.74 (95% CI 8.87-13.00) micromol.L(-1) and 18.83 (95% CI 14.57-24.33) micromol.L(-1) in tracheae and bronchi, respectively. Acetamide-45 also inhibited methacholine-induced contractile response of isolated guinea pig trachea in a concentration-dependent manner. At concentrations of 3, 10, 30 micromol.L(-1) acetamide-45 significantly decreased maximal contractile response of methacholine by 24.6%-43.2% and increased EC50 of methacholine by 3.1-to 21.4-fold. CONCLUSION: Acetamide-45 inhibits EFS-or methacholine-induced contraction of isolated airway smooth muscle, and these effects might be non-specific inhibition on cholinergic receptor" http://www.ncbi.nlm.nih.gov/pubmed/15812887 0 1813 "S. J. Weiss, N. J. Philp and E. F. Grollman" 1984 Effect of thyrotropin on iodide efflux in FRTL-5 cells mediated by Ca2+ Endocrinology 114 4 1108-1113 "A functioning rat thyroid cell line (FRTL-5) responds acutely to the addition of TSH, norepinephrine, and the Ca2+ ionophore A23187 by a depression in iodide (I-) uptake levels. The decrease in I- content measured at the steady state depends on the presence of external Ca2+ and can be accounted for by an effect on stimulated I- efflux. As contrasted to the prolonged time (hours and days) involved in the stimulatory effect of TSH on I- uptake, the acute response to TSH is 1) seen within 5 min and maintained for about 20 min, 2) maximum, at a 1 X 10(-7)M concentration of TSH compared with the concentration of 1 X 10(-9)M necessary for the stimulatory effect, 3) independent of whether the cells are growing in the presence or absence of TSH, and 4) not mimicked by the addition of (Bu)2cAMP. The results suggest that TSH and adrenergic stimulation lead to increased membrane permeability to I- which is mediated by an elevation in the intracellular Ca2+ concentration" http://www.ncbi.nlm.nih.gov/pubmed/6323130 0 1814 P. Onghena and H. B. van 1998 The antidepressant-induced analgesic effect "Bailliere's Clinical Anaesthesiology.12 (1) ()(pp 53-68), 1998.Date of Publication: 1998." 1 53-68 "Since 1960 clinicians and researchers have been claiming that there is evidence for an antidepressant-induced analgesic effect. The effect could be accomplished (1) as a secondary effect of a reduction in depression, (2) as a secondary effect of general sedation, or (3) by a biochemical mechanism that is independent of changes in mood or sedation but which is probably related to serotonin reuptake inhibition. Our meta-analysis summarized the results of the available double-blind, placebo-controlled trials for several chronic pain syndromes up to 1990 and found support for an independent biochemical mechanism but not for the crucial role of serotonin reuptake inhibition. Seventeen more recent (since 1990) double-blind, placebo-controlled trials have substantiated the meta-analytical results. Furthermore, recent animal and laboratory studies have confirmed that the antidepressant-induced analgesic effect is not a clinical chimaera and have made important progress with respect to possible sites and mechanisms of action" DO - http://dx.doi.org/10.1016/S0950-3501%2898%2980006-8 1 1815 "A. Vedeniapin, L. Cheng and M. S. George" 2010 Feasibility of simultaneous cognitive behavioral therapy and left prefrontal rTMS for treatment resistant depression Brain Stimul. 3 4 207-210 http://www.ncbi.nlm.nih.gov/pubmed/20965449 0 1816 M. S. Finkel 2003 Molecular signaling pathways that link depression and heart disease Postgrad.Med. 114 6 Suppl Managing Depression 14-27 "Patients with clinical depression and coronary artery disease (CAD) risk factors have chronic, persistent activation of potentially toxic mediators optimized for short-term survival from ischemia, infection, and hemorrhage. The mediators and pathways involved in these processes are beginning to be elucidated. This basic research has uncovered novel potential therapeutic targets to prevent or attenuate adverse cardiovascular consequences of clinical depression. Well-designed randomized controlled studies will be required to definitively demonstrate that treating depression decreases cardiac mortality and morbidity. The results of controlled clinical trials support the use of selective serotonin reuptake inhibitors (SSRIs) for patients with CAD. The possibility that the use of an SSRI may confer additional benefit through a platelet inhibitory effect independent of the level of depression warrants further investigation" http://www.ncbi.nlm.nih.gov/pubmed/19667661 0 1817 "M. F. Moraes, M. Chavali, P. K. Mishra, P. C. Jobe and N. Garcia-Cairasco" 2005 A comprehensive electrographic and behavioral analysis of generalized tonic-clonic seizures of GEPR-9s Brain Res. 1033 1 01-Dec "This study records noise-free intracerebral EEG of the genetically epilepsy prone rat (GEPR-9), along with behavioral correlates, during a seizure on unanesthetized freely behaving unrestrained animals. The GEPR-9 exhibits acoustically triggered generalized tonic-clonic seizures, and often times the EEG, recorded with conventional techniques, has resulted in data with imbedded movement artifact. For noise-free video-EEG recordings, we used a previously developed system that consists of a head connector with a FET preamplifier and battery, signal conditioning device (5000x gain, 1 Hz-100 Hz filters), A/D converter and video/PC-PC/video computer boards for recording image data. Each animal was implanted with three monopolar/referential electrodes chosen among the following areas: cortex, inferior colliculus, reticular formation and caudal medulla. The video-EEG data were quite similar for all recorded animals: (1) basal desynchronized EEG before sound stimulus; (2) increase in EEG frequency after stimulus and before seizure onset; (3) high-amplitude polyspikes during massive myoclonic thrusts with or without a very fast running episode; (4) an electrodecremental response during tonic extension; (5) wave and spike complex during forelimb and hindlimb tonic rigidity and posttonic clonus; (6) low-amplitude EEG during postictal depression. Time sequenced spectral analysis also highlights the epileptiform EEG pattern during seizure with high reproducibility between animals. While testing seizure naive GEPR-9s, there was a clear evolution from modest epileptiform EEG activity on the first acoustic stimulation to progressively higher amplitude, duration and frequency epileptiform EEG activity throughout seizure repetition" http://www.ncbi.nlm.nih.gov/pubmed/15680333 0 1818 "G. V. Vahouny, M. Ito, E. M. Blendermann, L. L. Gallo and C. R. Treadwell" 1977 Puromycin inhibition of cholesterol absorption in the rat J.Lipid Res. 18 6 745-752 "The effect of puromycin on the intestinal absorption of cholesterol has been studied in rats with indwelling catheters in the left thoracic lymphatic duct. Puromycin administration to female rats produced a marked depression of cholesterol absorption under conditions where the absorption of simultaneously administered fatty acid was also dramatically inhibited. The same treatment of male rats also produced a significant depression in cholesterol absorption, but was without effect on absorption of the fatty acid. Despite the depressions of lipid absorption in puromycin-treated animals, there was no accumlation of either cholesterol or fatty acid in the intestinal mucosa of either sex. Actinomycin D treatment of fasting male and female rats, receiving constant infusions of saline, had no effect on the rate of lymph production. This suggest that altered lymph production was not responsible for the depressed lipid absorption observed in fed animals treated with protein synthesis inhibitors. The selective inhibition of cholesterol absorption in male rats also precludes the possibility that the major effect of the inhibitor is on delayed gastric emptying" http://www.ncbi.nlm.nih.gov/pubmed/925518 0 1819 "S. Mehrotra, M. J. Pecaut, T. L. Freeman, J. D. Crapo, A. Rizvi, X. Luo-Owen, J. M. Slater and D. S. Gridley" 2012 Analysis of a metalloporphyrin antioxidant mimetic (MnTE-2-PyP) as a radiomitigator: prostate tumor and immune status Technol.Cancer Res.Treat. 11 5 447-457 "Due to radiation-induced immune depression and development of pathologies such as cancer, there is increasing urgency to identify radiomitigators that are effective when administered after radiation exposure. The main goal of this study was to determine the radiomitigation capacity of MnTE-2-PyP[Mn(III) tetrakis (N-ethylpyridinium-2-yl) porphyrin], a superoxide dismutase (SOD) mimetic, and evaluate leukocyte parameters in spleen and blood. C57BL/6 mice were total-body exposed to 2 Gy gamma-rays (Co-60), i.e., well below a lethal dose, followed by subcutaneous implantation of 5 x 10(5) RM-9 prostate tumor cells and initiation of MnTE-2-PyP treatment (day 0); interval between each procedure was 1-2 h. The drug was administered daily (12 times). Tumor progression was monitored and immunological analyses were performed on a subset per group on day 12. Animals treated with MnTE-2-PyP alone had significantly slower tumor growth compared to mice that did not receive the drug (P < 0.05), while radiation alone had no effect. Treatment of tumor-bearing mice with MnTE-2-PyP alone significantly increased spleen mass relative to body mass; the numbers of splenic white blood cells (WBC) and lymphocytes (B and T), as well as circulating WBC, granulocytes, and platelets, were high compared to one of more of the other groups (P < 0.05). The results show that MnTE-2-PyP slowed RM-9 tumor progression and up-regulated immune parameters, but mitigation of the effects of 2 Gy total-body irradiation were minimal" http://www.ncbi.nlm.nih.gov/pubmed/22475066 0 1820 J. G. Reves and W. H. Newman 1972 Cardiovascular response to hemorrhage after alcohol in dogs Q.J.Stud.Alcohol 33 2 464-475 http://www.ncbi.nlm.nih.gov/pubmed/5064203 0 1821 "V. G. Lukashin, V. V. Vshivtseva and I. N. Zamuraev" 1989 [Functional restructuring of the bush-like receptor during the suppression of anaerobic glycolysis] Biull.Eksp.Biol.Med. 107 4 486-488 "The bush-like receptors of frog's bladder have been investigated simultaneously by vital microscopic, and spectrophotometric studies and registration of biopotentials. It is demonstrated that electrogenic function of receptors is suppressed by monoiodacetate and anoxia more rapidly than without monoiodacetate. At the same time reducing of methylene blue into receptors is accelerated. This demonstrates a damage of power metabolism of sensory terminals. It is suggested that the changes result from blockade of anaerobic glycolysis being an alternative way for power maintenance of receptor function under anoxia" http://www.ncbi.nlm.nih.gov/pubmed/2785827 0 1822 "P. Bhansali, J. Dunning, S. E. Singer, L. David and C. Schmauss" 2007 Early life stress alters adult serotonin 2C receptor pre-mRNA editing and expression of the alpha subunit of the heterotrimeric G-protein G q J.Neurosci. 27 6 1467-1473 "Infant maternal separation, a paradigm of early life stress in rodents, elicits long-lasting changes in gene expression that persist into adulthood. In BALB/c mice, an inbred strain with spontaneously elevated anxiety and stress reactivity, infant maternal separation led to increased depression-like behavioral responses to adult stress and robustly increased editing of serotonin 2C receptor pre-mRNA. Chronic fluoxetine treatment of adult BALB/c mice exposed to early life stress affected neither their behavioral responses to stress nor their basal 5-HT2C pre-mRNA editing phenotype. However, when fluoxetine was administered during adolescence, depression-like behavioral responses to stress were significantly diminished in these mice, and their basal and stress-induced 5-HT2C pre-mRNA editing phenotypes were significantly lower. Moreover, when BALB/c mice exposed to early life stress were raised in an enriched postweaning environment, their depression-like behavioral responses to adult stress were also significantly diminished. However, their 5-HT2C pre-mRNA editing phenotype remained unaltered. Hence, the similar behavioral effects of enrichment and fluoxetine treatment during adolescence were not accompanied by similar changes in 5-HT2C pre-mRNA editing. Enriched and nonenriched BALB/c mice exposed to early life stress also exhibited significantly increased expression of mRNA and protein encoding the G alpha q subunit of G-protein that couples to 5-HT2A/2C receptors. In contrast, G alpha q expression levels were significantly lower in fluoxetine-treated mice. These findings suggest that compensatory changes in G alpha q expression occur in mice with persistently altered 5-HT2C pre-mRNA editing and provide an explanation for the dissociation between 5-HT2C receptor editing phenotypes and behavioral stress responses" http://www.ncbi.nlm.nih.gov/pubmed/17287521 1 1823 "B. M. Navarre, J. D. Laggart and R. M. Craft" 2010 Anhedonia in postpartum rats "Physiology and Behavior.99 (1) ()(pp 59-66), 2010.Date of Publication: 12 Jan 2010." 1 59-66 "Postpartum depression (PPD) is a debilitating illness, yet little is known about its causes. The purpose of this study was to examine a major symptom of depression during the postpartum period, anhedonia, by comparing sucrose preference in female rats that had undergone actual pregnancy or hormone-simulated pregnancy (HSP) to their respective controls. Whereas HSP rats showed significantly less preference than vehicle control rats for 1% sucrose solution during the first three weeks of the ""postpartum"" period, previously pregnant females showed only slightly depressed sucrose preference for the first 1-2 days postpartum, compared to non-pregnant controls. Habituation to 1% sucrose during the pregnancy period, which increased preference upon later testing in previously pregnant rats tested on postpartum day 2, did not significantly increase preference in HSP rats, suggesting that depressed preference in the latter group was not due to neophobia. Pre-treatment with desipramine did not prevent suppressed sucrose preference in HSP rats, and preference was even further suppressed following chronic sertraline treatment. These results suggest that estradiol withdrawal following HSP may cause anhedonia during the early ""postpartum"" period. In contrast, females that have undergone actual pregnancy are less likely to show this effect, suggesting that postpartum hormonal changes other than the dramatic decline in estradiol may buffer its negative mood effects. © 2009 Elsevier Inc. All rights reserved" DO - http://dx.doi.org/10.1016/j.physbeh.2009.10.011 1 1824 "G. E. Kelly, A. Scheibner and A. G. Sheil" 1987 Effects of therapy with azathioprine and prednisolone and ultraviolet irradiation on mouse skin immune function and immune cell markers Immunol.Cell Biol. 65 ( Pt 2) 153-161 "The effects of ultraviolet irradiation (UVI) (290-400 nm) and/or systemic immunosuppressive drug therapy (azathioprine and prednisolone) on the immunocompetence of the skin of hairless (HRA/Skh-1) mice were investigated. Mice were studied for the density of ATPase+, Ia+ and Thyl X 2+ cells in the dorsal epidermis and contact hypersensitivity (CH) of skin to dinitrofluorobenzene (DNFB). Prednisolone therapy alone and UVI alone each reduced the densities of the three skin immune cell markers and CH responsiveness; azathioprine therapy alone had no such effects. When a suberythemal dose of UVI that induced a moderately depressive effect on these two skin parameters was used, additional azathioprine therapy produced no further depression; additional prednisolone therapy further depressed the densities of ATPase+ and Ia+ cells and CH responsiveness; additional therapy with combined azathioprine and prednisolone induced profound depression of the incidences of the three immune cell markers and of CH responsiveness. These data point to interaction between azathioprine/prednisolone therapy and UVI in depressing local immune function within skin which may contribute to the increased susceptibility of the sun-exposed skin of immunosuppressed kidney transplant recipients to infective and carcinogenic processes" http://www.ncbi.nlm.nih.gov/pubmed/2956183 0 1825 "P. Zanos, S. C. Piantadosi, H.-Q. Wu, H. J. Pribut, M. J. Dell, A. Can, H. R. Snodgrass, C. A. Zarate, R. Schwarcz and T. D. Gould" 2015 "The prodrug 4-chlorokynurenine causes ketamine-like antidepressant effects, but not side effects, by NMDA/glycineB-site inhibitionS" "Journal of Pharmacology and Experimental Therapeutics.355 (1) ()(pp 76-85), 2015.Date of Publication: 01 Oct 2015." 1 76-85 "Currently approved antidepressant drug treatment typically takes several weeks to be effective. The noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has shown efficacy as a rapid-acting treatment of depression, but its use is associated with significant side effects. We assessed effects following blockade of the glycineB co-agonist site of the NMDA receptor, located on the GluN1 subunit, by the selective full antagonist 7-chloro-kynurenic acid (7-Cl-KYNA), delivered by systemic administration of its brain-penetrant prodrug 4-chlorokynurenine (4-Cl-KYN) in mice. Following administration of 4-Cl-KYN, 7-Cl-KYNA was promptly recovered extracellularly in hippocampal microdialysate of freely moving animals. The behavioral responses of the animals were assessed using measures of ketamine-sensitive antidepressant efficacy (including the 24-hour forced swim test, learned helplessness test, and novelty-suppressed feeding test). In these tests, distinct from fluoxetine, and similar to ketamine, 4-Cl-KYN administration resulted in rapid, dose-dependent and persistent antidepressant-like effects following a single treatment. The antidepressant effects of 4-Cl-KYN were prevented by pretreatment with glycine or the a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione (NBQX). 4-Cl-KYN administration was not associated with the rewarding and psychotomimetic effects of ketamine, and did not induce locomotor sensitization or stereotypic behaviors. Our results provide further support for antagonism of the glycineB site for the rapid treatment of treatment-resistant depression without the negative side effects seen with ketamine or other channelblocking NMDA receptor antagonists" DO - http://dx.doi.org/10.1124/jpet.115.225664 1 1826 M. Emamghoreishi and M. S. Talebianpour 2009 Antidepressant effect of melissa officinalis in the forced swimming test "Daru.17 (1) ()(pp 42-47), 2009.Date of Publication: 2009." 1 42-47 "Background: In Iranian and other traditional medicines, an antidepressant effect has been indicated for Melissa officinalis (Lamiaceae). However, studies showing its antidepressant effect is lacking. Therefore, the present study was undertaken to examine whether the aqueous extract and essential oil from leaves of Melissa officinalis have an antidepressant-like activity in mice. Materials and Methods: The effect of subchronic administration of different doses of the aqueous extract (25, 75, 150, 300 mg/kg or water; n=9-10) and the essential oil (10, 25, 75, 150, 300 mg/kg or almond oil; n=9-10) on immobility, climbing, and swimming behaviors were evaluated in the forced swimming test. Fluoxetine (20mg/kg) and imipramine (15 mg/kg) were used as reference drugs. Additionally, the effect of both plant preparations on spontaneous activity was examined. Results: All doses of the aqueous extract, used in this study, produced a significant reduction in immobility along with an increase in climbing behavior which is similar to those which have been observed with imipramine. Essential oil caused a dose-dependent reduction in immobility and an increase in climbing at all studied doses, compared to control group. Only the highest dose (300mg/kg) of essential oil showed a significant increase in swimming behavior. The aqueous extract, but not the essential oil, decreased spontaneous activity in a dose dependent manner. Conclusion: The results of this study suggests that the Melissa officinalis possess an antidepressant-like activity similar to imipramine which may have a potential clinical value for treatment of depression" 1 1827 "M. Wonnemann, A. Singer and W. E. Muller" 2000 "Inhibition of synaptosomal uptake of 3H-L-glutamate and 3H-GABA by hyperforin, a major constituent of St. John's Wort: the role of amiloride sensitive sodium conductive pathways" Neuropsychopharmacology 23 2 188-197 "Extracts of St. John's Wort are widely used for the treatment of depressive disorders. The active principles have not yet been finally elucidated. We have recently shown that hyperforin, a major active constituent of St. John's Wort, not only inhibits the neuronal uptake of serotonin, norepinephrine and dopamine, but also that of L-glutamate and GABA. No other antidepressant compound exhibits a similar broad uptake inhibiting profile. To investigate this unique kind of property, kinetic analyses were performed regarding the uptake of 3H-L-glutamate and 3H-GABA into synaptosomal preparations of mouse brain. Michaelis-Menten kinetics revealed a reduction of Vmax (8.27 to 1.80 pmol/mg/min for 3H-L-glutamate, 2.76 to 0.77 pmol/mg/min for 3H-GABA) while Km was nearly unchanged in both cases, suggesting non-competitive inhibition. The unselective uptake inhibition by hyperforin could be mimicked by the Na+-ionophore monensin and by the Na+-K+-ATPase inhibitor ouabain. However, both mechanisms can be discarded for hyperforin. Several amiloride derivatives known to affect sodium conductance significantly enhance 3H-GABA and 3H-L-glutamate uptake and inhibit the uptake inhibition by hyperforin, while monensin or ouabain inhibition were not influenced. Selective concentrations of benzamil for amiloride sensitive Na+-channels and selective concentrations of 5'-ethylisopropylamiloride (EIPA) for the Na+-H+-exchangers both had an attenuating effect on the hyperforin inhibition of L-glutamate uptake, suggesting a possible role of amiloride sensitive Na+-channels and Na+-H+-exchangers in the mechanism of action of hyperforin" http://www.ncbi.nlm.nih.gov/pubmed/10882845 0 1828 "M. R. Taylor, K. E. Agho, G. J. Stevens and B. Raphael" 2008 Factors influencing psychological distress during a disease epidemic: data from Australia's first outbreak of equine influenza BMC.Public Health 8 347 "BACKGROUND: In 2007 Australia experienced its first outbreak of highly infectious equine influenza. Government disease control measures were put in place to control, contain, and eradicate the disease; these measures included movement restrictions and quarantining of properties. This study was conducted to assess the psycho-social impacts of this disease, and this paper reports the prevalence of, and factors influencing, psychological distress during this outbreak. METHODS: Data were collected using an online survey, with a link directed to the affected population via a number of industry groups. Psychological distress, as determined by the Kessler 10 Psychological Distress Scale, was the main outcome measure. RESULTS: In total, 2760 people participated in this study. Extremely high levels of non-specific psychological distress were reported by respondents in this study, with 34% reporting high psychological distress (K10 > 22), compared to levels of around 12% in the Australian general population. Analysis, using backward stepwise binary logistic regression analysis, revealed that those living in high risk infection (red) zones (OR = 2.00; 95% CI: 1.57-2.55; p < 0.001) and disease buffer (amber) zones (OR = 1.83; 95% CI: 1.36-2.46; p < 0.001) were at much greater risk of high psychological distress than those living in uninfected (white zones). Although prevalence of high psychological distress was greater in infected EI zones and States, elevated levels of psychological distress were experienced in horse-owners nationally. Statistical analysis indicated that certain groups were more vulnerable to high psychological distress; specifically younger people, and those with lower levels of formal educational qualifications. Respondents whose principal source of income was from horse-related industry were more than twice as likely to have high psychological distress than those whose primary source of income was not linked to horse-related industry (OR = 2.23; 95% CI: 1.82-2.73; p < 0.001). CONCLUSION: Although, methodologically, this study had good internal validity, it has limited generalisability because it was not possible to identify, bound, or sample the target population accurately. However, this study is the first to collect psychological distress data from an affected population during such a disease outbreak and has potential to inform those involved in assessing the potential psychological impacts of human infectious diseases, such as pandemic influenza" http://www.ncbi.nlm.nih.gov/pubmed/18831770 0 1829 J. T. Andreasen and J. P. Redrobe 2009 "Nicotine, but not mecamylamine, enhances antidepressant-like effects of citalopram and reboxetine in the mouse forced swim and tail suspension tests" Behav.Brain Res. 197 1 150-156 "Current literature suggests that nicotinic acetylcholine receptors (nAChRs) are involved in major depression. In rodents, antidepressant-like effects of both nicotine and the non-selective nAChR antagonist mecamylamine have been reported. Nicotine increases serotonergic and noradrenergic neuronal activity and facilitates serotonin and noradrenaline release. Thus, we hypothesise that nicotine may enhance the behavioural effects of serotonin (e.g., citalopram) and/or noradrenaline (e.g., reboxetine) reuptake inhibitors. Here, we tested if nicotine enhanced the activity of citalopram or reboxetine in the mouse forced swim test (mFST) and the mouse tail suspension test (mTST). The potential for mecamylamine to augment antidepressant drug action was also investigated. Sub-threshold and threshold doses of citalopram (3 and 10mg/kg) or reboxetine (3, 10 and 20mg/kg) were tested alone and in combination with nicotine (0.3 and 1.0mg/kg) and mecamylamine (1 and 3mg/kg). Locomotor activity experiments were performed to rule out non-specific stimulant effects. Nicotine (1.0mg/kg) enhanced the effect of 10mg/kg citalopram and 20mg/kg reboxetine in the mFST. Similarly, nicotine (1.0mg/kg) enhanced the effect of 3 and 10mg/kg citalopram and 3 and 10mg/kg reboxetine in the mTST. No concomitant locomotor stimulation was observed at the tested dose combinations. Mecamylamine was effective on its own in some tests, but did not augment the effects of citalopram or reboxetine at the doses tested. The data show that nicotine enhances the effects of both serotonin and noradrenaline reuptake inhibitors, possibly reflecting nicotine's facilitating effects on the release of these two neurotransmitters, and indicating that nicotine may enhance antidepressant action" http://www.ncbi.nlm.nih.gov/pubmed/18786574 1 1830 "H. L. Saunders, J. Tomaszewski, J. Pauls and W. Zuccarello" 1969 Antifertility effect of 17 alpha-methyl-B-nortestosterone (SK&F 7690) Endocrinology 85 5 960-963 http://www.ncbi.nlm.nih.gov/pubmed/4241646 0 1831 "S. Nakayama, T. Seko, J. Takatsuki, K. Miura and T. Miyatake" 2010 Walking activity of flightless Harmonia axyridis (Coleoptera: Coccinellidae) as a biological control agent J.Econ.Entomol. 103 5 1564-1568 "The use of flightless strains of the multicolored Asian lady beetle, Harmonia axyridis (Pallas) (Coleoptera: Coccinellidae), established via artificial selection, can be highly effective as a biological control agent for aphids. However, flightless H. axyridis must depend on walking for dispersion. Therefore, data on the walking activity levels in flightless strains are important for the development of effective methods when releasing these agents in the field. Results of measurement of walking activity levels using an infrared actograph showed that walking activity levels during the daytime (but not nighttime) in both sexes of pure flightless strains tended to be lower than those of control strains. We also found that walking activity levels during the daytime for the F1 generation of hybrid strains, produced by reciprocal crossing between two pure flightless strains, were approximately equal to those of pure strains; the reduction in walking activity levels was not recovered by hybrid vigor. Our results indicate that the reduction in walking activity levels in the pure flightless strains was not caused merely by inbreeding depression stemming from the artificial selection process. Instead, potentially flight ability and walking activity levels in this species may be controlled by the pleiotropic effect of a gene" http://www.ncbi.nlm.nih.gov/pubmed/21061954 0 1832 "A. Plaznik, R. Stefanski, W. Palejko and W. Kostowski" 1990 An involvement of accumbens GABAergic innervation in the stressor-induced behavioural deficit "European Journal of Pharmacology.183 (5) ()(pp 1903), 1990.Date of Publication: 1990." 5 1903 1 1833 "S. B. Kombian, K. V. Ananthalakshmi and I. O. Edafiogho" 2006 Enaminones and norepinephrine employ convergent mechanisms to depress excitatory synaptic transmission in the rat nucleus accumbens in vitro Eur.J.Neurosci. 24 10 2781-2788 "We recently reported that anticonvulsant anilino enaminones depress excitatory postsynaptic currents (EPSCs) in the nucleus accumbens (NAc) indirectly via gamma-aminobutyric acid (GABA) acting on GABA(B) receptors [S.B. Kombian et al. (2005)Br. J. Pharmacol., 145, 945-953]. Norepinephrine (NE) and dopamine (DA), both known to be involved in seizure disorders, also depress EPSCs in this nucleus. The current study explored a possible interaction between enaminones and adrenergic and/or dopaminergic mechanisms that may contribute to their synaptic depression and anticonvulsant effect. Using whole-cell recording in rat forebrain slices containing the NAc, we show that NE-induced, but not DA-induced, EPSC depression occludes E139-induced EPSC depressant effect. UK14,304, a selective alpha(2) receptor agonist, mimicked the synaptic effect of NE and also occluded E139 effects. Phentolamine, a non-selective alpha-adrenergic antagonist that blocked NE-induced EPSC depression, also blocked the E139-induced EPSC depression. Furthermore, yohimbine, an alpha(2)-adrenoceptor antagonist, also blocked the E139-induced EPSC depression, while prazosin, a selective alpha(1)-adrenergic antagonist, and propranolol, a non-selective beta-adrenoceptor antagonist, did not block the E139 effect. Similar to the E139-induced EPSC depression, the NE-induced EPSC depression was also blocked by the GABA(B) receptor antagonist, CGP55845. By contrast, however, neither SCH23390 nor sulpiride, D1-like and D2-like DA receptor antagonists, respectively, blocked the E139-induced synaptic depression. These results suggest that NE and E139, but not DA, employ a similar mechanism to depress EPSCs in the NAc, and support the hypothesis that E139, like NE, may act on alpha(2)-adrenoceptors to cause the release of GABA, which then mediates synaptic depression via GABA(B) receptors" http://www.ncbi.nlm.nih.gov/pubmed/17156204 0 1834 "J. J. Hjelle, J. H. Grubbs, D. G. Beer and D. R. Petersen" 1983 Time course of the carbon tetrachloride-induced decrease in mitochondrial aldehyde dehydrogenase activity Toxicol.Appl.Pharmacol. 