28547854	(1) To identify trajectories of cannabis use across adolescence, (2) to measure the influence of cannabis use characteristics on functional connectivity of the nucleus accumbens (NAcc) and (3) to assess whether patterns of functional connectivity related to cannabis use are associated with psychosocial functioning 2 years later.The Pitt Mother and Child Project (PMCP) is a prospective, longitudinal study of male youth at high risk for psychopathology based on family income and gender.	Participants were recruited between age 6 and 17 months from the Women, Infants and Children Nutritional Supplement program (WIC) in the Pittsburgh, Pennsylvania area.	A total of 158 PMCP young men contributed functional magnetic resonance imaging (fMRI) and substance use data at age 20 years.	Latent class growth analysis was used to determine trajectories of cannabis use frequency from age 14 to 19 years. Psychophysiological interaction (PPI) analysis was used to measure functional connectivity between the NAcc and prefrontal cortex (PFC). Adolescent cannabis use trajectory, recent frequency of use and age of initiation were considered as developmental factors. We also tested whether functional connectivity was associated with depressive symptoms, anhedonia and educational attainment at age 22.	We identified three distinct trajectories of adolescent cannabis use, characterized by stable high, escalating or stable low use. The cannabis use trajectory group had a significant effect on NAcc functional connectivity to the medial PFC (F = 11.32, Z = 4.04, Pfamily-wise error-corrected (FWE-corr)  = 0.000). The escalating trajectory group displayed a pattern of negative NAcc-mPFC connectivity that was linked to higher levels of depressive symptoms (r = -0.17, P < .05), anhedonia (r = -0.19, P < .05) and lower educational attainment (t = -2.77, P < .01) at age 22.	Pattern of cannabis use frequency across adolescence in US youth could have consequences for mood symptoms and educational attainment in early adulthood via altered function in neural reward circuitry.	
28336742	To (1) establish the extent of opportunities for members of the public to check their own blood pressure (BP) outside of healthcare consultations (BP self-screening), (2) investigate the reasons for and against hosting such a service and (3) ascertain how BP self-screening data are used in primary care.A mixed methods, cross-sectional study.	Primary care and community locations in Oxfordshire, UK.	325 sites were surveyed to identify where and in what form BP self-screening services were available. 23 semistructured interviews were then completed with current and potential hosts of BP self-screening services.	18/82 (22%) general practices offered BP self-screening and 68/110 (62%) pharmacies offered professional-led BP screening. There was no evidence of permanent BP self-screening activities in other community settings.Healthcare professionals, managers, community workers and leaders were interviewed. Those in primary care generally felt that practice-based BP self-screening was a beneficial activity that increased the attainment of performance targets although there was variation in its perceived usefulness for patient care. The pharmacists interviewed provided BP checking as a service to the community but were unable to develop self-screening services without a clear business plan. Among potential hosts, barriers to providing a BP self-screening service included a perceived lack of healthcare commissioner and public demand, and a weak-if any-link to their core objectives as an organisation.	BP self-screening currently occurs in a minority of general practices. Any future development of community BP self-screening programmes will require (1) public promotion and (2) careful consideration of how best to support-and reward-the community hosts who currently perceive little if any benefit.	
28274677	Irritability, defined as an increased propensity to exhibit increased anger relative to one's peers, is a common clinical problem in youth. Irritability can be conceptualized as aberrant responses to frustration (where frustration is the emotional response to blocked goal attainment) and/or aberrant 'approach' responses to threat. Irritable youth show hyper-reactivity to threat mediated by dysfunction in amygdala, medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), insula, striatum, and association cortex. Irritable youth also show abnormalities in reward learning, cognitive control, and responses to frustration. These abnormalities are mediated by circuitry that includes the inferior frontal gyrus (iFG), striatum, ACC, and parietal cortex. Effective treatments for irritability are lacking, but pathophysiological research could lead to more precisely targeted interventions.
27926436	By definition, instrumental actions are performed in order to obtain certain goals. Nevertheless, the attainment of goals typically implies obstacles, and response vigor is known to reflect an integration of subjective benefit and cost. Whereas several brain regions have been associated with cost/benefit ratio decision-making, trial-by-trial fluctuations in motivation are not well understood. We review recent evidence supporting the motivational implications of signal fluctuations in the mesocorticolimbic system. As an extension of "set-point" theories of instrumental action, we propose that response vigor is determined by a rapid integration of brain signals that reflect value and cost on a trial-by-trial basis giving rise to an online estimate of utility. Critically, we posit that fluctuations in key nodes of the network can predict deviations in response vigor and that variability in instrumental behavior can be accounted for by models devised from optimal control theory, which incorporate the effortful control of noise. Notwithstanding, the post hoc analysis of signaling dynamics has caveats that can effectively be addressed in future research with the help of two novel fMRI imaging techniques. First, adaptive fMRI paradigms can be used to establish a time-order relationship, which is a prerequisite for causality, by using observed signal fluctuations as triggers for stimulus presentation. Second, real-time fMRI neurofeedback can be employed to induce predefined brain states that may facilitate benefit or cost aspects of instrumental actions. Ultimately, understanding temporal dynamics in brain networks subserving response vigor holds the promise for targeted interventions that could help to readjust the motivational balance of behavior.
27923496	There has been growing interest under the Research Domain Criteria initiative to investigate behavioral constructs and their underlying neural circuitry. Abnormalities in reward processes are salient across psychiatric conditions and may precede future psychopathology in youth. However, the neural circuitry underlying such deficits has not been well defined. Therefore, in this pilot, we studied youth with diverse psychiatric symptoms and examined the neural underpinnings of reward anticipation, attainment, and positive prediction error (PPE, unexpected reward gain). Clinically, we focused on anhedonia, known to reflect deficits in reward function.Twenty-two psychotropic medication-free youth, 16 with psychiatric symptoms, exhibiting a full range of anhedonia, were scanned during the Reward Flanker Task. Anhedonia severity was quantified using the Snaith-Hamilton Pleasure Scale. Functional magnetic resonance imaging analyses were false discovery rate corrected for multiple comparisons.	Anticipation activated a broad network, including the medial frontal cortex and ventral striatum, while attainment activated memory and emotion-related regions such as the hippocampus and parahippocampal gyrus, but not the ventral striatum. PPE activated a right-dominant fronto-temporo-parietal network. Anhedonia was only correlated with activation of the right angular gyrus during anticipation and the left precuneus during PPE at an uncorrected threshold.	Findings are preliminary due to the small sample size.	This pilot characterized the neural circuitry underlying different aspects of reward processing in youth with diverse psychiatric symptoms. These results highlight the complexity of the neural circuitry underlying reward anticipation, attainment, and PPE. Furthermore, this study underscores the importance of RDoC research in youth.	
27876165	The Research Domain Criteria (RDoC) initiative provides a large-scale, dimensional framework for the integration of research findings across traditional diagnoses, with the long-term aim of improving existing psychiatric treatments. A neurodevelopmental perspective is essential to this endeavor. However, few papers synthesizing research findings across childhood and adolescent disorders exist. Here, we discuss how the RDoC framework may be applied to the study of childhood and adolescent impulsive and addictive disorders in order to improve neurodevelopmental understanding and to enhance treatment development. Given the large scope of RDoC, we focus on a single construct highly relevant to addictive and impulsive disorders - initial responsiveness to reward attainment. Findings from genetic, molecular, neuroimaging and other translational research methodologies are highlighted.
26896723	Evidence consistently shows that low education is associated with unhealthy behaviors. A recent study in behavioral economics argued that high time preferences - the tendency to prefer immediate gain to later reward - explain the limited self-control of individuals in making preventive health-related choices. The aim of this study was to examine the mediating effect of time preference on the associations between education and smoking, binge drinking and overweight in young and middle-aged adults living in a Japanese metropolitan area, using a quantitatively measured time discount rate. A population-based probabilistic sample of residents of 25-50 years of age living in four municipalities within Japanese metropolitan areas where economic disparity is relatively large was obtained from the Japanese Study on Stratification, Health, Income, and Neighborhood (J-SHINE). Respondents answered the questionnaire items using a computer-aided personal instrument (CAPI). Data from 3457 respondents were used in this study. Time preferences measured as categorical responses were converted into a continuous number of time discount rates by using the maximum likelihood method. Smoking habit, binge drinking, and body mass index were regressed on educational attainment with demographics and other confounders. The mediating effects of the time discount rate were examined with the bootstrapping method. Results showed that the time discount rate did not mediate the association between education and binge drinking and BMI. Even for smoking, the mediating effect of time discount rate was quite limited, indicating that the proportion of total effect of education mediated was only 4.3% for men and 3.0% for women. The results suggest that modifying time preferences through educational intervention has only limited efficacy in closing disparities in health-related behaviors, and that other mediators fostered by schooling, such as knowledge/skills, group norms and supportive peers/networks, may be more important as modifiable mediators in the link between education and smoking. 
26834668	It is unequivocal that a wide variety of incentives can motivate behavior. However, few studies have explicitly examined whether and how different incentives are integrated in terms of their motivational influence. The current study examines the combined effects of monetary and liquid incentives on cognitive processing, and whether appetitive and aversive incentives have distinct influences. We introduce a novel task paradigm, in which participants perform cued task-switching for monetary rewards that vary parametrically across trials, with liquid incentives serving as post-trial performance feedback. Critically, the symbolic meaning of the liquid was held constant (indicating successful reward attainment), while liquid valence was blocked. In the first experiment, monetary rewards combined additively with appetitive liquid feedback to improve subject task performance. Aversive liquid feedback counteracted monetary reward effects in low monetary reward trials, particularly in a subset of participants who tended to avoid responding under these conditions. Self-report motivation ratings predicted behavioral performance above and beyond experimental effects. A follow-up experiment replicated the predictive power of motivation ratings even when only appetitive liquids were used, suggesting that ratings reflect idiosyncratic subjective values of, rather than categorical differences between, the liquid incentives. Together, the findings indicate an integrative relationship between primary and secondary incentives and potentially dissociable influences in modulating motivational value, while informing hypotheses regarding candidate neural mechanisms. 
26794248	Depressive symptoms are common and economically relevant. Women suffer more often than men do. We analyze associations between social status inconsistency, psychosocial factors, and depressive symptoms stratified by gender.In the present study, 3340 employees of two age cohorts (1959, 1965) working in two waves (2011, 2014) of the prospective German lidA-study and who gave written consent to link register data regarding their employment histories were included. Gender-specific influences of social status inconsistency (deviation of observed income from expected average income based on acquired education) on depressive symptoms and mediation of these associations by work stress in terms of effort-reward-imbalance (ERI) and work-family-conflict (WFC) were analyzed with confirmatory cross-lagged path models.	Among men, consistent status (i.e., average income in a specific educational group) increased the frequency of depressive symptoms. No association between negative SSI (i.e., income below the average income given a specific educational attainment) or positive SSI (i.e., income above the average income given a specific educational attainment) and depressive symptoms was observed among men or women. ERI and WFC were longitudinally associated with the outcome and differed slightly regarding gender, i.e., showing stronger effects of ERI for women and of WFC for men. Mediation of the association between social status and depressive symptoms was observed for men and for consistent status (path: consistent status → ERI → depressive symptoms) but not for SSI.	ERI and WFC increase the risk of future episodes with depressive symptoms in men and in women irrespective of SSI, occupational position, full- or part-time work, regional factors or individual characteristics.	
26647004	There is a growing body of research into the development of prospective memory (PM) in typically developing children but research is limited in autistic children (Aut) and rarely includes children with more severe symptoms.This study is the first to specifically compare event-based PM in severely autistic children to mildly autistic and typically developing children.	Fourteen mildly autistic children and 14 severely autistic children, aged 5-13 years, were matched for educational attainment with 26 typically developing children aged 5-6 years. Three PM tasks and a retrospective memory task were administered.	Results showed that severely autistic children performed less well than typically developing children on two PM tasks but mildly autistic children did not differ from either group. No group differences were found on the most motivating (a toy reward) task.	The findings suggest naturalistic tasks and motivation are important factors in PM success in severely autistic children and highlights the need to consider the heterogeneity of autism and symptom severity in relation to performance on event-based PM tasks.	
26115223	Research in motivation and emotion has been increasingly influenced by the perspective that processes underpinning the motivated approach of rewarding goals are distinct from those underpinning enjoyment during reward consummation. This distinction recently inspired the construction of the Temporal Experience of Pleasure Scale (TEPS), a self-report measure that distinguishes trait anticipatory pleasure (pre-reward feelings of desire) from consummatory pleasure (feelings of enjoyment and gratification upon reward attainment). In a university community sample (N = 97), we examined the TEPS subscales as predictors of (1) the willingness to expend effort for monetary rewards, and (2) affective responses to a pleasant mood induction procedure. Results showed that both anticipatory pleasure and a well-known trait measure of reward motivation predicted effort-expenditure for rewards when the probability of being rewarded was relatively low. Against expectations, consummatory pleasure was unrelated to induced pleasant affect. Taken together, our findings provide support for the validity of the TEPS anticipatory pleasure scale, but not the consummatory pleasure scale. 
25812142	Several studies report socioeconomic differences in work stress, where people in lower socioeconomic positions (SEP) are more likely to experience this burden. In the current study, we analyse associations between education and work stress in a large sample of workers from 16 European countries. In addition we explore whether distinct national labour market policies are related to smaller inequalities in work stress according to educational attainment.We use data collected in 2010/11 in two comparative studies ('Survey of Health, Ageing and Retirement in Europe' and the 'English Longitudinal Study of Ageing'; N = 13695), with samples of men and women aged 50 to 64 from 16 European countries. We measure highest educational degree according to the international standard classification of education (ISCED) and assess work stress in terms of the demand-control and the effort-reward imbalance model. National labour market policies are measured on the basis of policy indicators which are divided into (1) 'protective' policies offering financial compensation to those excluded from the labour market (e.g. replacement rate), and (2) 'integrative' policies supporting disadvantaged individuals on the labour market (e.g. investments into active labour market policies or possibilities for further qualification in later life). In addition to country-specific analyses, we estimate multilevel models and test for interactions between the indicators of national policies and individual education.	Main findings demonstrate consistent associations between lower education and higher levels of work stress in all countries. The strength of this association, however, varies across countries and is comparatively small in countries offering pronounced 'integrative' policies, in terms of high investments into measures of an active labor market policy and high participation rates in lifelong learning activities.	Our results point to different types of policies that may help to reduce educational differences in work stress, in particular policies supporting those who are disadvantaged on the labour market.	
25753286	Occupational stress as a key determinant for explaining health inequalities has been well established while the impact of stress related to family work has rarely been considered. This study investigates whether stress in household and family work may contribute to health inequalities in women. We used a population-based sample of German mothers (n = 3129) to determine the total, direct and indirect effects of education on somatic complaints by means of OLS regression-based mediation models. Inference about indirect effects was determined by 95% bias corrected bootstrap confidence intervals. Education was assessed by a measure combining school education and vocational training. Stress was measured using the adopted effort-reward-imbalance (ERI) questionnaire for household and family work. The von Zerssen list of somatic complaints was used as measure of subjective health. We found a significant total effect of education on somatic complaints (p ≤ 0.001) as well as significant indirect effects through 'effort' (p = 0.006) and 'reward' in household and family work (p ≤ 0.001). However, the subscales of ERI pointed into different directions: while levels of 'effort' increased with women's educational attainment, levels of distress related to low 'reward' decreased with higher levels of education. Our findings suggest that the effect of women's education on somatic complaints is mediated through stress related to low reward for household and family work. In particular, lack of 'societal esteem' for household and family work contributed to health disadvantages in lower educated mothers. We conclude that research on health inequality would benefit from taking stressful experiences in household and family work greater into account. 
25697184	Social groups across species rapidly self-organize into hierarchies, where members vary in their level of power, influence, skill, or dominance. In this review, we explore the nature of social hierarchies and the traits associated with status in both humans and nonhuman primates, and how status varies across development in humans. Our review finds that we can rapidly identify social status based on a wide range of cues. Like monkeys, we tend to use certain cues, like physical strength, to make status judgments, although layered on top of these more primitive perceptual cues are sociocultural status cues like job titles and educational attainment. One's relative status has profound effects on attention, memory, and social interactions, as well as health and wellness. These effects can be particularly pernicious in children and adolescents. Developmental research on peer groups and social exclusion suggests teenagers may be particularly sensitive to social status information, but research focused specifically on status processing and associated brain areas is very limited. Recent evidence from neuroscience suggests that there may be an underlying neural network, including regions involved in executive, emotional, and reward processing, that is sensitive to status information. We conclude with questions for future research as well as stressing the need to expand social neuroscience research on status processing to adolescents. 
25468174	Goal pursuit is known to be impaired in schizophrenia, but nothing much is known in these patients about unconscious affective processes underlying goal pursuit. Evidence suggests that in healthy individuals positive subliminal cues are taken as a signal that goal pursuit is easy and therefore reduce the effort that is mobilized for goal attainment. Patients with schizophrenia and healthy controls were instructed that a long run of successive correct responses in a visual attention task would entitle them to a reward (the goal to attain). Affective pictures were displayed supraliminally or subliminally during each run and electrophysiological activity was recorded. Patients self-assessed the emotional content of the pictures correctly. However, differences between patients and controls emerged during the goal pursuit task. Healthy controls mobilized less effort for the positive than the neutral subliminal pictures, as suggested by increased error rates and the weaker contingent negative variation (CNV). For the patients, no influence of positive subliminal pictures was found on performance and on the CNV. Similarly the influence of positive pictures was absent or abnormal on components which are usually impaired in patients (fronto-central P2 and N2). In contrast, positive pictures influenced normally the parieto-occipital N2, related to a component of visual attention which has been proposed to be preserved in schizophrenia. The present study indicates the difficulties of patients to modulate effort mobilization during goal pursuit in the presence of positive subliminal cues. The results question the role of cognitive deficits on affective influences. 
25241675	Growing evidence indicates that risk for bipolar disorder is characterized by elevated activation in a fronto-striatal reward neural circuit involving the ventral striatum and orbitofrontal cortex, among other regions. It is proposed that individuals with abnormally elevated reward-related neural activation are at risk for experiencing an excessive increase in approach-related motivation during life events involving rewards or goal striving and attainment. In the extreme, this increase in motivation is reflected in hypomanic/manic symptoms. By contrast, unipolar depression (without a history of hypomania/mania) is characterized by decreased reward responsivity and decreased reward-related neural activation. Collectively, this suggests that risk for bipolar disorder and unipolar depression are characterized by distinct and opposite profiles of reward processing and reward-related neural activation. The objective of the present paper is threefold. First, we review the literature on reward processing and reward-related neural activation in bipolar disorder, and in particular risk for hypomania/mania. Second, we propose that reward-related neural activation reflects a biological marker of differential risk for bipolar disorder versus unipolar depression that may help facilitate psychiatric assessment and differential diagnosis. We also discuss, however, the challenges to using neuroscience techniques and biological markers in a clinical setting for assessment and diagnostic purposes. Lastly, we address the pharmacological and psychosocial treatment implications of research on reward-related neural activation in bipolar disorder. 
25174632	As the search for more effective HIV prevention strategies continues, increased attention is being paid to the potential role of cash transfers in prevention programming in sub-Saharan Africa. To date, studies testing the impact of both conditional and unconditional cash transfers on HIV-related behaviours and outcomes in sub-Saharan Africa have been relatively small-scale and their potential feasibility, costs and benefits at scale, among other things, remain largely unexplored. This article examines elements of a successful cash transfer program from Latin America and discusses challenges inherent in scaling-up such programs. The authors attempt a cost simulation of a cash transfer program for HIV prevention in South Africa comparing its cost and relative effectiveness--in number of HIV infections averted--against other prevention interventions. If a cash transfer program were to be taken to scale, the intervention would not have a substantial effect on decreasing the force of the epidemic in middle- and low-income countries. The integration of cash transfer programs into other sectors and linking them to a broader objective such as girls' educational attainment may be one way of addressing doubts raised by the authors regarding their value for HIV prevention.
24291504	Animals approach rewards and cues associated with reward, even when this behavior is irrelevant or detrimental to the attainment of these rewards. Motivated by these findings we study the biology of financially-costly approach behavior in humans. Our subjects passively learned to predict the occurrence of erotic rewards. We show that neuronal responses in ventral striatum during this Pavlovian learning task stably predict an individual's general tendency towards financially-costly approach behavior in an active choice task several months later. Our data suggest that approach behavior may prevent some individuals from acting in their own interests. 
23949069	Behavioral aspects of motor learning such as definition and assessment of patient-centered goals, specific motivation, training in the patients' environment, autonomous training and generalization of newly learned skills to daily life are not an explicit part of physiotherapy in neurorehabilitation.Specific goals are defined and applied in a step by step manner. Exercises and application in daily life were trained and anticipated as a "self control cue" for the following week. Motivation was sustained via supervision, feedback after successful trials and reward. Exercises have to occure at a daily basis and have to be implemented in everyday life.	A 54 year old man who suffered cerebral bleeding with left hemiparesis 25 years ago. We report goal attainment, change of symptoms and walking capacities over a period of 18 months.	Back pain and knee pain reduced to zero, rhythmic walking, walking speed increased, left leg less resistance, running possible.	The here described principles of behavioral physiotherapy are crucial for successful outcome in extremely stable and persistent consequences of stroke. Studies with more patients are needed to strengthen our hypothesis.	
23288323	Human motivation is sensitive to value-to the outcomes of actions. People invest mental and physical resources for obtaining desired results or for stopping and reversing undesired ones. Accordingly, people's motivation is sensitive to information about their standing in relation to outcome attainment ('outcome feedback'). In this paper, we argue and present the first evidence for the existence of another motivational sensitivity in humans-a sensitivity to our degree of control on the environment and hence to information about that control ('control feedback'). We show that when actions have even trivial and constant perceptual effects, participants' motivation to perform is enhanced. We then show that increased motivation is not because more information about task performance is available and that motivation is increased only in conditions in which control over the effects can be firmly established by the mind. We speculate on the implications for understanding motivation, and potentially, physical and mental health. 
22524766	Aggressive donor management protocols have evolved to maximize the number of procured organs. Our study assessed donor management time and the number and types of organs procured with the hypothesis that shorter management time yields increased organ procurement and transplant rates.  We prospectively analyzed 100 donors managed by a regional organ procurement organization (OPO) during 2007 to 2008. Data included patient demographics, number and types of organs procured and transplanted, patient management time by the OPO, and achievement of donor preprocurement goals.  One hundred consecutive organ donors were managed with a mean age 41 ± 18 years and mean management time 23 ± 9 hours; 376 organs were procured and 327 successfully transplanted. Donors managed greater than 20 hours yielded significantly more heart (5 vs 26, P <  0.01) and lung (6 vs 40, P < 0.01) procurements, more organs procured per donor (3.2 ± 1.4 vs 4.2 ± 1.6, P < 0.01), and more organs transplanted per donor (2.6 ± 1.5 vs 3.7 ± 1.8, P < 0.01) than those managed 20  hours or less. No difference in the attainment of donor management goals was observed between these populations. Contrary to our initial hypothesis, donor management times greater than 20 hours yielded increased organ procurement and transplant rates, particularly for hearts and lungs, despite  no differences in the achievement of donor preprocurement management goals.
22468672	When in pursuit of rewards, humans weigh the value of potential rewards against the amount of effort that is required to attain them. Although previous research has generally conceptualized this process as a deliberate calculation, recent work suggests that rudimentary mechanisms-operating without conscious intervention-play an important role as well. In this article, we propose that humans can perform a basic integration of reward value and effort requirements without conscious awareness. Furthermore, we propose that conscious awareness of rewards allows for the use of more advanced functions in reward pursuit, which consider the specific course of action that leads to reward attainment. Using a monetary reward priming paradigm that allows us to dissect the performance effects of rewards (i.e., coins of different value) into conscious and unconscious components, we tested this proposal in 3 experiments. Overall, results indicate that people rely on a simple yet adaptive mechanism that unconsciously conserves effort during reward pursuit, because it makes people more reward sensitive whenever more effort is required of the body. Moreover, consciousness supports a more sophisticated mode of reward pursuit, via which people can strategically conserve effort even further. We discuss these findings in the context of decision making, motivation, and consciousness.
21875226	Four studies explored the motivational and experiential dynamics of psychological needs, applying both self-determination theory and motive disposition theory. In all 4 studies, motive dispositions toward achievement and affiliation ("wanting" particular experiences) predicted corresponding feelings of competence and relatedness ("having" those experiences). Competence and relatedness in turn predicted well-being, again indicating that these 2 experiences may really be "needed." Illuminating how wanting gets to having, in Studies 2 and 3, participants reported greater self-concordance for motive-congruent goals, which, in longitudinal Study 3, predicted greater attainment of those goals and thus enhanced well-being. Study 4 replicated selected earlier results using an implicit as well as an explicit motive disposition measure. Supporting the presumed universality of competence and relatedness needs, in no studies did motive dispositions moderate the effects of corresponding need-satisfaction on well-being. Discussion focuses on a "sequential process" model of psychological needs that views needs as both motives that instigate and outcomes that reward behavior.
21624476	Functional magnetic resonance imaging (fMRI) research suggests that the ventral striatum (VS)/nucleus accumbens, medial prefrontal cortex (mPFC), and broader mesocorticolimbic dopamine system mediate aspects of reward processing from expectation of reward to pleasantness experienced upon reward attainment. In parallel, research utilizing event-related potentials (ERP) indicates that the feedback negativity (FN) is sensitive to reward vs. non-reward feedback and outcome expectation. The FN has been source localized to the mPFC and dorsal striatum, and converging evidence suggests that the FN reflects reward processing in the mesocorticolimbic system. However, the extent to which ERP and fMRI measures of reward processing are correlated has yet to be explored within the same individuals. The primary aim of the current study was to examine the convergence between fMRI (i.e., VS and mPFC) and ERP (i.e., FN) measures of reward processing in forty-two participants who completed counterbalanced fMRI and ERP sessions while performing the same monetary gambling task. For the Win>Loss comparison, fMRI activation in the mesocorticolimbic reward circuit including the VS and mPFC was positively correlated with the FN. Here, we demonstrate that monetary gains activate the VS, mPFC, caudate, amygdala, and orbital frontal cortex, enhance the FN ERP component within 300 ms post feedback, and that these measures are related. Thus, fMRI and ERP measures provide complementary information about mesocorticolimbic activity during reward processing, which may be useful in assessing pathological reward sensitivity.
21112842	The attainment of oncology nursing certification indicates that a nurse has the knowledge and expertise to competently care for patients with an actual or potential diagnosis of cancer. Research regarding the value nurses associate with certification is lacking; therefore, the Oncology Nursing Certification Corporation participated in a national study led by the American Board of Nursing Specialties Research Committee to explore the value of certification in a sample of certified and noncertified nurses and nurse managers. A total of 940 oncology nurses participated and completed a demographic survey and the Perceived Value of Certification Tool. Most were Caucasian women, with a mean age of 54 years; 36% were staff nurses, 19% were nurse managers, and 10% were advanced practice nurses. A high value of certification was reported. Barriers to certification included cost issues and lack of institutional reward and support. Benefits included institutional reimbursement and listing certification credentials on name badges or business cards. Both certified and noncertified nurses value certification. Increasing institutional recognition and financial support could improve nurse certification rates and ultimately may result in improved patient care.
21111010	Clinical investigators have long theorized about the role of reward processing and positive affect in depression. One theory posits that compared to nonmelancholic depressives, melancholic depressives experience less consummatory (i.e., post-reward), but comparably low anticipatory (prior to reward), positive affect. We tested whether frontal EEG asymmetry, a putative marker of the anticipatory reward system, is present only before an individual receives a reward or also after receiving a reward (i.e., during consummatory reward processing). We also examined whether melancholic depression, a condition characterized by a deficit in consummatory reward processing, is associated with abnormal EEG asymmetries in alpha band power. Effects in other frequency bands (delta, theta, or beta) were also explored. EEG was recorded in 34 controls, 48 nonmelancholic depressives, and 17 melancholic depressives during a slot machine task designed to elicit anticipatory and consummatory reward processing. Results indicated that, for alpha, the frontal EEG asymmetry of greater relative left activity was specific to anticipatory reward processing. During the consummatory phase, individuals with melancholic depression exhibited different posterior EEG asymmetries than individuals with nonmelancholic depression (and controls at a trend level). This second finding was largely due to melancholics exhibiting relatively lower right posterior activity and nonmelancholics exhibiting relatively lower left activity. These results suggest that a posterior asymmetry may be a marker for melancholic depression and aberrant consummatory reward processing.
20958844	Counselor attitudes toward evidence-based practices, such as motivational incentives/contingency management (MI/CM), are important in bridging the gap between research and practice. Mailed surveys from 1,959 substance abuse treatment counselors showed ambivalence toward MI/CM and strong disagreement with using monetary rewards for achievement of treatment goals. Attitudes were associated with counselors' educational attainment, a 12-step treatment ideology, affiliation with NIDA's Clinical Trials Network, and working in opioid treatment programs. Exposure to MI/CM via training was more strongly associated with attitudes when counselors worked in programs that had adopted MI/CM. While there is substantial resistance to MI/CM, dissemination and training about the essential elements of MI/CM may enhance counselors' receptivity toward this intervention. 
20677850	Research indicates that life events involving goal attainment and goal striving trigger hypomania/mania and that negative life events trigger bipolar depression. These findings are consistent with the behavioral approach system (BAS) dysregulation model of bipolar disorders, which suggests that individuals with bipolar disorders are hypersensitive to cues signaling opportunity for reward and cues signaling failure and loss of rewards. However, no studies to date have investigated whether individuals with bipolar spectrum disorders experience increased rates of these BAS-relevant life events, which would place them at double risk for developing bipolar episodes. The present study found that individuals with bipolar II disorder and cyclothymia experience increased rates of BAS-activating and BAS-deactivating, but not goal-attainment, life events. Finally, for bipolar spectrum individuals only, BAS-activating events predicted BAS-deactivating events' rates.
20421489	Increasing the reward value of behavioral goals can facilitate cognitive processes required for goal achievement. This facilitation may be accomplished by the dynamic and flexible engagement of cognitive control mechanisms operating in distributed brain regions. It is still not clear, however, what are the characteristics of individuals, situations, and neural activation dynamics that optimize motivation-linked cognitive enhancement. Here we show that highly reward-sensitive individuals exhibited greater improvement of working memory performance in rewarding contexts, but exclusively on trials that were not rewarded. This effect was mediated by a shift in the temporal dynamics of activation within right lateral prefrontal cortex, from a transient to predominantly tonic mode, with an additional anticipatory transient boost. In contexts with intermittent rewards, a strategy of proactive cognitive control may enable globally optimal performance to facilitate reward attainment. Reward-sensitive individuals appear preferentially motivated to adopt this resource-demanding strategy, resulting in paradoxical benefits selectively for nonrewarded events.
20357127	Memory retrieval is typically a goal-directed behavior, and as such, potentially influenced by reinforcement and motivation processes. Although striatal activation is often evident during memory retrieval, its functional significance remains unclear because typical memory paradigms do not control the motivational significance of memory decisions. We used event-related functional magnetic resonance imaging (fMRI) to investigate striatal activation during recognition with and without performance-linked monetary incentives. During initial performance in the absence of incentives, dorsal striatal activation for "Old" memory conclusions nonetheless exceeded that for "New" conclusions regardless of the accuracy of these conclusions. In contrast, subsequent scans paired incentives with either "Old" or "New" conclusions and demonstrated greater activation for whichever judgment was potentially rewarded, both with and without performance feedback. The data demonstrate that striatal activation during recognition judgments does not signal monetary reward receipt, cognitive feedback, or successful episodic retrieval. Instead, it is heavily dependent upon satisfaction of the subjective goals of the observer.
19684882	This article reviews the role of social factors, notably life events and family relationships, in the course of bipolar illness in adults and youth. We also discuss psychological variables that help explain the vulnerability of bipolar patients to social environments, including personality factors (e.g., neuroticism), reward sensitivity, and difficulty with the accurate perception of facial emotions. Bipolar patients are highly sensitive to reward, and excessive goal pursuit after goal-attainment events may be one pathway to mania. Negative life events predict depressive symptoms, as do levels of familial expressed emotion. Psychosocial interventions can speed recoveries from episodes and delay recurrences over 1-2 year intervals. Future research should examine the nature of vulnerability/stress interactions at different phases of development, and the role of psychosocial interventions in altering these processes.
18836703	Dopamine is strongly implicated in the ability to shift behavior in response to changing stimulus-reward contingencies.We investigated the effects of systemic administration of the D2/D3 receptor agonist quinpirole (0.1, 0.3 mg/kg), the D2/D3 receptor antagonist raclopride (0.1, 0.3 mg/kg), the selective D3 antagonist nafadotride (0.3, 1.0 mg/kg), and combined administration of raclopride (0.1 mg/kg) or nafadotride (1.0 mg/kg) with quinpirole (0.3 mg/kg) on spatial discrimination and reversal learning.	Rats were trained on an instrumental two-lever spatial discrimination and reversal learning task. Both levers were presented, only one of which was reinforced. The rat was required to respond on the reinforced lever under a fixed ratio 3 schedule of reinforcement. Following attainment of criterion, a reversal was introduced.	None of the drugs altered performance during retention of the previously reinforced contingencies. Quinpirole (0.3 mg/kg) significantly impaired reversal learning by increasing both trials and incorrect responses to criterion in reversal phase, a pattern of behavior manifested as increased perseverative responding on the previously reinforced lever. In contrast, neither raclopride nor nafadotride when administered alone altered reversal performance. However, raclopride blocked the quinpirole-induced reversal deficit, whereas combined administration of nafadotride and quinpirole affected not only performance during the reversal but also the retention phase. The reversal impairment resulting from co-administration of nafadotride and quinpirole was associated with both perseverative and learning errors.	Our data indicate distinct roles for D2 and D3 receptors in the capacity to modify behavior flexibly in the face of environmental change.	
18090321	Actions and their associated consequences, such as reward attainment, are often temporally distant. Animals nevertheless learn such associations thereby solving the 'distal reward' problem. We sought to determine whether dopamine signaling plays a role in such learning. Wild-type and dopamine type I receptor knockout mice executed three left/right choices leading to one of eight differentially rewarded goal sites. Compared with wild-type mice, knockouts exhibited selective impairments in decision making at choice points distal, but not proximal, to goal sites. We conclude that dopamine's role in reinforcement learning depends on the temporal relationship of actions to reward and that dopamine signaling through D1 receptors constitutes a component of those brain mechanisms responsible for solving the distal reward problem.
17957219	Serotonin (5-hydroxytryptamine, or 5-HT) is strongly implicated in the ability to shift behavior in response to changing stimulus-reward contingencies. However, there is little information on the contribution of different 5-HT receptors in reversal learning. Thus, we investigated the effects of systemic administration of the 5-HT(2A) antagonist M100907 (0, 0.01, 0.03, and 0.1 mg/kg, i.p.) and the 5-HT(2C) antagonist SB 242084 (0, 0.1, 0.3, and 1.0 mg/kg, i.p.) on the performance of an instrumental two-lever spatial discrimination and serial spatial reversal learning task, where both levers were presented and only one was reinforced. The rat was required to respond on the reinforced lever under a fixed ratio 3 schedule of reinforcement. Following attainment of criterion, a series of within-session reversals was presented. Neither M100907 nor SB 242084 altered performance during spatial discrimination and retention of the previously reinforced contingencies. M100907 significantly impaired reversal learning by increasing both trials to criterion (only at the highest dose) and incorrect responses to criterion in Reversal 1, a pattern of behavior manifested as increased perseverative responding on the previously reinforced lever. In contrast, SB 242084 improved reversal learning by decreasing trials and incorrect responses to criterion in Reversal 1, with significantly fewer perseverative responses. These data support the view that 5-HT(2A) and 5-HT(2C) receptors have distinct roles in cognitive flexibility and response inhibition. The improved performance in reversal learning observed following 5-HT(2C) receptor antagonism suggests these receptors may offer the potential for therapeutic advances in a number of neuropsychiatric disorders where cognitive deficits are a feature, including obsessive-compulsive disorder.
17318502	The idea that nucleus accumbens (Acb) dopamine transmission contributes to the neural mediation of reward, at least in a general sense, has achieved wide acceptance. Nevertheless, debate remains over the precise nature of dopamine's role in reward and even over the nature of reward itself. In the present article, evidence is reviewed from studies of food intake, feeding microstructure, instrumental responding for food reinforcement, and dopamine efflux associated with feeding, which suggests that reward processing in the Acb is best understood as an interaction among distinct processes coded by discrete neurotransmitter systems.In agreement with several theories of Acb dopamine function, it is proposed here that allocation of motor effort in seeking food or food-associated conditioned stimuli can be dissociated from computations relevant to the hedonic evaluation of food during the consummatory act. The former appears to depend upon Acb dopamine transmission and the latter upon striatal opioid peptide release. Moreover, dopamine transmission may play a role in 'stamping in' associations between motor acts and goal attainment and perhaps also neural representations corresponding to rewarding outcomes. Finally, evidence is reviewed that amino acid transmission specifically in the Acb shell acts as a central 'circuit breaker' to flexibly enable or terminate the consummatory act, via descending connections to hypothalamic feeding control systems.	The heuristic framework outlined above may help explain why dopamine-compromising manipulations that strongly diminish instrumental goal-seeking behaviors leave consummatory activity relatively unaffected.	
17182427	In order to understand predictors of relapse among adolescents treated for alcohol use disorders (AUD), it is important to accurately assess the daily circumstances associated with use. This pilot study investigates the feasibility and acceptability of an interactive voice response (IVR) system in adolescents with AOSUD. Twenty-six adolescents 14 to 19 years old, with a mean age of 16.8, who were enrolled into an adolescent treatment program for AUD consented to make phone calls for 14 successive evenings to an IVR system and answer 14 questions pertaining to daily use of alcohol and other drugs. The subjects were compensated for their participation. A satisfaction questionnaire was administered at the end of the study. Participants completed 72% of scheduled recordings, with an average of 10.1 calls per subject. Most participants reported that they answered the questions honestly and accurately and were very much satisfied with the IVR system. The preliminary data presented here suggests that the use of IVR for the purpose of generating daily reports in youth is feasible and acceptable. The utilization of IVR systems should be explored to improve efficacy and attainment of generalizability to heterogeneous adolescent populations and lifestyles including for other psychiatric disorders.
17087574	The authors propose that people use 2 routes in justifying self-gratification: 1st through hard work or excellence (entitlement) and the 2nd through the attainment of vices without depleting income. This framework was tested using real tasks and choices adopted from prior research on self-control. The results indicate that (a) higher effort and (bogus) excellence feedback increase preferences for vice rewards, but these effects are reversed or attenuated when the interchangeability of effort and income is implied; (b) willingness to pay in effort is greater for vices than virtues, but willingness to pay in income is higher for virtues; and (c) these effects are magnified among individuals with stronger (chronic or manipulated) guilt. The authors discuss the ability of the justification routes to explain the findings of prior self-control research.
16823385	The present experiments were undertaken to clarify the role of central alpha(1)-adrenoceptors in reward processes. Rats, trained to self-stimulate via electrodes in the medial forebrain bundle of the lateral hypothalamus, were administered alpha(1)-selective drugs near the locus coeruleus (LC), a site of a dense concentration of alpha(1)-receptors. Effects on reward potency were assessed from shifts in rate-frequency curves while effects on motor response capacity were judged from changes in the maximal rates of responding. It was found that local blockade of LC alpha(1)-receptors with terazosin produced a significant dose-dependent and site-dependent rightward shift of 0.08 log units and a significant decrease of 16.3% in the maximum response rate. Both effects were completely reversed by coadministration of the alpha(1)-agonist, phenylephrine and were not attributable to terazosin's weak action at alpha(2)-adrenoceptors. It is concluded that LC alpha(1)-adrenoceptors are involved both in reward/motivational processes and operant response elaboration which are postulated to work together to facilitate goal attainment.
11383401	The purpose of this descriptive qualitative study was to examine and understand the challenges faced by elderly women from India who immigrated to Canada. Ten women were interviewed about their experiences with immigration and resettlement. The analysis of interview data involved iterative process, through which four themes were identified. These themes were isolation and loneliness, family conflict, economic dependence, and setting in and coping. The participants experienced loss because of changes in traditional values and lack of social support. Because the participants could not manage resettlement on their own, personal independence was not very important. Interdependence for the attainment of emotional security and social rewards was more desirable. Health care professionals must take into account the nature of stress and impact of these experiences on health of older immigrant women.
11195996	Bipolar disorder has been conceptualized as an outcome of dysregulation in the behavioral activation system (BAS), a brain system that regulates goal-directed activity. On the basis of the BAS model, the authors hypothesized that life events involving goal attainment would promote manic symptoms in bipolar individuals. The authors followed 43 bipolar I individuals monthly with standardized symptom severity assessments (the Modified Hamilton Rating Scale for Depression and the Bech-Rafaelsen Mania Rating Scale). Life events were assessed using the Goal Attainment and Positivity scales of the Life Events and Difficulties Schedule. As hypothesized, manic symptoms increased in the 2 months following goal-attainment events, but depressed symptoms were not changed following goal-attainment events. These results are congruent with a series of recent polarity-specific findings.
11028931	Biochemical research has identified many failures in reproductive processes with specific nutrient deficits, xenobiotics and some infectious illnesses. This has led to some effective safeguards. During meiosis and fertilization, as genetic material divides and rearranges, it is exposed and open to mutation. A nutritionally unfavourable environment is a major risk factor. At stages of rapid cell division, differentiation and organisation, as in the embryo and later in the fetal brain, the child's survival, completeness and future health and ability are at stake. From months before conception, reproduction needs preparing for, especially with today's environmental pollution, even entering the foodchain. Care from before conception can contribute not only to the child's healthy basis for life, full development of brain, eyesight and other complex attributes, but also to the health of at least the subsequent generation. Since the female baby's oocytes are being formed while she is still in the womb, the grandmother's nutritional status, around the time of conceiving a daughter, can permanently affect a grandchild. Recent insights into evolution, particularly of the brain, give us fresh indications of dietary needs to fulfil human potential for health and acuity. Despite the hazards, nature is remarkably successful. This paper is not designed to alarm but to help attainment of full genetic potential. With healthy parents serious malformations are a low percentage. The numbers of babies with avoidable disorders, however, calls urgently for action, especially in our own inner cities and in developing countries where there is inadequate nutrition. Action will more than justify itself, including financially. It will reward handsomely.
11013335	Successful engagement of clients with serious and persistent mental illnesses in the planning and implementation of treatment requires the identification of individualized reinforcers through motivational analyses. Reinforcer surveys are interviews or questionnaires that list numerous objects, persons, activities, and settings, and then assess the client's perception of the value of each item. Such surveys help identify the type of reward that might be useful for motivating the client. If properly assessed and delivered, reinforcers can increase clients' skill acquisition, attainment of goals, and feelings of self-efficacy.
10867117	The Unified Biosocial Theory of Personality postulates that human personality is organized around four temperaments - Novelty Seeking, Harm Avoidance, Reward Dependence, and Persistence - and three characters - Self-Directedness, Cooperativeness, and Self-Transcendence. The objective of the present study was to investigate the influence of sociodemographic factors on temperament and character without the confounding influence of mental disorders. Volunteers (n=94) did not meet criteria for any Axis I and Axis II diagnosis, had no first-degree relatives with mental disorders, and were medically healthy. After giving written informed consent, volunteers completed the Temperament and Character Inventory. Analyses were conducted to determine the degree of association of each sociodemographic factor (i.e., age, gender, ethnicity, marital status, educational attainment, and occupational status) to personality dimension, while controlling for possible interactions with other sociodemographic factors. Partial correlation analysis showed a significant association between gender and Reward Dependence, and occupational status was significantly related to Reward Dependence, Cooperativeness, and Self-Transcendence. Stepwise regression analysis indicated that gender and occupational status were significant predictors of Reward Dependence. Occupational status was the only predictor of Cooperativeness and Self-Transcendence. These data suggest that sociodemographic factors should be considered in studies investigating temperaments and characters as defined by the Unified Biosocial Theory of Personality.
10223005	Certification is a growing area of nursing that allows nurses the ability to attain additional credentials in their specialty. While certification has been present for many years in some professions, it is relatively new in nursing. There are many reasons to obtain certification, but the overwhelming one is personal satisfaction and professional growth. Suggestions for selecting a certification test and guides to prepare for the exam are provided in this article as well as suggestions for employers to reward employees for attainment of certification.