67 2 159-165 "Hepatic microsomal enzymes like cytochrome P-450 and glucose 6-phosphatase are inhibited after exposure to CCl4 in vivo. Since comparatively less is known about the effects of CCl4 on nonmicrosomal enzymes, we investigated the rapidity by which CCl4 inhibits the low Km mitochondrial aldehyde dehydrogenase (ALDH) isozyme, an enzyme known to be inhibited 24 hr after CCl4 treatment. The activity of this ALDH isozyme was significantly lowered 6 and 12 hr after a single 1 ml/kg intragastric dose of CCl4. The mitochondrial low Km ALDH specific activities exhibited a similar pattern of destruction/inhibition to the documented target enzyme microsomal cytochrome P-450 in that lowest values were observed 6 hr after CCl4. These values were 44 and 37% of control for cytochrome P-450 content and the low Km ALDH activity, respectively. Alcohol dehydrogenase activity, expressed as activity per gram liver, was depressed 12 hr after CCl4 dosing. Finally, the activity of the low Km cytosolic ALDH, the isozyme that metabolizes malondialdehyde at low concentrations, was not affected by CCl4 treatment. The CCl4-induced decline in the activity of the matrix ALDH isozyme occurs earlier than previously reported mitochondrial damage. The study of sensitive enzymes like the low Km ALDH may provide valuable information by which it may be possible to determine the relationship of the truly rapid biochemical effects of CCl4 such as microsomal lipid peroxidation with later effects on nonmicrosomal components" http://www.ncbi.nlm.nih.gov/pubmed/6836571 0 1835 "R. A. Hartz, K. K. Nanda, C. L. Ingalls, V. T. Ahuja, T. F. Molski, G. Zhang, H. Wong, Y. Peng, M. Kelley, N. J. Lodge, R. Zaczek, P. J. Gilligan and G. L. Trainor" 2004 "Design, synthesis, and biological evaluation of 1,2,3,7-tetrahydro-6h-purin-6-one and 3,7-dihydro-1h-purine-2,6-dione derivatives as corticotropin-releasing factor(1) receptor antagonists" J.Med.Chem. 47 19 4741-4754 "A growing body of evidence suggests that CRF(1) receptor antagonism offers considerable therapeutic potential in the treatment of diseases resulting from elevated levels of CRF, such as anxiety and depression. A series of novel 1,2,3,7-tetrahydro-6H-purin-6-one and 3,7-dihydro-1H-purine-2,6-dione derivatives was synthesized and evaluated as corticotropin releasing factor-1 (CRF(1)) receptor antagonists. Compounds within this series, represented by compound 12d (IC(50) = 5.4 nM), were found to be highly potent CRF(1) receptor antagonists. In addition, compounds 12d and 12j were determined to be selective CRF(1) antagonists. The synthesis, structure-activity relationships and pharmacokinetic properties of compounds within this series is presented" http://www.ncbi.nlm.nih.gov/pubmed/15341489 0 1836 R. N. Karunasinghe and J. Lipski 2013 Oxygen and glucose deprivation (OGD)-induced spreading depression in the Substantia Nigra Brain Res. 1527 209-221 "Spreading depression (SD) is a profound depolarization of neurons and glia that propagates in a wave-like manner across susceptible brain regions, and can develop during periods of compromised cellular energy such as ischemia, when it influences the severity of acute neuronal damage. Although SD has been well characterized in the cerebral cortex and hippocampus, little is known of this event in the Substantia Nigra (SN), a brainstem nucleus engaged in motor control and reward-related behavior. Transverse brain slices (250 mum; P21-23 rats) containing the SN were subject to oxygen and glucose deprivation (OGD) tests, modeling brain ischemia. SD developed in lateral aspects of the SN within 3.3+/-0.2 min of OGD onset, and spread through the Substantia Nigra pars reticulata (SNr), as indicated by fast-occurring and propagating increased tissue light transmittance and negative shift of extracellular DC potential. These events were associated with profound mitochondrial membrane depolarization (DeltaPsim) throughout the SN, as demonstrated by increased Rhodamine 123 fluorescence. Extracellular recordings from individual SNr neurons indicated rapid depolarization followed by depolarizing block, while dopaminergic neurons in the Substantia Nigra pars compacta (SNc) showed inhibition of firing associated with hyperpolarization. SD evoked in the SNr was similar to OGD-induced SD in the CA1 region in hippocampal slices. In the hippocampus, SD also developed during anoxia or aglycemia alone (associated with less profound DeltaPsim than OGD), while these conditions rarely led to SD in the SNr. Our results demonstrate that OGD consistently evokes SD in the SN, and that this phenomenon only involves the SNr. It remains to be established whether nigral SD contributes to neuronal damage associated with a sudden-onset form of Parkinson's disease known as 'vascular parkinsonism'" http://www.ncbi.nlm.nih.gov/pubmed/23796781 0 1837 "D. J. Wells, L. S. Stoddard, M. J. Getz and H. L. Moses" 1979 alpha-Amanitin and 5-fluorouridine inhibition of serum-stimulated DNA synthesis in quiescent AKR-2B mouse embryo cells J.Cell Physiol 100 2 199-214 "AKR-2B mouse embryo cells undergoing the serum-stimulated transition from a quiescent to a proliferating state exhibit an increase in the rate of hnRNA synthesis which appears to be mediated through an increase in the actual number of RNA polymerase II molecules. alpha-Amanitin, administered early in the prereplication interval following stimulation, effectively inhibits hnRNA synthesis, polysomal mRNA accumulation, polyribosome formation, and subsequent DNA synthesis, and cell division. Unexpectedly, alpha-amanitin treatment also produces almost complete inhibition of the synthesis of 45S rRNA precursor and the increase in accumulation of cytoplasmic rRNA following serum stimulation. In order to determine whether the inhibition of new ribosomal synthesis might in itself be sufficient to prevent serum-stimulated DNA synthesis, the effects of 5-fluorouridine (5-FU), a specific inhibitor of 45S rRNA processing, were investigated. If added within eight hours following serum stimulation, 5-FU was found to completely inhibit subsequent DNA synthesis. These results suggest that quiescent AKR-2B cells do not contain a sufficient excess of ribosomes to support the synthesis of proteins which are required for DNA synthesis in response to serum growth factors. Furthermore, an early polymerase II mediated synthesis of mRNA(s) coding for some factor(s) necessary for ribosomal gene transcription may be an essential step in the serum-stimulated synthesis of new ribosomes" http://www.ncbi.nlm.nih.gov/pubmed/159908 0 1838 S. K. Ercanbrack and A. D. Knight 1983 "Yearling trait comparisons among inbred lines and selected noninbred and randomly bred control groups of Rambouillet, Targhee and Columbia ewes" J.Anim Sci. 56 2 316-329 "Inbreeding with concurrent selection was used to develop 26 Rambouillet, 20 Targhee and 10 Columbia inbred lines of sheep. Inbreeding coefficients averaged 30, 29 and 30% for the three breeds, respectively, at the conclusion of the study. A selected noninbred control group and a randomly bred unselected control group were maintained for each breed. Yearling traits were evaluated for 545 Rambouillet, 572 Targhee and 411 Columbia yearling ewes, each belonging to one of the inbred lines or control groups. In each breed, the selected controls were generally of greatest overall merit, the unselected controls intermediate and the inbred lines of least merit. Only a few yearling traits of only a few inbred lines were superior (P less than .05) to those of their appropriate selected control groups. Selection within inbred lines was generally ineffective in offsetting inbreeding depression. However, single trait selection for traits of high heritability, notably yearling weight, clean fleece weight and staple length, appeared to compensate for inbreeding effects on those traits. Deleterious consequences of inbreeding were particularly apparent in yearling weight, average daily gain, type and condition scores, grease and clean fleece weights and index of overall merit. Inbreeding also resulted in fewer neck folds among inbreds of all three breeds. Correlations between the rankings of inbred lines at weaning and yearling ages were high for traits of higher heritability. Superiority of the selected controls in most traits was of about the same magnitude at weaning and yearling ages. In no case did the final overall merit (index value) of an inbred line of any of the three breeds significantly exceed the overall merit of its respective selected control group" http://www.ncbi.nlm.nih.gov/pubmed/6841289 0 1839 "B. D. Guth, G. Heusch, R. Seitelberger and J. Ross, Jr." 1987 Elimination of exercise-induced regional myocardial dysfunction by a bradycardiac agent in dogs with chronic coronary stenosis Circulation 75 3 661-669 "We have previously demonstrated that the beneficial effect of cardioselective beta-blockade on exercise-induced ischemia is due entirely to negative chronotropism. Therefore we studied the effect of a new bradycardiac agent (UL-FS 49) in 10 dogs with chronic coronary artery stenosis produced by an ameroid constrictor. Regional myocardial function (sonomicrometers, wall thickness) and blood flow (microspheres) were measured during a control treadmill exercise bout and an identical run 3 hr later after the administration of UL-FS 49 (1.0 mg/kg iv). In the control run, heart rate increased from 114 +/- 20 to 230 +/- 19 beats/min and systolic wall thickening (%WT) in the poststenotic myocardium decreased from 23.3 +/- 5.2% at rest to 9.3 +/- 5.0%, a 60% reduction. Subendocardial blood flow in the ischemic area decreased from 1.04 +/- 0.30 to 0.55 +/- 0.40 ml/min/g, blood flow per beat decreased from 9.1 X 10(-3) to 2.5 X 10(-3) ml/g, and mean transmural flow failed to increase (1.06 +/- 0.30 vs 1.08 +/- 0.39 ml/min/g). During exercise with UL-FS 49, heart rate increased from 89 +/- 10 to only 139 +/- 10 beats/min. End-diastolic left ventricular pressure was increased compared with that during the control run (35.7 +/- 3.0 vs 28.9 +/- 5.5 mm Hg) but left ventricular peak systolic pressure and dP/dt were unchanged. %WT in the ischemic zone did not change significantly during exercise with UL-FS 49 (23.3 +/- 7.9% at rest, 21.5 +/- 8.4% during the run), and in the nonischemic zone it increased to the same extent as during the control run.(ABSTRACT TRUNCATED AT 250 WORDS)" http://www.ncbi.nlm.nih.gov/pubmed/3815774 0 1840 "F. Chenu, E. Dailly and M. Bourin" 2007 Effect of antidepressant drugs on 6-OHDA-treated mice in the FST Eur.Neuropsychopharmacol. 17 3 187-193 "There is growing evidence suggesting that dopamine could be indirectly involved in the appearance of behavioural effects of antidepressants. In this study, we induced a partial (over 70%) and non-reversible depletion of dopamine-containing neurons in mice by i.c.v. infusion of 6-OHDA. Then, we compared the antidepressant-like effect of drugs (citalopram, paroxetine, desipramine and imipramine) with or without dopamine depletion in the mice forced swimming test. Our results clearly show that lesion with 6-OHDA does not modify the response of mice to desipramine and imipramine, whereas dopamine depletion abolished the antidepressant-like effect of citalopram and paroxetine. It could then be suggested that antidepressant-like effect of selective serotonin reuptake inhibitors (paroxetine and citalopram) in the mice FST requires the activation of dopaminergic pathways to occur" http://www.ncbi.nlm.nih.gov/pubmed/16757155 1 1841 "M. T. Zavy, T. O. Lindsey and R. D. Hedde" 1988 Gizzard ulceration in chicks fed cysteamine alone or in combination with a histamine H2-receptor antagonist J.Vet.Pharmacol.Ther. 11 4 362-373 "A study was carried out to evaluate the effect of cysteamine-HCl administration on gizzard ulceration and growth performance in broiler chicks. The effectiveness of the histamine H2-receptor antagonist, SKF 93479, in preventing gizzard ulcerations when given in combination with cysteamine-HCl was also examined. In the initial experiment cysteamine-HCl at the level of 2400 mg/kg of the diet caused severe gizzard ulceration and mortality and decreased feed intake and growth in chicks. The effect was not seen when cysteamine-HCl was administered at 600 or 1200 mg/kg of the diet. In Experiment 2 broiler chicks administered cysteamine-HCl at 1800 mg/kg of the diet had an increased incidence of gizzard ulceration and decreased growth performance. The severity of gizzard lesions and the depression of growth performance were not as great as in the group in Experiment 1 which received the 2400 mg/kg level of cysteamine-HCl. Addition of the H2 antagonist SKF 93479 at 54 mg/kg of the diet had no effect on improving gizzard ulcer score or growth performance in chicks which received cysteamine-HCl at the 1800 mg/kg of the diet level. From these data it appears that the administration of ulcerogenic levels of cysteamine-HCl in the chicken may involve a more complex pathogenesis in which factors other than acid hypersecretion are involved" http://www.ncbi.nlm.nih.gov/pubmed/2905391 0 1842 "C. Y. Tsai, C. H. Chen, A. Y. Chang, J. Y. Chan and S. H. Chan" 2015 "Upregulation of FLJ10540, a PI3K-association protein, in rostral ventrolateral medulla impairs brain stem cardiovascular regulation during mevinphos intoxication" Biochem.Pharmacol. 93 1 34-41 "FLJ10540, originally identified as a microtubule-associated protein, induces cell proliferation and migration during tumorigenesis via the formation of FLJ10540-PI3K complex and enhancement of PI3K kinase activity. Interestingly, activation of PI3K/Akt cascade, leading to upregulation of nitric oxide synthase II (NOS II)/peroxynitrite signaling in the rostral ventrolateral medulla (RVLM), the brain stem site that maintains blood pressure and sympathetic vasomotor tone, mediates the impairment of brain stem cardiovascular regulation induced by the pesticide mevinphos. We evaluated the hypothesis that upregulation of FLJ10540 in the RVLM is upstream to this repertoire of signaling cascade that underpins mevinphos-induced circulatory depression. Microinjection bilaterally of mevinphos (10nmol) into the RVLM of anesthetized Sprague-Dawley rats induced a progressive hypotension that was accompanied by an increase (Phase I), followed by a decrease (Phase II) of an experimental index for baroreflex-mediated sympathetic vasomotor tone. There was augmentation in FLJ10540 mRNA in the RVLM or FLJ10540 protein in RVLM neurons, both of which were causally and temporally related to an augmentation of binding between the catalytic subunit (p110) and regulatory subunit (p85) of PI3K, phosphorylation of Akt at Thr308 site, and NOS II, superoxide or peroxynitrite level in the RVLM. Immunoneutralization of FJL10540 in the RVLM significantly antagonized those biochemical changes, and blunted the progressive hypotension and the reduced baroreflex-mediated sympathetic vasomotor tone during mevinphos intoxication. We conclude that upregulation of FLJ10540 in the RVLM elicits impairment of brain stem cardiovascular regulation that underpins circulatory depression during mevinphos intoxication via activation of PI3K/Akt/NOS II/peroxynitrite signaling cascade in the RVLM" http://www.ncbi.nlm.nih.gov/pubmed/25449601 0 1843 H. Kewitz and O. Pleul 1977 "Inhibition of choline incorporation into brain lipids in rats by urethane, a proposed mechanism of depression of the central nervous system" Naunyn Schmiedebergs Arch.Pharmacol. 298 3 205-210 "Concentrations and specific radioactivities of choline, acetylcholine, phosphorylcholine, lipid choline, and sn-glycero-3-phosphorylcholine after i.v. injection of methyl-14C-choline were measured in the brain of untreated controls and of rats anesthesized with urethane. The specific activity was found to be decreased during deep anesthesia by 40% in acetylcholine, 20-30% in phosphorylcholine, 50-75% in lipid choline, and 30-40% in sn-glycero-3-phosphoryl-choline. No significant change was detected in the specific activity of choline. The brain concentration of acetylcholine was increased by 40%, the concentration of sn-glycero-3-phosphorylcholine, however, was diminished by 10% during anesthesia. No change was found in the concentration of the other choline containing compounds investigated. Measuring choline incorporation into 4 subcellular fractions of brain tissue specific activities were found to be decreased by the same percentage, although 2 fractions (nuclei and microsomes) were higher labelled than the 2 other fractions (crude mitochondria with synaptosomes and lysosomes). A correlation between the biochemical and the functional alterations is supported by the dose-effect relationships on both parameters. It is suggested that urethane reduces turnover of lipids and by that mechanism inhibits the exocytotic release of the transmitter from presynaptic nerve endings" http://www.ncbi.nlm.nih.gov/pubmed/895894 0 1844 "M. E. Pedersen, B. Szewczyk, K. Stachowicz, J. Wieronska, J. Andersen, G. I. Stafford, S. J. van, A. Pilc and A. K. Jager" 2008 Effects of South African traditional medicine in animal models for depression J.Ethnopharmacol. 119 3 542-548 "ETHNOPHARMACOLOGICAL RELEVANCE: The four South African medicinal plants Agapanthus campanulatus (AC), Boophone distica (BD), Mondia whitei (MW) and Xysmalobium undulatum (XU) are used in traditional medicine to treat depression. AIM: To evaluate the effect of ethanolic extracts of the plants in models for depression. MATERIALS AND METHODS: The extracts were screened for affinity for the serotonin transporter (SERT) in the [(3)H]-citalopram-binding assay. The inhibitory potency of the extracts towards the SERT, the noradrenalin transporter (NAT) and the dopamine transporter (DAT) were determined in a functional uptake inhibition assay. Antidepressant-like effects of the extracts were investigated using the tail suspension test (TST) and the forced swim test in both rats (rFST) and mice (mFST). RESULTS: All four plants showed affinity for SERT in the binding assay. AC and BD showed functional inhibition of SERT, NAT and DAT, MW affected SERT while XU showed no effect. BD showed significant effect in the TST and in the mFST/rFST, AC showed significant effect in mFST, MW showed significant effect in the rFST and XU showed significant effect in the mFST. CONCLUSION: In this study we have demonstrated the antidepressant activity of four South African medicinal plants in vitro and in vivo, supporting their rational use in traditional medicine" http://www.ncbi.nlm.nih.gov/pubmed/18809486 1 1845 "P. Prakash, Z. Merali, M. Kolajova, B. M. Tannenbaum and H. Anisman" 2006 Maternal factors and monoamine changes in stress-resilient and susceptible mice: cross-fostering effects Brain Res. 1111 1 122-133 "Genetic factors influence stressor-provoked monoamine changes associated with anxiety and depression, but such effects might be moderated by early life experiences. To assess the contribution of maternal influences in determining adult brain monoamine responses to a stressor, strains of mice that were either stressor-reactive or -resilient (BALB/cByJ and C57BL/6ByJ, respectively) were assessed as a function of whether they were raising their biological offspring or those of the other strain. As adults, offspring were assessed with respect to stressor-provoked plasma corticosterone elevations and monoamine variations within discrete stressor-sensitive brain regions. BALB/cByJ mice demonstrated poorer maternal behaviors than C57BL/6ByJ dams, irrespective of the pups being raised. In response to a noise stressor, BALB/cByJ mice exhibited higher plasma corticosterone levels and elevated monoamine turnover in several limbic and hypothalamic sites. The stressor-provoked corticosterone increase in BALB/cByJ mice was diminished among males (but not females) raised by a C57BL/6ByJ dam. Moreover, increased prefrontal cortical dopamine utilization was attenuated among BALB/cByJ mice raised by a C57BL/6ByJ dam. These effects were asymmetrical as a C57BL/6ByJ mice raised by a BALB/cByJ dam did not exhibit increased stressor reactivity. It appears that stressors influence multiple neurochemical systems that have been implicated in anxiety and affective disorders. Although monoamine variations were largely determined by genetic factors, maternal influences contributed to stressor-elicited neurochemical changes in some regions, particularly dopamine activation within the prefrontal cortex" http://www.ncbi.nlm.nih.gov/pubmed/16876768 0 1846 "J. Schull, J. Walker, K. Fitzgerald, L. Hiilivirta, J. Ruckdeschel, D. Schumacher, D. Stanger and D. L. McEachron" 1989 "Effects of sex, thyro-parathyroidectomy, and light regime on levels and circadian rhythms of wheel-running in rats" Physiol Behav. 46 3 341-346 "Intact and thyro-parathyroidectomized (TPX) Sprague-Dawley rats of both sexes were observed for 24 days under a 12:12 light:dark cycle (Entrainment), followed by 20 days in constant dim red light (Free-Run). Circadian periods and levels of wheel-running activity were examined. Intact females and TPX males were significantly more active and had significantly shorter free-running circadian periods than intact males, and the effects of TPX in females were different from those in males. Circadian periods in TPX females were slightly, but not significantly, shorter than in intact females, and activity levels in TPX females were nonsignificantly depressed relative to intact females. It was also found that day versus night activity levels differed more in TPX animals than in intact animals, especially during entrainment, suggesting that TPXs may be more sensitive to some effects of light. A number of possible explanations for the effects of TPX are considered, including changes in thyroid and calcitonin levels, interactions with gonadal hormones, and possible developmental effects of thyroid hormones on the circadian system. It is also possible that rhythm changes are secondary to alterations in activity levels. Human manic depressives reportedly have an unusually high incidence of thyroid, parathyroid, and calcium regulation abnormalities, display shortened circadian sleep-wake rhythms and abnormal levels of activity, and may also be hypersensitive to some effects of light; in addition, depression predominates in women, whereas mania predominates in men. The present results suggest that thyroid dysfunction could be partially responsible for the some of these abnormalities, and for sex differences in the manifestations of these disorders" http://www.ncbi.nlm.nih.gov/pubmed/2623053 0 1847 K. J. Sufka and S. W. White 2013 "Identification of a treatment-resistant, ketamine-sensitive genetic line in the chick anxiety-depression model" Pharmacol.Biochem.Behav. 113 63-67 "The introduction of pharmacotherapies for treatment-resistant depression is hindered by translational challenges with existing preclinical screening models that fail to adequately model the clinical features of this syndrome. This research sought to screen antidepressants in two selected genetic lines previously identified as stress-vulnerable and -resilient in the chick anxiety-depression model. Separate groups of socially-raised 5-6 day-old Black Australorps (stress-vulnerable) and Production Reds (stress-resilient) were administered imipramine (0-20 mg/kg), fluoxetine (0-10 mg/kg), maprotiline (0-10 mg/kg) or ketamine 0-15 mg/kg) IP (1 ml/kg) and placed into isolation for 90 min. Distress vocalizations (DVoc) were recorded. Onset of behavioral despair and Dvoc rates during the depression-like phase (30-90 min) were calculated. Black Australorps entered behavioral despair approximately 25% faster than Productions Reds highlighting stress-vulnerability in this Black Australorp line. In the depression-like phase, Black Australorps were insensitive to imipramine and fluoxetine but sensitive to ketamine, a finding that parallels stress-vulnerable, treatment resistant depressive disorder. The chick anxiety-depression model using the Black Australorp line may prove useful in pre-clinical screening of novel antidepressant targets for use in treatment-resistant depression" http://www.ncbi.nlm.nih.gov/pubmed/24157688 1 1848 "A. E. Dickinson, E. A. Rozanski and J. E. Rush" 2007 Reversible myocardial depression associated with sepsis in a dog J.Vet.Intern.Med. 21 5 1117-1120 http://www.ncbi.nlm.nih.gov/pubmed/17939574 0 1849 R. B. Duckrow 1995 Decreased cerebral blood flow during acute hyperglycemia Brain Res. 703 01-Feb 145-150 "Cerebral blood flow (CBF) decreases during acute hyperglycemia but the mechanism of this change is unknown. The role that plasma osmolality plays in this effect was reexamined in pentobarbital-anesthetized rats using a continuous measure of CBF, laser-Doppler flowmetry. CBF decreased 25% during acute elevation of plasma osmolality induced by intraperitoneal injection of concentrated solutions of glucose or mannitol. In addition there were brief transient increases of CBF with peak magnitude 2-4-times the baseline level that were not accompanied by transient depression of electroencephalographic activity. These transient CBF increases may explain why discontinuous methods of CBF measurement fail to detect flow decreases after mannitol injection. Decreased CBF measured during acute hyperglycemia may be the result of increased plasma osmolality" http://www.ncbi.nlm.nih.gov/pubmed/8719626 0 1850 "I. A. Orlovskaia, L. V. Dubinina, S. K. Khaldoianidi and V. A. Kozlov" 1994 [Changes in the age structure of the hematopoietic stem cells of older mice under the influence of a factor inhibiting their proliferative activity] Ontogenez 25 3 26-32 "The effect of stem cell proliferation inhibitor (PIF) on hemopoietic stem cell and committed precursor cell subpopulations in aged mice was studied. The following parameters were analyzed: the number of CFUs-5, CFUs-8, and CFUs-12 in bone marrow and spleen, the number of BFUe, CFUs-GM, CFUs-M, and the ability of bone marrow cells of aged mice to repopulate bone marrow of lethally irradiated recipients (MRA). Characteristic of aged mice were an increased number of precursors (mainly in bone marrow), changes in their erythropoietic differentiation, and a decreased MRA of bone marrow cells. The suppression of stem cell proliferation by PIF was accompanied by a decrease in the total number of precursors and led to changes in their migration and differentiation, which might provide for restoration of hemopoiesis in aged mice to the level characteristic of young mice" http://www.ncbi.nlm.nih.gov/pubmed/8047326 0 1851 "S. Laye, R. M. Bluthe, S. Kent, C. Combe, C. Medina, P. Parnet, K. Kelley and R. Dantzer" 1995 Subdiaphragmatic vagotomy blocks induction of IL-1 beta mRNA in mice brain in response to peripheral LPS Am.J.Physiol 268 5 Pt 2 R1327-R1331 "To test the possibility that the vagus nerve is involved in the communication between the immune system and the brain, we injected sham-operated and vagotomized mice with physiological saline or lipopolysaccharide (LPS; 400 micrograms/kg ip). Vagotomy attenuated LPS-induced depression of general activity measured 2 h after treatment but did not alter the increase in plasma levels of IL-1 beta in response to LPS. In addition, vagotomy abrogated the LPS-induced increase in the levels of transcripts for IL-1 beta, as determined by semiquantitative polymerase chain reaction after reverse transcription, in the hypothalamus and hippocampus, but not in the pituitary of vagotomized mice. This relationship between the effects of vagotomy on the behavioral effects of LPS and the LPS-induced brain expression of IL-1 beta mRNA indicates that vagal afferent fibers play a prominent role in the pathways of communication between the immune system and the brain" http://www.ncbi.nlm.nih.gov/pubmed/7771597 0 1852 "F. Kobayashi, H. Kakushi and T. Miyake" 1970 Delayed implantation induced by antiestrogenic compounds in rats Endocrinol.Jpn. 17 4 313-321 http://www.ncbi.nlm.nih.gov/pubmed/5537139 0 1853 "H. Yasuda, Y. Huang and T. Tsumoto" 2008 Regulation of excitability and plasticity by endocannabinoids and PKA in developing hippocampus Proc.Natl.Acad.Sci.U.S.A 105 8 3106-3111 "The activity-dependent strengthening and weakening of synaptic transmission are hypothesized to be the basis of not only memory and learning but also the refinement of neural circuits during development. Here we report that, in the developing CA1 area of the hippocampus, endocannabinoid (eCB)-mediated heterosynaptic long-term depression (LTD) of glutamatergic excitatory synaptic transmission is associated with PKA-mediated homosynaptic long-term potentiation (LTP). This form of LTD was dominant at postnatal days 2-10 (P2-P10), attenuated during development, and finally disappeared in the mature hippocampus. Heterosynaptic LTD of excitatory postsynaptic currents in the developing hippocampus was expressed presynaptically, spread to neighboring neurons, and was mediated by eCBs. Heterosynaptic LTD of field excitatory postsynaptic potentials was associated with a decrease in fiber volley amplitude with a similar time course. Depression of fiber volleys was blocked by K(+) channel blockers, suggesting the involvement of the decrease in presynaptic excitability in heterosynaptic LTD. In the P2-P5 hippocampus, eCBs also attenuate LTP and fiber volleys in homosynaptic pathways and help to prevent too much excitability in the neonatal hippocampus where the GABAergic system is poorly developed and even excitatory. In the hippocampus older than P6 (P > 6), however, LTP is protected from eCB-mediated depression by PKA activated at presynaptic sites by high-frequency stimulation, serving to highlight PKA-mediated LTP by weakening inactive synapses even in adjacent cells. Thus, eCBs and PKA make synapses plastic without changing excitability homeostasis in the developing hippocampus" http://www.ncbi.nlm.nih.gov/pubmed/18287074 0 1854 "B. M. Tchiteya, A. R. Lecours, R. Elie and S. J. Lupien" 2003 Impact of a unilateral brain lesion on cortisol secretion and emotional state: Anterior/posterior dissociation in humans "Psychoneuroendocrinology.28 (5) ()(pp 674-686), 2003.Date of Publication: July 2003." 5 674-686 "The main goal of this study was to evaluate whether a unilateral brain lesion in a human population is associated with a modification of the circadian cortisol secretion profile, and/or patient's emotional state. The second goal of this study was to assess whether there would be differences in both the pattern of cortisol secretion and emotional state in brain-damaged patients as a function of side of lesion, and localization (anterior vs posterior) of lesion. Eight patients with a left cortical lesion, six patients with a right cortical lesion, four patients with basal ganglia lesions (2 left and 2 right) and ten healthy volunteers were evaluated daily on measures of salivary cortisol levels and subjective feelings of joy and sadness at 0700, 1200, 1600 and 1900 hours over a 15-day period. Patients with cortical brain lesions presented higher cortisol levels and higher scores of sadness at the time of the morning peak (7:00 am), when compared to healthy volunteers and patients with basal ganglia lesions. Laterality of the lesion was not related to cortisol secretion, but frontal damage (anterior lesion) was associated with higher cortisol levels at the time of the morning peak (7:00 am) when compared to more posterior damage. There was no significant correlation between basal circulating levels of cortisol and emotional states in patients and healthy subjects. The results of this study suggest that hypothalamic-pituitary-adrenal (HPA) axis dysregulation is associated with unilateral injury particularly in frontal areas. These results, obtained in a human population, go along with recent animal studies reporting an implication of frontal regions in HPA activity. © 2003 Elsevier Science Ltd. All rights reserved" DO - http://dx.doi.org/10.1016/S0306-4530%2802%2900050-1 0 1855 "T. F. Krzeminski, K. Mitrega, B. Varghese, D. Hudziak, M. Porc, A. Kedzia, A. W. Sielanczyk, A. Jablecka and M. Jasinski" 2011 Cardioprotective effects of an active metabolite of furnidipine in 2 models of isolated heart and on in vivo ischemia-induced and reperfusion-induced arrhythmias in rats J.Cardiovasc.Pharmacol. 