10052577	Adaptation to research paradigms such as rotating rooms and optical alteration of visual feedback during movement results in development of perceptual-motor programs that provide the reflexive assistance that is necessary to skilled control of movement and balance. The discomfort and stomach awareness that occur during the adaptation process has been attributed to conflicting sensory information about the state of motion. Vestibular signals depend on the kinematics of head movements irrespective of the presence or absence of signals from other senses. We propose that sensory conflict when vestibular signals are at least one component of the conflict are innately disturbing and unpleasant. This innate reaction is part of a continuum that operates early in life to prevent development of inefficient perceptual-motor programs. This reaction operates irrespective of and in addition to reward and punishment from parental guidance or goal attainment to yield efficient control of whole body movement in the operating environment of the individual. The same mechanism is involved in adapting the spatial orientation system to strange environments. This conceptual model "explains" why motion sickness is associated with adaptation to novel environments and is in general consistent with motion sickness literature.
9709515	This investigation examined the motivational structures of 26 patients diagnosed with alcoholism in comparison to 30 demographically similar technical university students. Responding to the Motivational Structure Questionnaire, the clinical group listed 40% fewer goals, responded as if they needed richer incentives to form strong commitments to goal striving, displayed marginally less average commitment to their goals, and, after other variables were partialled out, expressed less ability to influence the course of goal attainment. There were no differences in their scores on over-all subjective probability of success, the time frame for goal attainment, and their relative scores on anticipated positive and negative emotions and ambivalence. The results suggest group differences in the effects of brain-reward mechanisms.
9084347	To describe the behavioral management of conversion disorder in children and to preliminarily assess its effectiveness.Retrospective case series.	Inpatient pediatric rehabilitation unit.	The first eight patients with conversion disorder treated on our pediatric rehabilitation unit, between 9 and 18 years of age. Six were girls. Three cases are described in detail.	All patients were treated as inpatients, using a behavioral approach. Inadvertent reinforcement of illness behavior was identified, and a reward system was established for good attainment. Some patients had a "level" system instituted, with increasing privileges for goal achievement. All patients and their families had psychological assessment and instruction in pain and stress management strategies.	Restoration of normal gait and function, independence in activities of daily living (ADL), and symptom recurrence after discharge.	All patients attained normal gait and ADL function before discharge.	(1) Behavioral management of conversion disorder in children appears to be as effective as in adults, although at times a behavioral reward or "level" system may be necessary for adequate reinforcement. (2) Instruction of the patient and family in appropriate stress and pain management appears key to maintaining treatment effect over time.	
22302944	Two experiments examined the effect of pharmacological stimulation of the locus coeruleus in a non-reversal shift paradigm to test predictions concerning the role of the ceruleo-cortical noradrenergic system in processes of selective attention. Food-deprived rats were trained to make either visual (experiment 1) or spatial (experiment 2) discriminations in a parallel alley with both sets of cues being present at all times. Two groups of rats received treatments of either 2 mg/kg i.p. of the selective α(2) adrenoceptor antagonist idazoxan or saline control injections before each daily block of trials. Following attainment of criterion, the reinforcement contingencies were altered according to a non-reversal shift design, so that the alternative (i.e. either spatial or visual) set of cues now predicted reward. Rats treated with idazoxan were not impaired in the acquisition of either the spatial or visual discrimination task, but they were impaired in both forms of non-reversal shift. These deficits are interpreted as resulting from narrowed attention in idazoxan-treated rats, thus supporting a selective attention hypothesis of locus coeruleus function.
10127903	In sum, I believe that we know how to develop good practice guidelines today, even though we currently invest paltry sums to do so. Well-constructed guidelines can have a substantial positive impact on quality. By focusing on problems of overuse, costs can be reduced as well. Implementation of guidelines is an absolutely central step in the application of this important quality improvement tool. Practitioners of continuous quality improvement require few external incentives to capitalize on the value of guidelines in the effort to improve quality and are likely to experience their full potential benefit. They may require some prodding to address problems of overuse. Others will need additional inducements. Using reimbursement to reward the attainment of high quality, publishing data on provider performance on various quality measures, and recognizing the salutary effect of adherence to guidelines on liability can provide such incentives.
8245910	Elementary school and college students rated the kindness of helping by story protagonists with different attributed motivations. Of particular interest was the effect of the endocentric (self-serving) motivations of anticipated pride and guilt on the kindness ratings. A number of prosocial theorists view such endocentrically motivated helping as less altruistic than exocentrically (other-serving) motivated helping. Compared with helping attributed to the exocentric motivation of sympathy, helping attributed to guilt avoidance led to lower ratings of kindness by all but second graders. Pride-attributed helping, however, did not result in lower kindness ratings at any grade level. The motivational attributions of praise and reward attainment and criticism and punishment avoidance led to relatively low kindness ratings, with the two avoidance motivations leading to the lowest ratings. The latter finding suggests an alternative explanation of the kindness ratings for guilt-motivated helping.
2363056	A central component of the primary health care approach in developing countries has been the development and utilization of community-based health workers (CHWs) within the national health system. While the use of these front line workers has the potential to positively influence health behavior and health status in rural communities, there continues to be challenges to effective implementation of CHW programs. Reports of high turnover rates, absenteeism, poor quality of work, and low morale among CHWs have often been associated with weak organizational and managerial capacity of government health systems. However, no systematic research has examined the contribution of work-related factors to CHW job performance. The research reported in this paper examines the relative influence of reward and feedback factors associated with the community compared to those associated with the health system on the performance of CHWs. The data are drawn from a broader study of health promoters (CHWs) conducted in two departments (provinces) in Colombia in 1986. The research was based on a theoretical model of worker performance that focuses on job related sources of rewards and feedback. A survey research design was employed to obtain information from a random sample of rural health promoters (N = 179) and their auxiliary nurse supervisors about CHW performance and contributing factors. The findings indicate that feedback and rewards from the community have a greater influence on work performance (defined as degree of perceived goal attainment on job tasks) than do those stemming from the health system.(ABSTRACT TRUNCATED AT 250 WORDS)
2810948	The purpose of this study was to examine the effect of the goal attainment difficulty upon interpersonal attraction for the partner. Eighty female undergraduates participated the experiment. They were given tasks with one of four different goal attainment level (very easy, easy, difficult, and very difficult). Each subject solved it with partners of one of three ability levels (superior, similar, inferior to the subject). After the completion of the task, all subjects were requested to evaluate the three partners' instrumental and emotional attractiveness. The main results were as follows: (1) The subjects evaluated the more capable partner as more attractive on the instrumental attraction dimension. (2) The subjects in easy and difficult goal attainment conditions evaluated the superior partner as most attractive on the emotional attraction dimension. While the subjects in very easy and very difficult goal conditions evaluated the similar partner as most attractive on that dimension. These results were discussed in terms of the relationship between the reward value of interaction partner and the task environment.
2921634	Nursing administrators can be more successful in stabilizing the major labor force in the hospital by ensuring that organizational values are explicitly shared, discussed, and visible to those in the nursing department. Standards and expectations that operationalize the values must be developed and implemented. Methods to measure accomplishment of the standards must be quantifiable and measured on an ongoing basis and staff and management must be held accountable for the standards. Finally, reward and recognition systems must flow from attainment of the standards that operationalize organizational values. If any one of the components of the model is missing, organizational values cannot be actualized, employees will not experience the stabilizing effect of understanding the values that drive the organization's decision-making, and resources will not be used maximally to move the organization toward its vision of quality patient care.
2875217	The hypothesis linking decreased serotonin transmission to reduced anxiety as the mechanism in the anxiolytic activity of benzodiazepines conflicts with most clinical observations. Serotonin antagonists show no marked capacity to alleviate anxiety. On the other hand, clinical signs of reduced serotonergic transmission (low 5-HIAA levels in the cerebrospinal fluid) are frequently associated with aggressiveness, suicide attempts and increased anxiety. This brief review attempts to reconcile these human and animal findings by investigating whether anxiety reduction or increased impulsivity are likely to account for animal behavioral changes associated with decreased serotonergic transmission. The effects of manipulating central serotonin on experimental anxiety paradigms in animals (punishment, novelty) are reviewed and compared to the effects of anti-anxiety drugs. Anxiety seems neither necessary nor sufficient to induce control by serotonergic neurons on behavior. Further evidence suggests that behavioral effects of anxiolytics thought to be mediated by decreases in anxiety are not caused by the ability of these drugs to reduce serotonin transmission. Blockade of serotonin transmission, especially at the level of the substantia nigra, results in a shift of behavior towards facilitation of responding. This behavioral shift is particularly marked when there is competition between acting and restraining response tendencies and when obstacles prevent the immediate attainment of an anticipated reward. It is proposed that serotonergic neurons are not only involved in behavioral arousal but also in enabling the organism to arrange or tolerate delay before acting. Decreases in serotonin transmission seem to be associated with the increased performance of behaviors which are usually suppressed though not necessarily because of the alleviation of anxiety which might contribute to the suppression.
3627296	Traditionally, theories of addiction have stressed that drug urges are characterized by dysphoria, occur in response to decreasing levels of drug or drug effect, and are associated with withdrawal symptoms/signs or drug-antagonistic responses arising from a homeostatic mechanism. However, recent research has shown that urges, drug self-administration, and relapse all occur concomitant with both positive and negative affect, rising and falling levels of drug, and with drug-agonistic responses, as well as antagonistic/withdrawal responses. In keeping with recent theorizing about motivation and emotions, we believe that affective responding provides a readout of the motivational status of an organism (e.g., Buck, 1985). We conceive of urges as affects, whose activation mediates drug pursuit and self-administration. Moreover, we believe that affects are represented in neural networks comprising information on affect-relevant stimuli, responses, and meaning/expectancy. We believe that there are two types of urge networks. One, a "positive-affect" network, is activated, associatively and nonassociatively, by appetitive stimuli, especially appetitive drug actions that activate "GO" motivational incentive systems. Activation of this network is characterized by positive affect, drug isodirectional responding, attentional focus on a dominant response, and enhanced pursuit of appetitive stimuli--especially the drug. The operating characteristics of the positive-affect network, and the associated motivational systems, result in a drug's instating a positive feedback loop. Appetitive drug actions increase the likelihood of the pursuit of appetitive stimuli, and additional drug constitutes a prepotent candidate from among the available appetitive stimuli. This positive feedback loop may account in part for cardinal features of addiction: for example, the great relapse likelihood once any drug is sampled, the attainment of very high blood levels of a drug, and the pursuit of adjunctive appetitive stimuli while using a drug. The second type of urge network we have labeled a "negative-affect" network, and we believe it is activated, associatively and nonassociatively, by inappetitive stimuli or consequences (punishment, signals of punishment, frustrating lack of reward, etc.) and by withdrawal and signals of withdrawal (e.g., drug cues, which during the course of addiction are associated with both direct drug effects and withdrawal). Activation of the network is characterized by withdrawal symptoms and signs, negative affect, and drug seeking.(ABSTRACT TRUNCATED AT 400 WORDS)
3842804	An evaluation of Project Redirection, a two-year demonstration program designed to help pregnant teenagers and teenage mothers, shows that teenagers from a comparison group, who were not enrolled in the demonstration program, were significantly more likely than project participants to experience a repeat pregnancy after one year, but that after two years the difference was small and nonsignificant. Likewise, at 12 months into the program, the project participants proved more likely to be using contraceptives, but by 24 months the comparison group had caught up. After one year of participation, the project teenagers were more likely than the others either to be in school or to have graduated (56 and 49 percent, respectively). However, this differential also disappeared by 24 months. Nonetheless, even at that point, project teenagers who had dropped out prior to joining the program and those who had had a repeat pregnancy were more likely to be in school or to have completed school than were similar comparison teens. Project teenagers also were somewhat more likely to have held a job during the two-year period than were teenagers not enrolled in the program. All in all, the evaluation demonstrated that teenagers who participated in the project and remained in it for more than a year had consistently better outcomes in education, employment and repeat pregnancy than any other group had. Comparison teenagers who had never participated in any special program for pregnant teenagers, on the other hand, demonstrated consistently poorer outcomes than any other group.An evaluation of Project Redirection, a 2-year demonstration program designed to help economically disadvantaged teenage mothers, shows short-term gains but few long-term results in effecting significant changes' in repeat pregnancies, use of contraceptives and schooling.  Conducted from mid-1980 to 1983 under the sponsorship of the Ford Foundation and US Department of Labor, Project Redirection coordinated a wide range of services by developing relationships with other service providers in 4 communities--Boston, Mass., New York City (Harlem), Phoenix, Ariz., and Riverside, Calif.  Based on a series of interviews with some 675 teenagers (305 from the experimental group and 370 from a comparison group), it was found that, 12 months after the program began, a significantly higher proportion of the comparison than of the project teenagers had a repeat pregnancy (22% and 14%, respectively).  However, 12 months later, or a year after the average teenager had completed the program, 49% of the comparison group and 45% of the project teenagers had experienced repeat pregnancies.  Similarly, 45% of the comparison group and 54% of the project participants had used some form of contraceptive at last intercourse when the teenagers were interviewed after 12 months.  But a year later, the use of a contraceptive at the last intercourse was the same for both groups--54%.  In addition, while project teenagers were more likely than the comparison group to have been enrolled in school (87% and 71%, respectively) after 2 years, the difference between the groups was similar to the difference that existed after 1 year.  The study indicates the need to extend family planning program services for teenagers for a longer period.  This can be accomplished by removing mandatory exit criteria based on the length of time spent in the program, the use of incentives to reward teenagers for longevity or the attainment of major goals, and as an alternative to continuous enrollment, offering teenagers the option of returning periodically for short-term targeted services perhaps every 6 months, or at times of crisis.	
12311951	Self-instruction (SI), also termed programmed learning, is a fairly new family planning training tool adopted in 1975 by the National Population Program in the Philippines.  According to Antonia Coronel, project officer of the Population Center Foundation (PCF), SI uses carefully designed materials in order to meet specific objectives.  The information is presented in logically sequenced small frames or sets and is followed by a series of practice exercises requiring immediate feedback from the learner.  The learner's reward takes the form of correct answers at the frames' end.  There are many forerunners to SI, including the Greek philosopher Socrates, the Roman orator Quintilian, and the American social scientist Sidney Pressey who thought of a programmed instructional review and multiple-choice testing materials as devices which required the learner's active participation and provided immediate knowledge of his/her accuracy.  SI has 6 characteristics:  emphasis on the needs of the learner shown by allowing self pacing, meaning, the learner proceeds at his/her own learning rate, and stressing feedback from the trainer who holds individual meetings with the learners; a clear statement of objectives; a breakdown of learning tasks into smaller and easy to absorb units; a self administered posttest which enables the learner and others to see whether or not the objectives have been realized; inclusion of frequent practice exercises relevant to the objectives and the posttest; and provision of immediate feedback, which reinforces and lets the learner improve his/her comprehension and retention.  Operationally, the method takes 4 steps:  the objectives of instruction are specified in terms of learner behavior; the learner is rated as to his/her level of knowledge with respect to the objectives; instructional activities built into SI modules are designed to bring about the intended objectives; and the learner's attainment of the objectives is evaluated.  The modules referred to are the 12 SI modules on various aspects of family planning developed by the PCF.  In the Philippines the need for programmed learning became apparent with the signing of Presidential Decree No. 79.  Among the provisions of this decree are the following:  nurses and midwives can dispense oral contraceptives (OCs) and insert IUDs; large business firms and factories must provide family planning services to their employees; and family planning services like sterilizations costs can be charged to Medicare.  The SI method met the criteria of giving uniform training, cutting down training costs, and ability to upgrade knowledge, attitudes, and skills.  Thus far there are 21 completed program learning materials and these are identified and described.
107279	1. The experiments described here are addressed at identifying some of the processes underlying arm movements in monkeys. 2. We used three adult monkeys that were trained to point to a target light with the forearm and hold at that position for about 1 s in order to obtain a reward. During the experimental sessions the monkey was seated in a primate chair and its forearm was fastened to an apparatus that permitted flexion and extension of the forearm about the elbow in the horizontal plane. 3. We tested their performance prior to and after bilateral dorsal rhizotomy (C2--T3). Forearm movements were performed without the sight of the arm both before and after the surgical intervention. In intact animals we unexpectedly displaced the arm prior to movement initiation (150--200 ms) and observed the outcome of this displacement on movement termination. Our results indicated that the arm moved accurately to the target. The same procedure was used in the deafferented monkeys, yielding qualitatively the same results; i.e., a displacement of the initial position did not affect the attainment of the intended final position. 4. These results are relevant to the question of what is being controlled by motor commands. It appears that the controlled variable is an equilibrium point resulting from the interaction of agonist and antagonist muscles. Consequently, a change in the equilibrium leads to movement and the attainment of a new posture. The fact that both intact and deafferent monkeys display essentially similar motor behavior in our highly practiced task should not obliterate the dramatic difference in motor performance that exists between intact and rhizotomized animals. In fact, the successful execution of the learned motor performance in the deafferented animal is contingent on the animal's body being in a fixed relation to the arm apparatus. Whenever we changed the usual spatial relationship between the monkey's body and the arm apparatus, the animal's pointing response to the target was inaccurate. All of our intact monkeys, in contrast, were able to compensate quickly for any variations in their accustomed position with respect to the arm apparatus. The dramatic inability of the deafferented monkey to execute accurate pointing responses in an unusual postural setting underscores the great importance of the afferent monkey to execute accurate pointing responses in an unusual postural settiing underscores the great importance of the afferent feedback. These findings suggest that, in the performance of visually evoked learned movements, one of the major functions of the afferent feedback is in the adaptive modifications of learned motor programs.
717610	Family allowances designed to promote maternal and child health and welfare could be self-defeating if they stimulated otherwise unwanted births, as often assumed. That assumption, with its public health and demographic implications, needs testing. An attempt to test it was made in Chile in 1969--1970 through interviews with 945 wives receiving an allowance and 690 non-recipients. Recipients practiced contraception significantly more than did non-recipients. This was not explained by wives' educational attainment or employment, the couples' earnings, or number of living children, but was associated with a 50 per cent greater utilization of professional prenatal care by recipients during the most recent pregnancy; women with such care (regardless of allowance status) were 75 per cent more likely than others to control their fertility. Prenatal care was probably sought more by recipients in part because an additional stipend was provided as soon as pregnancy was confirmed, usually at clinics with integrated family planning. Greater family income, attributable to the allowance, probably also contributed to the recipients' better prenatal attention and to contraceptive practice. Noteworthy, too, was the finding that with the number of living children controlled, contraceptive practice was significantly greater amoung couples who had never lost a child.




28533759	According to the ambivalence model of craving, alcohol craving involves the dynamic interplay of separate approach and avoidance inclinations. Cue-elicited increases in approach inclinations are posited to be more likely to result in alcohol consumption and risky drinking behaviors only if unimpeded by restraint inclinations. Current study aims were (1) to test if changes in the net balance between approach and avoidance inclinations following alcohol cue exposure differentiate between low and high risk drinkers, and (2) if this balance is associated with alcohol consumption on a subsequent taste test. In two experiments (N = 60; N = 79), low and high risk social drinkers were exposed to alcohol cues, and pre- and post- approach and avoidance inclinations measured. An ad libitum alcohol consumption paradigm and a non-alcohol exposure condition were also included in Study 2. Cue-elicited craving was characterized by a predominant approach inclination only in the high risk drinkers. Conversely, approach inclinations were adaptively balanced by equally strong avoidance inclinations when cue-elicited craving was induced in low risk drinkers. For these low risk drinkers with the balanced craving profile, neither approach or avoidance inclinations predicted subsequent alcohol consumption levels during the taste test. Conversely, for high risk drinkers, where the approach inclination predominated, each inclination synergistically predicted subsequent drinking levels during the taste test. In conclusion, results support the importance of assessing both approach and avoidance inclinations, and their relative balance following alcohol cue exposure. Specifically, this more comprehensive assessment reveals changes in craving profiles that are not apparent from examining changes in approach inclinations alone, and it is this shift in the net balance that distinguishes high from low risk drinkers.
28471224	Pairing a taste with either internal pain (e.g., from hypertonic saline injection) or nausea (e.g., from LiCl administration) will reduce subsequent consumption of that taste. Here we examine the responses to a taste paired with either hypertonic saline or LiCl using the analysis of licking microstructure (mean lick cluster size: Experiments 1-3), taste reactivity (examining the distribution of appetitive and aversive orofacial responses: Experiments 2-3), and immobility (as a measure of fear: Experiments 2-3). At both high (10 ml/kg 0.15 M LiCl, 10 ml/kg 1.5 M NaCl) and low dose levels (2 ml/kg 0.15 M LiCl, 4 ml/kg 1.5 M NaCl), pairing a taste with either LiCl-induced nausea or internal pain produced by hypertonic NaCl caused reductions in voluntary consumption, in appetitive taste reactivity responses, and in lick cluster size. However, only pairing with LiCl resulted in conditioned aversive taste reactivity responses to the taste. In contrast, pairing with hypertonic NaCl resulted in the taste eliciting higher levels of immobility (reflecting fear) than did pairing the taste with LiCl. The clearly dissociable effects of LiCl and hypertonic saline on aversive taste reactivity and fear responses, despite equivalent effects on consumption, demonstrates selective conditioning effects between internal pain and nausea. (PsycINFO Database Record
28455231	Multiple functional attributes of glucose-monitoring neurons in the medial orbitofrontal (ventrolateral prefrontal) cortex. NEUROSCI BIOBEHAV REV 73(1) XXX-XXX, 2017.- Special chemosensory cells, the glucose-monitoring (GM) neurons, reportedly involved in the central feeding control, exist in the medial orbitofrontal (ventrolateral prefrontal) cortex (mVLPFC). Electrophysiological, metabolic and behavioral studies reveal complex functional attributes of these cells and raise their homeostatic significance. Single neuron recordings, by means of the multibarreled microelectrophoretic technique, elucidate differential sensitivities of limbic forebrain neurons in the rat and the rhesus monkey to glucose and other chemicals, whereas gustatory stimulations demonstrate their distinct taste responsiveness. Metabolic examinations provide evidence for alteration of blood glucose level in glucose tolerance test and elevation of plasma triglyceride concentration after destruction of the local GM cells by streptozotocin (STZ). In behavioral studies, STZ microinjection into the mVLPFC fails to interfere with the acquisition of saccharin conditioned taste avoidance, does cause, however, taste perception deficit in taste reactivity tests. Multiple functional attributes of GM neurons in the mVLPFC, within the frame of the hierarchically organized central GM neuronal network, appear to play important role in the maintenance of the homeostatic balance.