57 2 183-193 "Dihydropyridines are known not only to have antiarrhythmic effects but also to exert a significant cardiac depressive influence. We previously showed that M-2, an active and final metabolite of furnidipine, had cardioprotective effects without the marked cardiac depression seen with this dihydropyridine. We studied the influence of M-2 infusion (10(-7) M) on hemodynamics during low-flow and regional ischemia in the rat working heart. We examined the protection conferred by M-2 infusion (10(-7) M) against effects of veratridine-induced intracellular calcium overload in the Langendorff heart. Additionally, we performed an in vivo study to explore the effects of oral administration of M-2 at different times and doses, in the ischemia- and reperfusion-induced arrhythmias model. M-2 improved coronary flow during low-flow and regional ischemia while favorably maintaining aortic pressure parameters. M-2 provided outstanding protection against deleterious effects of calcium overloading by significantly preventing rise in left ventricular diastolic pressure and decrease in coronary flow. M-2 reduced mortality and incidence and duration of severe arrhythmias while exhibiting differential influence on blood pressure, which depended on dose and time of administration and could suggest its clinical indication. The results of our entire study establish a beneficial cardioprotective role of M-2, which exhibited pleiotropic effects on the ischemic heart by imparting protection in various ways. This combined with good tolerance, long duration of action, low toxicity, and relatively large therapeutic window makes M-2 a promising candidate as a precursor for a new chemical class of cardioprotective drugs" http://www.ncbi.nlm.nih.gov/pubmed/21052014 0 1856 "T. G. Dinan, V. Crunelli and J. S. Kelly" 1987 Neuroleptics decrease calcium-activated potassium conductance in hippocampal pyramidal cells Brain Res. 407 1 159-162 "Intracellular recordings were made from pyramidal CA1-neurones of the hippocampal slice preparation. Bath application of a wide variety of neuroleptics was found to depress the slow afterhyperpolarization, which is mediated in these neurons by a calcium-dependent potassium conductance occurring following a burst of spikes. The depression of this conductance took place in the presence of calcium spikes of normal amplitude and duration, and except in the case of trifluoperazine, without alteration in resting membrane potential or input resistance" http://www.ncbi.nlm.nih.gov/pubmed/2884012 0 1857 "P. Borenstein, C. Champion, P. Cujo, F. Gekiere, C. Olivenstein and P. Kramarz" 1969 [An original psychotropic drug: sulpiride] Sem.Hop. 45 19 1301-1314 http://www.ncbi.nlm.nih.gov/pubmed/4307000 1 1858 "F. Sauer, S. Mahadevan and J. D. Erfle" 1971 The accumulation of citrate cycle intermediates in rat liver cells oxidizing palmitate Biochim.Biophys.Acta 239 1 26-32 http://www.ncbi.nlm.nih.gov/pubmed/5569938 0 1859 "A. Guyon, C. Rovere, A. Cervantes, I. Allaeys and J. L. Nahon" 2005 Stromal cell-derived factor-1alpha directly modulates voltage-dependent currents of the action potential in mammalian neuronal cells J.Neurochem. 93 4 963-973 "Stromal cell-derived factor-1alpha (SDF-1alpha) is a chemokine whose receptor, CXCR4, is distributed in specific brain areas including hypothalamus. SDF-1alpha has recently been found to play important roles in neurons, although direct modulation of voltage-gated ionic channels has never been shown. In order to clarify this issue, we performed patch-clamp experiments in fetal mouse hypothalamic neurons in culture. SDF-1alpha (10 nm) decreased the peak and rising slope of the action potentials and spike discharge frequency in 22% of hypothalamic neurons tested. This effect was blocked by the CXCR4 antagonist AMD 3100 (1 microm) but not by the metabotropic glutamate receptor antagonist MCPG (500 microm), indicating a direct action of SDF-1alpha on its cognate receptor. This effect involved a depression of both inward and outward voltage-dependent currents of the action potential. We confirmed these effects in the human neuroblastoma cell line SH-SY5Y, which endogenously expresses CXCR4. Voltage-clamp experiments revealed that SDF-1alpha induced a 20% decrease in the peak of the tetrodotoxin-sensitive sodium current and tetraethylammonium-sensitive delayed rectifier potassium current, respectively. Both effects were concentration dependent, and blocked by AMD 3100 (200 nm). This dual effect was reduced or blocked by 0.4 mm GTPgammaS G-protein pre-activation or by pre-treatment with the G-protein inhibitor pertussis toxin (200 ng/mL), suggesting that it is mediated via activation of a G(i/o) protein. This study extends the functions of SDF-1alpha to a direct modulation of voltage-dependent membrane currents of neuronal cells" http://www.ncbi.nlm.nih.gov/pubmed/15857399 0 1860 "L. Stojanovich, D. Smiljanich-Miljkovich, R. Omdal and B. Sakic" 2009 Neuropsychiatric lupus and association with cerebrospinal fluid immunoglobulins: A pilot study "Israel Medical Association Journal.11 (6) ()(pp 359-362), 2009.Date of Publication: 2009." 6 359-362 "Background: Recent experimental evidence points to brain-reactive antibodies as a key factor in the pathogenesis of neuropsychiatric systemic lupus erythematosus (central nervous system-SLE). However, clinical studies in which circulating (serum) autoantibodies were correlated with neuropsychiatric manifestations have not produced consistent findings. Objectives: To test the hypothesis that autoantibodies in cerebrospinal fluid are more reflective of functional brain damage. Methods: We compared the behavioral profiles of 12 NP-SLE patients, some of whom had immunoglobulin G in their CSF. Results: Western blotting revealed heavy and light chain IgG bands in six patients similar in age to the subgroup of CSF IgG-free patients. A series of serological measures did not differ between the subgroups, but SLEDAI scores and daily steroid doses were higher in patients with IgG in their CSF. All three patients with severe deficits in verbal and executive functions were positive for the CSF IgG, while three other patients with psychosis were CSF IgG-negative. Conclusions: Although the present sample size is relatively small, the results support the relationship between disease severity and central manifestations of autoimmunity. They also emphasize the importance of clinical studies that compare subpopulations of NP-SLE patients and justify development of animal models in which controlled immune mechanisms induce specific deficits in behavior" 0 1861 "M. E. Glinka, B. A. Samuels, A. Diodato, J. Teillon, D. F. Mei, B. M. Shykind, R. Hen and A. Fleischmann" 2012 Olfactory deficits cause anxiety-Like behaviors in mice "Journal of Neuroscience.32 (19) ()(pp 6718-6725), 2012.Date of Publication: 09 May 2012." 19 6718-6725 "Anxiety disorders are characterized by persistent fear in the absence of immediate threat and represent the most common psychiatric diseases, with an estimated 28% lifetime prevalence worldwide (Kessler et al., 2010). While symptoms of anxiety are typically evoked by sensory stimuli, it is unknown whether sensory deficits contribute to the development of anxiety disorders. Here we examine the effect of defined genetic mutations that compromise the function of the olfactory system on the development of anxiety-like behaviors in mice. We show that the functional inactivation of the main olfactory epithelium, but not the vomeronasal organ, causes elevated levels of anxiety. Anxiety-like behaviors are also observed in mice with a monoclonal nose, that are able to detect and discriminate odors but in which the patterns of odor-evoked neural activity are perturbed. In these mice, plasma corticosterone levels are elevated, suggesting that olfactory deficits can lead to chronic stress. These results demonstrate a central role for olfactory sensory cues in modulating anxiety in mice. © 2012 the authors" DO - http://dx.doi.org/10.1523/JNEUROSCI.4287-11.2012 0 1862 "R. Choudhuri, L. Cui, C. Yong, S. Bowyer, R. M. Klein, K. M. Welch and N. E. Berman" 2002 Cortical spreading depression and gene regulation: relevance to migraine Ann.Neurol. 51 4 499-506 "Cortical spreading depression (CSD) may be the underlying mechanism of migraine aura. The role of CSD in initiating a migraine headache remains to be determined, but it might involve specific changes in gene expression in the brain. To examine these changes, four episodes of CSD at 5-minute intervals were induced in the mouse brain by application of 300mM KCl, and gene expression was examined 2 hours later using cDNA array and reverse transcriptase-polymerase chain reaction. Controls consisted of groups that received anesthesia only, attachment of recording electrodes only, and application of 0.9% NaCl. Of the over 1,180 genes examined in our experiments, those consistently regulated by CSD included vasoactive peptides; the vasodilator atrial natriuretic peptide was induced by CSD, while the vasoconstrictor neuropeptide Y was downregulated. Other genes specifically regulated by CSD were involved in oxidative stress responses (major prion protein, glutathione-S-transferase-5, and apolipoprotein E). L-type calcium channel mRNA was upregulated. In summary, CSD regulates genes that are intrinsic to its propagation, that identify accompanying vascular responses as a potential source of pain, and that protect against its potential pathological consequences. We believe these observations have strong relevance to the mechanisms of migraine and its outcomes" http://www.ncbi.nlm.nih.gov/pubmed/11921056 0 1863 "A. J. Bradbury, B. Costall, M. E. Kelly, R. J. Naylor and J. A. Smith" 1985 Biochemical correlates of motor changes caused by the manipulation of dopamine function in the substantia nigra of the mouse Neuropharmacology 24 12 1155-1161 "2-Di-n-propylamino-5,6-dihydroxytetralin, injected bilaterally into the substantia nigra of the mouse, caused dose-dependent motor inhibition which was associated with decreased levels of DOPAC and increased levels of dopamine in the striatum. (-)Sulpiride, injected into the substantia nigra, antagonised the locomotor depression although the partial antagonism of the elevation in the level of dopamine in the striatum and of the reduction in levels of DOPAC did not achieve significance. The specificity of the action of tetralin on dopamine receptors was shown by the failure of prazosin and yohimbine to antagonise the locomotor depression induced by tetralin and the reduction in levels of DOPAC. The selectivity of the action of tetralin for the dopamine system was shown by its failure to affect levels of noradrenaline, serotonin and 5-hydroxyindoleacetic acid in the striatum. The injection of tetralin into the substantia nigra also caused biochemical changes in limbic areas (nucleus accumbens and tuberculum olfactorium), where the levels of dopamine and DOPAC were elevated, and in the frontal cortex where the levels of DOPAC were reduced. These changes were antagonised by a concomitant injection of (-)sulpiride into the substantia nigra. It is concluded that the action of dopamine agonists in the midbrain can decrease the functional activity in the ascending dopaminergic pathways" http://www.ncbi.nlm.nih.gov/pubmed/4094652 0 1864 J. Deuchars and A. M. Thomson 1996 CA1 pyramid-pyramid connections in rat hippocampus in vitro: dual intracellular recordings with biocytin filling Neuroscience 74 4 1009-1018 "In adult rat hippocampus, simultaneous intracellular recordings from 989 pairs of CA1 pyramidal cells revealed nine monosynaptic, excitatory connections. Six of these pairs were sufficiently stable for electrophysiological analysis. Mean excitatory postsynaptic potential amplitude recorded at a postsynaptic membrane potential between -67 and -70 mV was 0.7 +/- 0.5 mV (0.17-1.5 mV), mean 10-90% rise time was 2.7 +/- 0.9 ms (1.5-3.8 ms) and mean width at half-amplitude was 16.8 +/- 4.1 ms (11.6-25 ms). Cells were labelled with biocytin and identified histologically. For one pair that was fully reconstructed morphologically, excitatory postsynaptic potential average amplitude was 1.5 mV, 10-90% rise time 2.8 ms and width at half-amplitude 11.6 ms (at -67 mV). In this pair, correlated light and electron microscopy revealed that the presynaptic axon formed two synaptic contacts with third-order basal dendrites of the postsynaptic pyramid, one with a dendritic spine, the other with a dendritic shaft. In the four pairs tested, postsynaptic depolarization increased excitatory postsynaptic potential amplitude and duration. In two, D-2-amino-5-phosphonovalerate (50 microM) reduced the amplitude and duration of the excitatory postsynaptic potential. The remainder of the excitatory postsynaptic potential now increased with postsynaptic hyperpolarization and was abolished by 20 microM 6-cyano-7-nitroquinoxaline-2,3-dione (n = 1). Paired-pulse depression was evident in the four excitatory postsynaptic potentials tested. This depression decreased with increasing inter-spike interval. These results provide the first combined electrophysiological and morphological illustration of synaptic contacts between pyramidal neurons in the hippocampus and confirm that connections between CA1 pyramidal neurons are mediated by both N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate/kainate receptors" http://www.ncbi.nlm.nih.gov/pubmed/8895869 0 1865 "R. Holemans, E. J. Mlynarczyk and M. J. Silver" 1968 Enhancement of fibrinolysis and blood clotting: role of microvascular changes Med.Exp.Int.J.Exp.Med. 18 4 299-307 http://www.ncbi.nlm.nih.gov/pubmed/4981645 0 1866 J. Servais and P. Hubin 1968 "[Synthesis of current knowledge of an inhibitor of libido in the male, the methylestrenolone]" Encephale 57 4 333-352 http://www.ncbi.nlm.nih.gov/pubmed/4237574 0 1867 "S. Najmi, A. C. Tobin and N. Amir" 2012 Psychometric properties of a behavioral test of contamination-related obsessive-compulsive symptoms "Cognitive Therapy and Research.36 (3) ()(pp 228-233), 2012.Date of Publication: June 2012." 3 228-233 "In this study, we evaluated the psychometric properties of a Behavioral Approach Task (BAT) for contamination-related obsessive-compulsive symptoms. We adapted the BAT from Cougle et al's. (2007) design, which comprised three tests corresponding to three different contamination-related stimuli and a hierarchy of six steps of approach within each test. We obtained anxiety and disgust ratings at each BAT step. Participants with low or high contamination fear completed self-report measures of obsessive-compulsive symptoms and depression before completing the BAT. Internal consistency of the BAT was high. Furthermore, the BAT demonstrated good convergent validity with a self-report measure of contamination-related obsessive-compulsive symptoms. The BAT also had sound discriminant validity with self-report measures of depression and of obsessive-compulsive symptoms other than contamination. Our study suggests that the use of this test as an observable measure of contamination-related fears is not only psychometrically sound but also easy to administer. © Springer Science+Business Media, LLC 2010" DO - http://dx.doi.org/10.1007/s10608-010-9332-0 0 1868 "T. E. Owope, I. O. Ishola, M. O. Akinleye, R. Oyebade and O. O. Adeyemi" 2016 "Antidepressant Effect of Cnestis ferruginea Vahl ex DC (Connaraceae): Involvement of Cholinergic, Monoaminergic and L-arginine-nitric Oxide Pathways" Drug Res.(Stuttg) 66 5 235-245 "BACKGROUND: We have previously reported antidepressant effect of Cnestis ferruginea (CF) in behavioral models of depression. Due to the promise shown by this extract, this study was carried out to investigate the contribution of monoaminergic, cholinergic and nitrergic systems to the antidepressant-like effect elicited by CF. METHODS: Male albino mice were pretreated with monoaminergic or cholinergic receptor antagonists, L-arginine or N(G)-nitro-L-arginine (nitric oxide synthase inhibitor) (at doses reported to block the in vivo effect of the agonists), 15 min before oral administration of CF (100 mg/kg), 1 h later, the forced swim test (FST) in mice was carried out. RESULTS: CF treatment produced significant changes in the duration of swimming (F(5,42)=9.86, P<0.001), climbing behaviour (F(5,42)=4.51, P=0.004) and mean time spent immobile (F(5,42)=11.55, P<0.001) vs. vehicle-treated control. Co-administration of CF with fluoxetine or imipramine potentiated their effect. However, pretreatment of mice with reserpine (F(1,16)=119.20, P<0.001), prazosin (F(1,16)=68.98, P<0.001), sulpiride (F(1,16)=15.46, P<0.01), RS 127445 ((F(1,20)=8.22, P<0.01), SB 399885 ((F(1,20)=38.44, P<0.001), atropine (F(1,16)=53.77, P<0.001), or L-arginine (nitric oxide precursor) (F(1,16)=10.35, P<0.01) prevented CF-induced antidepressant-like effect in mice. In addition, pretreatment of mice with L-NNA (10 mg/kg) augmented the effect of CF. CONCLUSION: C. ferruginea exerts its antidepressant-like action through interaction with alpha-adrenoceptor, dopamine D2, 5-HT2B, 5-HT6 and muscarinic cholinergi1c receptors as well as L-arginine-nitric oxide systems. C. ferruginea could be used as adjuvant with conventional antidepressants in the treatment of major depressive disorder" http://www.ncbi.nlm.nih.gov/pubmed/26789652 1 1869 "D. J. Hearse, G. M. Powell, A. H. Olavesen and K. S. Dodgson" 1969 The influence of some physico-chemical factors on the biliary excretion of a series of structurally related aryl sulphate esters Biochem.Pharmacol. 18 1 181-195 http://www.ncbi.nlm.nih.gov/pubmed/4889090 0 1870 "M. Yang, J. S. Kim, J. Kim, S. Jang, S. H. Kim, J. C. Kim, T. Shin, H. Wang and C. Moon" 2012 Acute treatment with methotrexate induces hippocampal dysfunction in a mouse model of breast cancer Brain Res.Bull. 89 01-Feb 50-56 "Methotrexate (MTX) is a well-known cytostatic agent used in adjuvant chemotherapy for breast cancer, that has neurological side effects, including depression and cognitive impairment. We investigated the neurotoxic effects of MTX on the hippocampus and hippocampus-dependent behaviors in breast cancer cell line (FM3A)-inoculated tumor-bearing mice. In addition, we evaluated the changes in inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in the hippocampus of tumor-bearing mice after treatment with MTX. Depressive-like behavior test (tail-suspension test, TST) and learning and memory tasks (passive avoidance) were administered 24h after MTX (40 mg/kg, i.p.) injection. MTX-treated tumor-bearing mice showed significant depressive-like behaviors and cognitive impairment. Treatment with MTX significantly decreased the number of doublecortin (a marker for immature progenitor neurons)-positive cells in the hippocampal dentate gyrus of tumor-free and tumor-bearing mice. Moreover, treatment with MTX significantly upregulated proinflammatory enzymes, including iNOS and COX-2, in tumor-bearing mice. These findings indicate that the acute neurotoxic effect of MTX leads to hippocampal dysfunction including depressive-like behaviors and memory deficits, which may be related to an inhibition of neurogenesis and an increase of the inflammatory response in the hippocampus of a mouse model of breast cancer" http://www.ncbi.nlm.nih.gov/pubmed/22796103 1 1871 "M. T. Ott, M. Vore, D. E. Barker, W. E. Strodel and C. J. McClain" 1989 Monokine depression of bile flow in the isolated perfused rat liver J.Surg.Res. 47 3 248-250 "Multiple system organ failure (MSOF) is a progressive dysfunction of vital organs that may develop in clinical settings such as sepsis or multiple trauma. One component of this syndrome is cholestasis and impaired liver function. The mechanism(s) for this liver failure (and the failure of other organs) remains obscure. Macrophages and Kupffer cells have been shown to secrete cytokines such as interleukin-1 and tumor necrosis factor. These cytokines mediate many aspects of the acute phase response, and they also can produce cellular injury. The purpose of this study was to evaluate the effects of a semipurified murine monokine preparation having interleukin-1 activity on bile flow in the rat isolated perfused liver (IPL). The monokine preparation produced a significant reduction of bile flow in the IPL system. The effect could not be explained by a venoocclusive phenomenon or residual endotoxin in the monokine preparation. We conclude that a semipurified monokine preparation having interleukin-1 but not tumor necrosis activity produced a significant depression of bile flow in the IPL, and we suggest that macrophage secretory product(s) may be responsible for the cholestasis in MSOF" http://www.ncbi.nlm.nih.gov/pubmed/2770282 0 1872 P. A. Revell 1978 Effect of long-term cyclophosphamide treatment on T and B lymphocytes in normal guinea pigs Int.Arch.Allergy Appl.Immunol. 56 5 443-448 "The effect of long-term repeated cyclophosphamide administration at low doses on T and B lymphocyte levels in the blood, lymph nodes and thymus of the guinea pig has been studied. A significant depletion of B cell levels occurred in the blood and the lymph nodes. Although there was evidence of depression of T cell levels in both blood and thymus, these changes were not statistically significant, except in the case of total T lymphocyte levels in the blood in one experiment. It is suggested that differences in sensitivity of T and B cells to cyclophosphamide may be related to differences in proliferative turnover and in their capacity to repair damage to DNA" http://www.ncbi.nlm.nih.gov/pubmed/305419 0 1873 "G. Pfeifer, G. Tauberger and E. J. Schulte am" 1978 "[An experimental study of the effect of etomidate on central sympathetic activity, respiration and circulation (author's transl)]" Prakt.Anaesth. 13 6 495-501 "The effect of Etomidate on central sympathetic activity, respiration and circulation were studied in animals at rest and under asphyctic conditions. The doses used were 0.15, 0.3 and 0.6 milligrams/kilogram bodyweight. Injection of the drug into animals at rest caused excitation lasting for about 10 seconds and then lowering of sympathetic activity by about 15-30 per cent. With doses of 0.6 mg the depression lasted for about 15 minutes. Central stimulation by asphyxia often a more pronounced dose-dependent depression of sympathetic activity by about 15-40% of the original level was observed. Activity of the phrenic nerve was affected only with doses of 0.6 mg; the reduction by about 30% lasted for up to 15 min. Injection of 0.6 mg was followed within one minute by a short-lasting fall in blood pressure by about 10%. The heart rate remained unchanged at rest but during asphyctic conditions the heart rate was less slowed down than would normally occur with vagal stimulation. Etomidate apparently also depressed the vagal centres. Similarities and differences in action between Etomidate and propanidid are discussed" http://www.ncbi.nlm.nih.gov/pubmed/740630 0 1874 "H. Kimura, M. Mikami, T. Kuriyama and Y. Fukuda" 1989 Effect of a synthetic progestin on ventilatory response to hypoxia in anesthetized rats J.Appl.Physiol (1985.) 67 5 1754-1758 "Effects on ventilatory responses to progressive isocapnic hypoxia of a synthetic potent progestin, chlormadinone acetate (CMA), were determined in the halothane-anesthetized male rat. Ventilation during the breathing of hyperoxic gas was largely unaffected by treatment with CMA when carotid chemoreceptor afferents were kept intact. The sensitivity to hypoxia evaluated by hyperbolic regression analysis of the response curve did not differ between the control and CMA groups. The reduction of ventilation after bilateral section of the carotid sinus nerve (CSN) in hyperoxia was less severe in CMA-treated than in untreated animals. Furthermore, the CMA-treated rats showed a larger increase in ventilation during the hypoxia test and a lower PO2 break point for ventilatory depression. Inhibition of hypoxic ventilatory depression by CMA persisted even after the denervation of CSN. We conclude that exogenous progestin likely protects regulatory mechanism(s) for respiration against hypoxic depression through a stimulating action independent of carotid chemoreceptor afferents and without a change in the sensitivity of the ventilatory response to hypoxia" http://www.ncbi.nlm.nih.gov/pubmed/2480946 0 1875 M. D. Layne and S. R. Farmer 1999 Tumor necrosis factor-alpha and basic fibroblast growth factor differentially inhibit the insulin-like growth factor-I induced expression of myogenin in C2C12 myoblasts Exp.Cell Res. 249 1 177-187 "Tumor necrosis factor-alpha (TNF-alpha) plays a role in several disease states such as sepsis, cachexia, and non-insulin-dependent diabetes. TNF-alpha interferes with insulin signaling and inhibits differentiation-specific gene expression in adipose tissue and skeletal muscle. We have examined the mechanisms by which TNF-alpha, in comparison to basic fibroblast growth factor (bFGF), inhibits the insulin-like growth factor-I (IGF-I)-induced differentiation of C2C12 myoblasts. Adhesion of quiescent, suspended myoblasts to collagen in high concentrations of IGF-I (10 nM) induced these cells to proliferate during the initial 24 h postplating and in so doing transiently inhibited the expression of myogenin, an essential transcription factor controlling myoblast differentiation. Low doses of IGF-I (1 nM) were minimally mitogenic and enhanced muscle-specific gene expression. Quiescent myoblasts treated with bFGF in combination with IGF-I did not express myogenin, but expressed proliferating cell nuclear antigen and underwent DNA synthesis. In contrast, TNF-alpha in the presence or absence of 1 nM IGF-I, did not stimulate DNA synthesis in myoblasts. However, TNF-alpha inhibited myogenin mRNA and protein expression. Expression of the cyclin-dependent kinase inhibitor p21 correlated with myogenin expression and myoblast differentiation, but not with growth arrest. These results indicate that both TNF-alpha and bFGF inhibit myogenin expression but differentially influence myoblast proliferation" http://www.ncbi.nlm.nih.gov/pubmed/10328964 0 1876 "H. H. Kohl, M. E. Friedman, P. Melius, E. C. Mora and C. A. McAuliffe" 1979 Enhanced inhibition of both cellular protein synthesis and malate dehydrogenase by aged aquoplatinum(II) complexes Chem.Biol.Interact. 24 2 209-215 "Previous studies have shown cis-diamminedichloroplatinum(II) (Cis) an effective anti-tumour agent in man and animals. Evidence is presented here that formation of aquo complexes of this platinum derivative will significantly enhance its inhibitory properties with respect to two separate biochemical functions, namely inhibition of protein synthesis in hamster medulloblastoma cells and in inhibiting the activity of L-malate dehydrogenase (MDH) in a cell free system. Inhibition of cell protein synthesis rises from 8% using freshly dissolved drug to 30% when aged solutions of drug are employed at an inhibitor concentration of 0.1 mM. The inhibitory enhancement seen using purified malic dehydrogenase increases from 16% (fresh) to 57% (aged) at an inhibitor concentration of 1 mM" http://www.ncbi.nlm.nih.gov/pubmed/428011 0 1877 J. F. Macdonald and A. Nistri 1977 Actions of microiontophoretically applied ibotenate on cat spinal interneurones Can.J.Physiol Pharmacol. 55 4 965-967 "Microiontophoretic applications of ibotenate, an amino acid analogue of glutamate, evoked biphasic responses from single dorsal horn interneurones of the cat spinal cord, i.e., an initial increase in the firing rate followed by a sustained depression of spontaneous firing. A reduced cell sensitivity to excitatory amino acids or peripheral field stimulation was also found during the ibotenate-induced depression. These effects were not produced by glutamate, quisqualate, or kainate, although occasional transient reductions of spontaneous cell firing were observed after application of glutamate. It is suggested that ibotenate might act on inhibitory as well as excitatory receptors of cat spinal interneurons" http://www.ncbi.nlm.nih.gov/pubmed/902170 0 1878 "W. E. Hauser, Jr. and J. S. Remington" 1983 Effect of amphotericin B on natural killer cell activity in vitro J.Antimicrob.Chemother. 11 3 257-262 "Incubation of murine peritoneal and spleen natural killer cells with amphotericin B at concentrations of 2.5, 5 and 10 mg/l in vitro, resulted in depression of their tumoricidal activity which had been augmented in vivo by infection with Toxoplasma gondii. In contrast, amphotericin B at the same concentrations had little or no effect on spontaneous natural killer cell activity in vitro. These in-vitro data suggest amphotericin B may have adverse effects on natural killer cell function in vivo" http://www.ncbi.nlm.nih.gov/pubmed/6841308 0 1879 "M. Nishiyori, H. Uchida, J. Nagai, K. Araki, T. Mukae, S. Kishioka and H. Ueda" 2011 Permanent relief from intermittent cold stress-induced fibromyalgia-like abnormal pain by repeated intrathecal administration of antidepressants Mol.Pain 7 69 "BACKGROUND: Fibromyalgia (FM) is characterized by chronic widespread pain, which is often refractory to conventional painkillers. Numerous clinical studies have demonstrated that antidepressants are effective in treating FM pain. We previously established a mouse model of FM-like pain, induced by intermittent cold stress (ICS). RESULTS: In this study, we find that ICS exposure causes a transient increase in plasma corticosterone concentration, but not in anxiety or depression-like behaviors. A single intrathecal injection of an antidepressant, such as milnacipran, amitriptyline, mianserin or paroxetine, had an acute analgesic effect on ICS-induced thermal hyperalgesia at post-stress day 1 in a dose-dependent manner. In addition, repeated daily antidepressant treatments during post-stress days 1-5 gradually reversed the reduction in thermal pain threshold, and this recovery was maintained for at least 7 days after the final treatment. In addition, relief from mechanical allodynia, induced by ICS exposure, was also observed at day 9 after the cessation of antidepressant treatment. In contrast, the intravenous administration of these antidepressants at conventional doses failed to provide relief. CONCLUSIONS: These results suggest that the repetitive intrathecal administration of antidepressants permanently cures ICS-induced FM pain in mice" http://www.ncbi.nlm.nih.gov/pubmed/21933442 0 1880 "J. D. York, J. W. Ponder and P. W. Majerus" 1995 Definition of a metal-dependent/Li(+)-inhibited phosphomonoesterase protein family based upon a conserved three-dimensional core structure Proc.Natl.Acad.Sci.U.S.A 92 11 5149-5153 "Inositol polyphosphate 1-phosphatase, inositol monophosphate phosphatase, and fructose 1,6-bisphosphatase share a sequence motif, Asp-Pro-(Ile or Leu)-Asp-(Gly or Ser)-(Thr or Ser), that has been shown by crystallographic and mutagenesis studies to bind metal ions and participate in catalysis. We compared the six alpha-carbon coordinates of this motif from the crystal structures of these three phosphatases and found that they are superimposable with rms deviations ranging from 0.27 to 0.60 A. Remarkably, when these proteins were aligned by this motif a common core structure emerged, defined by five alpha-helices and 11 beta-strands comprising 155 residues having rms deviations ranging from 1.48 to 2.66 A. We used the superimposed structures to align the sequences within the common core, and a distant relationship was observed suggesting a common ancestor. The common core was used to align the sequences of several other proteins that share significant similarity to inositol monophosphate phosphatase, including proteins encoded by fungal qa-X and qutG, bacterial suhB and cysQ (identical to amtA), and yeast met22 (identical to hal2). Evolutionary comparison of the core sequences indicate that five distinct branches exist within this family. These proteins share metal-dependent/Li(+)-sensitive phosphomonoesterase activity, and each predicted tree branch exhibits unique substrate specificity. Thus, these proteins define an ancient structurally conserved family involved in diverse metabolic pathways including inositol signaling, gluconeogenesis, sulfate assimilation, and possibly quinone metabolism. Furthermore, we suggest that this protein family identifies candidate enzymes to account for both the therapeutic and toxic actions of Li+ as it is used in patients treated for manic depressive disease" http://www.ncbi.nlm.nih.gov/pubmed/7761465 0 1881 "C. C. Veloso, A. D. Bitencourt, L. D. Cabral, L. S. Franqui, D. F. Dias, M. H. dos Santos, R. Soncini and A. Giusti-Paiva" 2010 Pyrostegia venusta attenuate the sickness behavior induced by lipopolysaccharide in mice J.Ethnopharmacol. 132 1 355-358 "AIM OF THE STUDY: Pyrostegia venusta (Ker.) Miers (Bignoniaceae) is native to the Brazilian Cerrado and popularly known as ""cipo-de-sao-joao."" In traditional Brazilian medicine, the Pyrostegia venusta are used as a general tonic as well as a treatment for diarrhea, vitiligo, cough, and common diseases of the respiratory system related to infections, such as bronchitis, flu and cold. This study was conducted to evaluate the effects of a hydroethanolic extract of flowers of Pyrostegia venusta on sickness behaviors induced by lipopolysaccharide in mice. MATERIALS AND METHODS: To evaluate the effects of orally administered Pyrostegia venusta hydroethanolic extract (PvHE) on lipopolysaccharide-induced sickness behaviors, mice were submitted to the forced swim test (FST) and the open field test. RESULTS: Lipopolysaccharide (LPS, 100 mug/kg, i.p.) administration increased the time spent floating in the FST and depressed locomotor activity in the open field. Pretreatment with PvHE at test doses of 100 and 300 mg/kg, p.o. attenuated the behavioral changes induced by LPS in the FST and open field test. This effect was similar to pretreatment with dexamethasone (1 mg/kg), which is a steroidal drug that inhibits immune and inflammatory responses, including cytokine production. CONCLUSION: The extract of Pyrostegia venusta attenuated the depressive-like and exploratory behaviors induced by lipopolysaccharide. Thus, our results supported previous claims of the usefulness of these plants in traditional therapies and suggest that these plants may be useful in the treatment of disorders that induced sickness behavior, such as flu and cold" http://www.ncbi.nlm.nih.gov/pubmed/20727400 0 1882 R. K. Sanyal and M. Dave 1971 Further studies on the sympathomimetic action of tetanus toxin Jpn.J.Pharmacol. 21 3 317-323 http://www.ncbi.nlm.nih.gov/pubmed/4397667 0 1883 "G. R. Dias, T. M. de Almeida, J. H. Sudati, F. Dobrachinski, S. Pavin, F. A. Soares, C. W. Nogueira and N. B. Barbosa" 2014 Diphenyl diselenide supplemented diet reduces depressive-like behavior in hypothyroid female rats Physiol Behav. 124 116-122 "Hypothyroidism has been associated to psychiatric disorder development and tissue oxidative damage. In this study, we evaluated the effect of diphenyl diselenide supplementation on depressive-like behavior triggered by methimazole exposure in female rats. Additionally, thiobarbituric acid reactive substances (TBARS), reactive oxygen species (ROS) and non-protein thiol (NP-SH) levels were analyzed in cerebral cortex, hippocampus and striatum structures of rats. Monoamine oxidase (MAO) activity was evaluated in total brain. Firstly, female rats received methimazole (MTZ) 20mg/100ml in the drinking water for 30days and were evaluated in open-field and forced swimming tests (FST). In this set of experiments, the rats exposed to MTZ presented a depressive-like behavior, which was evidenced by a significant increase in the immobility time when compared to control group. Thereafter, MTZ-induced hypothyroid rats received either a standard or a diet containing 5ppm of diphenyl diselenide, and then they were evaluated monthly in open-field and FST tests during 3months. No alteration on the locomotor performance was observed among the groups. The depressive-like behavior of hypothyroid rats was blunted by diphenyl diselenide supplementation during all experimental periods. The levels of thyroid hormones remained low in MTZ exposed groups until the end of experimental period. The MTZ group had an increase in TBARS and ROS levels that were restored by diphenyl diselenide supplementation. NP-SH content of cerebral structures was not modified by MTZ exposure and/or diphenyl diselenide supplementation. Diphenyl diselenide supplementation restored the MAO B activity that was decreased in MTZ group. In summary, our results show that hypothyroidism induced by MTZ methimazole triggers a depressive-like behavior in female rats and that dietary diphenyl diselenide was able to reduce this effect" http://www.ncbi.nlm.nih.gov/pubmed/24239994 1 1884 "M. Chhina, O. A. Shlobin, G. Grant and S. D. Nathan" 2008 Potential of imatinib mesylate as a novel treatment for pulmonary fibrosis "Expert Review of Respiratory Medicine.2 (4) ()(pp 419-431), 2008.Date of Publication: August 2008." 4 419-431 "Pulmonary fibrosis is a disease characterized by progressive scarring of the lungs, with idiopathic pulmonary fibrosis (IPF) being the most aggressive form. The diagnosis of IPF is made after other conditions are excluded and is based on a characteristic clinical presentation, radiographic features and, sometimes, pathologic specimen. Existing IPF drug regimens, including corticosteroids and cytotoxic medications, are generally ineffective. To date, only lung transplantation has been shown to improve mortality in carefully selected patients. Multiple therapeutic agents have been investigated but none have proven to be successful. Novel drugs are constantly being sought in an attempt to find a therapy that halts or reverses this disease. Imatinib mesylate is used for chronic myelogenous leukemia and gastrointestinal stromal tumors. It also has antifibrotic properties, as demonstrated in several studies using mouse models of pulmonary fibrosis. Currently, trials are underway to investigate its efficacy in human subjects with IPF" DO - http://dx.doi.org/10.1586/17476348.2.4.419 0 1885 "P. Ngamprasertwong, E. C. Michelfelder, S. Arbabi, Y. S. Choi, C. Statile, L. Ding, A. Boat, P. Eghtesady, K. Holland and S. Sadhasivam" 2013 Anesthetic techniques for fetal surgery: effects of maternal anesthesia on intraoperative fetal outcomes in a sheep model Anesthesiology 118 4 796-808 "BACKGROUND: Use of high-dose inhalational anesthesia during open fetal surgery may induce maternal-fetal hemodynamic instability and fetal myocardial depression. The authors' preliminary human retrospective study demonstrated less fetal bradycardia and left ventricular systolic dysfunction with lower dose desflurane supplemented with propofol and remifentanil IV anesthesia (SIVA). In this animal study, the authors compare maternal-fetal effects of high-dose desflurane anesthesia (HD-DES) and SIVA. METHODS: Of 26 instrumented midgestational ewes, data from 11 animals exposed to both SIVA and HD-DES in random sequences and six animals exposed to HD-DES while maternal normotension was maintained were analyzed. Maternal electroencephalography was used to guide comparable depths of anesthesia in both techniques. Hemodynamic parameters, blood gas, and fetal cardiac function from echocardiography were recorded. RESULTS: Compared with SIVA, HD-DES resulted in significant maternal hypotension (mean arterial pressure difference, 19.53 mmHg; 95% CI, 17.6-21.4; P < 0.0001), fetal acidosis (pH 7.11 vs. 7.24 at 150 min, P < 0.001), and decreased uterine blood flow. In the HD-DES group with maternal normotension, uterine blood flow still declined and fetal acidosis persisted, with no statistically significant difference from the group exposed to HD-DES that had maternal hypotension. There was no statistically significant difference in fetal cardiac function. CONCLUSION: In sheep, SIVA affects maternal hemodynamics less and provides better fetal acid/base status than high-dose desflurane. Fetal echocardiography did not reflect myocardial dysfunction in this model" http://www.ncbi.nlm.nih.gov/pubmed/23343650 0 1886 "S. Bhaduri, N. R. Bardhan and A. Chatterjee" 1968 "Effect of estrogen on the vocal sac pigmentation, throat colouration and the nature of croaking in the toad (Bufo melanostictus) during breeding season" Endokrinologie. 53 1 46-47 http://www.ncbi.nlm.nih.gov/pubmed/5721744 0 1887 D. E. Carr and M. D. Eubanks 2002 Inbreeding alters resistance to insect herbivory and host plant quality in Mimulus guttatus (Scrophulariaceae) Evolution 56 1 22-30 "Previous studies have demonstrated genetic variation for resistance to insect herbivores and host plant quality. The effect of plant mating system, an important determinant of the distribution of genetic variation, on host plant characteristics has received almost no attention. This study used a controlled greenhouse experiment to examine the effect of self- and cross-pollination in Mimulus guttatus (Scrophulariaceae) on resistance to and host plant quality for the xylem-feeding spittlebug Philaenus spumarius (Homoptera: Cercopidae). Spittlebugs were found to have a negative effect on two important fitness components in M. guttatus, flower production and above ground biomass. One of two M. guttatus populations examined showed a significant interaction between the pollination and herbivore treatments. In this case, the detrimental effects of herbivores on biomass and flower production were much more pronounced in inbred (self) plants. The presence of spittlebug nymphs increased inbreeding depression by as much as three times. Pollination treatments also had significant effects on important components of herbivore fitness, but these effects were in opposite directions in our two host plant populations. Spittlebug nymphs maturing on self plants emerged as significantly larger adults in one of our host plant populations, indicating that inbreeding increased host plant quality. In our second host plant population, spittlebug nymphs took significantly longer to develop to adulthood on self plants, indicating that inbreeding decreased host plant quality. Taken together these results suggest that the degree of inbreeding in host plant populations can have important and perhaps complex effects on the dynamics of plant-herbivore interactions and on mating-system evolution in the host" http://www.ncbi.nlm.nih.gov/pubmed/11913665 0 1888 "A. Kleimann, W. Theilmann, C. Brandt, M. Rhein, A. Kotsiari, W. Sperling, M. Groschl, J. Kornhuber, W. Loscher, S. Bleich and H. Frieling" 2014 Effects of electroconvulsive stimulation on p11 promoter methylation in humans and rats "European Neuropsychopharmacology.Conference: 27th European College of Neuropsychopharmacology, ECNP Congress Berlin Germany.Conference Start: 20141018 Conference End: 20141021.Conference Publication: (var.pagings).24 ()(pp S170-S171), 2014.Date of Pu" var.pagings S170-S171 "Purpose of the study: Several lines of evidence have linked the multifunctional protein p11 (S100A10) to the pathophysiology and pharmacotherapy of depression [1]. For instance, p11 mRNA and protein are down-regulated in genetic rodent models of depression and depressed individuals. Furthermore, antidepressant treatment and electroconvulsive stimulation (ECS) have been shown to increase p11 expression in the frontal cortex and hippocampus of rodents. Melas et al. reported a hypermethylation of the p11 promoter in the prefrontal cortex (PFC) of rats with a genetic model of depression, which was reversed to normal after antidepressant treatment with escitalopram [2]. The purpose of the present study is to investigate p11 peripheral levels and promoter methylation in patients during a series of electroconvulsive therapy (ECT) and p11 promoter methylation in rats receiving ECS. Methods: Eleven patients with a treatment-resistant Major Depressive Disorder were included in the study. Depression severity was measured using the Beck's Depression Inventary (BDI) and the Montgomery Asperg Depression Scale (MADRS). Fasting blood samples were taken directly before, one hour and 24 hours after ECT number 1, 4, 7 and 10. For the animal experiments 19 male Wistar rats were subjected to a chronic unpredictable mild stress model and then randomly assigned to ECS or sham stimulation. ECS was applied via cortical stimulation and delivered once daily for 5 days as described previously [3]. Sucrose Preference Test (1%) (SPT), immobility in forced Swimming Test and open field test were tested before and 48 h after the treatment series. Methylation analysis of the P11 promoter was performed in human blood and rat blood, hippocampus and PFC with bisulfite sequencing. Results: Six patients reached the remission criterion (MADRS <12). The p11 serum levels negatively correlated with BDI and MADRS (p<0.000). Mean methylation of the p11 promoter only showed a correlation with the p11 levels when measured before ECT. Mixed linear modelling showed higher p11 levels and higher promoter methylation in remitters than in non responders at all timepoints (both p<0.000). Analysis of the rat p11 promoter methylation in the blood of the observed animals showed no difference between ECS and sham stimulation. PFC p11 promoter methylation was significantly lowered in the two rats which responded to ECS as measured by SPT (p = 0.007). In the hippocampus treatment with ECS led to a significantly higher methylation compared to sham stimulation (p<0.05). Conclusions: Our preliminary resultsare in line with previously reported data on p11 and depression as lowered p11 levels have been reported in depressed patients previously. Additionaly, the lower p11 methylation in the PFC of rats that responded to ECS correspond to the reported hypomethylation of the p11 promoter after treatment with escitalopram. The higher p11 levels and promoter methylation of remitters could point to a subgroup of depressed patients who are sensitive to ECT. In summary our results indicate an involvement of p11 in ECT, but should be interpreted carefully due to our small sample size. Ongoing work should establish wether peripheral p11 expression could serve as a biomaker for responsiveness to ECT" 0 1889 "M. J. Miller, H. McNeill, K. M. Mullane, S. J. Caravella and D. A. Clark" 1988 SOD prevents damage and attenuates eicosanoid release in a rabbit model of necrotizing enterocolitis Am.J.Physiol 255 5 Pt 1 G556-G565 "Necrotizing enterocolitis (NEC) was produced in anesthetized rabbits by transmural injection of intestinal loops with an acidified solution of casein and calcium gluconate, mimicking the luminal milieu of afflicted neonates. Intravenous infusion of superoxide dismutase (SOD) 15 min after NEC induction prevented intestinal damage. In ex vivo perfused intestinal loops, we determined the sites of eicosanoid release and their contribution to the vascular effects of N-formyl-methionyl-leucyl-phenylalanine (fMLP) and platelet-activating factor (PAF) in damaged and SOD-salvaged intestine. The vascular effluent was the primary site of stimulated eicosanoid release. The vascular responses to fMLP (vasoconstriction) and PAF (vasodilation) were not altered by SOD, although vascular resistance was higher in the SOD group. SOD treatment attenuated 1) transmural fluid shifts in ex vivo perfused intestinal preparations, an index of vascular permeability, 2) fMLP-induced prostaglandin E2, 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), and leukotriene B4 (LTB4) release, and 3) PAF-induced release of 6-keto-PGF1 alpha and LTB4. Stimulated thromboxane B2 release was not altered by SOD. Thus NEC can be established by a luminal insult that causes local generation of free radicals and exaggerated release of prostaglandins and leukotrienes" http://www.ncbi.nlm.nih.gov/pubmed/2847541 0 1890 "S. Shim, M. M. El and P. Blier" 2013 Modulation of the antidepressant-like effects of sustained administration of carisbamate and lamotrigine on monoaminergic systems: electrophysiological studies in the rat brain J.Pharmacol.Exp.Ther. 347 2 487-496 "Carisbamate and lamotrigine are anticonvulsants that act on neuronal voltage-gated sodium channels. Carisbamate has shown antidepressant-like effects in animal models of depression, and lamotrigine is a mood stabilizer with a therapeutic effect in depressive episodes of patients with bipolar disorder. This study examined the effects of carisbamate and lamotrigine on monoaminergic transmission in rodents, which could contribute to their antidepressant action. In vivo electrophysiological recordings were carried out in rats after 2 and 14 days administration of vehicle, carisbamate (60 mg/kg daily), or lamotrigine (25 mg/kg daily). Overall firing activity of the dorsal raphe nucleus (DRN) serotonin (5-HT), locus coeruleus norepinephrine, and ventral tegmental area dopamine (DA) neurons was decreased with carisbamate. Lamotrigine also decreased 5-HT neuronal firing, and this effect was abolished by lesion of the prefrontal cortex. Despite these decreases in firing activity after their prolonged administration, both anticonvulsants exhibited a significant increase in tonic activation of hippocampus 5-HT1A receptors, as shown by a disinhibition of the firing activity of pyramidal neurons in response to the selective antagonist WAY-100635 (N-{2-[4(2-methoxyphenyl)-1-piperazinyl] ethyl}-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride). This finding reveals an increase in the 5-HT level that may be attributed to a desensitization of the terminal 5-HT1B autoreceptors. This study demonstrates that sustained carisbamate and lamotrigine administration decreases 5-HT firing in the DRN but nevertheless enhances 5-HT transmission in the forebrain. This serotonergic effect may be associated with an antiglutamatergic action and may contribute to the antidepressant-like effect of carisbamate in the forced swim test and the antidepressant properties of lamotrigine" http://www.ncbi.nlm.nih.gov/pubmed/23986541 1 1891 "J. Garzon, J. A. Fuentes and R. J. Del" 1979 Antidepressants selectively antagonize the hyperactivity induced in rats by long-term isolation Eur.J.Pharmacol. 59 03-Apr 293-296 Rats isolated at 16--18 days of age showed after 10--12 months a complex behavioural syndrome in which locomotor activity was markedly increased when compared to that of group-housed controls. The hyperactivity of the socially deprived animals was selectively blocked by clinically effective antidepressants but not by other classes of psychotropic drugs. The present animal model may be of value for the detection of new antidepressants and contribute to elucidate the aetiology of depression http://www.ncbi.nlm.nih.gov/pubmed/527650 1 1892 "J. P. Landers, L. M. Birse, J. S. Nakai, M. J. Winhall and N. J. Bunce" 1990 "Chemically induced hepatic cytosol from the Sprague-Dawley rat: evidence for specific binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin to components kinetically distinct from the Ah receptor" Toxicol.Lett. 51 3 295-302 "A series of exogenous chemicals was used as potential inducers for the hepatic Ah receptor in the Sprague-Dawley rat. 2,3,7,8-Tetrachlorodibenzo-p-dioxin, 2,2',4,4',5,5'-hexachlorobiphenyl and phenobarbital all induced an elevated level of 3H-2,3,7,8-tetrachlorodibenzo-p-dioxin specific binding, while 3,3',4,4'-tetrachloroazobenzene and trans-3,3',4,4'-tetrachlorostilbene caused a depression. Mixtures of these chemicals caused additive effects. Elevated levels of specific binding appeared to be heterologous, comprising a binding species having the normal high stability of the Ah receptor in its liganded form, and another less stable substance having a half-life of approximately 2 h at 37 degrees C" http://www.ncbi.nlm.nih.gov/pubmed/2160139 0 1893 C. Sroka and N. Woehrle 2014 Evidence for the involvement of 5-HT1A receptors in the mechanisms underlying the antidepressant effects of exercise "Biological Psychiatry.Conference: 69th Annual Scientific Convention and Meeting of the Society of Biological Psychiatry, SOBP 2014 New York, NY United States.Conference Start: 20140508 Conference End: 20140510.Conference Publication: (var.pagings).75" var.pagings 316S "Background: Evidence supports the effectiveness of exercise in treating major depressive disorder, yet the mechanisms underlying the antidepressant effects of exercise remain unclear. Serotonin 1A receptors (5-HT1A) have been strongly implicated in the therapeutic effects of antidepressant drugs such as selective serotonin reuptake inhibitors (SSRIs). This study investigated the role of 5-HT1A receptors in the antidepressant effects of exercise. Methods: Following 3 weeks of ad libitum (n=10) or no (n=10) homecage running-wheel access, male C57BL/6J mice were acutely administered 5-HT1A agonist 8-OH-DPAT (1 mg/kg), 5-HT1A antagonist NAN-190 (1 mg/kg), or vehicle. Mice received each injection-type on separate test days in a counterbalanced fashion. Following injection, antidepressant-like behavior was assessed in the forced-swim test (FST). ANOVAs were performed with exercise as a between-subject factor and drug as a within-subject factor. Results: A significant drug x exercise interaction (F(1 18)=8.69, p<0.01) and post hoc tests showed that 8-OH-DPAT decreased immobility in the FST in exercise-control mice (F(1 9)=10.85, p<0.01) but not in exercise-treated mice. Exercise decreased immobility in vehicle-treated mice but not in 8-OH-DPATtreated mice. No effect of NAN-190 on immobility was found in exercise-control mice, and a trend was found for NAN-190 to block exercise-induced decreases in immobility (F(1 9)=5.25, p=0.05). Conclusions: 5-HT1A activation blocked exercise-induced antidepressant-like behavior. These results provide the first direct evidence, to our knowledge, of 5-HT1A receptor involvement in the mechanisms underlying the antidepressant effects of exercise. Moreover, our results suggest that the mechanisms through which exercise and antidepressants such as SSRIs produce therapeutic effects may overlap" DO - http://dx.doi.org/10.1016/j.biopsych.2014.03.016 0 1894 "I. M. Tereshin, I. I. Belousova and R. E. El'gart" 1969 [Interbacterial transfer of episomal (RTF) resistance to antibiotics in mice] Antibiotiki. 14 8 749-753 http://www.ncbi.nlm.nih.gov/pubmed/4907796 0 1895 "L. L. Pavlik, N. R. Turas, I. D. Pakhotina and D. A. Moshkov" 1999 [Effect of cytochalasin D on the structure of mixed synapses and their electrotonic conductivity] Tsitologiia 41 7 590-597 "By methods of qualitative and quantitative electronmicroscopy the ultrastructure of mixed synapses of the goldfish Mauthner cell (MC) and their ability to strengthen electrotonic transmission after application of cytochalasin D, a highly specific inhibitor of actin polymerization. On the background of cytochalasin action tetranization of afferent rootlets of acoustic nerve, terminated with mixed synapses on the MC lateral dendrite, failed to induce any long-term potentiation of electronic coupling. On the contrary, a long-term depression of electrotonic transmission was evoked in this case. On the ultrastructureal level such a depression of synaptic conductivity was seen to correlate with a decrease in the number and total length per synaptic apposition of the desmosome-like contacts, known as actin-containing structures, as compared with unstimulated control preparations. In addition, experimental preparations were characterized with unusual quantity of asymmetric desmosome-like contacts, hemidesmosome, whose number during a long-term depression became 4 fold higher than in the control synapses. The data obtained support our recent suggestion on the role of filamentous actin in induction and long-term maintenance of enhanced electrotonic conductivity at mixed synapses" http://www.ncbi.nlm.nih.gov/pubmed/10496020 0 1896 "J. B. Murphy, W. Nakahara and E. Sturm" 1921 STUDIES ON LYMPHOID ACTIVITY : V. RELATION BETWEEN THE TIME AND EXTENT OF LYMPHOID STIMULATION INDUCED BY PHYSICAL AGENTS AND THE DEGREE OF RESISTANCE TO CANCER IN MICE J.Exp.Med. 33 4 423-428 "It has been shown that resistance to transplanted cancer follows stimulation of the lymphoid tissue when the stimulation is induced by either heat or small doses of x-rays. In this paper we have attempted to determine whether the degree of immunity had a quantitative relation to the amount of the stimulation. Fortunately, the two methods at our disposal give stimulation of markedly different characters. The small dose of x-rays gives a sluggish lymphoid cell reaction of short duration with a definite latent period between the treatment and the evidence of marked stimulation, while after heat a short period of depression is followed by a sharp stimulation continuing over a much longer period. The cancer inoculation into groups of mice made immediately after exposure to x-rays shows little resistance, while the inoculation made at the height of the stimulation phase shows a definite increase in the immunity. Animals inoculated with cancer immediately after the heat treatment exhibit a pronounced immunity, but not so marked as that shown when the inoculation is made at the height of the stimulation. The amount of resistance shown when the cancer inoculation is made at the height of the moderately stimulating effect following exposure to x-rays, is much less than that seen when the inoculation is made at the height of the heat effect when the degree of stimulation is much greater. When the lymphocytosis sets in after the tumor graft is established only a slight effect is noted. All these results together are taken to indicate that the degree of immunity is dependent on the amount of lymphoid stimulation existing either at the time of or following soon after the cancer inoculation" http://www.ncbi.nlm.nih.gov/pubmed/19868506 0 1897 P. E. Came and D. H. Moore 1972 Effect of exogenous interferon treatment on mouse mammary tumors J.Natl.Cancer Inst. 48 4 1151-1154 http://www.ncbi.nlm.nih.gov/pubmed/4336879 0 1898 E. Mezey and P. R. Holt 1971 The inhibitory effect of ethanol on retinol oxidation by human liver and cattle retina Exp.Mol.Pathol. 15 2 148-156 http://www.ncbi.nlm.nih.gov/pubmed/4398759 1 1899 "F. Kondo, N. Kitano and H. Domon" 1974 "Aspiculamycin, a new cytosine nucleoside antibiotic. IV. Antimycoplasma activity of aspiculamycin in vitro and in vivo" "Journal of Antibiotics.27 (7) ()(pp 529-534), 1974.Date of Publication: 1974." 7 529-534 "Aspiculamycin, a new cytosine nucleoside antibiotic produced by Streptomyces toyocaensis var. aspiculamyceticus, showed strong activity against various strains of Mycoplasma in vitro and in vivo. The minimal inhibitory concentration of the antibiotic ranged between 50 to 0.05 mcg/ml by agar dilution, broth dilution or microtiter method. No influences of inoculum size and pH of the medium on the activity were observed. A number of strains of Mycoplasma gallisepticum showing resistance to macrolide antibiotics were all susceptible to the antibiotic. L Forms derived from Staphylococcus aureus and Proteus vulgaris were insensitive to the antibiotic. After administration of 0.04% (w/w) of aspiculamycin in the basal diet for 7 days, the lung and trachea of mice infected intranasally with Mycoplasma pulmonis were free of pathogen. In the experimental mice arthritis induced with M. pulmonis, the Mycoplasma could not be detected in joints of the mice after treatment with aspiculamycin at a dose of 0.05% (w/w) in the diet for 10 days" 0 1900 "C. Winter, B. Vollmayr, A. Djodari-Irani, J. Klein and A. Sartorius" 2011 Pharmacological inhibition of the lateral habenula improves depressive-like behavior in an animal model of treatment resistant depression Behav.Brain Res. 216 1 463-465 Identifying new treatment approaches for treatment resistant depression (TRD) is an important topic for translational psychiatry. Functional inhibition of the lateral habenula (LHb) has recently been claimed to offer such an option for TRD. Rats which are bred for high susceptibility to develop learned helplessness provide a genetic model for TRD. We used the gamma-aminobutyric acid agonist muscimol to inhibit the LHb in Sprague-Dawley rats with congenital learned helplessness (cLH). Stereotactic pharmacological inhibition of the LHb exerted antidepressive effects in treatment resistant cLH rats http://www.ncbi.nlm.nih.gov/pubmed/20678526 1 1901 S. M. Turner and S. M. Johnson 2015 "Abrupt changes in pentobarbital sensitivity in preBotzinger complex region, hypoglossal motor nucleus, nucleus tractus solitarius, and cortex during rat transitional period (P10-P15)" Respir.Physiol Neurobiol. 207 61-71 "On postnatal days P10-P15 in rat medulla, neurotransmitter receptor subunit composition shifts toward a more mature phenotype. Since medullary GABAARs regulate cardiorespiratory function, abrupt alterations in GABAergic synaptic inhibition could disrupt homeostasis. We hypothesized that GABAARs on medullary neurons become more resistant to positive allosteric modulation during P10-P15. Medullary and cortical slices from P10 to P20 rats were used to record spontaneous action potentials in pre-Botzinger Complex (preBotC-region), hypoglossal (XII) motor nucleus, nucleus tractus solitarius (NTS), and cortex during exposure to pentobarbital (positive allosteric modulator of GABAARs). On P14, pentobarbital resistance abruptly increased in preBotC-region and decreased in NTS, but these changes in pentobarbital resistance were not present on P15. Pentobarbital resistance decreased in XII motor nucleus during P11-P15 with a nadir at P14. Abrupt changes in pentobarbital resistance indicate changes in GABAergic receptor composition and function that may compensate for potential increased GABAergic inhibition and respiratory depression that occurs during this key developmental transitional period" http://www.ncbi.nlm.nih.gov/pubmed/25550216 0 1902 "M. L. Errington, M. A. Lynch and T. V. Bliss" 1987 Long-term potentiation in the dentate gyrus: induction and increased glutamate release are blocked by D(-)aminophosphonovalerate Neuroscience 20 1 279-284 "D(-)Aminophosphonovalerate, a specific antagonist of the N-methyl-D-aspartate subtype of glutamate receptor, was perfused through a push-pull cannula into the dentate gyrus of rats anaesthetized with urethan in order to observe its effect on the induction and maintenance of long-term potentiation and on the increase in release of endogenous glutamate associated with long-term potentiation. The amplitude of the population spike evoked by single test shocks to the perforant path was significantly depressed by 100 microM D(-)aminophosphonovalerate, but there was a minimal effect on the slope of the population excitatory postsynaptic potential, or on the concentration of glutamate released into the perfusate. A brief high-intensity tetanus given to the perforant path while D(-)aminophosphono-valerate was being perfused failed to induce long-term potentiation or the sustained increase in glutamate release associated with long-term potentiation. Short-term post-tetanic potentiation was not affected. After wash-out of D(-)aminophosphonovalerate, a second high-frequency train produced both long-term potentiation and an increase in glutamate release which was sustained for the subsequent 1 h period of observation. D(-)Aminophosphonovalerate did not suppress long-term potentiation once it had been induced. D(-)Aminophosphonovalerate (100 microM) did not itself affect in vivo release of glutamate. However, in a separate series of in vitro experiments, D(-)aminophosphonovalerate at concentrations of 50 microM and above was found to depress the Ca2+ -dependent, K+-stimulated release of preloaded [14C]-glutamate from dentate slices.(ABSTRACT TRUNCATED AT 250 WORDS)" http://www.ncbi.nlm.nih.gov/pubmed/2882444 0 1903 "V. N. Uebele, C. E. Nuss, S. V. Fox, S. L. Garson, R. Cristescu, S. M. Doran, R. L. Kraus, V. P. Santarelli, Y. Li, J. C. Barrow, Z. Q. Yang, K. A. Schlegel, K. E. Rittle, T. S. Reger, R. A. Bednar, W. Lemaire, F. A. Mullen, J. E. Ballard, C. Tang, G. Dai, O. B. McManus, K. S. Koblan and J. J. Renger" 2009 Positive allosteric interaction of structurally diverse T-type calcium channel antagonists Cell Biochem.Biophys. 