28383939	We investigated, using orofacial reactivity assessment, whether nonflavor context cues can elicit conditioned aversive reactions, and also whether context cues interfere, through blocking, with the reduction in taste palatability during taste aversion conditioning. Experiment 1 showed that a context previously paired with LiCl evoked aversive orofacial reactions, and also attenuated the reduction in palatability of a saccharin solution which was paired with LiCl in that context. In Experiment 2, this blocking effect was abolished when the rats were given nonreinforced exposure to the previously LiCl-paired context (context extinction) before aversive conditioning of the saccharin in compound with the context. These results confirm that context stimuli can elicit conditioned aversive reactions in the absence of any flavor component, and demonstrate that context cues can interfere with the affective aspects of taste aversion learning. Thus nonflavor cues appear to engage the same processes as taste cues in aversion learning. These results are consistent with the idea that taste aversion learning is governed by general associative mechanisms and the special properties of nausea, rather than by a selective mechanism for poison-avoidance. (PsycINFO Database Record
28371523	Recent reports identify sensory subtypes in ASD based on shared patterns of responses to daily sensory stimuli [Ausderau et al., 2014; Lane, Molloy, & Bishop, 2014]. Lane et al. propose that two broad sensory dimensions, sensory reactivity and multisensory integration, best explain the differences between subtypes, however this has yet to be tested. The present study tests this hypothesis by examining the latent constructs underlying Lane's sensory subtypes. Participants for this study were caregivers of children with autism spectrum disorder (ASD) aged 2-12 years. Caregiver responses on the Short Sensory Profile (SSP), used to establish Lane's sensory subtypes, were extracted from two existing datasets (total n = 287). Independent component analyses were conducted to test the fit and interpretability of a two-construct structure underlying the SSP, and therefore, the sensory subtypes. The first construct was largely comprised of the taste/smell sensitivity domain, which describes hyper-reactivity to taste and smell stimuli. The second construct had a significant contribution from the low energy/weak domain, which describes behaviors that may be indicative of difficulties with multisensory integration. Findings provide initial support for our hypothesis that sensory reactivity and multisensory integration underlie Lane's sensory subtypes in ASD. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
28363812	The taste reactivity test is considered as an objective measure to assess the hedonic impact of tastes. Both the appetitive and aversive pattern of responses are plastic and can change based on previous experience. The present study assessed the repertoire of taste responses elicited by sucrose and quinine in preweanling rats, and described changes in these taste reactivity patterns after exposure to the other tastant. We exposed infant rats (17 days old at the start of training) to sweet (2% sucrose) or bitter (0.01% quinine) tastants during 4, 10-min trials in two different random sequences. The subjects were weighed before and after each trial to provide a measure of percent body weight gained. The following taste reactivity responses were registered: duration of mouthing and paw lick, frequency of chin rub, head shake and flailing of the forelimbs, frequency and duration of face washing, wall climbing and paw tread. The consummatory and affective taste responses changed depending on the order in which the solutions were administered. The order of exposure to the tastants did not affect the levels of sucrose intake. Conversely, rat pups showed more ingestive, and fewer aversive, responses to the sweet tastant when access to the solution followed the intraoral infusion of quinine. Likewise, intraoral delivery of quinine elicited a more aversive taste reactivity pattern when delivered after the access to sucrose than when presented to sucrose-naïve pups. This research contributes to the analysis of taste reactivity responses during the early ontogeny of the rat and highlights the importance of previous experiences on the subsequent assessment of rewards.
28323090	This study examined c-Fos expression in selected brain areas consequent to intraperitoneal (IP) administration of saccharin and lithium chloride. Rats were tested for aversion to the saccharin as measured by flavor consumption and orofacial reactions in the taste reactivity (TR) test. It was found that intraperitoneal conditioning resulted in the reduction in voluntary consumption but not in the production of aversive orofacial responses to the saccharin. The immunohistochemistry quantification revealed increased c-Fos activity in the insular cortex, the shell and core regions of the nucleus accumbens, and the basolateral nucleus of the amygdala. These results show that a conditioned taste aversion can be induced without direct oropharyngeal gustatory stimulation at the time of conditioning. In addition, this study provide evidence of increased neural activity in response to intraperitoneal saccharin injections.
28092615	Habanero pepper fruits contain capsaicin (CAP) characterised by a spicy taste. Astrocytes express vanilloid receptor (TRPV1), which interacts with cannabinoids including CAP. Only a few studies revealed that CAP leads to alterations of the arcuate nucleus (ARC) structures. The aim of this study was to analyse the GFAP (GFAP-IR) and S100β (S100β-IR) immunoreactive astrocytes of ARC in adult rats after intragastric administration of habanero pepper fruits. Adult, Wistar rats received a peanut oil - control group (C) - and oil suspension of habanero pepper fruits at a dose of 0.08 g dm/kg b.w. for 7 days - E1 group - and 28 days - E2 group. After euthanasia, the brains were embedded in paraffin blocks using a routine histological technique. Frontal slices of ARC were immunohistochemically stained for GFAP and S100β using specific antibodies in the peroxidase-antiperoxidase method. Astrocytes of ARC were morphologically and morphometrically analysed under a light microscope. The results of the study did not reveal statistically significant changes in the density of GFAP-IR cells in E1 and E2 groups of rats in comparison with group C. A statistically significant increase in the density of S100β-IR astrocytes was observed in the E1 group and a decrease in the E2 group. Astrocytes with expression of both studied proteins were characterised by morphological alterations in ARC in the E2 group. The obtained results suggest an influence of CAP contained in habanero pepper fruits on the reactivity of astroglia, which may have an impact on the astrocyte-neuron interactions in order to maintain a proper activity of nervous cells in ARC.
28054099	Whereas reward-modulatory opioid actions have been intensively studied in subcortical sites such as the nucleus accumbens (Acb), the role of cortical opioid transmission has received comparatively little attention.The objective of this study is to describe recent findings on the motivational actions of opioids in the prefrontal cortex (PFC), emphasizing studies of food motivation and ingestion. PFC-based opioid effects will be compared/contrasted to those elicited from the Acb, to glean possible common functional principles. Finally, the motivational effects of opioids will be placed within a network context involving the PFC, Acb, and hypothalamus.	Mu-opioid receptor (μ-OR) stimulation in both the Acb and PFC induces eating and enhances food-seeking instrumental behaviors; μ-OR signaling also enhances taste reactivity within a highly circumscribed zone of medial Acb shell. In both the Acb and PFC, opioid-sensitive zones are aligned topographically with the sectors that project to feeding-modulatory zones of the hypothalamus and intact glutamate transmission in the lateral/perifornical (LH-PeF) hypothalamic areas is required for both Acb- and PFC-driven feeding. Conversely, opioid-mediated feeding responses elicited from the PFC are negatively modulated by AMPA signaling in the Acb shell.	Opioid signaling in the PFC engages functionally opposed PFC➔hypothalamus and PFC➔Acb circuits, which, respectively, drive and limit non-homeostatic feeding, producing a disorganized and "fragmented" pattern of impulsive food-seeking behaviors and hyperactivity. In addition, opioids act directly in the Acb to facilitate food motivation and taste hedonics. Further study of this cortico-striato-hypothalamic circuit, and incorporation of additional opioid-responsive telencephalic structures, could yield insights with translational relevance for eating disorders and obesity.	
27984199	Midazolam is a benzodiazepine agonist that affects the acquisition, retention, and retrieval of malaise-induced conditioned taste aversion (CTA) in rats. Our previous study suggested that the palatability-enhancing rather than amnesic effects of midazolam were responsible for impaired retrieval of conditioned aversion to palatable conditioned stimuli (CSs). However, it remains unclear whether this effect is opioid-dependent. In the present study, we examined the involvement of opioid signaling with the ability of peripheral midazolam administration to transiently impair CTA retrieval in mice. CTA was established by pairing 5mM saccharin ingestion (conditioned stimulus, CS) with an intraperitoneal (i.p.) injection of 0.15M lithium chloride (LiCl, 2% body weight) (unconditioned stimulus) for two consecutive days. Conditioned mice that received midazolam (1.5mg/kg, i.p.) before the first retention test consumed significantly more saccharin (CS) than conditioned mice that received vehicle (phosphate-buffered physiological saline, PBS; i.p.). On the next day, both conditioned groups showed strong aversions to the CS. Next, naloxone, an opioid receptor antagonist, was peripherally administered prior to the midazolam injection before the retention test. Pre-administration of naloxone but not PBS attenuated midazolam-induced increases in CS intake. Finally, we examined aversive orofacial taste reactions (TRs) to an oral infusion of the CS with pre-administration of naloxone or PBS prior to midazolam using a taste reactivity test. Conditioned mice that received midazolam showed significantly longer latencies to express aversive orofacial TRs than those that received PBS. Pre-administration of naloxone eliminated the effect of midazolam on latency to express aversive TRs. Taken together, these data suggest that midazolam activates opioidergic transmission and opioid-dependent palatability enhancement of the CS to eliminate conditioned aversion to a sweet taste.
27876640	Sodium deficit poses a life-threatening challenge to body fluid homeostasis and generates a sodium appetite - the behavioral drive to ingest sodium. Dr. Randall R. Sakai greatly contributed to our understanding of the hormonal responses to negative sodium balance and to the central processing of these signals. Reactivity to the taste of sodium solutions and the motivation to seek and consume sodium changes dramatically with body fluid balance. Here, we review studies that collectively suggest that sodium deficit recruits the mesolimbic system to play a role in the behavioral expression of sodium appetite. The recruitment of the mesolimbic system likely contributes to intense sodium seeking and reinforces sodium consumption observed in deficient animals. Some of the hormones that are released in response to sodium deficit act directly on both dopamine and nucleus accumbens elements. Moreover, the taste of sodium in sodium deficient rats evokes a pattern of dopamine and nucleus accumbens activity that is similar to responses to rewarding stimuli. A very different pattern of activity is observed in non-deficient rats. Given the well-characterized endocrine response to sodium deficit and its central action, sodium appetite becomes an ideal model for understanding the role of mesolimbic signaling in reward, reinforcement and the generation of motivated behavior.
27870442	Remarkable variability between males and females occurs for an array of taste-guided behaviors in both rodents and humans. Sex differences have been noted for taste preference, detection thresholds, and reactivity to taste stimuli. Manipulating sex hormones during early postnatal development or altering the amount of circulating estrogen in adulthood can dramatically alter the pattern of these behaviors. Receptors for sex hormones appear to be prominent in several nuclei associated with central gustatory pathways, indicating that steroid hormones may modulate central taste processing. Electrophysiological recordings from the rat brainstem suggest that taste-elicited activity to sweet stimuli is organized by hormones during early development, and activity during bitter stimulation is altered by circulating ovarian hormones. Sex differences in gustatory function appear to emerge at the level of the taste bud. Among ovariectomized rats, estradiol treatment decreases activity in the chorda tympani nerve during NaCl stimulation. Although there is no evidence that chorda tympani responses to NaCl differ between intact male and female rats, glossopharyngeal nerve responses are lower in intact females for both NaCl and sodium acetate. Responses in the glossopharyngeal nerve to citric acid stimulation are also higher in female rats relative to males. These findings suggest that, in addition to differential central modulation of taste input based on sex, taste information from the periphery varies between males and females. Although the extent of sex differences in taste processing and the underlying causal mechanisms require further clarification, it is clear that studying one sex alone provides an incomplete picture of gustatory function. © 2016 Wiley Periodicals, Inc.
27825896	Conditioned taste aversion (CTA) causes a shift in the hedonic evaluation of a conditioned stimulus (CS) from positive to negative, and reduces the CS intake. Mu-opioid receptors (MORs) in the ventral pallidum (VP) are known to be involved in the hedonic evaluation of positive rewarding stimuli; however, their involvement in evaluation of a negative aversive stimulus is still unclear. To explore the neural mechanisms of the negative hedonic evaluation of the CS in CTA, we examined the effects of the activation of VP MORs on the behavioral responses of rats to a CS. Rats implanted with guide cannulae into the bilateral VP received a pairing of 5mM saccharin solution as a CS with an intraperitoneal injection of 0.15M lithium chloride as an unconditioned stimulus. On the test day, after microinjections of MOR agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO) into the VP, we observed the behavioral responses to the intraorally infused CS solution. The DAMGO injections caused a larger number of ingestive taste reactivity responses to the CS solution. We also measured the consumption of the CS solution in a separate group of rats, using a single-bottle test. The DAMGO injected rats drank a higher volume of the CS solution than the saline injected rats. These results indicate that the activation of MORs in the VP results in the attenuation of aversion to the CS solution, thereby inducing the larger CS intake. Therefore, it is likely that VP MORs are involved in not only positive but also negative hedonic evaluation.
27650100	The global increase in obesity rates has been tied to the rise in junk-food availability and consumption. Increasingly, children are exposed to a junk-food diet during gestation and early development. Excessive consumption of junk-food during this period may negatively impact the development of brain motivation and reward pathways. In this study we investigated the effects of a chronic junk-food diet throughout development on cue-motivated behavior ('wanting'), hedonic 'liking' for sweet tastes, as well as anxiety and weight gain in male and female Long-Evans (LE) and Sprague-Dawley (SD) rats. Here we found that chronic exposure to a junk-food diet resulted in large individual differences in weight gain (gainers and non-gainers) despite resulting in stunted growth as compared to chow-fed controls. Behaviorally, junk-food exposure attenuated conditioned approach (autoshaping) in females, particularly in non-gainers. In contrast, junk-food exposed rats that gained the most weight were willing to work harder for access to a food cue (conditioned reinforcement), and were more attracted to a junk-food context (conditioned place preference) than non-gainers. Hedonic 'liking' reactions (taste reactivity) were severely blunted in LE, but not SD rats, and 'liking' for sucrose negatively correlated with greater weight gain. Finally, junk-food exposure reduced anxiety-like behavior (elevated plus maze) in males but not females. These results suggest that junk-food exposure during development may give rise to dissociable differences in 'liking' and 'wanting' neural systems that do not depend on weight gain and may not be detected through Body Mass Index monitoring alone.
27687926	Behavioural indicators provide a promising approach for objective assessment of the perceptions of animals. In cats, the frequency of specific behaviours as indicators of perception has been studied in connection with food palatability. The aim of this study was to expand that knowledge by identifying behavioural indicators correlating with three degrees of palatability. Thirty-four pet cats were presented with three types of items: favoured food (FF), favoured food with a placebo mini-tablet hidden inside (TFF) and non-favoured food (NFF). The items were presented in a pseudo-randomised sequence, with six trials per item and 18 trials per cat. The behaviour of cats before, during and after eating, or refusing to eat, was video-recorded. Two trained observers, blinded to the types of food items, independently determined the frequency of 16 behavioural patterns on the video recordings. The data were analysed using a mixed logistic regression model. Five behavioural patterns differentiated FF from NFF; 'flick ears backwards', 'lick nose, not eaten', 'flick tail' and 'groom body' were more frequent with NFF, whereas 'lick lips' was more frequent with FF. One indicator, 'drop item', was more frequent with TFF than FF. These findings provide evidence of new behavioural indicators for objective assessment of food perception in cats. The findings also have practical applicability in designing a novel palatability test to be utilised in developing veterinary pharmaceuticals with improved palatability for cats. 
27594419	Genetic variations in the mu-opioid receptor (OPRM1) gene have been related to high sensitivity to rewarding effects of alcohol. The current study focuses on the neural circuitry underlying this phenomenon using an alcohol versus water taste-cue reactivity paradigm in a young sample at relatively early stages of alcohol use, thus limiting the confound of variations in duration of alcohol use. Drinkers (17-21 years old) were selected on genotype carrying the AA-(n = 20) or the AG-(n = 16) variant of the A118G single nucleotide polymorphism (SNP) of the OPRM1 gene (rs1799971), and underwent functional magnetic resonance imaging (fMRI). Magnitude of the neural activity and frontostriatal functional connectivity in response to alcohol versus water were investigated. The AG-group demonstrated reduced activation in prefrontal and parietal regions, including the inferior and middle frontal gyrus, superior and inferior parietal lobule, compared with the AA-group. No activation differences were observed in the mesolimbic pathway. Connectivity from the ventral-striatum to frontal regions for alcohol > water trials was higher in the AG than the AA group. For the dorsal-striatum seed region, the AG group showed increased connectivity to non-PFC regions. These results indicate that adolescents carrying the G-allele may be more vulnerable for the alcohol to hijack the reward system in the absence of frontal control to regulate craving. This implies that findings of hyperactivation in the mesolimbic structures of G-allele carriers in earlier studies might result from both genetic susceptibility and heavy drinking.
27511277	Several recent studies have shown that postoral sugar sensing rapidly stimulates ingestion. Here we explored the specificity with which early phase postoral sugar sensing influenced ingestive motivation. In Experiment 1, rats were trained to associate the consumption of 0.3M sucrose with injections of LiCl (3.0 mEq/kg IP, conditioned taste aversion) or given equivalent exposures to the stimuli, but in an unpaired fashion (UNPAIRED). Then, all rats were given two brief access tests to assess appetitive and consummatory responses to the taste properties of sucrose (0.01-1.0 M), 0.12M NaCl, and dH2O (in 10-s trials in randomized blocks). Intraduodenal (ID) infusions of either 0.3M sucrose or equiosmolar 0.15M NaCl (3.0 ml) were administered, beginning just before each test. For UNPAIRED rats, ID sucrose specifically enhanced licking for 0.03-1.0 M sucrose, with no effect on trial initiation, relative to ID NaCl. Rats with an aversion to sucrose suppressed licking responses to sucrose in a concentration-dependent manner, as expected, but the ID sucrose preload did not appear to further influence licking responses; instead, ID sucrose attenuated trial taking. Using a serial taste reactivity (TR) paradigm, however, Experiment 2 demonstrated that ID sucrose preloads suppressed ingestive oromotor responses to intraorally-delivered sucrose in rats with a sucrose aversion. Finally, Experiment 3 showed that ID sucrose preloads enhanced preferential licking to some representative tastants tested (sucrose, Polycose, and Intralipid), but not others (NaCl, quinine). Together, the results suggest the early phase reinforcing efficacy of postoral sugar is dependent on the sensory and motivational properties of the ingesta.
27491591	The present experiment examined the neuronal networks involved in the latent inhibition of conditioned disgust by measuring brain oxidative metabolism. Rats were given nonreinforced intraoral (IO) exposure to saccharin (exposed groups) or water (non-exposed groups) followed by a conditioning trial in which the animals received an infusion of saccharin paired (or unpaired) with LiCl. On testing, taste reactivity responses displayed by the rats during the infusion of the saccharin were examined. Behavioral data showed that preexposure to saccharin attenuated the development of LiCl-induced conditioned disgust reactions, indicating that the effects of taste aversion on hedonic taste reactivity had been reduced. With respect to cumulative oxidative metabolic activity across the whole study period, the parabrachial nucleus was the only single region examined which showed differential activity between groups which received saccharin-LiCl pairings with and without prior non-reinforced saccharin exposure, suggesting a key role in the effects of latent inhibition of taste aversion learning. In addition, many functional connections between brain regions were revealed through correlational analysis of metabolic activity, in particular an accumbens-amygdala interaction that may be involved in both positive and negative hedonic responses. 
27422085	We investigated the potential of deep brain stimulation (DBS) in the central nucleus of the amygdala (CeA) in rats to modulate functional reward mechanisms. The CeA is the major output of the amygdala with direct connections to the hypothalamus and gustatory brainstem, and indirect connections with the nucleus accumbens. Further, the CeA has been shown to be involved in learning, emotional integration, reward processing, and regulation of feeding. We hypothesized that DBS, which is used to treat movement disorders and other brain dysfunctions, might block reward motivation. In rats performing a lever-pressing task to obtain sugar pellet rewards, we stimulated the CeA and control structures, and compared stimulation parameters. During CeA stimulation, animals stopped working for rewards and rejected freely available rewards. Taste reactivity testing during DBS exposed aversive reactions to normally liked sucrose tastes and even more aversive taste reactions to normally disliked quinine tastes. Interestingly, given the opportunity, animals implanted in the CeA would self-stimulate with 500 ms trains of stimulation at the same frequency and current parameters as continuous stimulation that would stop reward acquisition. Neural recordings during DBS showed that CeA neurons were still active and uncovered inhibitory-excitatory patterns after each stimulus pulse indicating possible entrainment of the neural firing with DBS. In summary, DBS modulation of CeA may effectively usurp normal neural activity patterns to create an 'information lesion' that not only decreased motivational 'wanting' of food rewards, but also blocked 'liking' of rewards.
27353315	The prevalence of overweight and obesity has increased substantially over the last decades. Weight loss attempts in overweight individuals are common, though they seldom result in successful long-term weight loss. One very promising treatment is food cue exposure therapy, during which overweight individuals are repeatedly exposed to food-associated cues (e.g., the sight, smell and taste of high-calorie foods, overeating environments) without eating in order to extinguish cue-elicited appetitive responses to food cues. However, only few studies have tested the effectiveness of cue exposure, especially with regards to weight loss. For exposure treatment of anxiety disorders, it has been proposed that inhibitory learning is critical for exposure to be effective. In this RCT, we translated techniques proposed by Craske et al. (2014) to the appetitive domain and developed a novel cue exposure therapy for overeating aimed at maximizing inhibitory learning. The current RCT tested the effectiveness of this 8-session cue exposure intervention relative to a control intervention in 45 overweight adult (aged 18-60) females at post-treatment and 3-month follow-up, of which 39 participants completed the study. Weight loss, eating psychopathology, food cue reactivity, and snacking behaviour were studied as main treatment outcomes, and mediators and moderators of treatment effects were studied. The presented study design represents an innovative effort to provide valuable clinical recommendations for the treatment of overeating and obesity. 
27251581	Subjects trained in successive positive contrast are usually given an appetitive stimulus of relatively low quality during a pre-shift, followed by exposure to a significantly greater quality of the same stimulus. Enhanced responsiveness to the high-quality stimulus during the post-shift phase, compared to a control group that receives the superior reward in both phases, is taken as an index of successive positive contrast. Successive positive contrast reports are rare, probably due to performance limitations inherent to the experimental protocols available. We exposed infant rats (14 days old at the start of training) to .1% or .01% quinine during 4, 10 min, trials (pre-shift phase). All animals were then given two trials of exposure to .01% quinine (post-shift phase). During the pre-shift the level of intake was greater in pups stimulated with the relatively less aversive .01% quinine solution. These animals also exhibited, compared to those stimulated with .1% quinine, lower emission of the aversive response paw treading. During the post-shift phase, the group that had been exposed to .1% quinine exhibited significantly greater intake of .01% quinine, along with a reduction in the emission of paw treading and an enhancement in paw licking, an ingestive, appetitive response. Altogether, the evidence is suggestive of the emergence of consummatory successive positive contrast during the second week of life of the rat. To our knowledge, this is the first evidence of positive contrast using an aversive solution.