55 2 81-93 "Low-voltage-activated (T-type) calcium channels play a role in diverse physiological responses including neuronal burst firing, hormone secretion, and cell growth. To better understand the biological role and therapeutic potential of the target, a number of structurally diverse antagonists have been identified. Multiple drug interaction sites have been identified for L-type calcium channels, suggesting a similar possibility exists for the structurally related T-type channels. Here, we radiolabel a novel amide T-type calcium channel antagonist (TTA-A1) and show that several known antagonists, including mibefradil, flunarizine, and pimozide, displace binding in a concentration-dependent manner. Further, we identify a novel quinazolinone T-type antagonist (TTA-Q4) that enhanced amide radioligand binding, increased affinity in a saturable manner and slowed dissociation. Functional evaluation showed these compounds to be state-dependent antagonists which show a positive allosteric interaction. Consistent with slowing dissociation, the duration of efficacy was prolonged when compounds were co-administered to WAG/Rij rats, a genetic model of absence epilepsy. The development of a T-type calcium channel radioligand has been used to demonstrate structurally distinct TTAs interact at allosteric sites and to confirm the potential for synergistic inhibition of T-type calcium channels with structurally diverse antagonists" http://www.ncbi.nlm.nih.gov/pubmed/19582593 0 1904 V. Critchlow 1972 Selectivity of acute feedback effects of corticosteroids on ACTH secretion UCLA Forum Med.Sci. 15 51-58 http://www.ncbi.nlm.nih.gov/pubmed/4342983 1 1905 "H. R. Weiss, J. D. Sadoff, P. M. Scholz and R. E. Klabunde" 1997 Nitric oxide reduces myocardial contractility in isoproterenol-stimulated rat hearts by a mechanism independent of cyclic GMP or cyclic AMP Pharmacology 55 4 202-210 "Nitric oxide has been shown to decrease myocardial contractility and O2 consumption. This study was designed to evaluate the hypothesis that nitric oxide-mediated increases in cyclic GMP require elevated cyclic AMP to produce cardiac depression. Using isolated, Langendorff-perfused rat hearts, we determined the effects of intracoronary nitroprusside (NP, 1 and 10 mM) in the absence and presence of isoproterenol (ISO, 10(-8) M) on cardiac function, O2 consumption, cyclic GMP and cyclic AMP. ISO, with and without NP, increased cyclic AMP (from 287 +/- 21 to 477 +/- 33 pmol/g) without altering cyclic GMP. Left-ventricular pressure increased from 97 +/- 12 to 178 +/- 9 mm Hg and dP/dtmax from 1,786 +/- 275 to 4,049 +/- 354 mm Hg/s. NP increased cyclic GMP (from 4 to 30 pmol/g) in both the absence and presence of ISO, but NP did not alter cyclic AMP. Without ISO, NP insignificantly altered left-ventricular pressure; however, in the presence of ISO, NP significantly decreased left-ventricular pressure by -25 +/- 4 mm Hg and decreased dP/dtmax by -619 +/- 142 mm Hg/s. Isoproterenol increased O2 consumption, but the changes with NP were not significant. When this study was repeated in the presence of LY83583, a guanylate cyclase inhibitor, NP still produced cardiac depression in the presence of ISO. Therefore, cardiodepressant effects of NP were only observed against a background of inotropic stimulation with ISO. However, effects of NP on contractility were unrelated to increases in cyclic GMP or cyclic GMP-induced changes in cyclic AMP" http://www.ncbi.nlm.nih.gov/pubmed/9396080 0 1906 1974 Editorial: Somatostatin (somatotrophin release inhibiting factor) S.Afr.Med.J. 48 28 1180 http://www.ncbi.nlm.nih.gov/pubmed/4599981 0 1907 "M. D. Scofield, H. Trantham-Davidson, M. Schwendt, K. C. Leong, J. Peters, R. E. See and C. M. Reichel" 2015 Failure to Recognize Novelty after Extended Methamphetamine Self-Administration Results from Loss of Long-Term Depression in the Perirhinal Cortex Neuropsychopharmacology 40 11 2526-2535 "Exposure to methamphetamine (meth) can produce lasting memory impairments in humans and rodents. We recently demonstrated that extended access meth self-administration results in novel object recognition (NOR) memory deficits in rats. Recognition of novelty depends upon intact perirhinal (pRh) cortex function, which is compromised by meth-induced downregulation of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors. NMDA receptors containing this subunit have a critical role in pRh long-term depression (LTD), one of the primary physiological processes thought to underlie object recognition memory. We hypothesized that meth-induced downregulation of GluN2B receptors would compromise pRh LTD, leading to loss of NOR memory. We found that meth self-administration resulted in an inability to induce pRh LTD following 1 Hz stimulation, an effect that was reversed with bath application of the NMDA receptor partial agonist D-cycloserine (DCS). In addition, pRh microinfusion of DCS restored meth-induced memory deficits. Furthermore, blockade of GluN2B-containing NMDA receptors with Ro 25-6981 prevented DCS restoration of pRh LTD in meth subjects. Thus, targeting pRh LTD may be a promising strategy to treat meth-induced cognitive impairment" http://www.ncbi.nlm.nih.gov/pubmed/25865928 0 1908 "R. H. Tolba, K. Yonezawa, S. Song, C. Burger and T. Minor" 2004 Synergistic value of fibrinolysis and hypothermic aerobic preservation with oxygen in the protection of livers from non-heart-beating donors: an experimental model Transplant.Proc. 36 10 2927-2930 "The chronic organ shortage has led to the reconsideration of marginal donor pools such as non-heart-beating donors (NHBD). The use of these livers is limited due to their minimal tolerance for cold preservation. The aim of this study was to examine the combination of two different therapeutic strategies for the preservation of livers from NHBD. The livers of male Wistar rats were harvested after the induction of cardiac arrest via phrenotomy (30, 90 minutes). Livers were perfused with 10 mL of UW solution (UW), followed by hypothermic preservation with or without insufflation of gaseous oxygen (O2). In one group a fibrinolytic preflush (10 mL of Ringer's containing 7500 IU of streptokinase) was performed with subsequent preservation with O2 (O2+SK). After storage (24 h/4 degrees C/UW) livers were reperfused in vitro. Livers retrieved from heart beating donors served as controls. The results showed that even after only 30 minutes of warm ischemia livers displayed a serious disturbance in vascular perfusion (portal venous pressure, PVP = 7.4 +/- 0.2* versus control: 4.1 +/- 0.5 mmHg), associated with a more than 10-fold increase in enzyme release (ALT: 26819 +/- 513* versus control 683 +/- 152 mU/g/L), which was consistent with a significant depression in bile synthesis (1.21 +/- 0.35* versus 19.36 +/- 2.16 microL/g/45 min). However, these impairments could be prevented with O2. Even after 90 minutes of WI, the function was significant better using aerobic preservation (ALT: 3204 +/- 549 mU/g/L). With a supplementary fibrinolytic preflush, we effectively preserved livers up to 90 minutes of WI with results comparable to livers from heart beating donors with no WI (ALT: 1623 +/- 432 mU/g/L). The combination of these two techniques represents a new therapeutic approach for livers with extended or unclear WI periods in non-heart-beating donors (*P <.05 versus control)" http://www.ncbi.nlm.nih.gov/pubmed/15686662 0 1909 "S. E. Johnson, D. Lawrence, J. Hafekost, S. Saw, W. J. Buckingham, M. Sawyer, J. Ainley and S. R. Zubrick" 2016 Service use by Australian children for emotional and behavioural problems: Findings from the second Australian Child and Adolescent Survey of Mental Health and Wellbeing Aust.N.Z.J.Psychiatry "OBJECTIVE: To identify the proportion of children and adolescents in Australia and the proportion of those with mental disorders who used services for emotional and behavioural problems, the type of services used and what characteristics were associated with service use. METHOD: During 2013-2014, a national face-to-face household survey of mental health and wellbeing (Young Minds Matter) was conducted, involving 6310 parents and carers of 4- to 17-year-olds (55% of eligible households) and self-report surveys from 2967 11- to 17-year-olds in these households (89% of eligible youth). The survey identified 12-month mental disorders based on the Diagnostic Interview Schedule for Children-Version IV and asked about service use for emotional or behavioural problems in the previous 12 months. RESULTS: Overall, 17.0% of all 4- to 17-year-olds used services for emotional or behavioural problems in the previous 12 months. Of those with mental disorders, 56.0% used services (48.9% of 4- to 11-year-olds; 65.1% of 12- to 17-year-olds). Service use was highest among 4- to 17-year-olds with major depressive disorder (79.6%) and lowest for those with attention-deficit/hyperactivity disorder (52.7%). Two-fifths (41.2%), 72.5% and 87.6% of those with mild, moderate and severe disorders used services. General practitioners, psychologists, paediatricians and counsellors/family therapists were the most commonly accessed health service providers. Two-fifths with mental disorders had attended school services. About 5% of adolescents reported use of online personal support or counselling for help with their problems. From multivariate models, service use was higher in sole carer families, but also among those living in the least socially and economically disadvantaged compared to the most disadvantaged areas. CONCLUSION: Rates of service use for mental disorders in Australia's children and adolescents appear to have increased substantially. Health services and schools are the major providers of services for emotional and behavioural problems, but telephone counselling and online services have become well-established parts of the service environment" http://www.ncbi.nlm.nih.gov/pubmed/26769979 0 1910 "F. Murray, D. Bell, E. J. Kelso, B. C. Millar and B. J. McDermott" 2001 Positive and negative contractile effects of somatostatin-14 on rat ventricular cardiomyocytes J.Cardiovasc.Pharmacol. 37 3 324-332 "Somatostatin-14 elicits negative inotropic and chronotropic actions in atrial myocardium. Less is known about the effects of somatostatin-14 in ventricular myocardium. The direct contractile effects of somatostatin-14 were assessed using ventricular cardiomyocytes isolated from the hearts of adult rats. Cells were stimulated at 0.5 Hz with CaCl2 (2 mM) under basal conditions and in the presence of the beta-adrenoceptor agonist, isoprenaline (1 nM), or the selective inhibitor of the transient outward current (Ito), 4-aminopyridine (500 microM). Somatostatin-14 did not alter basal contractile response but it did inhibit (IC50 = 13 nM) the response to isoprenaline (1 nM). In the presence of 4-aminopyridine (500 microM), somatostatin-14 stimulated a positive contractile response (EC50 = 118 fM) that was attenuated markedly by diltiazem (100 nM). These data indicate that somatostatin-14 exerts dual effects directly in rat ventricular cardiomyocytes: (1) a negative contractile effect, observed in the presence of isoprenaline (1 nM), coupled to activation of Ito; and (2) a previously unreported and very potent positive contractile effect, unmasked by 4-aminopyridine (500 microM), coupled to the influx of calcium ions via L-type calcium channels. The greater potency of somatostatin-14 for producing the positive contractile effect indicates that the peptide may exert a predominantly stimulatory influence on the resting contractility of ventricular myocardium in vivo, whereas the negative contractile effect, observed at much higher concentrations, could indicate that localized elevations in the concentration of the peptide may serve as a negative regulatory influence to limit the detrimental effects of excessive stimulation of cardiomyocyte contractility" http://www.ncbi.nlm.nih.gov/pubmed/11243423 0 1911 A. L. Goldberg 1969 Protein turnover in skeletal muscle. II. Effects of denervation and cortisone on protein catabolism in skeletal muscle J.Biol.Chem. 244 12 3223-3229 http://www.ncbi.nlm.nih.gov/pubmed/5792658 0 1912 "T. Peng, X. Lu and Q. Feng" 2005 Pivotal role of gp91phox-containing NADH oxidase in lipopolysaccharide-induced tumor necrosis factor-alpha expression and myocardial depression Circulation 111 13 1637-1644 "BACKGROUND: Lipopolysaccharide (LPS) induces cardiomyocyte tumor necrosis factor-alpha (TNF-alpha) production, which is responsible for myocardial depression during sepsis. The aim of this study was to investigate the role of gp91phox-containing NADH oxidase signaling in cardiomyocyte TNF-alpha expression and myocardial dysfunction induced by LPS. METHODS AND RESULTS: In cultured mouse neonatal cardiomyocytes, LPS increased NADH oxidase (gp91phox subunit) expression and superoxide generation. Deficiency of gp91phox or inhibition of NADH oxidase blocked TNF-alpha expression stimulated by LPS. TNF-alpha induction was also inhibited by tempol, N-acetylcysteine, or 1,3-dimethyl-2-thiourea. NADH oxidase activation by LPS increased ERK1/2 and p38 phosphorylation, and inhibition of ERK1/2 and p38 phosphorylation blocked the effect of NADH oxidase on TNF-alpha expression. Isolated mouse hearts were perfused with LPS (5 microg/mL) alone or in the presence of apocynin for 1 hour. Myocardial TNF-alpha production was decreased in gp91phox-deficient or apocynin-treated hearts compared with those of wild type (P<0.05). To investigate the role of gp91phox-containing NADH oxidase in endotoxemia, mice were treated with LPS (4 mg/kg IP) for 4 and 24 hours, and their heart function was measured with a Langendorff system. Deficiency of gp91phox significantly attenuated LPS-induced myocardial depression (P<0.05). CONCLUSIONS: gp91phox-Containing NADH oxidase is pivotal in LPS-induced TNF-alpha expression and cardiac depression. Effects of NADH oxidase activation are mediated by ERK1/2 and p38 MAPK pathway. The present results suggest that gp91phox-containing NADH oxidase may represent a potential therapeutic target for myocardial dysfunction in sepsis" http://www.ncbi.nlm.nih.gov/pubmed/15795323 0 1913 J. D. Goutman and E. Glowatzki 2007 Time course and calcium dependence of transmitter release at a single ribbon synapse Proc.Natl.Acad.Sci.U.S.A 104 41 16341-16346 "At the first synapse in the auditory pathway, the receptor potential of mechanosensory hair cells is converted into a firing pattern in auditory nerve fibers. For the accurate coding of timing and intensity of sound signals, transmitter release at this synapse must occur with the highest precision. To measure directly the transfer characteristics of the hair cell afferent synapse, we implemented simultaneous whole-cell recordings from mammalian inner hair cells (IHCs) and auditory nerve fiber terminals that typically receive input from a single ribbon synapse. During a 1-s IHC depolarization, the synaptic response depressed >90%, representing the main source for adaptation in the auditory nerve. Synaptic depression was slightly affected by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor desensitization; however, it was mostly caused by reduced vesicular release. When the transfer function between transmitter release and Ca(2+) influx was tested at constant open probability for Ca(2+) channels (potentials >0 mV), a super linear relation was found. This relation is presumed to result from the cooperative binding of three to four Ca(2+) ions at the Ca(2+) sensor. However, in the physiological range for receptor potentials (-50 to -30 mV), the relation between Ca(2+) influx and afferent activity was linear, assuring minimal distortion in the coding of sound intensity. Changes in Ca(2+) influx caused an increase in release probability, but not in the average size of multivesicular synaptic events. By varying Ca(2+) buffering in the IHC, we further investigate how Ca(2+) channel and Ca(2+) sensor at this synapse might relate" http://www.ncbi.nlm.nih.gov/pubmed/17911259 0 1914 I. A. Drzhevetskaia 1972 [Role of serotonin-sensitive structures in the central nervous system in the development of compensatory adrenal hypertrophy] Probl.Endokrinol.(Mosk) 18 5 69-72 http://www.ncbi.nlm.nih.gov/pubmed/4367008 0 1915 H. Kuhnen 1970 [Effect of a new monoquaternary pyridiniumoxime on uninhibited and by highly toxic organophosphate inhibited acetylcholinesterase in vitro] Arzneimittelforschung. 20 6 774-776 http://www.ncbi.nlm.nih.gov/pubmed/5468892 0 1916 "B. Tagliari, C. G. Noschang, A. G. Ferreira, O. A. Ferrari, L. R. Feksa, C. M. Wannmacher, C. Dalmaz and A. T. Wyse" 2010 Chronic variable stress impairs energy metabolism in prefrontal cortex and hippocampus of rats: prevention by chronic antioxidant treatment Metab Brain Dis. 25 2 169-176 "Since chronic stress has been used widely for studying clinical depression and that brain energy metabolism and oxidative stress might be involved in the pathophysiology of this illness, the objective of this study was investigate the activities of pyruvate kinase, complex II and IV (cytocrome c oxidase) in hippocampus and prefrontal cortex of rats submitted to chronic variable stress. We also evaluated if vitamins E and C administration could prevent such effects. During 40 days adult rats from the stressed group were subjected to one stressor per day, at a different time each day, in order to minimize predictability. The stressed group had gained less weight while its immobilization time in the forced swimming test was greater than that of the control group. Results showed that stressed group presented an inhibition in the activities of complex II and cytochrome c oxidase in prefrontal cortex, while in hippocampus just complex IV was inhibited. Pyruvate kinase activity was not altered in stressed group when compared to control. Vitamins E and C administration prevented the alterations on respiratory chain caused by stress. These data suggest that the impairment of energy metabolism and oxidative stress could be related with the pathogenic pathways in stress related disorders" http://www.ncbi.nlm.nih.gov/pubmed/20505986 1 1917 A. A. Kandutsch and R. M. Packie 1970 "Comparison of the effects of some C27-, C21-, and C19-steroids upon hepatic sterol synthesis and hydroxymethylglutaryl-CoA reductase activity" Arch.Biochem.Biophys. 140 1 122-130 http://www.ncbi.nlm.nih.gov/pubmed/5460174 0 1918 R. Jarvinen and A. Ahlstrom 1975 "Effect of the dietary manganese level on tissue manganese, iron, copper and zinc concentrations in female rats and their fetuses" Med.Biol. 53 2 93-99 "In order to study the effect of dietary manganese on the content of manganese, iron, copper and zinc in maternal and fetal tissues, six diets with different levels of manganese (4, 24, 54, 154, 504 and 1004 mg Mn/kg dry diet) were fed to Sprague-Dawley female rats from the time of weaning. The animals were mated and the offspring collected by cesarean section at day 21 of pregnancy. Non-pregnant female rats served as respective reference groups. Concentrations of copper as well as manganese were higher in the livers of pregnant rats with the highest manganese intake, whereas in non-pregnant animals the dietary manganese level had no appreciable effect on manganese or copper concentrations in the liver. On the other hand, the iron content of the livers of both pregnant and non-pregnant female rats fell as the manganese level of the diet increased. The hemoglobin values of dams on the highest levels of dietary manganese were also slightly reduced. The manganese content was highest in the offspring of dams given the largest amounts of manganese. The manganese level in the maternal diet had the opposite effect on the fetal iron concentration, and the zinc content of fetuses of dams on the highest dietary manganese level was slightly elevated. No gross malformations or bone structure anomalies could be observed in the fetuses, and the manganese intake of the dams was not found to have influenced essentially the fetal weights and the dry matter and ash contents" http://www.ncbi.nlm.nih.gov/pubmed/1152553 0 1919 D. Wang and D. E. Potter 1996 "Ocular action of an opioid peptide, DPDPE" J.Ocul.Pharmacol.Ther. 12 2 131-139 "This study was performed to examine some ocular actions of an opioid agonist. Experiments were performed to evaluate the effects of a delta opioid agonist, DPDPE ([D-pen2, D-pen5]enkephalin (where pen = penicillamine)), on: 1) intraocular pressure (IOP) in rabbits; 2) cAMP accumulation in rabbit iris ciliary bodies (ICBs). Unilateral, topical administration of DPDPE caused bilateral depression of IOP. Intravitreal injection of DPDPE caused a greater IOP decrease than intravitreal injection of NaH2PO4 (vehicle). Topical administration of naloxone partially inhibited the effect of DPDPE on IOP in normal rabbits. In other experiments, DPDPE suppressed both basal and isoproterenol (ISO)-stimulated cAMP accumulation in ICBs. The presence of naltrindole (NTI), a delta receptor antagonist, did not prevent the suppression of cAMP levels by DPDPE. The conclusions drawn from the findings suggest that the lowering of IOP by DPDPE is mediated, in part, by actions at postjunctional (ciliary body) sites and may involve an atypical opioid receptor" http://www.ncbi.nlm.nih.gov/pubmed/8773929 0 1920 "M. Nikolova, C. Ivanov, N. Ivanova, S. Vankov and R. Nikolov" 1982 "1,4-Benzodiazepines. V" Farmaco Sci. 37 8 555-565 "The pharmacological activity of four new groups of isoquino [2,1-d] ((1,4]benzodiazepines, i.e. the 6-oxo-12,13-dimethoxy-5H-7H--9,10-dihydroisoquino [2,1-d] [1,4]benzodiazepinium bromides (I); 5,9,10,14b--tetrahydroisoquino [2,1-d] [1,4]benzodiazepin-7H-6-ones (II); 6-phenyl-12,13--dimethoxy-7,9,10,14b-tetrahydroisoquino [2,1-d] [1,4]benzodiazepines (III) and 6-phenyl-12,13-dimethoxy-7H-9,10-dihydroisoquino [2,1-d] [1,4]benzodiazepinium bromides (IV) was studied. All the compounds studied are biologically active. They show a depressive effect on the central nervous system, which is most pronounced in (II). It was established that the presence of alkyl substituents in the position-7 of the structure (II) as well as the chlorine atom in position-2 resulted in an increase of activity. Most of these compounds possess a mild or strong antinociceptive effect. Some of them exhibited an antireserpine activity as well. The spasmolytic effect of (IV) was strong while the rest of the compounds exerted a very weak spasmolytic effect. All the compounds tested on the autonomous nervous system possess the characteristics of weak sympathomimetics" http://www.ncbi.nlm.nih.gov/pubmed/6127233 0 1921 "R. P. Warren, R. A. Burger, R. W. Sidwell and L. L. Clark" 1992 Effect of triacontanol on numbers and functions of cells involved in inflammatory responses Proc.Soc.Exp.Biol.Med. 200 3 349-352 "A preparation of a triacontanol-containing compound was studied for its effect on cells involved in the inflammatory response. C57BL/6 mice were injected intraperitoneally with various concentrations of this compound and investigated for total body weight, wet weight of thymus tissue, number of thymus cells and splenocytes, interleukin 1 production of spleen monocytes, and response of splenocytes to the T cell mitogen, phytohemagglutinin. Mice treated with the triacontanol preparation exhibited decreased total body weight, 24% reduction in thymus weights, 39% decrease in the number of thymus cells, and 21% depression in total splenocytes. Splenic monocytes of these animals produced a significantly reduced amount of interleukin 1 and splenocytes had a significantly depressed response to phytohemagglutinin. It is concluded that triacontanol has an inhibitory effect on at least some of the cells responsible for inflammation" http://www.ncbi.nlm.nih.gov/pubmed/1615010 0 1922 "J. Saint-Blancard, M. Allary and P. Jolles" 1972 [Influence of Biebrich Scarlet on the lysis kinetics of Micrococcus lysodeikticus by several lysozymes] Biochimie 54 10 1375-1376 http://www.ncbi.nlm.nih.gov/pubmed/4654570 0 1923 U. Giger and J. Bucheler 1991 Transfusion of type-A and type-B blood to cats J.Am.Vet.Med.Assoc. 198 3 411-418 "Although nearly all domestic shorthair and longhair cats have type-A blood (greater than 99%), the frequency of blood type B in various feline breeds ranges from 0 to 59%. All blood-type-B cats have strong natural alloantibodies, predominantly of the IgM class, whereas blood-type-A cats have low alloantibody titers of the IgG and IgM classes. We therefore studied the efficacy and safety of transfusing 20 ml of matched and mismatched 14C-potassium cyanate-labeled blood to cats. In autologous and allogeneic matched transfusions of blood-type-A and type-B cats, the half-life of labeled erythrocytes proved to be similar (29 to 39 days). In contrast, type-B erythrocytes transfused into 5 blood-type-A cats had a mean (+/- SD) half-life of only 2.1 +/- 0.2 days and induced minor transfusion reactions. Half of the type-A blood given to 4 blood-type-B cats was destroyed within minutes to 6 hours (mean +/- SD = 1.3 +/- 2.3 hours), depending on the alloantibody titer. After 1 day, none of the labeled erythrocytes were detected. Mismatched transfusions in blood-type-B cats caused marked transient reactions including systemic anaphylactic signs (hypotension, bradycardia, apnea, urination, defecation, vomiting, and severe neurologic depression) and hemolytic signs (hemoglobinemia and pigmenturia) associated with severe reduction in plasma alloantibody titer and complement activity.(ABSTRACT TRUNCATED AT 250 WORDS)" http://www.ncbi.nlm.nih.gov/pubmed/2010334 0 1924 "G. H. Blocks, J. C. Vernooy and J. H. Verheijden" 1994 Integrated quality control project: relationships between pathological findings detected at the slaughterhouse and information gathered in a veterinary health scheme at pig farms Vet.Q. 16 2 123-127 "In September 1986 an Integrated Quality Control Project (IQC) was started in the Netherlands. Over a period of 2 years a veterinary herd health scheme was applied to 21 growing and finishing pig herds. Information was collected concerning medical treatment, classified as group treatment and individual treatment, clinical observations, and housing factors. The main purpose of this project was to investigate relationships between pathological findings detected at the slaughterhouse and information gathered on the farm. Medical group treatments, clinical observations and housing did not reliably predict pathological findings. Individual medical treatment for respiratory disorders, started in the last 30 days before slaughter, proved to be positively related to the pathological findings 'pneumonia' and 'pleuritis' detected at the slaughterhouse. This may be useful for selecting pigs at the slaughterhouse that will require special treatment for the removal of the pleura parietalis. During the first year of the project the average daily gain (ADG) was 27.2 g. more than during the preceding 2 years (P < 0.0001). Coughing was negatively related with the ADG. More than 75 coughs per compartment during 10 minutes, recorded more than 50 days before slaughter, was positively related to a depression of the ADG (20 g; P < 0.05). Relationships between group medical treatments and ADG were statistically significant, when the group medical treatment was started more than 20 days before slaughter. Negative influences on the ADG were higher if the treatment was started closer to the slaughter date.(ABSTRACT TRUNCATED AT 250 WORDS)" http://www.ncbi.nlm.nih.gov/pubmed/7985354 0 1925 "T. Welt, M. Engelmann, U. Renner, A. Erhardt, M. B. Muller, R. Landgraf, F. Holsboer and M. E. Keck" 2006 Temazepam triggers the release of vasopressin into the rat hypothalamic paraventricular nucleus: novel insight into benzodiazepine action on hypothalamic-pituitary-adrenocortical system activity during stress Neuropsychopharmacology 31 12 2573-2579 "We investigated the influence of a representative classical benzodiazepine on the regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis activity both under basal conditions and stress. Adult male Wistar rats were intravenously administered with temazepam (0.5, 1, and 3 mg/kg body weight) and plasma concentrations of corticotropin (ACTH) and vasopressin (AVP) were measured in blood samples collected via chronically implanted jugular venous catheters. Simultaneously, the release of AVP within the hypothalamic paraventricular nucleus (PVN) was monitored via microdialysis. Plasma AVP levels remained unaffected by the different treatment conditions. Temazepam blunted the stressor exposure-induced secretion of ACTH in a dose-dependent manner. Concurrently, and also in a dose-dependent manner temazepam enhanced the intra-PVN release of AVP, known to originate from magnocellular neurons of the hypothalamic neurohypophyseal system. Furthermore, temazepam did not affect the in vitro secretion of ACTH from the adenohypophyseal cells. Taken together, the results of this study suggest that temazepam modulates the central nervous regulation of the HPA axis by altering intra-PVN AVP release. An increasingly released AVP of magnocellular origin seems to provide a negative tonus on ACTH secretion most probably via inhibiting the release of ACTH secretagogues from the median eminence into hypophyseal portal blood" http://www.ncbi.nlm.nih.gov/pubmed/16395302 0 1926 "J. Dalal, J. H. Roh, S. E. Maloney, A. Akuffo, S. Shah, H. Yuan, B. Wamsley, W. B. Jones, S. C. de Guzman, P. A. Gray, D. M. Holtzman, N. Heintz and J. D. Dougherty" 2013 Translational profiling of hypocretin neurons identifies candidate molecules for sleep regulation Genes Dev. 27 5 565-578 "Hypocretin (orexin; Hcrt)-containing neurons of the hypothalamus are essential for the normal regulation of sleep and wake behaviors and have been implicated in feeding, anxiety, depression, and reward. The absence of these neurons causes narcolepsy in humans and model organisms. However, little is known about the molecular phenotype of these cells; previous attempts at comprehensive profiling had only limited sensitivity or were inaccurate. We generated a Hcrt translating ribosome affinity purification (bacTRAP) line for comprehensive translational profiling of all ribosome-bound transcripts in these neurons in vivo. From this profile, we identified >6000 transcripts detectably expressed above background and 188 transcripts that are highly enriched in these neurons, including all known markers of the cells. Blinded analysis of in situ hybridization databases suggests that ~60% of these are expressed in a Hcrt marker-like pattern. Fifteen of these were confirmed with double labeling and microscopy, including the transcription factor Lhx9. Ablation of this gene results in a >30% loss specifically of Hcrt neurons, without a general disruption of hypothalamic development. Polysomnography and activity monitoring revealed a profound hypersomnolence in these mice. These data provide an in-depth and accurate profile of Hcrt neuron gene expression and suggest that Lhx9 may be important for specification or survival of a subset of these cells" http://www.ncbi.nlm.nih.gov/pubmed/23431030 0 1927 "J. Liu, B. Liu, X. Zhang, B. Yu, W. Guan, K. Wang, Y. Yang, Y. Gong, X. Wu, Y. Yanagawa, S. Wu and C. Zhao" 2014 Calretinin-positive L5a pyramidal neurons in the development of the paralemniscal pathway in the barrel cortex Mol.Brain 7 84 "BACKGROUND: The rodent barrel cortex has been established as an ideal model for studying the development and plasticity of a neuronal circuit. The barrel cortex consists of barrel and septa columns, which receive various input signals through distinct pathways. The lemniscal pathway transmits whisker-specific signals to homologous barrel columns, and the paralemniscal pathway transmits multi-whisker signals to both barrel and septa columns. The integration of information from both lemniscal and paralemniscal pathways in the barrel cortex is critical for precise object recognition. As the main target of the posterior medial nucleus (POm) in the paralemniscal pathway, layer 5a (L5a) pyramidal neurons are involved in both barrel and septa circuits and are considered an important site of information integration. However, information on L5a neurons is very limited. This study aims to explore the cellular features of L5a neurons and to provide a morphological basis for studying their roles in the development of the paralemniscal pathway and in information integration. RESULTS: 1. We found that the calcium-binding protein calretinin (CR) is dynamically expressed in L5a excitatory pyramidal neurons of the barrel cortex, and L5a neurons form a unique serrated pattern similar to the distributions of their presynaptic POm axon terminals. 