27138206	Touch can be highly emotional, and depending on the environment, it can be perceived as pleasant and comforting or disgusting and dangerous. Here, we studied the impact of context on the processing of tactile stimuli using a functional magnetic resonance imaging (fMRI) paradigm. This was achieved by embedding tactile stimulation in a variable olfactory environment. Twenty people were scanned with BOLD fMRI while receiving the following stimulus blocks: Slow stroking Touch, Civette odor (feces like), Rose odor, Touch+Civette, and Touch+Rose. Ratings of pleasantness and intensity of tactile stimuli and ratings of disgust and intensity of olfactory stimuli were collected. The impact of the olfactory context on the processing of touch was studied using covariance analyses. Coupling between olfactory processing and somatosensory processing areas was assessed with psychophysiological interaction analysis (PPI). A subjectively disgusting olfactory environment significantly reduced the perceived pleasantness of touch. The touch fMRI activation in the secondary somatosensory cortex, operculum 1 (OP1), was positively correlated with the disgust towards the odors. Decreased pleasantness of touch was related to decreased posterior insula activity. PPI analysis revealed a significant interaction between the OP1, posterior insula, and regions processing the disgust of odors (orbitofrontal cortex and amygdala). We conclude that the disgust evaluation of the olfactory environment moderates neural reactivity in somatosensory regions by upregulation of the OP1 and downregulation of the posterior insula. This adaptive regulation of affective touch processing may facilitate adaptive reaction to a potentially harmful stimulus. 
27048155	Drugs that block fatty acid amide hydrolase (FAAH, which elevates anandamide [AEA]) and drugs which block monoacylglycerol (MAGL, which elevates 2-arachidonyl glycerol [2-AG]) have promise in treating both acute and anticipatory nausea in human patients.This study aims to evaluate the relative effectiveness of dual MAGL/FAAH inhibition with either alone to reduce acute and anticipatory nausea in rat models.	AM4302, a new dual MAGL/FAAH inhibitor, was compared with a new selective MAGL inhibitor, AM4301, and new selective FAAH inhibitor, AM4303, for their potential to reduce acute nausea (gaping in taste reactivity) and anticipatory nausea (contextually elicited conditioned gaping) in two rat models.	Our in vitro studies indicate that AM4302 blocks human and rat FAAH: IC50 60 and 31 nM, respectively, with comparable potencies against human MAGL (IC50 41 nM) and rat MAGL (IC50 200 nM). AM4301 selectively blocks human and rat MAGL (IC50 8.9 and 36 nM, respectively), while AM4303 selectively inhibits human and rat FAAH (IC50 2 and 1.9 nM), respectively. Our in vivo studies show that the MAGL inhibitor, AM4301, suppressed acute nausea in a CB1-mediated manner, when delivered systemically or into the interoceptive insular cortex. Although the dual FAAH/MAGL inhibitor, AM4302, was equally effective as the FAAH inhibitor or MAGL inhibitor in reducing acute nausea, it was more effective than both in suppressing anticipatory nausea.	Dual FAAH and MAGL inhibition with AM4302 may be an especially effective treatment for the very difficult to treat symptom of anticipatory nausea.	
26948120	Cocaine experience affects motivation structures such as the nucleus accumbens (NAc) and its major output target, the ventral pallidum (VP). Previous studies demonstrated that both NAc activity and hedonic responses change reliably as a taste cue comes to predict cocaine availability. Here we extended this investigation to examine drug-experience induced changes in hedonic encoding in the VP. VP activity was first characterized in adult male Sprague-Dawley rats in response to intraoral infusions of palatable saccharin and unpalatable quinine solutions. Next, rats received 7 daily pairings of saccharin that predicted either a cocaine (20mg/kg, ip) or saline injection. Finally, the responses to saccharin and quinine were again assessed. Of 109 units recorded in 11 rats that received saccharin-cocaine pairings, 71% of responsive units significantly reduced firing rate during saccharin infusions and 64% increased firing rate during quinine exposure. However, as saccharin came to predict cocaine, and elicited aversive taste reactivity, VP responses changed to resemble quinine. After conditioning, 70% of saccharin-responsive units increased firing rate. Most units that encoded the palatable taste (predominantly reduced firing rate) were located in the anterior VP, while most units that were responsive to aversive tastes were located in the posterior VP. This study reveals an anatomical complexity to the nature of hedonic encoding in the VP. 
26905371	In pre-clinical models of marijuana abuse, there is relatively limited evidence of delta-9-tetrahydrocannabinol's (THC) rewarding effects, as indexed by its general inability to induce a place preference. One explanation for this failure is that its rewarding effects are masked by its concurrently occurring aversive properties. Consistent with this explanation, THC pre-exposure, which presumably weakens its aversive effects, induces place preferences. Such demonstrations are limited to mice and given reported species differences in THC reactivity, it is unknown to what extent the same shift in affective properties would be evident in rats.The present experiment examined the effect of THC history (3.2mg/kg) on THC (1 or 3.2mg/kg) induced place preference conditioning in rats. An assessment of taste avoidance was also run to independently characterize THC's aversive effects and any changes that occurred with drug pre-exposure. These assessments were made in a combined taste avoidance/place preference procedure in which a novel saccharin solution and environment were paired with THC (0, 1 or 3.2mg/kg).	THC did not induce place conditioning, and a history of THC was ineffective in increasing THC's ability to do so, despite the fact that this same history significantly attenuated the aversive effects of THC.	The failure of THC to consistently induce place preferences has been argued to be a function of its concurrently occurring aversive effects masking its rewarding properties. The fact that pre-exposure to THC significantly reduced its aversive effects without impacting THC's ability to induce place preferences suggests that THC has weak rewarding effects and/or its residual aversive affects may have still masked its rewarding properties. An important area for future work will be characterizing under what conditions THC is rewarding and whether its overall reinforcing effects are impacted by the relationship between its affective properties.	
26805766	Nutritional deficiencies during neural development may lead to irreversible changes, even after nutritional rehabilitation, promoting morphological and functional adaptations of structures involved with various behaviours including feeding behaviour. However, the ability of the exposure low protein diet during gestation and lactation to affect the hedonic component of food intake is still poorly understood, especially in females.Wistar rats were divided into two groups according to the diet offered to the dams during pregnancy and lactation: control female (CF; diet with 17% protein, n=7) and low protein female (LPF; diet with 8% protein, n=7). The following parameters were evaluated: (a) body weight during weaning, 30, 45, 60, 75, 90 days of life; (b) standard diet intake from 110 to 132 days of life; (c) fat diet and consumption of simple carbohydrates (HFHS) for 1h at 145 days of life; (d) incentive runway task 60 days after 82 days of life; (e) taste reactivity at 90 days of life; and (f) neuronal activation in the caudate putamen, amygdala, paraventricular nucleus of the hypothalamus under stimulus HFHS at 145 days of life.	The exposure, a low protein diet during gestation and lactation, decreased the body weight throughout the study period from weaning to 90 days of life. However, there was no significant change in the body weight of low protein females from 110 to 132 days of life compared with the control females. There was an increase in the rate of the search for reward and reduced the latency of the perception of bitter taste. The exposure, a low protein diet during gestation and lactation, also promoted hypophagy in adult females compared with control animals. The low protein female had increased HFHS diet consumption compared with the control. Undernutrition increased neuronal activation in response to HFHS diet consumption compared with female controls in the amygdala and in the caudate putamen.	Females subjected to the exposure, a low protein diet during gestation and lactation, exhibit hypophagy on a standard diet but a higher consumption of a diet rich in lipids and simple carbohydrates. And also were more motivated by the pursuit of reward and reduced latency of the bitter taste reactivity, and increased the number of immunoreactive cells c-fos protein activated in the caudate putamen, amygdala and paraventricular nucleus.	

26762310	Adolescence is a critical period characterized by major neurobiological changes. Chronic stimulation of the reward system might constitute an important factor in vulnerability to pathological development. In spite of the dramatic increase in the consumption of sweet palatable foods during adolescence in our modern societies, the long-term consequences of such exposure on brain reward processing remain poorly understood. Here, we investigated in rats the long-lasting effects of sugar overconsumption during their adolescence on their adult reactivity to the hedonic properties of sweet rewards. Adolescent rats with continuous access to 5% sucrose solution (from postnatal day 30-46) showed escalating intake. At adulthood (post-natal day 70), using two-bottle free choice tests, sucrose-exposed rats showed lower intake than non-exposed rats suggesting decreased sensitivity to the rewarding properties of sucrose. In Experiment 1, we tested their hedonic-related orofacial reactions to intraoral infusion of tasty solutions. We showed that sucrose-exposed rats presented less hedonic reactions in response to sweet tastes leaving the reactivity to water or quinine unaltered. Hence, in Experiment 2, we observed that this hedonic deficit is associated with lower c-Fos expression levels in the nucleus accumbens, a brain region known to play a central role in hedonic processing. These findings demonstrate that a history of high sucrose intake during the critical period of adolescence induces long-lasting deficits in hedonic treatment that may contribute to reward-related disorders. 
26577749	Adolescent initiation of drug use has been linked to problematic drug taking later in life and may represent an important variable that changes the balance of the rewarding and/or aversive effects of abused drugs which may contribute to abuse vulnerability. The current study examined the effects of adolescent THC exposure on THC-induced place preference (rewarding effects) and taste avoidance (aversive effects) conditioning in adulthood.Forty-six male Sprague-Dawley adolescent rats received eight injections of an intermediate dose of THC (3.2mg/kg) or vehicle. After these injections, animals were allowed to mature and then trained in a combined CTA/CPP procedure in adulthood (PND ~90). Animals were given four trials of conditioning with intervening water-recovery days, a final CPP test and then a one-bottle taste avoidance test.	THC induced dose-dependent taste avoidance but did not produce place conditioning. None of these effects was impacted by adolescent THC exposure.	Adolescent exposure to THC had no effect on THC taste and place conditioning in adulthood. The failure to see an effect of adolescent exposure was addressed in the context of other research that has assessed exposure of drugs of abuse during adolescence on drug reactivity in adulthood.	
26565096	Selective eating is common in children with autism spectrum disorder (ASD), but it is not yet well understood. The objectives of this study were to examine a new definition of selective eating, compare behavioral measures between children with ASD and selective eating and those without selective eating, and determine relationships among behavioral measures and measures of selective eating. Participants were assigned to groups on the basis of number of foods eaten compared with a population-based sample. Results of one-way multivariate analysis of variance indicated no overall effect of group for challenging behaviors, sensory reactivity, or repetitive behaviors. Between-participant tests indicated that scores for compulsive behaviors were significantly lower (p = .036) for the selective eating group. Correlations were moderately strong among variables relating to food intake and behavioral variables, but were not significant between selective eating and behavioral variables. Further research is needed to validate the definition of selective eating and to identify targets for intervention. 
26559754	Based on recent studies indicating that emotional eating is not the clearly defined problem it is often thought to be, the present study investigated whether emotional eaters overeat merely in response to negative emotional cues, or to other cues as well. It was hypothesized that emotional eaters would overeat after a variety of food cues, not limited to negative emotions. Participants took part in four conditions (negative mood manipulation, positive mood manipulation, food exposure and a control condition) divided over two sessions. Each condition was followed by a bogus taste test, after which food intake was measured. Results showed strong correlations between food intake after all four conditions, indicating that increased intake after one type of cue is related to increased intake after other cues. Participants were identified as emotional or non-emotional eaters based on food intake in the negative mood condition, and based on self-reported emotional eating scores. Both measures of emotional eating were significantly related to food intake after all cues. Based on the current findings, we conclude that individuals who show increased food intake when in a negative emotional state also overeat when experiencing other food-signalling cues. This indicates that 'emotional eating' may not fully capture the eating behaviour of individuals currently identified as 'emotional eaters'. 
26507444	The bitter taste of beer originates from resins in hops (Humulus lupulus L.), which are classified into two subtypes (soft and hard). Whereas the nature and reactivity of soft-resin-derived compounds, such as α-, β-, and iso-α-acids, are well studied, there is only a little information on the compounds in hard resin. For this work, hard resin was prepared from stored hops and investigated for its compositional changes in an experimental model of beer aging. The hard resin contained a series of α-acid oxides. Among them, 4'-hydroxyallohumulinones were unstable under beer storage conditions, and their transformation induced primary compositional changes of the hard resin during beer aging. The chemical structures of the products, including novel polycyclic compounds scorpiohumulinols A and B and dicyclohumulinols A and B, were determined by HRMS and NMR analyses. These compounds were proposed to be produced via proton-catalyzed cyclization reactions of 4'-hydroxyallohumulinones. Furthermore, they were more stable than their precursor 4'-hydroxyallohumulinones during prolonged storage periods.
26381155	Δ(9)-Tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) found in cannabis both reduce the distressing symptom of nausea, but their combined effects are not understood.The potential of combined doses of THC and CBDA to reduce acute nausea and anticipatory nausea in rodent models was assessed.	For acute nausea, the potential of cannabinoid pretreatment(s) to reduce LiCl-induced nausea paired with saccharin was evaluated in a subsequent drug free taste reactivity test, followed by a taste avoidance test. For anticipatory nausea, the potential of the cannabinoid pretreatment(s) to reduce the expression of LiCl-induced contextually elicited conditioned gaping was evaluated.	Combined subthreshold doses of THC (0.01 and 0.1 mg/kg) and CBDA (0.01 and 0.1 μg/kg) reduced acute nausea. Higher doses of THC (1.0, 10 mg/kg) or CBDA (1.0, 10 μg/kg) alone, as well as these combined doses also reduced acute nausea. THC (10 mg/kg) interfered with conditioned taste avoidance, an effect attenuated by CBDA (10 μg/kg). On the other hand, combined subthreshold doses of THC (0.01 and 0.1 mg/kg) and CBDA (0.01 and 0.1 μg/kg) did not suppress contextually elicited conditioned gaping in a test for anticipatory nausea. However, higher doses of THC (1.0, 10 mg/kg) or CBDA (1.0, 10 μg/kg) alone, as well as these combined doses, also reduced anticipatory nausea. Only at the highest dose (10 mg/kg) did THC impair locomotor activity, but CBDA did not at any dose.	Combined subthreshold doses of THC:CBDA are particularly effective as a treatment for acute nausea. At higher doses, CBDA may attenuate THC-induced interference with learning.	
26338886	Inaccuracies in energy intake (EI) measurement hinder identification of risk factors that predict weight gain and evaluation of obesity prevention and treatment interventions. Research has used objective measures of EI to identify underreporting correlates, producing mixed results, suggesting the need to examine novel potential correlates.With the use of an objective measure of EI from doubly labeled water (DLW) this report examined multiple potential underreporting correlates.	Adolescents from 2 studies (study 1, n = 91; mean age: 18.4 ± 0.58 y; 100% female; study 2, n = 162; mean age: 15.2 ± 1.99 y; 82 female adolescents; 80 male adolescents) completed a DLW assessment of EI, a food-frequency questionnaire, and measures of perceived pressure for thinness, thin-ideal internalization, body dissatisfaction, dieting, food-cue reactivity, eating disorder symptoms, socioeconomic status, and neural response to food; BMI (in kg/m(2)) was measured over a 2-y follow-up.	Elevated BMI correlated with underreported EI in study 1 (r = 0.26, P < 0.05) and study 2 (r = 0.20, P = 0.01), as did male sex in study 2 (r = 0.24, P < 0.01); the other survey measures did not. Underreporting correlated negatively (r = -0.29; uncorr P < 0.001) with responsivity of brain regions implicated in motor control to palatable food receipt and positively (r = 0.31; uncorr P < 0.001) with responsivity of a region implicated in taste processing to cues signaling impending milkshake receipt. Underreporting did not predict future change in BMI in either study.	
26272262	Motivational impairments are increasingly recognized as being critical to functional deficits and decreased quality of life in patients diagnosed with psychiatric disease. Accordingly, much preclinical research has focused on identifying psychological and neurobiological processes which underlie motivation . Inferring motivation from changes in overt behavioural responding in animal models, however, is complicated, and care must be taken to ensure that the observed change is accurately characterized as a change in motivation , and not due to some other, task-related process. This chapter discusses current methods for assessing motivation and related psychological processes in rodents. Using an example from work characterizing the motivational impairments in an animal model of the negative symptoms of schizophrenia, we highlight the importance of careful and rigorous experimental dissection of motivation and the related psychological processes when characterizing motivational deficits in rodent models . We suggest that such work is critical to the successful translation of preclinical findings to therapeutic benefits for patients. 
26253212	Preliminary findings suggest that food intake reduction induced by p-chloro-diphenyl diselenide [(p-ClPhSe)2] in rats is mediated by a satiating action; however, additional experiments are necessary to clarify its actions. The purpose of this study was to investigate the effects of diets supplemented with (p-ClPhSe)2 on feeding behavior of rats as well as the (p-ClPhSe)2 effectiveness in producing aversive reactions or specific flavor. The results demonstrated that behavioral satiety sequence (BSS) was preserved in animals exposed to (p-ClPhSe)2-supplemented diets (0.01 and 0.1%) and associated with a shift of the onset of resting to the left indicating a satiating action at the first contact. In addition, the frequency, the mean duration and the mean size of meals were decreased in rats exposed to a 0.1% (p-ClPhSe)2 diet. Alternatively, a second contact with a 0.01% (p-ClPhSe)2 diet caused disruption of BSS and pronounced changes in the meal pattern, suggesting that it produces aversiveness. In fact, rats developed a significant taste aversion to the saccharin solution after receiving the administration of (p-ClPhSe)2 (1 and 10mg/kg; i.p.). Lastly, a diet containing 0.1% of (p-ClPhSe)2 seems to alter the palatability of food given that rats had a preference for the control diet. The findings of the present study suggest that (p-ClPhSe)2 reduced the food intake of rats by inducing a satiating action at the first contact, but it also produced aversive reactions when rats were re-exposed to it. A specific flavor seems also to contribute to (p-ClPhSe)2 suppressant effects on feeding. 
26208908	Previous research has identified relationships between chemosensory reactivity and food neophobia in children. However, most studies have investigated this relationship using declarative data and without separately analysing smell and taste reactivity. Our first objective was to assess the relationships between smell and taste differential reactivity in toddlers (i.e. reactivity towards several stimuli), using experimental behavioural measurements. The second objective was to determine the relationships between smell (or taste) differential reactivity and food neophobia in toddlers, with the hypothesis that the more responsive a toddler was across food odours or tastes, the more neophobic s/he would be. An additional objective was to determine whether the potential relationships between smell (or taste) differential reactivity and food neophobia differ according to gender. One hundred and twenty-three toddlers aged from 20 to 22 months from the Opaline birth cohort (Observatory of Food Preferences in Infants and Children) were involved. A questionnaire was used to assess child's food neophobia. Toddlers' differential reactivity for smell (and for taste) was defined as the variability of behavioural responses over 8 odorants, and over the five basic tastes. Smell and taste differential reactivities were not correlated. Food neophobia scores were modestly but significantly positively correlated with smell differential reactivity but not with taste differential reactivity. When gender was considered, smell reactivity and neophobia were correlated only among boys. This indicates the need to study smell and taste reactivity separately to determine their associations with eating behaviours. This suggests that the rejection of novel foods in neophobic boys could be partly due to food odour. This finding is new and clearly requires further investigation. 
25939814	Alcohol use disorder (AUD) is suggested to have polygenic risk factors and also exhibits neurological complications, strongly encouraging a translational study to explore the associations between aggregates of genetic variants and brain function alterations related to alcohol use. In this study, we used a semiblind multivariate approach, parallel independent component analysis with multiple references (pICA-MR) to investigate relationships of genome-wide single nucleotide polymorphisms with alcohol cue-elicited brain activations in 315 heavy drinkers, where pICA-MR assesses multiple reference genes for their architecture and functional influences on neurobiological conditions. The genetic component derived from the cAMP-response element-binding protein and -brain derived neurotrophic factor (CREB-BDNF) pathway reference was significantly associated (r = -0.38, P = 3.98 × 10(-12) ) with an imaging component reflecting hyperactivation in precuneus, superior parietal lobule, and posterior cingulate for drinkers with more severe alcohol dependence symptoms. The highlighted brain regions participate in many cognitive processes and have been robustly implicated in craving-related studies. The genetic factor highlighted the CREB and BDNF references, as well as other genes including GRM5, GRM7, GRID1, GRIN2A, PRKCA, and PRKCB. Ingenuity Pathway Analysis indicated that the genetic component was enriched in synaptic plasticity, GABA, and protein kinase A signaling. Collectively, our findings suggest that genetic variations in various neural plasticity and signaling pathways partially explain the variance of precuneus reactivity to alcohol cues which appears to be associated with AUD severity.
25738759	In a preclinical model of natural reward devaluation by cocaine, taste cues elicit aversive taste reactivity when they predict impending but delayed cocaine self-administration. Here, we investigated this negative affective state as a function of cocaine dose. Male, Sprague-Dawley rats were given 45 brief intraoral infusions of a 0.15% saccharin solution before 2 h cocaine self-administration for 14 days. Rats were video recorded; taste reactivity and patterns of self-administration were quantified on the first and last days. On day 14, a significant decrease in appetitive taste reactivity and increase in aversive taste reactivity was observed (compared with day 1) that did not vary as a function of cocaine dose. In contrast, patterns of cocaine self-administration (i.e. the total number of lever presses and load-up behavior) varied as a function of dose across days. Further, load-up behavior was positively correlated with aversive taste reactivity (i.e. gapes) on day 14 across all doses tested. Collectively, these findings indicate that the emergence of negative affect in this preclinical model is not dependent on cocaine dose. 
25698079	Emotional eating has been suggested to be a learned behaviour; more specifically, classical conditioning processes might be involved in its development. In the present study we investigated whether a negative mood facilitates appetitive conditioning and whether trait impulsivity influences this process.After undergoing either a negative or neutral mood induction, participants were subjected to a differential classical conditioning procedure, using neutral stimuli and appetizing food. Two initially neutral distinctive vases with flowers were (CS+) or were not (CS-) paired with chocolate mousse intake. We measured participants' expectancy and desire to eat (4 CS+ and 4 CS- trials), salivation response, and actual food intake. The BIS-11 was administered to assess trait impulsivity.	In both mood conditions, participants showed a classically conditioned appetite. Unexpectedly, there was no evidence of facilitated appetitive learning in a negative mood with regard to expectancy, desire, salivation, or intake. However, immediately before the taste test, participants in the negative mood condition reported a stronger desire to eat in the CS+ compared to the CS- condition, while no such effect occurred in the neutral group. An effect of impulsivity was found with regard to food intake in the neutral mood condition: high-impulsive participants consumed less food when presented with the CS+ compared to the CS-, and also less than low-impulsive participants.	An alternative pathway to appetitive conditioning with regard to emotions is that it is not the neutral stimuli, but the emotions themselves that become conditioned stimuli and elicit appetitive responses.	