2. Infraorbital nerve transection disrupts this unique alignment, indicating that it is input dependent. 3. The formation of the L5a neuronal alignment develops synchronously with barrels, which suggests that the lemniscal and paralemniscal pathways may interact with each other to regulate pattern formation and refinement in the barrel cortex. 4. CR is specifically expressed in the paralemniscal pathway, and CR deletion disrupts the unique L5a neuronal pattern, which indicates that CR may be required for the development of the paralemniscal pathway. CONCLUSIONS: Our results demonstrate that L5a neurons form a unique, input-dependent serrated alignment during the development of cortical barrels and that CR may play an important role in the development of the paralemniscal pathway. Our data provide a morphological basis for studying the role of L5a pyramidal neurons in information integration within the lemniscal and paralemniscal pathways" http://www.ncbi.nlm.nih.gov/pubmed/25404384 0 1928 "N. A. Gillett, D. L. Brooks and P. C. Tillman" 1983 Medical and surgical management of gastric obstruction from a hairball in the rabbit J.Am.Vet.Med.Assoc. 183 11 1176-1178 "Gastric hairballs in a colony of mature laboratory rabbits were associated with chronic, partial, or complete gastric obstruction and inanition. Clinical signs included anorexia, decreased fecal output, weight loss, and depression. The differentiation of anorexia induced by hairballs, stress, and other causes presented a diagnostic dilemma. Radiographs could not be relied upon to differentiate gastric hairballs from normal gastric contents. Combined medical and surgical management optimized successful recovery. Supportive therapy was given 12 to 24 hours before surgical removal of the hairball and was continued postoperatively for 72 hours" http://www.ncbi.nlm.nih.gov/pubmed/6643229 0 1929 K. Vaddi and C. I. Wei 1991 Modulation of Fc tau receptor expression and function in mouse peritoneal macrophages by ammonium metavanadate Int.J.Immunopharmacol. 13 8 1167-1176 "Resident peritoneal macrophages (PEM) harvested from female B6C3F1 mice given an intraperitoneal injection of ammonium metavanadate (2.5 or 10 mg V/kg), an equivalent amount of ammonium in the form of ammonium chloride, or sodium phosphate buffer (0.1 M, pH 7.2) every third day for 6 weeks, were subjected to flow cytometric analysis of Fc tau 2a and Fc tau 2b receptor expression, and photometric microassay to measure receptor mediated binding and phagocytosis of sheep red blood cells (SRBC). The NH4Cl and 10V groups showed 21.7 and 17.2% lower mean fluorescence channel (MFC) values and 7.1 and 5.9% lower values in percentage fluorescence-positive cells than the phosphate buffer control with respect to Fc tau 2a expression. For Fc tau 2b expression, the 10V group showed significantly (P less than 0.05) lower MFC (31.2%) and percentage fluorescence-positive cells (15.7%) than the phosphate buffer control. Though the four groups did not show a significant difference in Fc tau 2a mediated binding and phagocytosis of SRBC, the 10V group showed a significantly lower Fc tau 2b mediated binding and phagocytosis. The results indicate that the reduction in Fc tau 2b expression and function could contribute toward the previously observed depression in phagocytosis, NADPH-oxidase and superoxide generation in peritoneal macrophages obtained from vanadate-treated animals" http://www.ncbi.nlm.nih.gov/pubmed/1667652 0 1930 A. L. Rovati 1976 Inhibition of gastric secretion by anti-gastrinic and H2-blocking agents Scand.J.Gastroenterol.Suppl 42 113-118 http://www.ncbi.nlm.nih.gov/pubmed/796963 0 1931 "M. A. Sheridan, E. M. Plisetskaya, H. A. Bern and A. Gorbman" 1987 "Effects of somatostatin-25 and urotensin II on lipid and carbohydrate metabolism of coho salmon, Oncorhynchus kisutch" Gen.Comp Endocrinol. 66 3 405-414 "Salmon (Oncorhynchus kisutch) somatostatin (sSS; 4 or 8 ng/g body wt) or synthetic Gillichthys urotensin II (UII; 2 or 4 ng/g body wt) were injected intraperitoneally into juvenile freshwater coho salmon. Both sSS and UII caused a dose-dependent increase in plasma free fatty acids (FFA) which diminished with time. sSS induced an initial (1 hr) transient hyperglycemia. By contrast, UII tended to induce hypoglycemia, this effect being significant 5 hr after injection of the higher dose. Both sSS and UII depressed plasma insulin titers 1 hr after injection. By 3 hr, the sSS-associated insulin depression was no longer observed. UII treatment induced a hyperinsulinemia which was present 3 and 5 hr after peptide administration. Although no decreases in liver total lipid concentration or in mesenteric fat total tissue mass were observed, lipolytic enzyme activity within each depot was significantly enhanced by both peptides. Neither sSS nor UII altered 3H2O incorporation into fatty acids or neutral lipids. However, enhanced lipogenesis, particularly by UII, was indicated by increased NADPH production resulting from glucose-6-phosphate dehydrogenase activity. Both sSS and UII enhanced glucose mobilization, as indicated by decreased liver glycogen content and increased liver glucose-6-phosphatase activity. UII, but not sSS, stimulated glycogen synthetase activity. These results suggest that both sSS and UII stimulate hyperlipidemia by enhancing depot lipase activity and that although both factors are potentially gluconeogenetic, sSS seems to be glycogenolytic and hyperglycemic, whereas UII may channel glucose to FFA synthesis" http://www.ncbi.nlm.nih.gov/pubmed/2886397 0 1932 B. Fjalland 1973 Adrenergic and serotoninergic mechanisms in gastric secretion in rats Acta Pharmacol.Toxicol.(Copenh) 33 2 103-112 http://www.ncbi.nlm.nih.gov/pubmed/4271165 0 1933 "A. M. Mileo, E. Palma, L. Polenzani, C. Limatola, F. Grassi and F. Eusebi" 1995 Protein kinase C modulates exogenous acetylcholine current in Xenopus oocytes J.Neurosci.Res. 41 4 443-451 "The modulation of acetylcholine-activated current (IACh) by protein kinase C (PKC) was studied in Xenopus laevis oocytes microinjected with either mRNA extracted from C2C12 myotubes (C2C12 mRNA) or RNAs encoding murine alpha beta gamma delta subunits of the nicotinic ACh receptor (nAChR). Voltage-clamped oocytes were treated for 90 sec with 12-O-tetradecanoylphorbol-13-acetate (TPA, 300 nM), a potent PKC activator. Transient increase in the amplitude and acceleration in the decay of IACh were invariably observed within minutes of TPA application, and were independent of extracellular Ca2+ concentration. Both parameters recovered to control within 20-30 min; then a slight depression of IACh developed. By this time, an initial PKC down regulation was observed. At the peak of TPA-induced potentiation, dose-response relations suggested an increased binding affinity of nAChR for the neurotransmitter. 4 alpha-phorbol 12,13-didecanoate (300 nM), a biologically inactive analogue of TPA, did not affect IACh, while staurosporine (5-10 microM), a potent inhibitor of PKC activity, suppressed the action of TPA on IACh. In oocytes co-injected with C2C12 mRNA and with rat brain mRNA, IACh was potentiated by 5-hydroxy-tryptamine (10 microM), whose receptors are coupled to phosphoinositide hydrolysis. The nAChR-channel activity in cell-attached patches increased when TPA was applied to the oocytes. In 50% of the oocytes examined, a sustained depression of the single channel activity followed. We conclude that in Xenopus oocytes an endogenous PKC system regulates the function of embryonic-type muscle nAChRs" http://www.ncbi.nlm.nih.gov/pubmed/7473875 0 1934 "M. G. Perrone, E. Santandrea, L. Bleve, P. Vitale, N. A. Colabufo, R. Jockers, F. M. Milazzo, A. F. Sciarroni and A. Scilimati" 2008 Stereospecific synthesis and bio-activity of novel beta(3)-adrenoceptor agonists and inverse agonists Bioorg.Med.Chem. 16 5 2473-2488 "Since it is widely distributed into the body, beta(3)-adrenoceptor is becoming an attractive target for the treatment of several pathologies such as obesity, type 2 diabetes, metabolic syndrome, cachexia, overactive bladder, ulcero-inflammatory disorder of the gut, preterm labour, anxiety and depressive disorders, and heart failure. New compounds belonging to the class of arylethanolamines bearing one or two stereogenic centres were prepared in good yields as racemates and optically active forms. They were, then, evaluated for their intrinsic activity towards beta(3)-adrenoceptor and their affinity for beta(1)- and beta(2)-adrenergic receptors. Stereochemical features were found to play a crucial role in determining the behaviour of such compounds. In particular, alpha-racemic, (alphaR)- and (alphaS)-2-{4-[2-(2-hydroxy-2-phenylethylamino)ethyl]phenoxy}-2- methylpropanoic acid, (alpha-rac, beta-rac)-, (alphaR, betaS)- and (alphaR, betaR)- 2-{4-[2-(2-hydroxy-2-phenylethylamino)ethyl]phenoxy}propanoic acid were found to be endowed with beta(3)-adrenoceptor agonistic activity. Whereas, (alphaS, betaS)- and (alphaS, betaR)-2-{4-[2-(2-hydroxy-2-phenylethylamino)ethyl]phenoxy}propanoic acid behaved as beta(3)-adrenoceptor inverse agonists. Such compounds showed no affinity for beta(1)- and beta(2)-adrenergic receptor, respectively. Thus, resulting highly selective beta(3)-adrenoceptor ligands" http://www.ncbi.nlm.nih.gov/pubmed/18083578 0 1935 "D. Swandulla, M. Hans, K. Zipser and G. J. Augustine" 1991 Role of residual calcium in synaptic depression and posttetanic potentiation: fast and slow calcium signaling in nerve terminals Neuron 7 6 915-926 "Trains of action potentials evoked rises in presynaptic Ca2+ concentration ([Ca2+]i) at the squid giant synapse. These increases in [Ca2+]i were spatially nonuniform during the trains, but rapidly equilibrated after the trains and slowly declined over hundreds of seconds. The trains also elicited synaptic depression and augmentation, both of which developed during stimulation and declined within a few seconds afterward. Microinjection of the Ca2+ buffer EGTA into presynaptic terminals had no effect on transmitter release or synaptic depression. However, EGTA injection effectively blocked both the persistent Ca2+ signals and augmentation. These results suggest that transmitter release is triggered by a large, brief, and sharply localized rise in [Ca2+]i, while augmentation is produced by a smaller, slower, and more diffuse rise in [Ca2+]i" http://www.ncbi.nlm.nih.gov/pubmed/1662519 0 1936 "B. E. Skoogh, M. J. Holtzman, J. R. Sheller and J. A. Nadel" 1982 Barbiturates depress vagal motor pathway to ferret trachea at ganglia J.Appl.Physiol Respir.Environ.Exerc.Physiol 53 1 253-257 "To determine which site in the vagal motor pathway to airway smooth muscle is most sensitive to depression by barbiturates, we recorded isometric muscle tension in vitro and stimulated the vagal motor pathway at four different sites before and after exposure to barbiturates. In isolated tracheal rings from ferrets, we stimulated muscarinic receptors in the neuromuscular junction by exogenous acetylcholine, postganglionic nerve fibers by electrical fluid stimulation, and the postsynaptic membrane in ganglia by 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP). We also developed a tracheal nerve-muscle preparation to stimulate preganglionic fibers in the vagus nerve electrically. Activation of ganglia by DMPP or by vagus nerve stimulation was depressed by barbiturates at 10-fold lower concentrations than those depressing the activation of postganglionic nerves or the neuromuscular junction. These findings suggest that the postsynaptic membrane in parasympathetic ganglia is the site in the vagal motor pathway most sensitive to depression by barbiturates" http://www.ncbi.nlm.nih.gov/pubmed/7118638 0 1937 "T. Suzuki, Y. Fukushi and A. Rikimaru" 1971 [Relaxant effect of adenosine triphosphate and its related nucleotides on the guinea-pig taenia coli] Nihon Heikatsukin.Gakkai Zasshi 7 4 207-212 http://www.ncbi.nlm.nih.gov/pubmed/5170388 0 1938 H. Toh and T. Ohmori 1991 Morphological studies of the foramen caecum linguae of the human and guinea pig tongue Acta Anat.(Basel) 141 2 97-103 "A three-dimensional study of the development of the thyroid gland in human and guinea pig embryos was made together with a histological investigation of the foramen caecum of the human adult tongue. In the human embryo, an epithelial depression was not seen between the first and second branchial arches except a shallow sulcus. Ciliated cells were observed on the dorsal surface of the tongue in all embryos which exceeded 18 mm in crown-rump length. The presence of a foramen caecum was observed in 18 (51%) cadavers from 35 human adults. Several circumvallate papillae were found in a 10-mm-deep foramen caecum on the side adjacent to the anterior two thirds of the tongue. In all specimens serous glands open into the foramen caecum" http://www.ncbi.nlm.nih.gov/pubmed/1746229 0 1939 J. Persson and J. Luthman 1975 Factors affecting the hypocalcaemic response to protamine Acta Vet.Scand. 16 1 51-62 http://www.ncbi.nlm.nih.gov/pubmed/1136909 0 1940 "S. A. Eisenstein, J. R. Clapper, P. V. Holmes, D. Piomelli and A. G. Hohmann" 2010 A role for 2-arachidonoylglycerol and endocannabinoid signaling in the locomotor response to novelty induced by olfactory bulbectomy Pharmacol.Res. 61 5 419-429 "Bilateral olfactory bulbectomy (OBX) in rodents produces behavioral and neurochemical changes associated clinically with depression and schizophrenia. Most notably, OBX induces hyperlocomotion in response to the stress of exposure to a novel environment. We examined the role of the endocannabinoid system in regulating this locomotor response in OBX and sham-operated rats. In our study, OBX-induced hyperactivity was restricted to the first 3 min of the open field test, demonstrating the presence of novelty (0-3 min) and habituation (3-30 min) phases of the open field locomotor response. Levels of the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide were decreased in the ventral striatum, a brain region deafferented by OBX, whereas cannabinoid receptor densities were unaltered. In sham-operated rats, 2-AG levels in the ventral striatum were negatively correlated with distance traveled during the novelty phase. Thus, low levels of 2-AG are reflected in a hyperactive open field response. This correlation was not observed in OBX rats. Conversely, 2-AG levels in endocannabinoid-compromised OBX rats correlated with distance traveled during the habituation phase. In OBX rats, pharmacological blockade of cannabinoid CB(1) receptors with either AM251 (1 mg kg(-1) i.p.) or rimonabant (1 mg kg(-1) i.p.) increased distance traveled during the habituation phase. Thus, blockade of endocannabinoid signaling impairs habituation of the hyperlocomotor response in OBX, but not sham-operated, rats. By contrast, in sham-operated rats, effects of CB(1) antagonism were restricted to the novelty phase. These findings suggest that dysregulation in the endocannabinoid system, and 2-AG in particular, is implicated in the hyperactive locomotor response induced by OBX. Our studies suggest that drugs that enhance 2-AG signaling, such as 2-AG degradation inhibitors, might be useful in human brain disorders modeled by OBX" http://www.ncbi.nlm.nih.gov/pubmed/20044005 1 1941 "A. F. Nunes, M. J. Saraiva and M. M. Sousa" 2006 Transthyretin knockouts are a new mouse model for increased neuropeptide Y FASEB J. 20 1 166-168 "Transthyretin (TTR) has access to the brain and nerve through the blood and cerebrospinal fluid. To investigate TTR function in nervous system homeostasis, differential gene expression in wild-type (WT) and TTR knockout (KO) mice was assessed. Peptidylglycine alpha-amidating monooxygenase (PAM), the rate-limiting enzyme in neuropeptide maturation, is overexpressed in the peripheral (PNS) and central nervous system (CNS) of TTR KOs that, consequently, display increased neuropeptide Y (NPY) levels. NPY acts on energy homeostasis by increasing white adipose tissue lipoprotein lipase (LPL) and decreasing thermogenesis; accordingly, we show increased LPL expression and activity in white adipose tissue, PNS, and CNS as well as decreased body temperature in TTR KOs. Associated to increased NPY levels, TTR KOs display increased carbohydrate consumption and preference. In neuronal cells, absence of TTR is related to increased PAM activity, NPY levels and LPL expression, reinforcing that TTR is involved in neuropeptide maturation and that increased NPY correlates with LPL overexpression in the nervous system. Furthermore, we provide molecular insights to the reduced depressive behavior of TTR KOs, as NPY is anti-depressant. Our findings demonstrate that TTR KOs are a model for increased NPY and that TTR plays a role in nervous system physiology" http://www.ncbi.nlm.nih.gov/pubmed/16263939 1 1942 S. Thorsen and S. Mullertz 1974 Rate of activation and electrophoretic mobility of unmodified and partially degraded plasminogen. Effects of 6-aminohexanoic acid and related compounds Scand.J.Clin.Lab Invest 34 2 167-176 http://www.ncbi.nlm.nih.gov/pubmed/4278395 0 1943 S. G. Korenman and B. W. O'Malley 1968 Progesterone action: regulation of avidin biosynthesis by hen oviduct in vivo and in vitro Endocrinology 83 1 Nov-17 http://www.ncbi.nlm.nih.gov/pubmed/5659423 0 1944 "F. J. Dowell, W. Martin, A. F. Dominiczak and C. A. Hamilton" 1999 Decreased basal despite enhanced agonist-stimulated effects of nitric oxide in 12-week-old stroke-prone spontaneously hypertensive rat Eur.J.Pharmacol. 379 02-Mar 175-182 "This study examined both basal and agonist-stimulated effects of nitric oxide in rings of thoracic aorta and carotid artery from 12-week-old stroke-prone spontaneously hypertensive rats (SHRSP) and compared them to those found in rings from normotensive Wistar Kyoto (WKY) controls. Acetylcholine-induced endothelium-dependent relaxation was found to be five-fold more sensitive in both male and female SHRSP when compared with those from age- and sex-matched WKY rats. In contrast, we found a reduction in the effects of basal nitric oxide in the SHRSP rat. Specifically, the ability of basal nitric oxide to depress contractile responses to phenylephrine was found to be reduced in vessels from SHRSP when compared with those from WKY rats. In addition, the endothelium-dependent depression of vasodilator responses to the nitric oxide donor, glyceryl trinitrate, was reduced in vessels from SHRSP when compared to those from WKY rats. Thus, we have shown that the effects of basal nitric oxide are impaired in the SHRSP rat at an age when the effects of agonist-stimulated nitric oxide are actually enhanced. This impairment may be related to the greater susceptibility of basal nitric oxide to destruction by superoxide anion which is known to be produced in excess in this model of hypertension" http://www.ncbi.nlm.nih.gov/pubmed/10497904 0 1945 J. Harvey and M. G. Lacey 1997 A postsynaptic interaction between dopamine D1 and NMDA receptors promotes presynaptic inhibition in the rat nucleus accumbens via adenosine release J.Neurosci. 17 14 5271-5280 "The mechanism underlying dopamine D1 receptor-mediated attenuation of glutamatergic synaptic input to nucleus accumbens (NAcc) neurons was investigated in slices of rat forebrain, using whole-cell patch-clamp recording. The depression by dopamine of EPSCs evoked by single-shock cortical stimulation was stimulus-dependent. Synaptic activation of NMDA-type glutamate receptors was critical for this effect, because dopamine-induced EPSC depressions were blocked by the competitive NMDA receptor antagonist D/L-2-amino-5-phosphonopentanoate (AP5). Application of NMDA also depressed the EPSC, and both this effect and the dopamine depressions were blocked by the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), implicating adenosine release in the EPSC depression. A1 receptor agonists also depressed EPSCs by a presynaptic action, causing increased paired-pulse facilitation, but this was insensitive to AP5. Activation of D1 receptors enhanced both postsynaptic inward currents evoked by NMDA application and the isolated NMDA receptor-mediated component of synaptic transmission. The biochemical processes underlying the dopamine-induced EPSC depression did not involve either protein kinase A or the production of cAMP and its metabolites, because this effect was resistant to the protein kinase inhibitors H89 and H7 and the cAMP-specific phosphodiesterase inhibitor rolipram. We conclude that activation of postsynaptic D1 receptors enhances the synaptic activation of NMDA receptors in nucleus accumbens neurons, thereby promoting a transsynaptic feedback inhibition of glutamatergic synaptic transmission via release of adenosine. Unusually for D1 receptors, this phenomenon occurs independently of adenylyl cyclase stimulation. This process may contribute to the locomotor stimulant action of dopaminergic agents in the NAcc" http://www.ncbi.nlm.nih.gov/pubmed/9204911 0 1946 "M. Popovic, M. Caballero-Bleda, N. Popovic, D. Bokonjic and S. Dobric" 1997 Neuroprotective effect of chronic verapamil treatment on cognitive and noncognitive deficits in an experimental Alzheimer's disease in rats Int.J.Neurosci. 92 01-Feb 79-93 "It is well known that disturbance of calcium homeostasis has a significant role in the development of neurodegenerative disorders, such as Alzheimer's disease (AD). Our recent data suggest that acute treatment with the calcium antagonist verapamil can improve some behavioral deficits in an experimental model of AD. Therefore, the present study was done to establish the effect of chronically administered verapamil on cognitive and noncognitive behavior of rats with bilateral electrolitical lesions of nucleus basalis manocellularis (NBM)--an animal model of AD. The NBM lesions produce a deficit in performance of diverse behavior tests: active avoidance (AA), low level of fear (the open field test) as well as aggressive (the test of foot-shock induced aggression) and depressive (the learned helplessness test) behavior. Verapamil (1.0, 2.5, 5.0 and 10.0 mg/kg i.p.) or saline solution (1 ml/kg i.p.) were injected 24 hr after the lesion of NBM and then repeatedly administered during the next 8 days (twice a day). Performance of the two-way active avoidance test, the open field test, the foot shock-induced aggression test and the learned helplessness test were done on day 4 after the last verapamil or saline treatment (day 13 after the lesion). Verapamil in doses of 2.5 and 5.0 mg/kg significantly ameliorated the deficit in the performance of AA, the open field behavior, and the depression, but not the aggressive behavior. The obtained beneficial effect of chronic administered verapamil suggests that the regulation of calcium homeostasis during the early period after NBM lesions might be a reasonable way to prevent the behavioral deficits in an experimental model of AD" http://www.ncbi.nlm.nih.gov/pubmed/9522258 1 1947 M. Weiner 1980 The kinetics of inhibition of hepatic drug metabolism by prostaglandins in rabbits Res.Commun.Chem.Pathol.Pharmacol. 29 3 561-571 "The in vitro effects of prostaglandin A1 and prostaglandin E1 on the hepatic microsomal metabolism of type I (aminopyrine) and type II (p-chloro-N-methylaniline and aniline) drug substrates in rabbits were investigated. Both prostaglandins competitively inhibited aminopyrine N-demethylation to the same extent with a 500 microM prostaglandin concentration decreasing metabolism by approximately 50 percent. Prostaglandin A1 and prostaglandin F1 decreased p-chloro-N-methylaniline biotransformation, and prostaglandin E1 depressed aniline metabolims, via mixed-inhibition kinetics. The degree of inhibition was greatest with aniline as substrate. Aniline (0.125 mM) metabolism was inhibitied 49 percent and 71 percent by 100 microM and 500 microM prostaglandin E1, respectively" http://www.ncbi.nlm.nih.gov/pubmed/6448462 1 1948 "S. I. Kim, A. P. Winnie, V. J. Collins and W. C. Shoemaker" 1971 Hemodynamic responses to doxapram in normovolemic and hypovolemic dogs Anesth.Analg. 50 5 705-710 http://www.ncbi.nlm.nih.gov/pubmed/4398848 0 1949 "K. Matsutani, M. Tsuruoka, A. Shinya, R. Furuya, T. Kawawa and T. Inoue" 2003 Coeruleotrigeminal suppression of nociceptive sensorimotor function during inflammation in the craniofacial region of the rat Brain Res.Bull. 61 1 73-80 "Descending action from the locus coeruleus (LC) on the trigeminal sensorimotor function was evaluated in a rat model of oral-facial inflammation. For the induction of oral-facial inflammation, mustard oil (20% solution in 20microl mineral oil) was injected into the region of the temporomandibular joint (TMJ). One week before testing, rats received bilateral lesions of the LC using a cathodal current. The electromyogram (EMG) threshold, which is the threshold intensity for the onset of EMG activity of the masseter muscle evoked by pressure on the TMJ region, was used in the present study as an indicator of the trigeminal sensorimotor function. Following mustard oil injection, in the LC-lesioned rats, EMG thresholds significantly decreased at 30min, which lasted up to 240min. In contrast, EMG thresholds in the LC-intact rats returned to the level before injection after 180min. Systemic naloxone (1.3mg/kg, i.v.) produced a further decrease of EMG thresholds in both the LC-intact and LC-lesioned rats. Under the existence of naloxone, EMG thresholds in the LC-lesioned rats were significantly lower than those of the LC-intact rats. These results suggest that oral-facial inflammation activates the coeruleotrigeminal modulating system and that an action of this system is independent of the opioid depressive mechanism" http://www.ncbi.nlm.nih.gov/pubmed/12788209 0 1950 "X. X. Chu, R. J. Dominic, S. C. Yang, J. H. Wang, Y. Y. Ma and X. T. Hu" 2014 A natural model of behavioral depression in postpartum adult female cynomolgus monkeys (Macaca fascicularis) Dongwuxue.Yanjiu 35 3 174-181 "Postpartum depression (PPD) is a modified form of major depressive disorders (MDD) that can exert profound negative effects on both mothers and infants than MDD. Within the postpartum period, both mothers and infants are susceptible; but because PPD typically occurs for short durations and has moderate symptoms, there exists challenges in exploring and addressing the underlying cause of the depression. This fact highlights the need for relevant animal models. In the present study, postpartum adult female cynomolgus monkeys (Macaca fascicularis) living in breeding groups were observed for typical depressive behavior. The huddle posture behavior was utilized as an indicator of behavioral depression postpartum (BDP) as it has been established as the core depressive-like behavior in primates. Monkeys were divided into two groups: A BDP group (n=6), which were found to spend more time huddling over the first two weeks postpartum than other individuals that formed a non-depression control group (n=4). The two groups were then further analyzed for locomotive activity, stressful events, hair cortisol levels and for maternal interactive behaviors. No differences were found between the BDP and control groups in locomotive activity, in the frequencies of stressful events experienced and in hair cortisol levels. These findings suggested that the postpartum depression witnessed in the monkeys was not related to external factors other than puerperium period. Interestingly, the BDP monkeys displayed an abnormal maternal relationship consisting of increased infant grooming. Taken together, these findings suggest that the adult female cynomolgus monkeys provide a natural model of behavioral postpartum depression that holds a number of advantages over commonly used rodent systems in PPD modeling. The cynomolgus monkeys have a highly-organized social hierarchy and reproductive characteristics without seasonal restriction-similar to humans-as well as much greater homology to humans than rodents. As such, this model may provide a greater translational efficiency and research platform for systematically investigating the etiology, treatment, prevention of PPD" http://www.ncbi.nlm.nih.gov/pubmed/24866487 0 1951 "J. Itskovitz, B. W. Goetzman and A. M. Rudolph" 1982 The mechanism of late deceleration of the heart rate and its relationship to oxygenation in normoxemic and chronically hypoxemic fetal lambs Am.J.Obstet.Gynecol. 142 1 66-73 "The responses of fetal heart rate and blood pressure to a transient reduction in uterine blood flow were studied in normoxemic and chronically hypoxemic lambs. In normoxemic fetuses, a reduction in uterine blood flow, if prolonged sufficiently, produced reflex bradycardia mediated through chemoreceptors and was associated with a decrease in carotid arterial PO2 to below 20 torr. The bradycardia was associated with a marked decrease in left ventricular output as measured by electromagnetic flowmeter; both were abolished by atropine. In chronically hypoxemic fetuses, a reduction in uterine blood flow produced a delayed deceleration of the heart rate which consisted of three components: reflex bradycardia due to chemoreceptor stimulation; baroreceptor-mediated reflex bradycardia which involved the slow and late recovery of the heart rate; and nonreflex bradycardia which was probably secondary to hypoxic myocardial depression. Quantitative analysis revealed a relationship between the components of delayed deceleration and the status of fetal oxygenation prior to the reduction in uterine blood flow. The lower the carotid arterial PO2, the shorter was the delay in the onset of bradycardia, the greater the decrease in heart rate, and the more prolonged the duration of bradycardia. The conclusion is that the response of fetal heart rate to a transient reduction in uterine blood flow is related to the duration of the reduction and to the status of fetal oxygenation prior to the decrease in uterine blood flow" http://www.ncbi.nlm.nih.gov/pubmed/7055173 0 1952 "M. E. Rio, B. L. Zago, H. Garcia and L. Winter" 2002 [The nutritional status change the effectiveness of a dietary supplement of lactic bacteria on the emerging of respiratory tract diseases in children] Arch.Latinoam.Nutr. 52 1 29-34 "One hundred children 6 to 24 month old, normal or undernourished according to weight for height index, received during three months--autumn to winter--a dietary supplement of live Lactobacillus acidophilus and Lactobacillus Casei, 10(7)-10(8)/ml in fermented milk (LB) or an equivalent amount of fluid milk (L) as control. Children's follow-up was performed as outpatients in the Hospital Posadas (Great Buenos Aires). Episodes of respiratory tract infections were recorded and classified according to severity as: Pneumonia (N); Bronchitis (B), Recurrent Obstructive Bronchitis (BOR) and upper respiratory tract infections (CVAS). 58% of children fitted the study protocol, 22 in the LB and 36 in the L group; 21 were undernourished and 37 presented normal weight/height. No deaths were recorded. Total episodes were 103: 34 in LB and 69 in L, that means a frequency of 1.55 and 1.92 episodes/children respectively. In LB a maximum of 3 episodes/children was recorded, meanwhile the number reached 7 in L (p = 0.0373). Severity was higher in L than LB: 0.06 vs. 0 for N; 0.69 vs. 0.45 for B + BOR and 1.17 vs. 1.09 for CVAS. In the control group frequency of severe pathologies was about twice in undernourished than in normal: 0.08 vs. 0.04 for N; 1.08 vs. 0.50 for B + BOR; no difference was found for CVAS. Live lactobacillus supplement suppressed pneumonia and decreased bronchitis in undernourished as well as in normal. In this study undernutrition not only increased the chance of suffering severe acute respiratory tract infections but also impaired the effectiveness of the supplement to decrease severity. The effect is explained on the basis of the immunocompetence depression linked to an inadequate nutritional status" http://www.ncbi.nlm.nih.gov/pubmed/12214543 0 1953 K. F. Martin and P. H. Redfern 1982 Plasma free and total tryptophan: Chronopharmacological effects of antidepressant drugs "Journal of Pharmacy and Pharmacology.34 (Suppl.) ()(pp 75P), 1982.Date of Publication: 1982." Suppl. 