25673916	Rats emit aversive taste reactivity (TR) behavior (i.e., gapes) following intraoral delivery of a cocaine-paired taste cue, and greater conditioned aversive TR in well-trained rats predicts greater drug-taking. Here, we used a between-groups design and tracked the development of this conditioned aversive TR behavior on a trial by trial basis in an effort to determine when the change in behavior occurs and at what point individual differences in cue reactivity become predictive of cocaine-seeking and cocaine-taking. The results demonstrate that conditioned aversive TR to a cocaine-predictive flavor cue appears very early in training (i.e., following as few as 1 to 2 taste-drug pairings), stabilizes quickly, and becomes predictive of terminal self-administration within 3 to 4 trials. Indeed, rats exhibiting high conditioned aversive TR to the cocaine-paired cue also exhibited greater goal-directed behavior, were faster to take drug, self-administered more cocaine, and exhibited greater seeking during periods of drug non-availability. High conditioned aversive TR, then, develops quickly and is associated with a greater motivation for drug.
25647696	Low doses of dopamine (DA) antagonists and accumbens DA depletions reduce food-reinforced instrumental behavior but do not impair primary food motivation, causing animals to reallocate behavior away from food-reinforced tasks with high response requirements and select less effortful alternatives. However, it is uncertain if this same pattern of effects would occur if sucrose was used as the reinforcer.These experiments studied the impact of DA depletion and antagonism on performance of an effort-related choice task using sucrose as the reinforcer, as well as sucrose consumption, preference, and taste reactivity tests.	The effects of DA manipulations were assessed using a task in which rats chose between lever pressing on a fixed ratio 7 schedule for 5.0 % sucrose versus freely consuming a less concentrated solution (0.3 %).	The DA depleting agent tetrabenazine shifted effort-related choice, decreasing lever pressing for 5.0 % sucrose but increasing intake of the concurrently available 0.3 % sucrose. Tetrabenazine did not affect sucrose appetitive taste reactivity, or sucrose consumption or preference, in free consumption tests. The D1 antagonist ecopipam and the D2 antagonist haloperidol also shifted choice behavior at doses that did not alter sucrose consumption or preference. In contrast, sucrose pre-exposure reduced consumption across all conditions. D3 antagonism had no effects.	D1 and D2 receptor blockade and DA depletion reduce the tendency to work for sucrose under conditions that leave fundamental aspects of sucrose motivation (intake, preference, hedonic reactivity) intact. These findings have implications for studies employing sucrose intake or preference in animal models of depression.	
25582522	There is evidence of altered neural taste response in female adolescents who are obese (OB), and in adolescents who are at risk for obesity. To further understand risk factors for the development of overeating and obesity, we investigated response to tastes of sucrose and water in 23 OB and healthy weight (HW) children.Thirteen HW and 10 OB 8-12-year-old children underwent functional magnetic resonance imaging while tasting sucrose and water. Additionally, children completed an eating in the absence of hunger paradigm and a sucrose-liking task.	A region of interest analysis revealed an elevated BOLD response to taste (sucrose and water) within the bilateral insula and amygdala in OB children relative to HW children. Whole-brain analyses revealed a group by condition interaction within the paracingulate, medial frontal, middle frontal gyri and right amygdala: post hoc analyses suggested an increased response to sucrose for OB relative to HW children, whereas HW children responded more strongly to water relative to sucrose. In addition, OB children, relative to HW, tended to recruit the right putamen as well as medial and lateral frontal and temporal regions bilaterally.	This study showed increased reactivity in the amygdala and insula in the OB compared with HW children, but no functional differentiation in the striatum, despite differences in the striatum previously seen in older samples. These findings support the concept of the association between increased neural processing of food reward in the development of obesity, and raise the possibility that emotional and interoceptive sensitivity could be an early vulnerability in obesity.	
25580524	The role of palladium and nickel sensitization in oral disease and dermatitis is not fully understood.To investigate whether sensitization to these metals was associated with exposure to dental alloys and oral and skin complaints/symptoms in a European multicentre study.	In six dermatology clinics, patch tests with palladium (3% Na2 PdCl4 ; Pd = 102.0 µmol/g) and nickel (5% NiSO4 .6H2 O; Ni = 190.2 µmol/g) were performed in consecutive patients, and patients' characteristics were collected with a questionnaire and a clinical investigation.	In total, 906 patients were included, of whom 24.3% reacted to palladium and 25.2% to nickel. The rate of monosensitization was 6-7% for both metals. Palladium sensitization (as opposed to no sensitization to both metals) was associated with exposure to dental crowns [odds ratio (OR) 2.0], skin reactivity to metals (OR 2.8), oral lichenoid lesions (OR 4.7), xerostomia (OR 7.3), and metal taste (OR 20.7), but not with eczema, stomatitis, or oral burning sensation. Additionally, xerostomia (OR 8.7) and metal taste (OR 4.6) were associated with sensitization to both metals.	Clinically, it is important for palladium-sensitized patients to undergo an oral examination, with particular attention to the presence of/exposure to dental crowns. In the case of metal contact allergy, exposure to dental crowns could play a role.	
25540053	Conditioned gaping occurs through a classically conditioned association between a flavor or a context (CS) and an unconditioned stimulus (US) that produces nausea, such as lithium chloride (LiCl; US). Rats display conditioned gaping to a flavor or context previously associated with nausea; thus, our aim was to investigate whether rats acquire second-order conditioning to a flavor experienced in a nausea-paired context. In Experiment 1, rats were assigned to one of three groups, based upon the contingency of the first order pairing (CS1 context and LiCl) and the contingency of the second-order pairing (CS2 saccharin CS1 context) including: Group Paired/Paired (P/P), Group Paired/Unpaired (P/U) and Group Unpaired/Paired (U/P). In the initial context conditioning, rats were injected with LiCl (Paired) or Saline (Unpaired) prior to a 30 min confinement in a distinctive context (CS1). Drug-free second-order conditioning training among Groups P/P and U/P then consisted of a 5 min intraoral infusion of 0.1 % saccharin (CS2) in the context (CS1), while Group P/U received saccharin in the home cage 24 hr prior to the CS1 exposure. Twenty four hr later, the rats were tested for second-order conditioning during a 2 min taste reactivity (TR) test. Saccharin (CS2) elicited gaping in Group P/P, but not Groups P/U or U/P. Experiment 2 revealed that second-order conditioning was produced in rats given 4 or 8 first-order conditioning trials, but not 2 trials. These results demonstrate that an excitatory contextual CS+ has the potential to confer second-order conditioning to a novel flavor in the absence of any direct pairing with LiCl.
25538581	The subthalamic nucleus (STN) belongs to the basal ganglia and is the current target for the surgical treatment of neurological and psychiatric disorders such as Parkinson's Disease (PD) and obsessive compulsive disorders (OCD), but also a proposed site for the treatment of addiction. It is therefore very important to understand its functions in order to anticipate and prevent possible side-effects in the patients. Although the involvement of the STN is well documented in motor, cognitive and motivational processes, less is known regarding emotional processes. Here we have investigated the direct consequences of STN inactivation by excitotoxic lesions on emotional processing and reinforcement in the rat. We have used various behavioral procedures to assess affect for neutral, positive and negative reinforcers in STN lesioned rats. STN lesions reduced affective responses for positive (sweet solutions) and negative (electric foot shock, Lithium Chloride-induced sickness) reinforcers while they had no effect on responses for a more neutral reinforcer (novelty induced place preference (NIPP)). Furthermore, when given the choice between saccharine, a sweet but non caloric solution, and glucose, a more bland but caloric solution, in contrast to sham animals that preferred saccharine, STN lesioned animals preferred glucose over saccharine. Taken altogether these results reveal that STN plays a critical role in emotional processing. These results, in line with some clinical observations in PD patients subjected to STN surgery, suggest possible emotional side-effects of treatments targeting the STN. They also suggest that the increased motivation for sucrose previously reported cannot be due to increased pleasure, but could be responsible for the decreased motivation for cocaine reported after STN inactivation. 
25536305	Rats display stereotypical oromotor and somatic responses to small volumes of intraorally infused taste solutions. These behaviors, known as taste reactivity, are categorized by their association with ingestion or rejection and are thought to reflect the palatability of the stimulus. Because supracollicular decerebrate rats display normal taste reactivity responses, it would appear that forebrain structures are not necessary for generating them. However, because moving the plane of transection rostrally, or damaging or manipulating specific ventral forebrain sites disrupts normal taste reactivity behavior, lesions of the gustatory cortex, a region that has been suggested to be involved with palatability processing, may do the same. In the current study, rats received two injections of either ibotenic acid (N=12) or vehicle (N=8), targeting the conventionally defined gustatory cortex in each hemisphere, and were implanted with intraoral cannulae. Following recovery, their responses to intraoral infusions (0.23ml in 1min) of dH2O, sucrose (1.0M and 0.1M), and quinine hydrochloride (3mM and 0.3mM) were video recorded. Analysis of brains with sufficient bilateral lesions (N=10) revealed that, on average, approximately 94% of the gustatory cortex was destroyed. These extensive bilateral lesions had no significant effect on taste reactivity; the numbers of ingestive and aversive responses to sucrose and quinine were similar between groups. Though these findings do not rule out involvement of the gustatory cortex in palatability processing, they make evident that the region of insular cortex destroyed is not necessary for the normal expression of unconditioned affective behavioral responses to taste stimuli. 
25528694	Previous studies have shown that one's brain response to high-calorie food cues can predict long-term weight gain or weight loss. The neural correlates that predict food intake in the short term have, however, hardly been investigated. This study examined which brain regions' activation predicts chocolate intake after participants had been either exposed to real chocolate or to control stimuli during approximately one hour, with interruptions for fMRI measurements. Further we investigated whether the variance in chocolate intake could be better explained by activated brain regions than by self-reported craving. In total, five brain regions correlated with subsequent chocolate intake. The activation of two reward regions (the right caudate and the left frontopolar cortex) correlated positively with intake in the exposure group. The activation of two regions associated with cognitive control (the left dorsolateral and left mid-dorsolateral PFC) correlated negatively with intake in the control group. When the regression analysis was conducted with the exposure and the control group together, an additional region's activation (the right anterior PFC) correlated positively with chocolate intake. In all analyses, the intake variance explained by neural correlates was above and beyond the variance explained by self-reported craving. These results are in line with neuroimaging research showing that brain responses are a better predictor of subsequent intake than self-reported craving. Therefore, our findings might provide for a missing link by associating brain activation, previously shown to predict weight change, with short-term intake. 
25526826	Obese individuals develop heightened reactivity to environmental cues associated with hedonic foods through Pavlovian conditioning. This study examined differences between overweight (n = 16) and lean (n = 17) 18-26 year-olds in their acquisition of a swallowing response to visual cues paired with chocolate milk, tasteless water and no taste stimulus. We hypothesized that, compared to lean participants, overweight participants would demonstrate a heightened conditioned swallowing response to the visual cue paired with chocolate milk as well as a resistance to extinction of this response. Results showed that overweight participants swallowed more in response to the visual cue previously paired with chocolate than the cue previously paired with tasteless water (t(15) = -3.057, p = .008) while lean participants showed no cue discrimination (t(16) = -1.027, p = .320). The results evaluating the extinction hypothesis could not be evaluated, as the lean participants did not acquire a conditioned response. In evaluating the conditioned swallow response of overweight participants only, results indicated that there was not a significant decrease in swallowing to cues paired with chocolate milk or water, but overall, overweight participants swallowed more to cues paired with chocolate than cues paired with water. These are the first results to show differential acquisition of Pavlovian conditioned responding in overweight individuals compared to lean individuals, as well as differential conditioning to cues paired with hedonic food stimuli compared to cues paired with neutral stimuli. 
25065764	The application of phenolic compounds to suppress Maillard chemistry and off-flavor development in ultrahigh-termperature (UHT)-processed milk during processing and storage was investigated. Five phenolic compounds were examined for structure-reactivity relationships (catechin, genistein, daidzein, 1,2,3-trihydroxybenzene, and 1,3,5-trihydroxybenzene). The levels of key transient Maillard reaction (MR) intermediates (reactive carbonyl species) and select off-flavor markers (methional, 2-acetyl-2-thiazoline, 2-acetyl-1-pyrroline) were quantified by LC-MS/MS and GC-MS/ToF, respectively. The addition of phenolic compounds prior to UHT processing significantly reduced the concentration of MR intermediates and related off-flavor compounds compared to a control sample (p < 0.05). All phenolic compounds demonstrated unique structure reactivity and, notably, those with a more activated A-ring for aromatic electrophilic substitution (catechin, genistein, and 1,3,5-trihydroxybenzene) showed the strongest suppression effect on the off-flavor markers and reactive carbonyl species. Sensory studies were in agreement with the analytical data. The cooked flavor intensity was rated lower for the recombination model samples of the catechin-treated UHT milk compared to the control UHT milk. Additionally, consumer acceptability studies showed catechin-treated UHT milk to have significantly higher liking scores when compared the control sample (Fisher's LSD = 0.728). 
24952002	Introduction: It has been found that the olfactorygustatory function is altered in patients with eating disorders, with an impairment affecting the perception of olfactory and gustatory stimuli. Objective: The aim was to explore the subjective reactivity after the exposure and tasting of foods with different gradient of sweetness and different fats textures. In addition, changes in the thought-shape fusion (TSF) cognitive distortion were assessed after tasting those different presentations as well as the correlations between the initial scores on TSF-Questionnaire (TSF-Q) and the different responses after that tasting. Method: A total of 15 healthy controls and 23 outpatients with anorexia nervosa underwent two sessions of tasting (sweets with different gradient of sweetness and fats with different textures) and they filled several questionnaires (pre- and post-tasting) to measure their responses after tasting. Results: Participants showed less “self-control” after tasting sweets. The score on TSF-Q increased significantly after the sweets tasting in the patients group. Patients had the worst response after tasting presentations with more quantity of glucose (less gradient of sweetness) than after tasting those with more amount of sucrose (much more sweetness). With respect to the fats, patients showed the worst reaction after tasting the most unfamiliar texture. Pre fats tasting TSF-Q scores correlated significantly with all responses in the patients group. Discussion: Both psychological and biological (e.g. genetic) factors could be involved in the reactions of patients with anorexia nervosa after tasting sweets and fats.It has been found that the olfactorygustatory function is altered in patients with eating disorders, with an impairment affecting the perception of olfactory and gustatory stimuli.	The aim was to explore the subjective reactivity after the exposure and tasting of foods with different gradient of sweetness and different fats textures. In addition, changes in the thought-shape fusion (TSF) cognitive distortion were assessed after tasting those different presentations as well as the correlations between the initial scores on TSF-Questionnaire (TSF-Q) and the different responses after that tasting.	A total of 15 healthy controls and 23 outpatients with anorexia nervosa underwent two sessions of tasting (sweets with different gradient of sweetness and fats with different textures) and they filled several questionnaires (pre- and post-tasting) to measure their responses after tasting.	Participants showed less "self-control" after tasting sweets. The score on TSF-Q increased significantly after the sweets tasting in the patients group. Patients had the worst response after tasting presentations with more quantity of glucose (less gradient of sweetness) than after tasting those with more amount of sucrose (much more sweetness). With respect to the fats, patients showed the worst reaction after tasting the most unfamiliar texture. Pre fats tasting TSF-Q scores correlated significantly with all responses in the patients group.	Both psychological and biological (e.g. genetic) factors could be involved in the reactions of patients with anorexia nervosa after tasting sweets and fats.	
24880692	Given numerous reports implicating involvement of the precuneus in cue-reactivity paradigms, the goal of this investigation was to examine the relationship between activation of the precuneus in response to drug cues and measures of subjective craving and severity of dependence in volunteers who were comorbid for alcohol and nicotine abuse.Forty research participants, who all reported heavy drinking and daily smoking, were recruited (15 women; 70% Caucasian; mean age=31.2 years) for a functional magnetic resonance imaging (fMRI) session involving a cigarette video-cues task and an alcohol taste-cues task. Mean precuneus activation from both tasks during cue presentation was subjected to bivariate correlation analyses with indices of dependence severity and subjective craving.	Precuneus activation in the contrast of Cigarette Cues vs. Control Cues was positively correlated with scores on the Fagerström Test of Nicotine Dependence (r=0.389, p=0.016), and activation in the Alcohol Cues vs. Control Cues contrast was positively correlated with Alcohol Dependence Scale scores (r=0.338, p=0.038). No correlations with subjective craving were observed (ps>0.05).	These findings indicate that the precuneus is involved in cue reactivity for both cigarettes and alcohol, and that this involvement is moderated by severity of drug dependence. The precuneus may be a cortical locus for neuroplastic changes related to drug dependence.	
24813806	We consider conditioned taste aversion to involve a learned reduction in the palatability of a taste (and hence in amount consumed) based on the association that develops when a taste experience is followed by gastrointestinal malaise. The present article evaluates the well-established finding that drugs of abuse, at doses that are otherwise considered rewarding and self-administered, cause intake suppression. Our recent work using lick pattern analysis shows that drugs of abuse also cause a palatability downshift and, therefore, support conditioned taste aversion learning. 
24773440	Rats emit aversive taste reactivity (TR) behavior (i.e., gapes) following intraoral delivery of a cocaine-paired taste cue and greater conditioned aversive TR at the end of training predicts greater drug-seeking and taking. Here, we examined the development of this conditioned aversive TR behavior on a trial-by-trial basis in an effort to determine when the change in behavior occurs and whether early changes in this behavior can be used to predict later drug taking. The results show that conditioned aversive TR to a cocaine-paired cue occurs very early in training (i.e., following as few as 1-2 taste-drug pairings) and, importantly, that it can be used to predict later drug seeking and drug taking in rats.
24739358	The ventral pallidum (VP) is involved in ingestive behaviour. It receives dense GABAergic projections from the nucleus accumbens. GABAergic terminals in the VP co-express enkephalin, an endogenous ligand of delta-opioid receptors. The role of the delta-opioid receptors in the VP in the context of ingestive behaviour remains unclear, in contrast to the well-understood involvement of the mu-opioid receptors. We used the single-bottle test to examine the effects of VP microinjections of the delta-opioid receptor antagonist naltrindole on consumption of a saccharin solution. Naltrindole injections significantly increased the intake of saccharin, but not water, during a 2-h test session. We also investigated perceived palatability of saccharin using a taste reactivity test. The drug treatments increased ingestive responses to intraorally infused saccharin. Further experimentation explored the role of VP delta-opioid receptors in behavioural responses to saccharin that were previously paired with malaise upon the retrieval of conditioned taste aversion (CTA). Naltrindole-injected rats exhibited longer latency for the first occurrence of aversive responses than vehicle-injected control rats. However, there was no between-group difference in total aversive responses. These results suggest that naltrindole injections into the VP induce an enhancement of perceived palatability of a normally preferred saccharin solution, and thereby facilitate consumption of the solution. On the other hand, delayed aversive responses to the conditioned aversive saccharin suggest that the delta-opioid receptors in the VP mediate the initiation of aversive taste reactivity responses to the conditioned stimulus upon CTA retrieval. 
24683509	Neuroimaging studies have shown that white matter damage accompanies excessive alcohol use, but the functional correlates of alcohol-related white matter disruption remain unknown. This study applied tract-based spatial statistics (TBSS) to diffusion tensor imaging (DTI) data from 332 heavy drinkers (mean age = 31.2 ± 9.4; 31% female) to obtain averaged fractional anisotropy (FA) values of 18 white matter tracts. Statistical analyses examined correlations of FA values with blood-oxygenation-level-dependent (BOLD) response to an alcohol taste cue, measured with functional magnetic resonance imaging (fMRI). FA values of nine white matter tracts (anterior corona radiata, body of corpus callosum, cingulate gyrus, external capsule, fornix, inferior frontooccipital fasciculus, posterior corona radiata, retrolenticular limb of internal capsule, and superior longitudinal fasciculus) were significantly, negatively correlated with BOLD activation in medial frontal gyrus, parahippocampal gyrus, fusiform gyrus, cingulum, thalamus, caudate, putamen, insula, and cerebellum. The inverse relation between white matter integrity and functional activation during the alcohol taste cue provides support for the hypothesis that lower white matter integrity in frontoparietal and corticolimbic networks is a factor in loss of control over alcohol consumption. 
24561923	This paper describes a novel method for studying the bio-behavioral basis of addiction to food. This method combines the surgical component of taste reactivity with the behavioral aspects of operant self-administration of drugs. Under very brief general anaesthesia, rats are implanted with an intraoral (IO) cannula that allows delivery of test solutions directly in the oral cavity. Animals are then tested in operant self-administration chambers whereby they can press a lever to receive IO infusions of test solutions. IO self-administration has several advantages over experimental procedures that involve drinking a solution from a spout or operant responding for solid pellets or solutions delivered in a receptacle. Here, we show that IO self-administration can be employed to study self-administration of high fructose corn syrup (HFCS). Rats were first tested for self-administration on a progressive ratio (PR) schedule, which assesses the maximum amount of operant behavior that will be emitted for different concentrations of HFCS (i.e. 8%, 25%, and 50%). Following this test, rats self-administered these concentrations on a continuous schedule of reinforcement (i.e. one infusion for each lever press) for 10 consecutive days (1 session/day; each lasting 3 hr), and then they were retested on the PR schedule. On the continuous reinforcement schedule, rats took fewer infusions of higher concentrations, although the lowest concentration of HFCS (8%) maintained more variable self-administration. Furthermore, the PR tests revealed that 8% had lower reinforcing value than 25% and 50%. These results indicate that IO self-administration can be employed to study acquisition and maintenance of responding for sweet solutions. The sensitivity of the operant response to differences in concentration and schedule of reinforcement makes IO self-administration an ideal procedure to investigate the neurobiology of voluntary intake of sweets.