75P 1 1954 "C. M. Chen, L. S. Gettes and B. G. Katzung" 1975 Effect of lidocaine and quinidine on steady-state characteristics and recovery kinetics of (dV/dt)max in guinea pig ventricular myocardium Circ.Res. 37 1 20-29 "We studied the effects of quinidine and lidocaine on the steady-state relationship between membrane potential and the maximum rate of rise of the action potential, (dV/dt)max, and on the recovery kinetics of (dV/dt)max in guinea pig papillary muscles. The steady-state relationships were determined in fibers stimulated at 0.2/sec and depolarized with KCl. Recovery kinetics were determined at various resting membrane potentials by assessing (dV/dt)max in progressively earlier premature action potentials. Lidocaine caused a dose-dependent decrease in (dV/dt)max, shifted the curve defining the steady-state relationship along the voltage axis in the direction of more negative potentials, and slowed the recovery kinetics of (dV/dt)max. Quinidine caused a dose-dependent decrease in (dV/dt)max but did not alter the shape of the curves defining either the steady-state relationship or the recovery kinetics of (dV/dt)max. Both drugs depressed membrane responsiveness as determined in premature action potentials originating from incompletely repolarized fibers. Our study indicates that the mechanisms whereby quinidine and lidocaine influence (dV/dt)max are different. It is possible that this difference may underlie some of the differences in the clinical effects of these two drugs" http://www.ncbi.nlm.nih.gov/pubmed/1149184 0 1955 "G. F. Grauer, M. A. Thrall, B. A. Henre and J. J. Hjelle" 1987 Comparison of the effects of ethanol and 4-methylpyrazole on the pharmacokinetics and toxicity of ethylene glycol in the dog Toxicol.Lett. 35 02-Mar 307-314 "The purpose of this investigation was to compare the effects of ethanol and 4-methylpyrazole (4MP) on the toxicity and pharmacokinetics of ethylene glycol (EG) in the dog. All dogs received 173 mmol/kg EG, p.o. Dogs were randomly assigned to 3 groups: EG-treated only, EG + ethanol (19.3 mmol/kg, i.v. 3, 7, 14 and 24 h after EG) and EG + 4MP (0.24 mmol/kg, i.v. 3 h after EG, 0.18 mmol/kg at 24 h and 0.06 mmol/kg at 36 h). EG produced a rapid onset of metabolic acidosis (within 3 h) and acute oliguric renal failure (after 48 h), whereas administration of ethanol or 4MP greatly attenuated acidosis and prevented renal toxicity. The administration of ethanol, however, severely increased the central nervous system (CNS) depression that existed after ingestion of EG. The half-life of FG in serum was 10.8 +/- 0.7 h in the EG-only treatment group, 6.8 +/- 0.7 (P less than 0.05) in the EG + ethanol group and 9.8 +/- 0.9 h in the EG + 4MP group. Approx. 10% and 48% of the dose of EG was excreted unchanged in the urine at the 0-3 and 3-72 h periods, respectively. Treatment with 4MP increased the amount of EG excreted in the urine (71% from 3-72 h), whereas ethanol did not (51%). However, both ethanol and 4MP increased the rate constant of EG excretion into urine approx. 70%. These data demonstrate the utility of 4MP over ethanol for the treatment of EG-induced toxicity in dogs and indicate that ethanol and 4MP cause an increase in the rate constant of EG excretion in the urine and not a prolongation in EG half-life" http://www.ncbi.nlm.nih.gov/pubmed/3824418 0 1956 "R. Smolik, W. Zukowski and S. Gruszka" 1967 "[Clinical observations on the action of NC 123, a new medium tranquilizer]" Wien.Med.Wochenschr. 117 44 998-1000 http://www.ncbi.nlm.nih.gov/pubmed/4873607 0 1957 J. Kapur and E. W. Lothman 1989 Loss of inhibition precedes delayed spontaneous seizures in the hippocampus after tetanic electrical stimulation J.Neurophysiol. 61 2 427-434 "1. The electrophysiological consequences of a ""continuous"" hippocampal stimulation protocol consisting of 10-s-long stimulus trains administered every 11 s for 90 min to the hippocampus of urethane-anesthetized rats were studied. During the period of stimulation, there was an initial phase with tonic discharges occurring every 1-2 min followed by a secondary phase in which there were well-demarcated recurrent clonic seizures. 2. At the end of the 90 min stimulation period, 7 out of a total of 14 animals studied show epileptiform activity that lasted one-half hour. The other half show disappearance of epileptiform activity within 2 min after terminating the stimulus. In all the animals a quiescent period then followed. In 11 of the animals studied, spontaneous seizures reappeared after the quiescent period had been present for several hours. 3. A paired-pulse method that in previous studies had been shown to reflect the functional state of GABAergic inhibition was employed. Paired-pulse depression in the CA1 region of the hippocampus was measured before administration of stimulus trains, in the quiescent period following the trains, and during and after spontaneous seizures. By comparing indices of maximal inhibition under the various experimental conditions, estimates of the relative amount of inhibition lost could be made. 4. All animals showed reduction of paired-pulse depression in the quiescent period following stimulation when compared with prestimulation values.(ABSTRACT TRUNCATED AT 250 WORDS)" http://www.ncbi.nlm.nih.gov/pubmed/2918364 0 1958 "M. Lai, J. A. McCormick, K. E. Chapman, P. A. Kelly, J. R. Seckl and J. L. Yau" 2003 Differential regulation of corticosteroid receptors by monoamine neurotransmitters and antidepressant drugs in primary hippocampal culture Neuroscience 118 4 975-984 "Hyperactivity of the hypothalamic-pituitary-adrenal axis is a characteristic feature of depressive illness. The centrally located corticosteroid receptors, the glucocorticoid and mineralocorticoid receptors, are thought to be important modulators of this axis and changes in the levels of these receptors, particularly in the hippocampus, may underlie the hyperactivity observed. Various antidepressant drugs increase hippocampal mineralocorticoid and glucocorticoid receptor levels in vivo. These effects are thought to be mediated via alterations in monoaminergic neurotransmission. We examined whether serotonin (5HT) and noradrenaline (NA) have direct effects on glucocorticoid receptor and mineralocorticoid receptor expression in primary hippocampal neurones, and whether antidepressants also exert direct effects on target neurones. Exposure of hippocampal cells to 5HT for 4 days increased both glucocorticoid and mineralocorticoid receptor mRNA and protein expression. The induction of mineralocorticoid receptor mRNA was completely blocked by the 5HT(7) receptor antagonist SB 269970. In contrast glucocorticoid receptor induction was insensitive to the 5HT(7) receptor, whilst studies with the 5HT(1A) receptor agonist 8-hydroxy-2-(di-n-proplamino) tetralin hydrochloride and the 5HT(1A) receptor antagonist N-[2-[4-2-[O-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane carboxamide trihydrochloride (WAY 100635) suggest a partial role for 5HT(1A) receptors in hippocampal glucocorticoid receptor regulation. Treatment with NA for 4 days also increased glucocorticoid receptor expression but had no effect on mineralocorticoid receptor expression. This was blocked by propanolol suggesting action via beta-adrenergic receptors. Similarly to NA, fluoxetine and amitriptyline also selectively increased glucocorticoid receptor mRNA and protein levels over this time course. However, glucocorticoid receptor induction by fluoxetine or amitriptyline was not blocked by WAY 100635 or propanolol. These results show that 5HT, NA and antidepressants act directly but via distinct mechanisms on hippocampal neurones to regulate mineralocorticoid and glucocorticoid receptor expression. Thusly, manipulation of neurotransmitter or antidepressant levels in the brain may aid in reversing hypothalamic-pituitary-adrenal axis hyperactivity by restoring hippocampal corticosteroid receptor balance" http://www.ncbi.nlm.nih.gov/pubmed/12732243 1 1959 "R. Faria, M. M. Santana, C. A. Aveleira, C. Simoes, E. Maciel, T. Melo, D. Santinha, M. M. Oliveira, F. Peixoto, P. Domingues, C. Cavadas and M. R. Domingues" 2014 Alterations in phospholipidomic profile in the brain of mouse model of depression induced by chronic unpredictable stress Neuroscience 273 01-Nov "Depression is a worldwide disability disease associated with high morbidity and has increased dramatically in the last few years. The differential diagnosis and the definition of an individualized therapy for depression are hampered by the absence of specific biomarkers. The aim of this study was to evaluate the phospholipidomic profile of the brain and myocardium in a mouse model of depression induced by chronic unpredictable stress (CUS). The lipidomic profile was evaluated by thin layer and liquid chromatography and mass spectrometry and lipid oxidation was estimated by FOX II assay. Antioxidant enzyme activity and the oxidized/reduced glutathione (GSH/GSSG) ratio were also evaluated. Results showed that chronic stress affects primarily the lipid profile of the brain, inducing an increase in lipid hydroperoxides, which was not detected in the myocardium. A significant decrease in phosphatidylinositol (PI) and in cardiolipin (CL) relative contents and also oxidation of CL and a significant increase of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were observed in the brain of mice after unpredictable chronic stress conditions. In the myocardium only an increase in PC content was observed. Nevertheless, both organs present a decreased GSH/GSSG ratio when compared to control groups, corroborating the occurrence of oxidative stress. The enzyme activities of catalase (CAT) and superoxide dismutase (SOD) were found to be decreased in the myocardium and increased in the brain, while glutathione reductase (GR) was decreased in the brain. Our results indicate that in a mouse model for studying depression induced by CUS, the modification of the expression of oxidative stress-related enzymes did not prevent lipid oxidation in organs, particularly in the brain. These observations suggest that depression has an impact on the brain lipidome and that further studies are needed to better understand lipids role in depression and to evaluate their potential as future biomarkers" http://www.ncbi.nlm.nih.gov/pubmed/24814727 1 1960 "H. Todt, N. Zojer and G. Raberger" 1993 Kinetics of rate-dependent slowing of intraventricular conduction by the class Ib antiarrhythmic agent tocainide in vivo Br.J.Pharmacol. 110 1 145-150 "1. The effects of the class I antiarrhythmic agent, tocainide, on intraventricular conduction were assessed in guinea-pigs, anaesthetized with pentobarbitone sodium 60 mg kg-1, i.p. 2. After electrical ablation of the sinus node, heart rate was controlled by atrial pacing. His bundle electrograms were recorded by means of an epicardial bipolar electrode. 3. During continuous stimulation, comparison of HV intervals measured at a cycle length of 475 ms, with HV intervals measured at a cycle length of 250 ms yielded the following results: 25.26 +/- 0.64 ms versus 25.02 +/- 0.70 ms (NS), at baseline, 26.65 +/- 0.80 ms versus 29.88 +/- 1.13 ms (P < 0.001) after i.v. administration of 30 mg kg-1 tocainide, and 28.04 +/- 0.64 ms versus 36.24 +/- 1.31 ms (P < 0.001), after addition of 20 mg kg-1 tocainide. Thus, tocainide caused HV intervals to increase in a strictly rate-dependent fashion. 4. In order to characterize the rate-dependent class I activity of tocainide in terms of its binding kinetics to sodium channels, fractional sodium channel block was estimated from drug induced reductions of intraventricular conduction velocity (delta theta). On abruptly changing the drive cycle length from 500 ms to 250 ms, delta theta reached a new steady state with rate constants of 1.23 +/- 0.09 beat-1 and 1.28 +/- 0.09 beat-1, after administration of 30 mg kg-1 and addition of 20 mg kg-1 tocainide, respectively. At a basic drive cycle length of 250 ms delta theta recovered with time constants of 250.29 +/- 23.32 ms and 183.04 +/- 8.03 ms after administration of 30 mg kg-1 and addition of 20 mg kg-1 tocainide, respectively.5. The experimentally determined kinetic parameters were implemented into a mathematical model that assumes drug binding to sodium channels in terms of a periodical two-state process. Rate-dependent reductions in conduction velocity during continuous stimulation after administration of tocainide were closely approximated by steady state reductions in sodium channel availability as calculated on the basis of the aforementioned model.6. In agreement with previously published in vitro studies, our data, obtained in vivo, confirm the classification of tocainide as a class I antiarrhythmic agent with fast onset and offset kinetics. The kinetic parameters obtained in vivo can be used in order to predict steady state reductions in conduction velocity at a wide range of frequencies" http://www.ncbi.nlm.nih.gov/pubmed/8220875 0 1961 "B. J. Whitehouse, S. J. Purdy and D. R. Abayasekara" 1993 Inhibition of corticosteroid production by sodium pentobarbitone in rat adrenocortical preparations J.Endocrinol. 136 1 75-83 "It is possible that some of the effects of sodium pentobarbitone on the hypothalamo-pituitary-adrenal axis in the intact animal may be attributable to direct actions on the adrenal cortex. The effects of the barbiturate on steroid production by rat adrenal preparations in vitro have therefore been examined. In zona glomerulosa cells, pentobarbitone inhibited basal steroid production in a dose-related fashion. For aldosterone and corticosterone, the doses required for 50% inhibition of production (IC50) were 1.2 mmol pentobarbitone/l and 3.7 mmol/l respectively. Steroidogenesis was inhibited at lower levels of pentobarbitone in the presence of 1 nmol ACTH/l (IC50 = 0.5 mmol pentobarbitone/l for aldosterone and 2.2 mmol/l for corticosterone). In zona fasciculata/reticularis cells, production of corticosterone was similarly reduced with an IC50 of 2.8 mmol pentobarbitone/l for basal production and 1.3 mmol/l for ACTH-stimulated production. The dose-related increases in corticosterone production produced by ACTH (0.1-1000 pmol/l) or dibutyryl cyclic AMP (0.1-1.0 mmol/l) were also eliminated in the presence of 2 mmol pentobarbitone/l. The effects of pentobarbitone (1-4 mmol/l) on the production of pregnenolone and deoxycorticosterone (DOC) were also studied. In zona fasciculata/reticularis cells, the responses of both pregnenolone and DOC were bell-shaped with increases at 1 mmol pentobarbitone/l, which fell back to control levels at 4 mmol pentobarbitone/l. Stimulation of DOC, accompanied by decreases in aldosterone and corticosterone production, was also seen in zona glomerulosa cells at 1 mmol pentobarbitone/l.(ABSTRACT TRUNCATED AT 250 WORDS)" http://www.ncbi.nlm.nih.gov/pubmed/8381458 0 1962 "M. Berk, L. J. Williams, A. C. Andreazza, J. A. Pasco, S. Dodd, F. N. Jacka, S. Moylan, E. J. Reiner and P. V. Magalhaes" 2014 "Pop, heavy metal and the blues: secondary analysis of persistent organic pollutants (POP), heavy metals and depressive symptoms in the NHANES National Epidemiological Survey" BMJ Open. 4 7 e005142 "OBJECTIVES: Persistent environmental pollutants, including heavy metals and persistent organic pollutants (POPs), have a ubiquitous presence. Many of these pollutants affect neurobiological processes, either accidentally or by design. The aim of this study was to explore the associations between assayed measures of POPs and heavy metals and depressive symptoms. We hypothesised that higher levels of pollutants and metals would be associated with depressive symptoms. SETTING: National Health and Nutrition Examination Survey (NHANES). PARTICIPANTS: A total of 15 140 eligible people were included across the three examined waves of NHANES. PRIMARY AND SECONDARY OUTCOME MEASURES: Depressive symptoms were assessed using the nine-item version of the Patient Health Questionnaire (PHQ-9), using a cut-off point of 9/10 as likely depression cases. Organic pollutants and heavy metals, including cadmium, lead and mercury, as well as polyfluorinated compounds (PFCs), pesticides, phenols and phthalates, were measured in blood or urine. RESULTS: Higher cadmium was positively associated with depression (adjusted Prevalence Ratios (PR)=1.48, 95% CI 1.16 to 1.90). Higher levels of mercury were negatively associated with depression (adjusted PR=0.62, 95% CI 0.50 to 0.78), and mercury was associated with increased fish consumption (n=5500, r=0.366, p<0.001). In addition, several PFCs (perfluorooctanoic acid, perfluorohexane sulfonic acid, perfluorodecanoic acid and perfluorononanoic acid) were negatively associated with the prevalence of depression. CONCLUSIONS: Cadmium was associated with an increased likelihood of depression. Contrary to hypotheses, many of persistent environmental pollutants were not associated or negatively associated with depression. While the inverse association between mercury and depressive symptoms may be explained by a protective role for fish consumption, the negative associations with other pollutants remains unclear. This exploratory study suggests the need for further investigation of the role of various agents and classes of agents in the pathophysiology of depression" http://www.ncbi.nlm.nih.gov/pubmed/25037643 0 1963 "B. Carnmalm, M. L. Persson and S. B. Ross" 1975 "Antidepressant agents. VI. 4,4 Diphenyl 1 methylcyclohexylamines" "Acta Pharmaceutica Suecica.12 (2) ()(pp 205-208), 1975.Date of Publication: 1975." 2 205-208 1 1964 "M. V. Doucet, H. Levine, K. K. Dev and A. Harkin" 2013 Small-molecule inhibitors at the PSD-95/nNOS interface have antidepressant-like properties in mice Neuropsychopharmacology 38 8 1575-1584 "Previous studies have demonstrated that nitric oxide (NO) synthase inhibitors are as efficacious as tricyclic antidepressants in preclinical antidepressant screening procedures and in attenuating behavioural deficits associated with animal models of depression. The N-methyl-D-aspartate receptor (NMDA-R) complex gates Ca(2+), which interacts with calmodulin to subsequently activate NO synthase. We hypothesised that uncoupling neuronal nitric oxide synthase (nNOS) from the NMDA-R through the scaffolding protein postsynaptic density protein 95 (PSD-95) would produce behavioural antidepressant effects similar to NO synthase inhibitors. Small-molecule inhibitors of the PSD-95/nNOS interaction, IC87201 (0.01-2 mg/kg) and ZL006 (10 mg/kg) were tested for antidepressant properties in tests of antidepressant activity namely the tail suspension and forced swim tests in mice. We now report that IC87201 and ZL006 produce antidepressant-like responses in the forced swimming test (FST) and tail suspension test (TST) following a single administration in mice. By contrast to the tricyclic antidepressant imipramine (25 mg/kg), the effects are not observed 1 h following drug administration but are apparent 24 and 72 h later. Furthermore prior exposure to the TST or FST is required in order to observe the antidepressant-related activity. Similar delayed and sustained antidepressant-like effects were observed following TRIM (50 mg/kg) and ketamine (30 mg/kg) in the TST. The antidepressant-like effects of ZL006 also generalise to IC87201 in the TST. IC87201 was devoid of effects on locomotor activity and step-through latency in the passive avoidance cognition test. These data support the hypothesis that targeting the PSD-95/nNOS interaction downstream of NMDA-R produces antidepressant effects and may represent a novel class of therapeutics for major depressive disorders" http://www.ncbi.nlm.nih.gov/pubmed/23446451 1 1965 K. Miyata 1973 [Studies on ejaculation. 5. The effects of autonomic drugs on seminal emission and ejaculation] Nihon Hinyokika Gakkai Zasshi 64 1 Dec-30 http://www.ncbi.nlm.nih.gov/pubmed/4738858 0 1966 A. L. Clatworthy and E. T. Walters 1993 Activity-dependent depression of mechanosensory discharge in Aplysia J.Neurophysiol. 70 3 1195-1209 "1. Inhibition of action potential discharge in Aplysia mechanosensory neurons after noxious stimulation has not been described previously. The present studies investigated depressive effects of prolonged noxious stimulation and repetitive intracellular activation on the number and latency of action potentials evoked by test stimuli applied to the tail or the nerve innervating the tail. Action potential discharge was monitored in the somata of mechanonociceptors in the pleural ganglia. 2. Repeated brief pinches delivered at 5-s intervals to a sensory neuron's receptive field on the tail initially caused intense activation (10-25 spikes recorded in the soma) followed by a progressive decrease or ""wind-down"" of spike number during subsequent pinches. 3. Repeated application to the tail of noxious shock that caused intense activation of sensory neurons (10-22 spikes during the initial shock) produced progressive wind-down of discharge similar to that produced by repeated tail pinch. However, sensory neurons that showed lower activation (1-9 spikes) to the same shock displayed wind-up of discharge during the 10 shocks. These results suggested that prolonged, intense activation depresses subsequent action potential discharge. 4. Changes in the time required for spikes evoked in the tail to reach the central soma were used as an indicator of changes in the excitability and/or conduction velocity of peripheral branches. Repeated pinch within a sensory neuron's receptive field caused an increase in the latency of discharge elicited by test shocks within the receptive field that lasted > or = 10 min. Repetitive intracellular stimulation of the sensory neuron soma caused a similar increase in latency. 5. Repetitive soma activation decreased the number of spikes evoked 10 s later by a test shock in the sensory neuron's receptive field, indicating that spike activity depresses the initiation and/or conduction of spikes in peripheral branches. Surprisingly, repeated pinch to the receptive field caused no significant change in the number of spikes evoked by the same test shock. This difference suggests that tail pinch produces concomitant facilitatory effects that oppose the depressive effects of intense spike activity. 6. Depressive effects of repeated pinch and repetitive soma activation were expressed in the axon between the receptive field and the CNS. Spikes evoked by brief test shocks delivered to the nerve containing the axon of the recorded sensory neuron showed a transient increase in latency (perhaps due to a decrease in conduction velocity) after either procedure. Repeated pinch, but not repetitive soma activation, also caused an increase in spike threshold in the nerve.(ABSTRACT TRUNCATED AT 400 WORDS)" http://www.ncbi.nlm.nih.gov/pubmed/8229168 0 1967 A. A. Zacaro and S. D. Porter 2003 Female reproductive system of the decapitating fly Pseudacteon wasmanni Schmitz (Diptera: Phoridae) Arthropod.Struct.Dev. 31 4 329-337 "Pseudacteon wasmanni is a South American decapitating fly that parasitizes workers of Solenopsis fire ants. We used light microscopy (historesin serial-sectioning stained with Haematoxylin/Eosin) and scanning electron microscopy to show and analyze internal and whole external views of the female reproductive system. All specimens analyzed (n=9) by light microscopy showed post-vitellogenic oocytes inside the ovaries. The lack of typical follicles (oocyte-nurse cell complexes) in all specimens suggests that oogenesis occurs during the pupal stage. The total number of eggs found ranged from 31 to 280 (X=142+/-73, SD). The egg has a slugform or torpedo shape (about 130 by 20 microm) with a pointed apex at the posterior pole as defined by the fly; the micropyle appears to be in a depression or invagination at the anterior pole. An acute hypodermic-like ovipositor is evaginated from the hard sclerotized external genitalia during egg laying. The existence of a muscular bulb associated with the end of the common oviduct suggests that the egg is injected into the ant's body by a strong contraction of the bulb which probably is stimulated by bending of several ventral sensilla. During contraction, the abdomen extends out along a large fold between the sixth and seventh tergites in such a way that the sclerotized genitalia is rotated ventrally into a slightly anterior orientation in preparation for oviposition" http://www.ncbi.nlm.nih.gov/pubmed/18088990 0 1968 "F. Kersante, S. C. S. Rowley, M. G. Mecinas, J. M. H. M. Reul and A. C. E. Linthorst" 2011 Differential role of the GABA transporters in the regulation of extracellular concentrations of GABA in the rat hippocampus "European Neuropsychopharmacology.Conference: 2011 ECNP Workshop on Neuropsychopharmacology for Young Scientists in Europe Nice France.Conference Start: 20110303 Conference End: 20110306.Conference Publication: (var.pagings).21 ()(pp S53-S54), 2011.Da" var.pagings S53-S54 "GABA signalling plays an important role in epilepsy and in stress-related psychiatric disorders, such as major depression and anxiety. Recent findings indicate that changes in GABAergic tonic inhibition may be implicated in these diseases. Tonic inhibition is a recently discovered phenomenon [1] which is mediated by high-affinity extrasynaptic GABA(A) receptors. Tonic inhibitory currents control neuronal and network excitability in various brain regions, among which the hippocampus. The magnitude of tonic inhibition depends on the concentration of extracellular GABA (e[GABA]), which is regulated by reuptake of the neurotransmitter via GABA transporters (GATs). Consequently, GATs and extrasynaptic GABA(A) receptors represent potential candidates for the development of psychopharmacological drugs. We have demonstrated that hippocampal e[GABA] increases during psychological stress in rats [2]. However, little is known about the regulation of e[GABA] by GATs under physiological conditions. Therefore, we investigated the differential role of GAT-1 and GAT-3, the two major GATs found in the hippocampus, in the regulation of e[GABA] using in vivo microdialysis in freely behaving male Sprague-Dawley rats. Briefly, seven days after the implantation of a guide cannula, a microdialysis probe was inserted into the hippocampus (CA3/dentate gyrus). The probe was perfused with Ringer solution at a flow rate of 2 mul/min and all drugs were administered locally into the hippocampus by reverse microdialysis. Samples were collected at 10-min intervals and GABA was measured using HPLC with electrochemical detection. Data were analysed by ANOVA with repeated measures and appropriate post-hoc tests, and by Student's t-test. Sixty minutes application of the GAT-1 specific inhibitor NNC-711 resulted in a dose-dependent increase in e[GABA] (EC50: 1.20+/-0.30 muM, Emax: 1001+/-92%), while application of 100 muM SNAP-5114, a GAT-2/3 specific inhibitor, failed to affect e[GABA]. However, combination of 1muM NNC-711 and 100muM SNAP-5114 resulted in a significantly higher and prolonged increase in e[GABA] than caused by 1muM NNC-711 alone (Emax: 716+/-30% vs. 566+/-32% respectively, P<0.01), suggesting a synergetic effect of the inhibitors. This observation indicates that both GAT-1 and GAT-3 (GAT-2 is hardly expressed in the hippocampus) regulate e[GABA] in the hippocampus but that, under normal conditions, either GAT-1 masks GAT-3 activity or e[GABA] is too low to engage GAT-3. We therefore assessed the involvement of GAT-3 in the regulation of e[GABA] under conditions of increased neuronal activation. Thirty minutes reverse dialysis of 50mM potassium chloride (KC1) profoundly increased e[GABA] (Emax: 976+/-165% vs. baseline). Importantly, simultaneous blockade of GAT-3 by 100 muM SNAP-5114 during KC1 infusion led to a further significant increase in e[GABA] (Emax: 1733+/-268%, P<0.05 vs. KC1 alone). Our data clearly demonstrate that in the hippocampus GAT-3 only plays a role when the levels of e[GABA] are profoundly elevated. We therefore hypothesise that GAT-1 and GAT-3 are differentially involved in the control of e[GABA] under particular (patho)physiological circumstances. We are currently investigating whether the specific neuroanatomical localisation of GAT1 and GAT3 in the hippocampus could explain their differential role. Sponsor: The Wellcome Trust (083163/B/07/Z)" DO - http://dx.doi.org/10.1016/S0924-977X%2811%2970063-3 0 1969 "H. C. Dringenberg, R. A. Kornelsen and C. H. Vanderwolf" 1994 Food carrying in rats is blocked by the putative anxiolytic agent buspirone Pharmacol.Biochem.Behav. 49 3 741-746 "The effects of the putative anxiolytic agent buspirone on food-handling behavior of laboratory rats were investigated. Rats trained to travel from a covered shelter to a food source were provided with food pellets of six sizes. Smaller pellets were eaten at the exposed food source, whereas larger pellets were carried back to the shelter for consumption. Subcutaneous administration of buspirone hydrochloride (0.2-2.0 mg/kg) reduced carrying of larger food pellets in a dose-dependent manner. Instead, these pellets were also eaten at the exposed food source. Carrying was maximally suppressed 1 h after drug administration. Handling of smaller pellets, travel times, and eating times were not affected by buspirone. Similar results have previously been obtained with diazepam. Buspirone appears to exert its effects through 5-HT1A and/or dopamine receptors, whereas diazepam interacts with benzodiazepine receptors. Thus, manipulations of distinct transmitter systems may have similar behavioral consequences on the food carrying responses of rats" http://www.ncbi.nlm.nih.gov/pubmed/7862731 0 1970 "M. Zhang, M. Paskvalin and J. C. Khatter" 1998 Pharmacological characterization of an endogenous negative inotrophic factor (ENIF) from porcine heart Mol.Cell Biochem. 