24512700	Data in animal models and surveys in humans have shown psychiatric complications of long-term anabolic androgenic steroids abuse. However, neurobiochemical mechanisms behind observed behavioral changes are poorly understood. The aim of the present study was to investigate the effects of nandrolone decanoate on emotional behavior and neurochemical brain alterations in gonadally intact male rats. Behavioral reactivity to elevated plus maze and social interaction test was used to assess anxiety-related symptoms, while sucrose preference test was used to evaluate anhedonia. Dopaminergic, serotonergic and noradrenergic transmissions were also evaluated in selected brain areas. Chronic administration of nandrolone, at 5 mg kg-1 injected for 4 weeks, induced loss of sweet taste preference, as sign of anhedonia and dysfunction of reward pathway. Behavioral outcomes were accompanied by reduction of dopamine, serotonin and noradrenaline contents in nucleus accumbens. Neither alterations in time spent in open arms nor in social interaction test were found, suggesting that nandrolone did not induce an anxiogenic profile. No differences were revealed between experimental groups in the amygdala in terms of neurotransmitters measured. Our data suggest that nandrolone-treated rats have a depressive, but not anxiogenic-like, profile, accompanied by brain region-dependent changes in dopaminergic, serotonergic and noradrenergic neurotransmission. As anabolic androgenic steroid dependence is plausibly the major form of worldwide substance dependence that remains largely unexplored, it should be underlined that our data could contribute to a better understanding of altered reward induced by nandrolone treatment and to develop appropriate treatment.
24490270	Data in animal models and surveys in humans have revealed psychiatric complications of long-term anabolic androgenic steroid abuse. However, the neurobiochemical mechanisms behind the observed behavioral changes are poorly understood. The aim of the present study was to investigate the effects of nandrolone decanoate on emotional behavior and neurochemical brain alterations in gonadally intact male rats. The behavioral reactivity to the elevated plus maze and the social interaction test was used to assess anxiety-related symptoms, and the sucrose preference test was used to evaluate anhedonia. Dopaminergic, serotonergic and noradrenergic transmissions were also evaluated in selected brain areas. The chronic administration of nandrolone, at 5 mg kg(-1) injected daily for 4 weeks, induced the loss of sweet taste preference, a sign of anhedonia and dysfunction of the reward pathway. The behavioral outcomes were accompanied by reductions in the dopamine, serotonin and noradrenaline contents in the nucleus accumbens. Alterations in the time spent in the open arms and in the social interaction test were not found, suggesting that nandrolone did not induce an anxiogenic profile. No differences were revealed between the experimental groups in the amygdala in terms of the neurotransmitters measured. Our data suggest that nandrolone-treated rats have a depressive, but not anxiogenic-like, profile, accompanied by brain region-dependent changes in dopaminergic, serotonergic and noradrenergic neurotransmission. As anabolic androgenic steroid dependence is plausibly the major form of worldwide substance dependence that remains largely unexplored, it should be highlighted that our data could contribute to a better understanding of the altered rewards induced by nandrolone treatment and to the development of appropriate treatments.
24477770	Remarkably, when lingual gustatory nerves are surgically rerouted to inappropriate taste fields in the tongue, some taste functions recover. We previously demonstrated that quinine-stimulated oromotor rejection reflexes and neural activity (assessed by Fos immunoreactivity) in subregions of hindbrain gustatory nuclei were restored if the posterior tongue, which contains receptor cells that respond strongly to bitter compounds, was cross-reinnervated by the chorda tympani nerve. Such functional recovery was not seen if instead, the anterior tongue, where receptor cells are less responsive to bitter compounds, was cross-reinnervated by the glossopharyngeal nerve, even though this nerve typically responds robustly to bitter substances. Thus, recovery depended more on the taste field being reinnervated than on the nerve itself. Here, the distribution of quinine-stimulated Fos-immunoreactive neurons in two taste-associated forebrain areas was examined in these same rats. In the central nucleus of the amygdala (CeA), a rostrocaudal gradient characterized the normal quinine-stimulated Fos response, with the greatest number of labeled cells situated rostrally. Quinine-stimulated neurons were found throughout the gustatory cortex, but a "hot spot" was observed in its anterior-posterior center in subregions approximating the dysgranular/agranular layers. Fos neurons here and in the rostral CeA were highly correlated with quinine-elicited gapes. Denervation of the posterior tongue eliminated, and its reinnervation by either nerve restored, numbers of quinine-stimulated labeled cells in the rostralmost CeA and in the subregion approximating the dysgranular gustatory cortex. These results underscore the remarkable plasticity of the gustatory system and also help clarify the functional anatomy of neural circuits activated by bitter taste stimulation.
24411804	Subjective responses to alcohol represent a biologically based, genetically moderated, and clinically informative marker of alcoholism risk; however, the physiology underlying this phenotype remains unclear. This study tested whether subjective responses during alcohol administration predict neural responses to alcohol cues in the scanner and whether these neural responses differ between OPRM1 genotypes.Twenty alcohol-dependent individuals were recruited (10 G-allele carriers; 6 women; Mage = 29.4) for a within-subjects alcohol administration in the laboratory and a functional magnetic resonance imaging session consisting of an alcohol taste cues task. Laboratory assessments of alcohol high, liking, craving, and positive and negative reinforcement during alcohol administration were entered as predictors of neural response to the presentation of alcohol cues versus water cues in the scanner and further tested for OPRM1 genotype moderation (whole-brain cluster-corrected at Z > 1.96, p < .05).	Alcohol craving during alcohol administration predicted less neural activity, whereas alcohol reinforcement predicted greater neural activity to alcohol cues versus water cues in regions including the precuneus, posterior cingulate gyrus, and lingual gyrus. Alcohol high predicted greater neural activity to alcohol cues in regions including the precuneus and anterior cingulate cortex. OPRM1 genotype was found to moderate these relationships. No results were observed for alcohol liking.	This study provides initial evidence that subjective responses to alcohol, namely craving, high, and the reinforcing properties of alcohol, predict neural markers of alcohol cue reactivity. These results support the validity of laboratory and neuroimaging measures of subjective responses to alcohol and offer an integration of these methods in a sample of alcohol-dependent individuals.	
24411803	Stress evokes thoughts about alcohol and enhances alcohol's rewarding value in drinkers who use alcohol to cope with negative affect. The present study extends prior research by examining whether this effect applies to actual alcohol consumption following a stressor and whether individuals with high and low coping motives for drinking differ in stress reactivity.Nondependent drinkers with high scores (﹥1 SD above national norms) on the coping motives subscale on the Drinking Motives Questionnaire (n = 41; 46% women) were enrolled along with age- and gender-matched nondependent drinkers with low coping motives (n = 41). Participants were randomized to receive the Trier Social Stress Test or a no-stress control condition. Following the stress manipulation, participants could consume up to 473 ml of beer in a "taste test," a covert measure of alcohol consumption. Stress reactivity was measured with both objective and subjective indices, and milliliters of beer consumed was the alcohol-relevant outcome.	Participants with high coping motives showed a less robust stress response to the Trier Social Stress Test than participants with low coping motives for drinking. However, the stressor did not result in greater consumption of alcohol (i.e., no main effect of stress induction) or differential drinking in the two motive groups (i.e., no Stressor × Coping Motive group interaction).	Findings suggest that nondependent drinkers with and without coping motives for drinking may experience a stress provocation differently, but exposure to a standardized social stressor does not lead to differential drinking in these groups in a clinical laboratory setting.	
24358861	The chorda tympani (CT), which innervates taste buds on the anterior portion of the tongue, is susceptible to damage during inner ear surgeries. Injury to the CT causes a disappearance of taste buds, which is concurrent with significant microglial responses at central nerve terminals in the nucleus of the solitary tract (nTS). The resulting taste disturbances that can occur may persist for months or years, long after the nerve and taste buds have regenerated. These persistent changes in taste sensation suggest alterations in central functioning and may be related to the microglial responses. This is reminiscent of nerve injuries that result in chronic pain, where microglial reactivity is essential in maintaining the altered sensation (i.e., pain). In these models, methods that diminish microglial responses also diminish the corresponding pain behavior. Although the CT nerve does not contain nociceptive pain fibers, the microglial reactivity after CT damage is similar to that described in pain models. Therefore, methods that decrease microglial responses in pain models were used here to test if they could also affect microglial reactivity after CT injury. Treatment with minocycline, an antibiotic that dampens pain responsive microglia, was largely ineffective in diminishing microglial responses after CT injury. In addition, signaling through the toll-like 4 receptor (TLR4) does not seem to be required after CT injury as blocking or deleting TLR4 had no effect on microglial reactivity. These results suggest that microglial responses following CT injury rely on different signaling mechanisms than those described in nerve injuries resulting in chronic pain. 
24315831	Endogenous opioid activity plays an important role in ethanol consumption and reinforcement in infant rats. Opioid systems are also involved in mediation and regulation of stress responses. Social isolation is a stressful experience for preweanling rats and changes the effects of ethanol through opioid-dependent mechanisms. The present study assessed effects of intracisternal (i.c.) administration of a selective mu-opioid antagonist (CTOP) and i.p. administration of a nonspecific opioid antagonist (naloxone) on voluntary intake and behavior in socially isolated 12-day-old (P12) pups treated with 0.5 g/kg ethanol. Voluntary intake of 0.1% saccharin or water, locomotion, rearing activity, paw licking and grooming were assessed during short-term isolation from littermates (STSI; 8-min duration). Thermal nociceptive reactivity was measured before and after this intake test, with normalized differences between pre- and post-test latencies of paw withdrawal from a hot plate (49°C) used as an index of isolation-induced analgesia (IIA). Results indicated several effects of social isolation and ethanol mediated through the mu-opioid system. Effects of low dose ethanol (0.5 g/kg) and voluntary consumption of saccharin interacted with endogenous mu-opioid activity associated with STSI. Blockade of mu-opioid receptors on saccharin consumption and paw licking-grooming affected intoxicated animals. Low dose ethanol and ingestion of saccharin blunted effects of CTOP on rearing behavior and nociceptive reactivity. Central injections of CTOP stimulated paw licking and grooming dependent on ethanol dose and type of fluid ingested. Ethanol selectively increased saccharin intake during STSI in females, naloxone and CTOP blocked ethanol-mediated enhancement of saccharin intake. We suggest that enhancement of saccharin intake by ethanol during STSI is the product of synergism between isolation-induced mu-opioid activity that increases the pup's sensitivity to appetitive taste stimulation and the anxiolytic effects of 0.5 g/kg ethanol that decreases behaviors otherwise competing with independent ingestive activity.
24289950	The release of intracellular microcystin-LR (MC-LR), 2-methylisoborneol (MIB), and geosmin was investigated after the oxidation of three cyanobacteria (Microcystis aeruginosa (MA), Oscillatoria sp. (OSC), and Lyngbya sp. (LYN)). During the oxidation of 200,000 cells/mL of MA, release of intracellular MC-LR exceeded the World Health Organization (WHO) guideline of 1 μg/L during the lowest oxidant exposures (CT) tested: ozone (0 mg-min/L, below the ozone demand), chlorine (<40 mg-min/L), chlorine dioxide (<560 mg-min/L), and chloramine (<640 mg-min/L). As the CT increased, ozone, chlorine, and chlorine dioxide were able to oxidize the released MC-LR. During the oxidation of OSC (2800 cells/mL) and LYN (1600 cells/mL), release of intracellular MIB and geosmin exceeded reported threshold odor values after exposure to chlorine, chlorine dioxide, and chloramine, which have low reactivity with these taste and odor compounds. Ozone oxidation of OSC yielded an increase in MIB concentration at lower exposures (≤2.9 mg-min/L), likely due to insufficient oxidation by hydroxyl radicals. The release of intracellular organic matter (IOM) was also measured to determine the potential of bulk measurements to act as a surrogate for cyanotoxins and metabolite release. In all cases, the dissolved organic carbon (DOC) release was less than 0.25 mgC/L, which lacked the sensitivity to indicate the release of MC-LR, MIB, or geosmin. The fluorescence index proved to be a more sensitive indicator of intracellular organic matter release than DOC for MA. These results illustrate that toxic or odorous compounds may be released from cyanobacteria cells during oxidation processes with minimal changes in the DOC concentration. 
24285091	Bitter taste receptors (TAS2Rs) mediate aversive response to toxic food, which is often bitter. These G-protein-coupled receptors are also expressed in extraoral tissues, and emerge as novel targets for therapeutic indications such as asthma and infection. Our goal was to identify ligands of the broadly tuned TAS2R14 among clinical drugs. Molecular properties of known human bitter taste receptor TAS2R14 agonists were incorporated into pharmacophore- and shape-based models and used to computationally predict additional ligands. Predictions were tested by calcium imaging of TAS2R14-transfected HEK293 cells. In vitro testing of the virtual screening predictions resulted in 30-80% success rates, and 15 clinical drugs were found to activate the TAS2R14. hERG potassium channel, which is predominantly expressed in the heart, emerged as a common off-target of bitter drugs. Despite immense chemical diversity of known TAS2R14 ligands, novel ligands and previously unknown polypharmacology of drugs were unraveled by in vitro screening of computational predictions. This enables rational repurposing of traditional and standard drugs for bitter taste signaling modulation for therapeutic indications.
24244696	Ethanol's action on the brain likely reflects altered function of key ion channels such as glutamatergic N-methyl-D-aspartate receptors (NMDARs). In this study, we determined how expression of a mutant GluN1 subunit (F639A) that reduces ethanol inhibition of NMDARs affects ethanol-induced behaviors in mice. Mice homozygous for the F639A allele died prematurely while heterozygous knock-in mice grew and bred normally. Ethanol (44 mM; ∼0.2 g/dl) significantly inhibited NMDA-mediated EPSCs in wild-type mice but had little effect on responses in knock-in mice. Knock-in mice had normal expression of GluN1 and GluN2B protein across different brain regions and a small reduction in levels of GluN2A in medial prefrontal cortex. Ethanol (0.75-2.0 g/kg; i.p.) increased locomotor activity in wild-type mice but had no effect on knock-in mice while MK-801 enhanced activity to the same extent in both groups. Ethanol (2.0 g/kg) reduced rotarod performance equally in both groups but knock-in mice recovered faster following a higher dose (2.5 g/kg). In the elevated zero maze, knock-in mice had a blunted anxiolytic response to ethanol (1.25 g/kg) as compared to wild-type animals. No differences were noted between wild-type and knock-in mice for ethanol-induced loss of righting reflex, sleep time, hypothermia or ethanol metabolism. Knock-in mice consumed less ethanol than wild-type mice during daily limited-access sessions but drank more in an intermittent 24 h access paradigm with no change in taste reactivity or conditioned taste aversion. Overall, these data support the hypothesis that NMDA receptors are important in regulating a specific constellation of effects following exposure to ethanol.
24012649	We aimed to determine the potential of various doses of metoclopramide (MCP, a dopamine antagonist) to reduce lithium chloride (LiCl)-induced conditioned gaping (a nausea-induced behaviour) in rats, using the taste reactivity test. We then evaluated whether an ineffective low dose of cannabidiolic acid (CBDA, 0.1 μg/kg, Rock and Parker, 2013), the potent acidic precursor of cannabidiol (CBD, a non-psychoactive component of cannabis) could enhance the anti-nausea effects of an ineffective low dose of MCP. MCP (3.0 mg/kg) reduced conditioned gaping responses. Coadministration of ineffective doses of MCP (0.3 mg/kg) and CBDA (0.1 μg/kg) enhanced the suppression of conditioned gaping, over that of either drug alone, without interfering with conditioned taste avoidance. MCP dose-dependently reduced nausea-induced conditioned gaping in rats. As well, the suppression of conditioned gaping was enhanced when ineffective doses of MCP and CBDA were coadministered. These data suggest that CBDA could be a powerful adjunct treatment to anti-emetic regimens for chemotherapy-induced nausea.
23991698	To understand how anandamide transport inhibition impacts the regulation of nausea and vomiting and the receptor level mechanism of action involved. In light of recent characterization of an anandamide transporter, fatty acid amide hydrolase-1-like anandamide transporter, to provide behavioural support for anandamide cellular reuptake as a facilitated transport process.The systemic administration of the anandamide transport inhibitor ARN272 ([(4-(5-(4-hydroxy-phenyl)-3,4-diaza-bicyclo[4.4.0]deca-1(6),2,4,7,9-pentaen-2-ylamino)-phenyl)-phenylamino-methanone]) was used to evaluate the prevention of LiCl-induced nausea-induced behaviour (conditioned gaping) in rats, and LiCl-induced emesis in shrews (Suncus murinus). The mechanism of how prolonging anandamide availability acts to regulate nausea in rats was explored by the antagonism of cannabinoid 1 (CB1) receptors with the systemic co-administration of SR141716.	The systemic administration of ARN272 produced a dose-dependent suppression of nausea-induced conditioned gaping in rats, and produced a dose-dependent reduction of vomiting in shrews. The systemic co-administration of SR141716 with ARN272 (at 3.0 mg·kg(-1)) in rats produced a complete reversal of ARN272-suppressed gaping at 1.0 mg·kg(-1). SR141716 alone did not differ from the vehicle solution.	These results suggest that anandamide transport inhibition by the compound ARN272 tonically activates CB1 receptors and as such produces a type of indirect agonism to regulate toxin-induced nausea and vomiting. The results also provide behavioural evidence in support of a facilitated transport mechanism used in the cellular reuptake of anandamide.	
23978688	Projections from the central amygdala (CeA) and lateral hypothalamus (LH) modulate the activity of gustatory brainstem neurons, however, the role of these projections in gustatory behaviors is unclear. The goal of the current study was to determine the effects of electrical stimulation of the CeA or LH on unconditioned taste reactivity (TR) behaviors in response to intra-oral infusion of tastants. In conscious rats, electrical stimulation of the CeA or LH was delivered with and without simultaneous intra-oral infusion of taste solutions via an intra-oral cannula. Immunohistochemistry for the Fos protein was used to identify neurons in the gustatory brainstem activated by the electrical and/or intra-oral stimulation. In the absence of intra-oral infusion of a tastant, electrical stimulation of either the CeA or the LH increased the number of ingestive, but not aversive, TR behaviors performed. During intra-oral infusions of taste solutions, CeA stimulation tended to increase aversive behaviors whereas LH stimulation dramatically reduced the number of aversive responses to quinine hydrochloride (QHCl). These data indicate that projections from the CeA and LH alter TR behaviors. A few of the behavioral effects were accompanied by changes in the number of Fos-immunoreactive neurons in the gustatory brainstem, suggesting a possible anatomical substrate for these effects. 
23973764	Evidence suggests that behavioural affective reactions to sweet and bitter substances are homologous in humans, nonhuman primates, and rodents. The sweet taste of sucrose elicits facial responses that include rhythmic tongue protrusions whereas the bitter taste of quinine elicits facial responses that include gapes, featuring an opening of the mouth and protrusion of the tongue. The present study using the horse (Equus caballus) was undertaken for three reasons: (1) there is debate about the presence of a sweet receptor gene in the horse, (2) there is a need to expand the examination of facial reactions to taste in lineages other than the closely related lineages of rodents and primates, and (3) the horse provides an opportunity to test the hypothesis that some social signals derive from movements related to taste reaction. The horses were given oral infusions of either sucrose or quinine and their behaviour was examined using frame-by-frame video analysis. Control groups were exposed received water or syringe insertion only. Amongst the many responses made to the infusions, the distinctive response to sucrose was a bob coupled with a slight tongue protrusion and forward movement of the ears; the distinctive response to quinine was a head extension and mouth gape accompanied by a large tongue protrusion and backward movement of the ears. Sucrose Bobs and Quinine Gapes are discussed with respect to: (1) the relevance of facial reactions to both sucrose and quinine to taste receptors in horses, (2) the similarity of features of taste expression in horses to those documented in rodents and primates, and (3) the dissimilarity between facial reactions to taste and other social signals displayed by horses. 
23876228	Endogenous opioids and striatal dopamine have been implicated in cue-induced alcohol craving and have been hypothesized to play a role in goal-directed, as opposed to habitual, alcohol use. This initial study examines dorsal and ventral striatal functional connectivity during alcohol-cue processing as a function of the A118G single-nucleotide polymorphism of the mu-opioid receptor (OPRM1) gene.Seventeen individuals with alcohol dependence (6 females; 90% Caucasian; mean age = 29.4) underwent blood oxygen level-dependent functional magnetic resonance imaging, while performing an alcohol taste-cues task. Psychophysiological interaction analyses investigated associations of the OPRM1 genotype with ventral and dorsal striatum functional connectivity, using the ventral striatum and the caudate as the seed region, respectively.	Compared to A-allele homozygotes, G-allele carriers of the OPRM1 gene showed (i) greater activation of the insula and orbitofrontal cortex and (ii) stronger negative fronto-striatal functional connectivity for both ventral and dorsal striatal seed regions during processing of alcohol versus water cues.	These preliminary findings suggest that, relative to A-allele homozygotes, G-allele carriers show unstable frontal regulation over reward and/or habit-driven inputs from the striatum resulting from greater reward sensitivity combined with limited self-control resources.	
23831016	Animals can learn that specific contexts are associated with important biological events such as food intake through classical conditioning. Very few studies suggest this is also possible in humans and contextual appetitive conditioning might even be a main determinant of habitual overeating in vulnerable humans. A Virtual Reality laboratory was used to test whether humans show conditioned responding (increased food desires and expectations, increased salivation and increased food intake) to a specific context after repeated pairings of this context with intake. It was also examined whether the personality trait impulsivity strengthens this contextual appetitive conditioning. Conditioned context-induced reactivity was indeed demonstrated and impulsivity predicted increased intake in only the intake-associated context. It is concluded that humans easily learn desires to eat in intake-related environments. The data also suggest that in particular more impulsive people are vulnerable for conditioned context-induced overeating. This relatively easy learning of associations between specific contexts and intake might stimulate habitual overeating and contribute to increased obesity prevalence. 
23813056	Nonreinforced exposure to a cue tends to attenuate subsequent conditioning with that cue-an effect referred to as latent inhibition (LI). In the two experiments reported here, we examined LI effects in the context of conditioned taste aversion by examining both the amount of consumption and the microstructure of the consummatory behavior (in terms of the mean size of lick clusters). The latter measure can be taken to reflect affective responses to, or the palatability of, the solution being consumed. In both experiments, exposure to a to-be-conditioned flavor prior to pairing the flavor with nausea produced by lithium chloride attenuated both the reduction in consumption and the reduction in lick cluster sizes typically produced by taste aversion learning. In addition, we observed a tendency (especially in the lick cluster measure) for nonreinforced exposure to reduce neophobic responses to the test flavors. Taken together, these results reinforce the suggestion from previous experiments using taste reactivity methods that LI attenuates the effects of taste aversion on both consumption and cue palatability. The present results also support the suggestion that the failure in previous studies to see concurrent LI effects on consumption and palatability was due to a context specificity produced by the oral taste infusion methods required for taste reactivity analyses. Finally, the fact that the pattern of extinction of conditioned changes in consumption and in lick cluster sizes was not affected by preexposure to the cue flavors suggests that LI influenced the quantity but not the quality of conditioned taste aversion.