178 01-Feb 135-139 "Recently we have been successful in isolating an endogenous negative inotropic factor (ENIF) from porcine left ventricular tissue. In this study, we have characterized its pharmacological properties. The results of the study demonstrated that ENIF produces a concentration-dependent negative inotropic response on both guinea pig left atria and right ventricular trabeculae. The maximal reduction in contractile force produced by 300 ul of ENIF (5 ml bath) on atria and trabeculae were 90.0 +/- 0.8% and 77.5 +/- 6%. Atria, however, was significantly more sensitive to ENIF than trabeculae. The ED 50 of ENIF for atria was found to be 38 ul as opposed to ED 50 of 100 ul of ENIF for trabeculae. Acetylcholine (ACh), a muscarinic receptor agonist, decreased the contractile force of guinea pig atria in a dose-dependent manner with a maximal decline in the contractile force of 90%. However, none of the concentration of ACh used affected the contractile function of the trabeculae. Atropine (1 uM) completely blocked the negative inotropic response on atria of all the doses of ACh used. The same dose of atropine, however, was unable to influence the negative inotropic effect of any of the doses of ENIF used on either the atria or trabeculae preparations in our study. The maximal decline in the contractile force of atria was e.g. 94 and 95% in the presence and absence of atropine respectively. These data demonstrate that the myocardial negative inotropic effect of ENIF is not mediated via the cholinegic receptor mechanism" http://www.ncbi.nlm.nih.gov/pubmed/9546592 0 1971 W. Spinelli and B. F. Hoffman 1989 Mechanisms of termination of reentrant atrial arrhythmias by class I and class III antiarrhythmic agents Circ.Res. 65 6 1565-1579 "We studied atrial flutter due to circus movement in chronically instrumented conscious dogs to identify the mechanism by which class I and class III antiarrhythmic drugs terminate reentrant excitation. We used a crossover experimental design administering five class I agents and one class III agent, by intravenous bolus followed by intravenous infusion. The class I agents other than lidocaine were almost uniformly effective in terminating the arrhythmia (disopyramide in six of seven dogs, propafenone in six of six, flecainide in seven of seven, and SC-40230 in seven of seven). Termination was preceded by a marked increase in cycle length (ranging from +78% with propafenone to +55% with disopyramide), but with the exception of disopyramide, class I agents did not significantly shorten the excitable gap. With disopyramide the gap decreased from 49 +/- 3% to 28 +/- 3% of the cycle length. With no class I agent did the wavelength of effective refractoriness increase to approach the cycle length of the arrhythmia. Lidocaine, used as a negative control, terminated the reentry in one dog with modest prolongation of the cycle length. Terminations with class I agents correlated with depression of conduction rather than prolongation of refractoriness. In contrast with class I agents, D-sotalol prolonged the cycle length minimally (+10%) and terminated the arrhythmia in six of seven dogs. It decreased the excitable gap from 42 +/- 4% to 26 +/- 6% of the cycle, but it still did not cause the wavelength of effective refractoriness to equal the cycle length. Terminations by D-sotalol seemed to result from either failure of the lateral boundaries of the circus path or reflection within the path" http://www.ncbi.nlm.nih.gov/pubmed/2510953 0 1972 "M. M. Hoskison, J. A. Connor and C. W. Shuttleworth" 2004 GABA(B)-receptor modulation of short-term synaptic depression at an excitatory input to murine hippocampal CA3 pyramidal neurons Neurosci.Lett. 365 1 48-53 "GABA(B) agonists inhibit excitatory transmission to hippocampal CA3 neurons during low frequency stimulation. We examined whether GABA(B) receptor activation can also enhance synaptic efficacy, when investigated at an input with high initial release probability. Short-term depression of field excitatory postsynaptic potential (EPSP) amplitude was observed during trains of stimuli applied to associational/commissural inputs (10-50 Hz; 22 degrees C). Baclofen (10 microM) reduced the amplitude of initial EPSPs in a train, and also reduced the degree of short-term depression. EPSPs recorded late in a train were significantly larger in baclofen than those recorded in control solution. These dual effects were mimicked by another selective GABA(B) agonist (SKF 97541, 10 microM), and abolished by a GABA(B)-selective antagonist (SCH 50911, 20 microM). The effects of baclofen were similar at a higher recording temperature (32 degrees C), where short-term depression was observed at higher stimulation frequencies. These results are consistent with the idea that a reduction of transmitter release probability could increase the fidelity of high-frequency transmission at this input, an effect that could help account for excitatory effects of GABA(B) agonists in some seizure models" http://www.ncbi.nlm.nih.gov/pubmed/15234471 0 1973 "J. Li, R. L. Duncan, D. B. Burr and C. H. Turner" 2002 L-type calcium channels mediate mechanically induced bone formation in vivo J.Bone Miner.Res. 17 10 1795-1800 "Cell and tissue culture studies suggest that the long-lasting (L-type) voltage-sensitive calcium channels (VSCC) play a role in the signaling cascade in bone cells after mechanical loading. We investigated whether the L-type VSCC mediates mechanically induced bone formation in vivo using two L-type VSCC antagonists verapamil and nifedipine. Female Sprague-Dawley rats were divided into five groups: control group (Veh), two verapamil-treated groups (20 mg/kg, Vera-L; 100 mg/kg, Vera-H), and two nifedipine-treated groups (20 mg/kg, Nife-L; 100 mg/kg, Nife-H). One bout of mechanical loading was applied to the right tibia 90 minutes after oral administration of verapamil or 30 minutes after oral administration of nifedipine. Mechanical loading increased mineralizing surface (MS/bone surface [BS]), mineral apposition rate (MAR), and bone formation rate (BFR/BS) on the endocortical surface in loaded tibias of control animals compared with nonloaded (left) tibias. Verapamil and nifedipine suppressed the load-induced increase in BFR/BS observed in vehicle-treated controls by 56-61% (p < 0.01) and 56-74% (p < 0.01), respectively. Yet, significant differences in MS/BS and BFR/BS between right and left limbs were found in verapamil- and nifedipine-treated animals, indicating that the treatments did not completely abolish load-induced bone formation. This study shows that blocking the L-type calcium channel in vivo substantially suppresses the mechanically induced increase in bone formation that normally would occur and suggests that the L-type calcium channel mediates mechanically induced bone adaptation in vivo" http://www.ncbi.nlm.nih.gov/pubmed/12369783 0 1974 "G. R. Scott, V. Cadena, G. J. Tattersall and W. K. Milsom" 2008 Body temperature depression and peripheral heat loss accompany the metabolic and ventilatory responses to hypoxia in low and high altitude birds J.Exp.Biol. 211 Pt 8 1326-1335 "The objectives of this study were to compare the thermoregulatory, metabolic and ventilatory responses to hypoxia of the high altitude bar-headed goose with low altitude waterfowl. All birds were found to reduce body temperature (T(b)) during hypoxia, by up to 1-1.5 degrees C in severe hypoxia. During prolonged hypoxia, T(b) stabilized at a new lower temperature. A regulated increase in heat loss contributed to T(b) depression as reflected by increases in bill surface temperatures (up to 5 degrees C) during hypoxia. Bill warming required peripheral chemoreceptor inputs, since vagotomy abolished this response to hypoxia. T(b) depression could still occur without bill warming, however, because vagotomized birds reduced T(b) as much as intact birds. Compared to both greylag geese and pekin ducks, bar-headed geese required more severe hypoxia to initiate T(b) depression and heat loss from the bill. However, when T(b) depression or bill warming were expressed relative to arterial O(2) concentration (rather than inspired O(2)) all species were similar; this suggests that enhanced O(2) loading, rather than differences in thermoregulatory control centres, reduces T(b) depression during hypoxia in bar-headed geese. Correspondingly, bar-headed geese maintained higher rates of metabolism during severe hypoxia (7% inspired O(2)), but this was only partly due to differences in T(b). Time domains of the hypoxic ventilatory response also appeared to differ between bar-headed geese and low altitude species. Overall, our results suggest that birds can adjust peripheral heat dissipation to facilitate T(b) depression during hypoxia, and that bar-headed geese minimize T(b) and metabolic depression as a result of evolutionary adaptations that enhance O(2) transport" http://www.ncbi.nlm.nih.gov/pubmed/18375857 0 1975 W. L. Shoop and K. C. Corkum 1984 Tegumental changes of Alaria marcianae (Trematoda) during migration in the domestic cat J.Parasitol. 70 2 244-252 "Mesocercariae of Alaria marcianae were removed from snake paratenic hosts and fed to domestic cats. The cats were necropsied at specified intervals, the parasites recovered, and studied by SEM. During the prepulmonary phase of migration in cats, mesocercariae recovered from the stomach wall, abdominal cavity, diaphragm, liver, and heart underwent no tegumental modification compared to those fixed immediately after removal from the paratenic host. The mesocercaria resembled the body of an enlarged cercaria. The oral sucker was encircled by 14 or 15 rows of simple, posteriorly directed spines. Similar spines were also located along the margins of the venter and equatorially at the level of the acetabulum. This spinal pattern left two regions, one anterior and one posterior to the acetabulum, devoid of spines. Uniciliate papillae were found in a distinct pattern associated with the spined areas. In the pulmonary phase, the mesocercariae transformed into diplostomula. Earlike lappets on either side of the oral sucker developed with subsequent differentiation of microvilliform processes on their ventral sides. Body spines divided to give rise to three-pronged serrations. A depression on the venter between the acetabulum and posterior end of the body gave rise to the tribocytic organ. Stout, densely-clustered spines arose de novo on this organ. A rudimentary cylindrical hindbody gave the diplostomulum a distinct scoop-shaped appearance. Worms coughed up from the lungs and swallowed were later found in the duodenum. This postpulmonary phase of migration was a quick event and young worms in the duodenum were indistinguishable from those in the lungs. Within 4 days, the diplostomula in the duodenum matured to adulthood.(ABSTRACT TRUNCATED AT 250 WORDS)" http://www.ncbi.nlm.nih.gov/pubmed/6470887 0 1976 C. Shively 2012 Sertraline has wide-ranging effects on socioemotional behavior in a female nonhuman primate model of depression "Biological Psychiatry.Conference: 67th Annual Scientific Convention and Meeting of the Society of Biological Psychiatry Philadelphia, PA United States.Conference Start: 20120503 Conference End: 20120505.Conference Publication: (var.pagings).71 (8 Supp" var.pagings 134S "Background: Effects of SSRIs on behavior and physiology have been rarely evaluated experimentally in nonhuman primates, and never in a nonhuman primate model of depression. Methods: 42 adult female cynomolgus monkeys (Macaca fascicularis), were housed in stable social groups (n=4 each) and consumed a Western diet. Baseline socioemotional behavior and physiology were characterized for 18 months and monkeys in the treatment group (n=21) began a 5-week cumulative dose response study. 0, 5, 10, 15, and 20 mg/kg doses of sertraline were administered orally for 1 week each. Aggression, submission, affiliation and activity were recorded during 10 min group scans before and 4 hrs after dosing. On the 7th day at each dose circulating sertraline/desmethylsertraline and CSF monoamines/ metabolites were determined 4 hrs after the last dose. Monkeys continued on the 20 mg/kg dose for 16 months and anxious and depressive behavior were assessed throughout. Results: At 20 mg/kg circulating sertraline/desmethylsertraline reached levels found in patients; CSF 5-HT and 5-HIAA decreased, and dopamine increased (all p's<0.05). Frequency of aggression and submission, and percent time locomoting and alone decreased, whereas percent time in body contact and grooming increased (all p's<0.05). While there were no significant changes in depressive behavior during the 16 months (p>0.10), scratching, an indicator of anxiety, decreased (p<0.05). Conclusions: In adult female monkeys, a clinically relevant oral dose of sertraline resulted in blood levels and CSF monoamine/metabolite changes similar to patients. Although depressive behavior was unaffected, sertraline reduced social strife as indicated by reduced aggression, increased affiliation, and decreased anxiety" DO - http://dx.doi.org/10.1016/j.biopsych.2012.02.013 0 1977 T. Kurata and M. Micksche 1978 Correlation of immune response with clinical stage in Lewis lung tumor-bearing mice Oncology 35 4 155-159 "The effect of Lewis lung tumor growth in mice on the induction of primary immune response to SRBC, was investigated by PFC assay for measuring antibody activity and by footpad test as a correlate for delayed type hypersensitivity reactions. With the appearance of micrometastases in the lungs there was a decline in the humoral and cellular immune response to the SRBC. An increase of number and size of metastases in the lungs led to a further depression of the immune reactivity. Since the reduction of general immune response in mice bearing this tumor is not due to a direct influence of tumor cells, it might be assumed that suppressor cells or factors, are actively abrogating the general and also the tumor directed immune reactions" http://www.ncbi.nlm.nih.gov/pubmed/704036 0 1978 "J. A. Bartz, J. Zaki, K. N. Ochsner, N. Bolger, A. Kolevzon, N. Ludwig and J. E. Lydon" 2010 Effects of oxytocin on recollections of maternal care and closeness Proceedings of the National Academy of Sciences of the United States of America 107 50 14 "Although the infant-caregiver attachment bond is critical to survival, little is known about the biological mechanisms supporting attachment representations in humans. Oxytocin plays a key role in attachment bond formation and maintenance in animals and thus could be expected to affect attachment representations in humans. To investigate this possibility, weadministered 24 IU intranasal oxytocin to healthy male adults in a double-blind, placebo-controlled, crossover designed study and then assessed memories of childhood maternal care and closeness - two features of the attachment bond. We found that the effects of oxytocin were moderated by the attachment representations people possess, with less anxiously attached individuals remembering their mother as more caring and close after oxytocin (vs. placebo) but more anxiously attached individuals remembering their mother as less caring and close after oxytocin (vs. placebo). These data contrast with the popular notion that oxytocin has broad positive effects on social perception and are more consistent with the animal literature, which emphasizes oxytocin's role in encoding social memories and linking those memories to the reward value of the social stimulus" 0 1979 "K. L. Eales, O. Palygin, T. O'Loughlin, S. Rasooli-Nejad, M. Gaestel, J. Muller, D. R. Collins, Y. Pankratov and S. A. Correa" 2014 The MK2/3 cascade regulates AMPAR trafficking and cognitive flexibility Nat.Commun. 5 4701 "The interplay between long-term potentiation and long-term depression (LTD) is thought to be involved in learning and memory formation. One form of LTD expressed in the hippocampus is initiated by the activation of the group 1 metabotropic glutamate receptors (mGluRs). Importantly, mGluRs have been shown to be critical for acquisition of new memories and for reversal learning, processes that are thought to be crucial for cognitive flexibility. Here we provide evidence that MAPK-activated protein kinases 2 and 3 (MK2/3) regulate neuronal spine morphology, synaptic transmission and plasticity. Furthermore, mGluR-LTD is impaired in the hippocampus of MK2/3 double knockout (DKO) mice, an observation that is mirrored by deficits in endocytosis of GluA1 subunits. Consistent with compromised mGluR-LTD, MK2/3 DKO mice have distinctive deficits in hippocampal-dependent spatial reversal learning. These novel findings demonstrate that the MK2/3 cascade plays a strategic role in controlling synaptic plasticity and cognition" http://www.ncbi.nlm.nih.gov/pubmed/25134715 0 1980 W. H. Taliaferro and L. G. Taliaferro 1964 "THE RELATION OF RADIATION DOSAGE TO ENHANCEMENT, DEPRESSION, AND RECOVERY OF THE INITIAL FORSSMAN HEMOLYSIN RESPONSE IN RABBITS" J.Infect.Dis. 114 285-303 http://www.ncbi.nlm.nih.gov/pubmed/14217927 0 1981 M. Abdelmoumene and J. M. Besson 1967 [Comparison of the action of barbiturates and chloralose on the potentials of the dorsal root] J.Physiol (Paris) 59 4 Suppl 323-324 http://www.ncbi.nlm.nih.gov/pubmed/4305998 0 1982 R. I. Mrongovius 1975 Structure activity correlations for central depressant acylureas and alkylureas "European Journal of Medicinal Chemistry.10 (5) ()(pp 474-479), 1975.Date of Publication: 1975." 5 474-479 0 1983 "G. N. M. Gurguis, J. Turkka, J. Karanian and M. Linnoila" 1998 The combined effects of chronic ethanol/desipramine treatment on beta-adrenoceptor density and coupling efficiency in rat brain "European Journal of Pharmacology.363 (2-3) ()(pp 241-251), 1998.Date of Publication: 18 Dec 1998." 02-Mar 241-251 "Both ethanol and desipramine influence beta-adrenoceptor regulation. We reported previously that ethanol partially counteracted desipramine's effects on beta-adrenoceptor. Previous studies utilized beta-adrenoceptor radioligands that also bind to 5-HT(1B) receptors, thus, changes in 5-HT(1B) receptors could have confounded the results. The effects of chronic ethanol, desipramine and ethanol/desipramine treatment on beta-adrenoceptor coupling efficiency to G(s) protein in rat brain were examined using 125I-iodocyanopindolol after blocking binding to 5-HT(1B) receptors. In the frontal cortex, ethanol uncoupled beta-adrenoceptor from G(s). Desipramine decreased beta-adrenoceptor density, particularly in the high-conformational state, with no effect on coupling. In combined treatment, desipramine prevented ethanol-induced uncoupling. In the hippocampus, desipramine enhanced beta-adrenoceptor coupling, but ethanol had no effect. In combination with desipramine, ethanol enhanced desipramine-induced decrease in beta-adrenoceptor density in the high-conformational state, but uncoupled beta-adrenoceptors, an effect not observed with ethanol alone. These results suggest a complex interplay between ethanol and antidepressants in modulating beta-adrenoceptor function. Copyright (C) 1998 Elsevier Science B.V" DO - http://dx.doi.org/10.1016/S0014-2999%2898%2900810-3 0 1984 "S. C. Cohen, H. L. Gabelnick, R. K. Johnson and A. Goldin" 1975 Effects of cyclophosphamide and adriamycin on the healing of surgical wounds in mice Cancer 36 4 1277-1281 "Administration of therapeutic dose levels of cyclophosphamide as a single dose or as daily treatments for 5 days during the perisurgical period resulted in a significant decrease in the strength of surgical skin wounds in mice as measured 21 days after surgery. Administration of a single dose of 200 mg/kg either at the time of surgery or up to 4 days prior to or after surgery impaired 21-day wound strength, with the most extensive depression observed when the drug was given 1 or 2 days after surgery. Earlier stages of wound healing (day 3 or day 7) were not as sensitive to cyclophosphamide. Adriamycin in the therapeutic dosage range for mice did not significantly impair wound healing. This drug had an effect only at the LD10 dosage level. Combination treatment with cyclophosphamide plus adriamycin at the time of surgery impaired 21-day wound strength to a greater degree than observed with either agent alone, but did not significantly depress wound strength 3 or 7 days after surgery. These studies indicate that dosage level, the time of drug administration relative to surgery, and the time at which wound strength measurements are made are important parameters in determination of the effects of antineoplastic agents on wound healing" http://www.ncbi.nlm.nih.gov/pubmed/1175126 0 1985 "P. J. Davey, J. M. Haslam and A. W. Linnane" 1970 Biogenesis of mitochondria. 12. The effects of aminoglycoside antibiotics on the mitochondrial and cytoplasmic protein-synthesizing systems of Saccharomyces cerevisiae Arch.Biochem.Biophys. 136 1 54-64 http://www.ncbi.nlm.nih.gov/pubmed/4313769 0 1986 "W. R. Paukovits, M. H. Moser, K. A. Binder and J. B. Paukovits" 1991 Protection from arabinofuranosylcytosine and n-mustard-induced myelotoxicity using hemoregulatory peptide pGlu-Glu-Asp-Cys-Lys monomer and dimer Blood 77 6 1313-1319 "We have previously shown that the synthetic peptide pGlu-Glu-Asp-Cys-Lys (pEEDCK monomer) inhibits the cytostatic drug-induced proliferation of hematopoietic stem cells CFU-S. Keeping CFU-S quiescent by pEEDCK treatment renders them insensitive to cycle-specific cytostatic drugs and leads to reduced toxicity. Here we show that pEEDCK application during repeated (twice) administration of clinically relevant (nonlethal) 1-beta-D-arabinofuranosylcytosine (Ara-C) doses reduced the percentage of CFU-S in S-phase from 60%-70% to 25%-30% and led to a sustained stem cell number in the bone marrow (BM), whereas unprotected mice had lost about 75% of their CFU-S population. Owing to its cysteine content, the pEEDCK monomer is easily oxidized. The resulting dimer (pEEDCK)2 is a potent stimulator of hematopoiesis. As we show, it can be used for postchemotherapy acceleration of hematologic recovery, similar to the use of recombinant hematopoietic growth factors. A single injection of 30 micrograms/kg pEEDCK monomer to mice 2 hours before the second Ara-C injection retarded onset of neutropenia (by 2 to 3 days) and improved recovery after depression. The quantitative degree of neutropenia was not changed. Postchemotherapy (Ara-C administered twice, followed by N-mustard) infusion of the stimulatory (pEEDCK)2 dimer (1.4 micrograms/kg/d) produced a 4.6-fold increase of progenitor levels (6.7 CFU-GM/1,000 BM cells v 1.45 CFU-GM/1,000 in normal mice) 2 days after the end of the cytostatic treatment when CFU-GM were not detectable in unprotected mice. This increase was followed after several days by strongly elevated granulocyte counts, which remained high for approximately 1 week. Up to 75% of the peripheral leukocytes were mature polymorphonuclear leukocytes (PMN) during this phase. Ara-C (twice) and monomer treatment as above followed by dimer infusion resulted in the complete protection of hematopoiesis. Mice treated with the protective pEEDCK monomer plus stimulatory dimer did not develop the leukocyte depression noted in unprotected animals. The inhibitory monomer appears to keep the stem cell population numerically and qualitatively intact, thus providing optimum target cell conditions for the subsequent stimulator (dimer) treatment. Our results show that the hemoregulatory peptide monomer and dimer can be used for improving the hematologic status of mice treated with clinically relevant doses of cytostatic drugs (antimetabolite and alkylating, alone and in combination). Combining both peptides can prevent occurrence of neutropenia completely. Both peptides can be obtained easily by chemical synthesis and are also active on human cells. They are thus highly promising candidates for application as multilevel hemoprotectors in cancer chemotherapy" http://www.ncbi.nlm.nih.gov/pubmed/2001454 0 1987 "P. Wang, Z. F. Ba and I. H. Chaudry" 1991 Hepatic extraction of indocyanine green is depressed early in sepsis despite increased hepatic blood flow and cardiac output Arch.Surg. 126 2 219-224 "Although active hepatocellular function is depressed during sepsis, it is not known whether this occurs in the very early stages of sepsis and whether it is due to depressed cardiac output or hepatic blood flow. To study this, rats were subjected to sepsis by cecal ligation and puncture and hepatocellular function was determined at various intervals thereafter by assessing the ability of the liver to clear different doses of indocyanine green. The indocyanine green concentration was continuously measured in vivo with a fiberoptic catheter and an in vivo hemoreflectometer. Maximal velocity and kinetic constant of the clearance of indocyanine green, hepatic blood flow, and cardiac output were determined in experimental and sham-operated rats. The results demonstrate that hepatic blood flow and cardiac output increased 2 to 10 hours after cecal ligation and puncture, while hepatocellular function (maximum velocity and kinetic constant) was decreased even 2 hours following cecal ligation and puncture. No linear correlation between hepatocellular function and hepatic blood flow or cardiac output was found under such conditions. The extremely early depression in active hepatocellular function, despite the increased hepatic blood flow and cardiac output, may form the basis for cellular dysfunctions leading to multiple organ failure during sepsis" http://www.ncbi.nlm.nih.gov/pubmed/1992997 0 1988 "F. C. Tanyel, A. Ayhan, N. Buyukpamukcu and A. Hicsonmez" 1989 The testes after unilateral incarcerated inguinal hernia in prepubertal rats Turk.J.Pediatr. 31 4 263-269 "The ipsilateral and contralateral testes after unilateral incarcerated inguinal hernia were evaluated, and compared to the contralateral testis after unilateral testicular torsion in 30 prepubertal rats. Control, torsion and detorsion at 24 hours, and incarcerated inguinal hernia and reduction in the 24 hour groups, each consisting of ten rats were established. The testes were harvested after 15 days. Mean seminiferous tubular diameters (MSTD) and mean testicular biopsy scores (MTBS) were determined and compared. A decrease in MSTD and depression in MTBS, which was more prominent in the ipsilateral testes, were found in both ipsilateral and contralateral testes following unilateral incarcerated inguinal hernia. The testicular damage encountered after unilateral incarcerated inguinal hernia was similar to the contralateral testicular damage following unilateral testicular torsion with the utilized parameters" http://www.ncbi.nlm.nih.gov/pubmed/2486425 0 1989 "K. E. Kinnamon, L. H. Blackwell and G. D. Ledney" 1975 Alterations in graft--ersus-host reactivity and peripheral leukocytes in mice after erythropoietin treatment Exp.Hematol. 3 4 234-243 "Treatment of mice on four consecutive days with either erythropoietin (EP) or rabbit antimouse thymocyte serum (ATS) resulted in a significant reduction in antigenic reactivity of spleen cells as measured by the Simonsen assay. In normal animals, treatment with either EP or ATS resulted in lymphopenia and in most instances a neutrophilia and a variable monocytopenia. Similar alterations in these cell types were recorded for polycythemic mice subsequent to treatment with either EP or ATS. These data plus histologic analyses support the idea that there is an inverse relationship between the cells committed to differentiate along the lymphoid cell line and the cells committed to differentiate along myeloid cell lines. Further, the data are consistent with the ""carrying capacity"" concept regarding the stem cell microenvironment and support the monophyletic theory" http://www.ncbi.nlm.nih.gov/pubmed/240732 0 1990 "E. Martisova, B. Aisa, R. M. Tordera, E. Puerta, M. Solas and M. J. Ramirez" 2015 Venlafaxine reverses decreased proliferation in the subventricular zone in a rat model of early life stress Behav.Brain Res. 292 79-82 "It is believed that glucocorticoids control the proliferation of neural progenitor cells, and this process is highly involved in mood disorders and cognitive processes. Using the maternal separation model of chronic neonatal stress, it has been found that stress induced depressive-like behavior, cognitive deficits and a decrease in proliferation in the subventricular zone (SVZ). Venlafaxine reversed all deleterious effects of chronic stress by modulating HPA activity. These outcomes suggest modulation of stress-mediated glucocorticoid secretion as a target for the treatment of mood disorders and neurodegenerative processes" http://www.ncbi.nlm.nih.gov/pubmed/26051818 1 1991 W. F. Jackson and R. Busse 1991 Elevated guanosine 3':5'-cyclic monophosphate mediates the depression of nitrovasodilator reactivity in endothelium-intact blood vessels Naunyn Schmiedebergs Arch.Pharmacol. 344 3 345-350 "The influence of endothelium-derived nitric oxide (EDNO) on relaxation induced by the nitrovasodilators, sodium nitroprusside and sodium nitrite was assessed in phenylephrine-stimulated hamster thoracic aortas, a preparation that displays significant basal release of EDNO. Removal of the endothelium or treatment with the NO synthase inhibitors, NG-nitro-L-arginine (L-NAG, 10-30 microM) or NG-methyl-L-arginine (L-NMMA; 100 microM) increased the potency and, except for sodium nitroprusside in endothelium-denuded segments, also increased the efficacy of the nitrovasodilators. Removal of the endothelium had no effect on relaxations induced by isoproterenol, an indication that these effects were specific for the nitrovasodilators. Removal of the endothelium, treatment of endothelium-intact preparations with L-NAG or L-NMMA, or exposure of these vessels to the guanylate cyclase inhibitor, methylene blue (10 microM) increased reactivity of the aortas to the guanosine 3':5'-cyclic monophosphate (cGMP) analogue, 8-Br cGMP. Measurement of cGMP revealed that endothelium-intact segments had a 6.5 fold higher level of cGMP than endothelium-denuded preparations and that sodium nitroprusside increased cGMP in both preparations by similar amounts in a concentration-dependent fashion. Exposure of endothelium-denuded or L-NAG-treated segments to sodium nitroprusside, to mimic the effects of basally released EDNO, depressed sodium nitrite and 8-Br cGMP reactivity in a manner similar to endothelium-intact segments. These data indicate that EDNO increases cGMP levels in vascular smooth muscle and that the elevated cGMP levels depress nitrovasodilator and 8-Br cGMP reactivities" http://www.ncbi.nlm.nih.gov/pubmed/1660105 0 1992 "B. Krespan, S. A. Springfield, H. Haas and H. M. Geller" 1984 Electrophysiological studies on benzodiazepine antagonists Brain Res. 295 2 265-274 "The actions of the benzodiazepine (BDZ) antagonists 3-hydroxymethyl-beta-carboline (3-HMC), Ro 14-7437 and Ro 15-1788 were tested on single cell activity of rat hypothalamic neurons in tissue cultures and on membrane properties of CA1 hippocampal pyramidal neurons in transverse slices. In addition, we examined the interactions of some of these agents with inhibitions elicited by gamma-aminobutyric acid (GABA) as well as the ability of Ro 14-7437 to reverse the GABA-enhancing action of the BDZ agonist flurazepam. BDZ antagonists did not alter patterns of spontaneous activity of hypothalamic neurons and did not affect resting membrane potential or membrane conductance in CA1 pyramidal cells. Ro 14-7437 either partially or totally reversed the potentiation by flurazepam of GABA-elicited depression of hypothalamic neuronal activity. Small and inconsistent actions on GABA-mediated inhibitions of hypothalamic neurons were noted. Electrically-elicited inhibitions of hypothalamic neurons were either not altered or slightly reduced. In the hippocampal slice, the frequency of spontaneous IPSPs, the amplitude of stratum-radiatum evoked IPSPs and the conductance increase caused by stratum-radiatum stimulation were either not altered or slightly reduced. These findings demonstrate that non-convulsant BDZ antagonists block the action of BDZ agonists in facilitating GABA and further that the presence of a BDZ agonist is not required for these GABA-mediated events to occur. However, these experiments do not exclude a modulatory role for an endogenous BDZ agonist on GABA-mediated events" http://www.ncbi.nlm.nih.gov/pubmed/6424866 0 1993 "N. Susa, S. Ueno, Y. Furukawa and M. Sugiyama" 1997 "Protective effect of deferoxamine on chromium (VI)-induced DNA single-strand breaks, cytotoxicity, and lipid peroxidation in primary cultures of rat hepatocytes" Arch.Toxicol. 71 6 345-350 "Incubation of primary cultures of rat hepatocytes with K2CR2O7 and deferoxamine (DFO), an iron chelator, resulted in a marked decrease in cellular levels of DNA single-strand breaks caused by K2Cr2O7. Cellular treatment with DFO also suppressed both dichromate-induced cytotoxicity--evaluated by the leakage of lactate dehydrogenase, and lipid peroxidation--as monitored by malondialdehyde formation. In addition, treatment with DFO attenuated the suppression of the levels of vitamin E and C as well as the inhibition of alkaline phosphatase and glutathione peroxidase activity attributed to K2Cr2O7. However, DFO had no influence on the cellular level of glutathione or the activity of glutathione reductase and superoxide dismutase suppressed by dichromate. Under the same experimental conditions, cellular uptake and distribution of chromium were not affected by DFO. These results indicate that DFO protects cells from chromium (VI)-induced DNA strand breaks, cytotoxicity, lipid peroxidation, vitamin E and C depression, and glutathione peroxidase inhibition The role of antioxidants in chromium (VI)-induced cytotoxicity, DNA breaks, and lipid peroxidation is discussed" http://www.ncbi.nlm.nih.gov/pubmed/9195015 0