23767873	Hesperetin dihydrochalcone 4'-glucoside, 1, and phloretin 4'-glucoside, 2, belong to a family of dihydrochalcone glycosides that exhibit flavorant properties. In this study was developed a competitive, indirect homologous ELISA for the detection of targets 1 and 2 in fermentation media. Immunogen and coating antigen were prepared by conjugating hapten, 4-(3-oxo-3-(2,6-dihydroxy-4-glucoside phenyl)propyl) benzoic acid, to thyroglobulin and bovine serum albumin, respectively. Antibodies raised in rabbits M6122, M6123, and M6124 and the coating antigen were screened and characterized to determine their optimum concentrations. The optimized ELISA, developed with antibody M6122, gave IC50 values of 27.8 and 21.8 ng/mL for 1 and 2, respectively. Selectivity of the assay was assessed by measuring cross-reactivity of antibody M6122 to related congeners such as aglycones and the 2'-glycosides of hesperetin dihydrochalcone, 5 and phloretin, 6. Antibody M6122 showed very low recognition of 5 and virtually no recognition of the aglycones and 6. 
23667346	Social anxiety may maintain alcohol dependence through increased reactivity to stressful events, a propensity to drink to cope with stressful events, or both. The current study is a secondary analysis of an existing dataset that examined differences between individuals with alcohol dependence and concurrent high and low social anxiety in objective and subjective stress reactivity to a laboratory stressor (Trier Social Stress Test; TSST), as well as consumption of alcohol following the stressor.Forty participants with alcohol dependence (20 women) were randomly assigned to the TSST condition as part of the parent study. Post-hoc analysis of social anxiety measures yielded high (n = 19) and low (n = 21) social anxiety groups. Participants completed the TSST, followed by a small dose of their favorite alcoholic beverage (target blood alcohol concentration 0.03g/dl) to prime subsequent laboratory drinking. Participants received a sham beer taste test of two glasses (710ml total) of beer. Differences between high and low social anxiety groups was assessed via subjective and objective (mean arterial pressure, serum cortisol) reactivity to the TSST and consumption of alcohol during the taste test (total mls consumed, mls/kg of body weight, and likelihood of consuming all the beer available).	No differences emerged in either objective or subjective measures of stress reactivity between high and low socially anxious groups. There were also no differences between social anxiety groups in amount of alcohol consumed during the taste test.	No differences were observed between high and low socially anxious participants with concurrent alcohol dependence on stress reactivity or alcohol consumption following a stressor. Given that all participants in this study had alcohol dependence, negative results may suggest that heightened stress reactivity and drinking to cope are more relevant to the development of alcohol dependence and that other factors may maintain alcohol use once dependence has developed.	
23639430	An important feature of cocaine addiction in humans is the emergence of negative affect (e.g., dysphoria, irritability, anhedonia), postulated to play a key role in craving and relapse. Indeed, the DSM-IV recognizes that social, occupational and/or recreational activities become reduced as a consequence of repeated drug use where previously rewarding experiences (e.g., food, job, family) become devalued as the addict continues to seek and use drug despite serious negative consequences. Here, research in the Carelli laboratory is reviewed that examined neurobiological mechanisms that may underlie these processes using a novel animal model. Oromotor responses (taste reactivity) were examined as rats learned that intraoral infusion of a sweet (e.g., saccharin) predicts impending but delayed access to cocaine self-administration. We showed that rats exhibit aversive taste reactivity (i.e., gapes/rejection responses) during infusion of the sweet paired with impending cocaine, similar to aversive responses observed during infusion of quinine, a bitter tastant. Critically, the expression of this pronounced aversion to the sweet predicted the subsequent motivation to self-administer cocaine. Electrophysiology studies show that this shift in palatability corresponds to an alteration in nucleus accumbens (NAc) cell firing; neurons that previously responded with inhibition during infusion of the palatable sweet shifted to excitatory activity during infusion of the cocaine-devalued tastant. This excitatory response profile is typically observed during infusion of quinine, indicating that the once palatable sweet becomes aversive following its association with impending but delayed cocaine, and NAc neurons encode this aversive state. We also review electrochemical studies showing a shift (from increase to decrease) in rapid NAc dopamine release during infusion of the cocaine-paired tastant as the aversive state developed, again, resulting in responses similar to quinine infusion. Collectively, our findings suggest that cocaine-conditioned cues elicit a cocaine-need state that is aversive, is encoded by a distinct subset of NAc neurons and rapid dopamine signaling, and promotes cocaine-seeking behavior. Finally, we present data showing that experimentally induced abstinence (30 days) exacerbates this natural reward devaluation by cocaine, and this effect is correlated with a greater motivation to lever press during extinction. Dissecting the neural mechanisms underlying these detrimental consequences of addiction is critical since it may lead to novel treatments that ameliorate negative affective states associated with drug use and decrease the drive (craving) for the drug. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'.
23463152	Orexin (hypocretin) is implicated in stimulating appetite as well as arousal, and in both food reward and drug reward. The ventral pallidum (VP) receives orexin projections from lateral hypothalamus neurons (LH), and orexin terminals are especially dense in the posterior half of VP, which is also the location of an opioid hedonic hotspot. The VP hotspot is a roughly cubic-millimeter site where mu opioid stimulation can amplify the hedonic impact of sweetness, expressed as an increase in 'liking' reactions to sucrose taste. The anatomical overlap in posterior VP between opioid hotspot and orexin inputs raises the possibility that the hedonic hotspot might allow orexin to amplify 'liking' too. We examined whether microinjections of orexin-A into the VP hotspot enhance the hedonic impact of sucrose, as assessed via affective taste reactivity measures of 'liking' reactions, and additionally compared effects at nearby sites in adjacent LH and extended amygdala. Taste reactivity results indicated that orexin stimulation specifically in the VP hotspot nearly doubled the magnitude of positive 'liking' reactions elicited by the taste of sucrose. Mapping results for localization of function, aided by Fos plume measures of the local spread of orexin impact, suggested that hedonic enhancement was generated by essentially the same cubic-millimeter of posterior VP previously identified as the opioid hotspot. By contrast, microinjection sites in the anterior half of VP, or in LH or extended amygdala, generally failed to produce any hedonic enhancement. We conclude that an orexin hedonic hotspot exists in posterior VP, with similar boundaries to the opioid hotspot. An orexin hedonic hotspot may permit regulatory hypothalamic circuitry to make foods more 'liked' during hunger by acting through VP. Dysfunction in a VP orexin hotspot in addiction or mood disorders might also contribute to some types of affective psychopathology. 
23382517	Cue reactivity and craving can be influenced by cue exposure with response prevention (CERP). This study investigated the neural correlates of CERP using functional magnetic resonance imaging, while participants smelled chocolate (17 participants) or a control object (17 participants). CERP was interrupted by 7 scanning sequences measuring the brain response to neutral and chocolate pictures. Chocolate craving was hypothesized to be mirrored by activation in brain reward regions. As expected, control group craving remained similar throughout the session. A short exposure (30 min) increased chocolate craving in the experimental group, which was mirrored by significant group differences in activation in brain reward regions. Unexpectedly, a long exposure (60 min) did not lead to craving extinction in the experimental group, although craving started to decrease at this point. On a neural level, however, activation in regions of interest in the experimental group seemed to have extinguished after the long exposure, as activation levels returned to or fell below control group levels. These results indicate that brain reward activation during CERP is linked to craving, at least for a short exposure. Regarding a longer exposure, the decline in brain reward activation in the experimental group may be a precursor of a decrease in craving. 
23332530	High levels of dietary sugar consumption may result in dysregulated glucose metabolism and lead to elevated cardiovascular disease risk via autonomic nervous system and cardiovascular dysfunction. Altered cardiovascular function can be examined using perturbation tasks such as mental challenge. This study examined the effects of controlled glucose intake on cardiovascular measures at rest and in responses to mental challenge in a laboratory setting.Using a double blind within-subjects design, participants were monitored at baseline, following ingestion of a glucose or taste-control solution, during structured speech (SS), anger recall (AR) and recovery (N=24, 288 repeated measures; age = 21±2 years). Pre-ejection period (PEP), heart rate (HR), stroke index (SI), cardiac index (CI), blood pressure and total peripheral resistance (TPR) were measured throughout the protocol.	Glucose resulted in sustained decreased PEP levels compared to control condition (Δ=11.98±9.52 vs. 3.27±7.65 m·s, P<.001) and transient increases in resting HR (P=.011), CI (P=.040) and systolic blood pressure (P=.009). Glucose did not result in increased cardiovascular reactivity to mental challenge tasks, but was associated with a delayed HR recovery following AR (P=.032).	Glucose intake resulted in a drop in PEP indicating increased sympathetic nervous system activity. No evidence was found for glucose-related exaggerated cardiovascular responses to mental challenge. Dysregulated glucose metabolism may result in elevated cardiovascular disease risk as a result of repeated glucose-induced elevations of sympathetic nervous system activity.	
23306104	Many laboratories obtain their experimental animals from commercial suppliers and are therefore dependent on their conditions and breeding schedules. A breeding stop or the substitution of a particular rat line by the supplier forces the customers to abandon their conventional test animals and to re-establish all behavioral paradigms with a new rat line. Therefore, it is vital to know whether behavioral differences emerge in various breeding lines of the same rat strain. In a recent case, the commercial supplier Harlan Laboratories GmbH is substituting the previous HsdHan:WIST line of Wistar rats with the RccHan:WIST line descending from a different breeding stock. We therefore tested animals of both lines (RccHan:WIST and HsdHan:WIST from Harlan Laboratories GmbH) as well as Wistar rats of the same line but obtained from a different supplier (Janvier) in a broad range of behavioral paradigms. We observed differences in locomotor activity, in classical anxiety-related paradigms (elevated plus maze and light/dark emergence test), as well as in object recognition memory and prepulse inhibition (PPI) of the acoustic startle reflex (ASR). We also found differences in ethanol intake and preference, but not regarding the intake of a palatable food reward and a bitter solution (quinine). These results demonstrate considerable variations in the behavioral phenotype between different breeding lines of the same Wistar rat strain and aim to increase the awareness of behavioral scientists for line and supplier differences affecting animal behavior.
23294371	Recent studies have indicated the presence of significant amount of highly polymerized and soluble proanthocyanidins in red wine and such compounds interacted readily with proteins, suggesting that they might be particularly astringent. Thus, the objective of this work was to verify the astringency of polymeric proanthocyanidins and their contribution to red wine astringency. The precipitation reactions of the purified oligomeric procyanidins (degree of polymerization ranging from 2 to 12-15) and polymeric procyanidins (degree of polymerization ranging from 12-15 to 32-34) with human salivary proteins were studied; salivary proteins composition changes before and after the reaction was verified by SDS-PAGE and procyanidins composition changes by spectrometric, direct HPLC and thiolysis-HPLC methods. The astringency intensity of these two procyanidin fractions was evaluated by a sensory analysis panel. For verifying the correlation between polymeric proanthocyanidins and young red wine astringency, the levels of total oligomeric and total polymeric proanthocyanidins and other phenolic composition in various young red wines were quantified and the astringency intensities of these wines were evaluated by a sensory panel. The results showed that polymeric proanthocyanidins had much higher reactivity toward human salivary proteins and higher astringency intensity than the oligomeric ones. Furthermore, young red wine astringency intensities were highly correlated to levels of polymeric proanthocyanidins, particularly at low concentration range (correlation coefficient r = 0.9840) but not significant correlated to total polyphenols (r = 0.2343) or other individual phenolic compounds (generally r < 0.3). These results indicate the important contribution of polymeric proanthocyanidins to red wine astringency and the levels of polymeric polyphenols in red wines may be used as an indicator for its astringency.
23146409	The Melanocortin (MC) system is one of the crucial neuropeptidergic systems that modulate energy balance. The roles of endogenous MC and MC-4 receptor (MC4-R) signaling within the hypothalamus in the control of homeostatic aspects of feeding are well established. Additional evidence points to a key role for the central MC system in ethanol consumption. Recently, we have shown that nucleus accumbens (NAc), but not lateral hypothalamic (LH), infusion of a selective MC4-R agonist decreases ethanol consumption. Given that MC signaling might contribute to non-homeostatic aspects of feeding within limbic circuits, we assessed here whether MC4-R signaling within the NAc and the lateral hypothalamus (LH) alters normal ingestive hedonic and/or aversive responses to ethanol in rats as measured by a taste reactivity test. Adult male Sprague-Dawley rats were given NAc- or LH- bilateral infusion of the selective MC4-R agonist cyclo (NH-CH(2)-CH(2)-CO-His-D-Phe-Arg-Trp-Glu)-NH(2) (0, 0.75 or 1.5μg/0.5μl/site) and following 30 min, the animals received 1 ml of ethanol solution (6% w/v) intraoral for 1 minute and aversive and hedonic behaviors were recorded. We found that NAc-, but not LH-administration, of a selective MC4-R agonist decreased total duration of hedonic reactions and significantly increased aversive reactions relative to saline-infused animals which support the hypothesis that MC signaling within the NAc may contribute to ethanol consumption by modulating non-homeostatic aspects (palatability) of intake.
23110349	The aim of this study was to evaluate the effect of oxygen exposure of red wine, before (micro-oxygenation) and after (nano-oxygenation) bottling, on the phenolic composition and astringency of wine. The astringency was evaluated by sensory analysis and by a method based on the SDS-PAGE of salivary proteins after reaction of saliva with wine (SPI, saliva precipitation index). Micro-oxygenation caused a stabilization of color, but this effect disappeared after long aging. For the wine with the lower pH a decrease of wine astringency and SPI was observed 42 months after micro-oxygenation. Oxygen ingress through the closure postbottling was positively correlated with the decrease of SPI. Therefore, the astringency and reactivity of wines toward salivary proteins of a bottled red wine can be modulated by controlled oxygen exposure during aging. For both experiments the effect of oxygen exposure depended on wine composition.
23103902	The acute effects of cannabinoid compounds have been investigated in animal models of anxiety-like behavior and palatability processing. However, the chronic effects of cannabinoids in such models are poorly understood. Experiment 1 compared the effects of both acute and chronic (14 days) exposure to the CB(1) receptor inverse agonist/antagonist, rimonabant, and the cannabis-derived CB(1) receptor neutral antagonist, tetrahydrocannabivarin (THCV), on: 1) time spent in the open, lit box in the Light-Dark (LD) immersion model of anxiety-like behavior and 2) saccharin hedonic reactions in the taste reactivity (TR) test of palatability processing. Experiment 2 compared the effects of chronic administration of cannabis-derived Δ(9)-tetrahydrocannabinol (Δ(9)-THC), cannabidiol (CBD) and cannabigerol (CBG) in these models. Tests were administered on Days 1, 7 and 14 of drug administration. In Experiment 1, rimonabant, but not THCV, produced an anxiogenic-like reaction in the LD immersion test and reduced saccharin palatability in the TR test; both of these effects occurred acutely and were not enhanced by chronic exposure. In Experiment 2, Δ(9)-THC also produced an acute anxiogenic-like reaction in the LD immersion test, without enhancement by chronic exposure. However, Δ(9)-THC enhanced saccharin palatability in the TR test on Day 1 of drug exposure only. CBD and CBG did not modify anxiety-like responding, but CBG produced a weak enhancement of saccharin palatability on Day 1 only. The results suggest that the anxiogenic-like reactions and the suppression of hedonic responding produced by rimonabant, are mediated by inverse agonism of the CB(1) receptor and these effects are not enhanced with chronic exposure.
23056367	For social omnivores such as rats and humans, taste is far more than a chemical sense activated by food. By virtue of evolutionary and epigenetic elaboration, taste is associated with negative affect, stress vulnerability, responses to psychoactive substances, pain, and social judgment. A crucial gap in this literature, which spans behavior genetics, affective and social neuroscience, and embodied cognition, concerns links between taste and social behavior in rats. Here we show that rats selectively bred for low saccharin intake are subordinate to high-saccharin-consuming rats when they compete in weight-matched dyads for food, a task used to model depression. Statistical and experimental controls suggest that differential resource utilization within dyads is not an artifact of individual-level processes such as apparatus habituation or ingestive motivation. Tail skin temperature measurements showed that LoS rats display larger hyperthermic responses to social interaction after status is established, evidence linking taste, social stress, autonomic reactivity, and depression-like symptoms. Based on regression using early- and late-competition predictors to predict dyadic disparity in final competition scores, we tentatively suggest that HiS rats emerge as dominant both because of an "early surge" on their part and because LoS acquiesce later. These findings should invigorate the comparative study of individual differences in social status and its relationship to mental and physical health.
23055953	Adaptive motivated behavior requires rapid discrimination between beneficial and harmful stimuli. Such discrimination leads to the generation of either an approach or rejection response, as appropriate, and enables organisms to maximize reward and minimize punishment. Classically, the nucleus accumbens (NAc) and the dopamine projection to it are considered an integral part of the brain's reward circuit, i.e., they direct approach and consumption behaviors and underlie positive reinforcement. This reward-centered framing ignores important evidence about the role of this system in encoding aversive events. One reason for bias toward reward is the difficulty in designing experiments in which animals repeatedly experience punishments; another is the challenge in dissociating the response to an aversive stimulus itself from the reward/relief experienced when an aversive stimulus is terminated. Here, we review studies that employ techniques with sufficient time resolution to measure responses in ventral tegmental area and NAc to aversive stimuli as they are delivered. We also present novel findings showing that the same stimulus - intra-oral infusion of sucrose - has differing effects on NAc shell dopamine release depending on the prior experience. Here, for some rats, sucrose was rendered aversive by explicitly pairing it with malaise in a conditioned taste aversion paradigm. Thereafter, sucrose infusions led to a suppression of dopamine with a similar magnitude and time course to intra-oral infusions of a bitter quinine solution. The results are discussed in the context of regional differences in dopamine signaling and the implications of a pause in phasic dopamine release within the NAc shell. Together with our data, the emerging literature suggests an important role for differential phasic dopamine signaling in aversion vs. reward.
22980834	The aim of this work was to evaluate the astringency of red wines by means of a SDS-PAGE based-method. The optimization of the in vitro assay, named SPI (Saliva Precipitation Index) that measured the reactivity of salivary proteins towards wine polyphenols, has been performed. Improvements included the choice of saliva:wine ratio, saliva typology (resting or stimulated saliva), and temperature of binding. The LOD (0.05 g/L of condensed tannin) and LOQ (0.1g/L of condensed tannin) for the binding reaction between salivary proteins and tannins added in white wine were also determined. Fifty-seven red wines were analysed by the optimised SPI, the Folin-Ciocalteu Index, the gelatine index, the content of total tannins and the sensory quantitative evaluation of astringency. A significant correlation between the SPI and the astringency of red wines was found (R(2)=0.969), thus indicating that this assay may be useful as estimator of astringency.
22974271	Ghrelin figures prominently in the regulation of appetite in normal-weighed individuals. The apparent failure of this mechanism in eating disorders and the connection to addictive behavior in general demand a deeper understanding of the endogenous central-nervous processes related to ghrelin. Thus, we investigated processing of pictures showing palatable food after overnight fasting and following a standardized caloric intake (i.e. a 75-g oral glucose tolerance test) using functional magnetic resonance imaging and correlated it with blood plasma levels of ghrelin. Twenty-six healthy female and male volunteers viewed food and control pictures in a block design and rated their appetite after each block. Fasting levels of ghrelin correlated positively with food-cue reactivity in a bilateral network of visual processing-, reward- and taste-related regions, including limbic and paralimbic regions. Notably, among those regions were the hypothalamus and the midbrain where ghrelin receptors are densely concentrated. In addition, high fasting ghrelin levels were associated with stronger increases of subjective appetite during the food-cue-reactivity task. In conclusion, brain activation and subjective appetite ratings suggest that ghrelin elevates the hedonic effects of food pictures. Thereby, fasting ghrelin levels may generally enhance subjective craving when confronted with reward cues.
22940019	Anecdotal experience and empirical evidence suggest animals approach or avoid conditioned stimuli based on the ability of those stimuli to elicit affective responses or interfere with affective assessments of ongoing stimuli. Thus, this study investigated the relationship between the ability of drug-conditioned environments to induce conditioned place preference or aversion and their ability to influence palatability responses to sucrose and quinine in those same environments. Mice were conditioned to methamphetamine (2mg/kg), morphine (10mg/kg) or naloxone (10mg/kg). Following testing for the expression of place conditioning, palatability responses to sucrose and quinine in the conditioned contexts were assessed. In general, virtually no effects of exposure to drug-conditioned contexts on overall positive or aversive palatability responses were observed. However, in naloxone-conditioned mice, the strength of conditioned place aversion to the naloxone-paired context correlated with aversive taste reactivity responses to quinine in that context. In morphine-conditioned mice, positive reactions to sucrose in the morphine-paired context negatively correlated with positive reactions to sucrose in the vehicle-paired context. Interestingly, the rate of methamphetamine-induced behavioral sensitization during conditioning and positive taste responses to sucrose in the methamphetamine-paired context positively correlated. These studies suggest that conditioned stimuli interact with or modulate the affective experience of ongoing unconditioned stimuli such as tastants, and these may reflect behavioral processes that guide behavior optimally.
22851979	Intrauterine growth restriction is associated with increased risk for adult metabolic syndrome and cardiovascular disease, which seems to be related to altered food preferences in these individuals later in life. In this study, we sought to understand whether intrauterine growth leads to fetal programming of the hedonic responses to sweet. Sixteen 1-day-old preterm infants received 24% sucrose solution or water and the taste reactivity was filmed and analyzed. Spearman correlation demonstrated a positive correlation between fetal growth and the hedonic response to the sweet solution in the first 15 seconds after the offer (r = 0.864, P = 0.001), without correlation when the solution given is water (r = 0.314, P = 0.455). In fact, the more intense the intrauterine growth restriction, the lower the frequency of the hedonic response observed. IUGR is strongly correlated with the hedonic response to a sweet solution in the first day of life in preterm infants. This is the first evidence in humans to demonstrate that the hedonic response to sweet taste is programmed very early during the fetal life by the degree of intrauterine growth. The altered hedonic response at birth and subsequent differential food preference may contribute to the increased risk of obesity and related disorders in adulthood in intrauterine growth-restricted individuals.
22766215	The mediodorsal prefrontal cortex (mdPFC), as an integrant part of the forebrain glucose-monitoring neural network, plays important roles in neural control of feeding. Previous studies suggested that streptozotocin (STZ) causes selective destruction of forebrain glucose-monitoring (GM) neurons leading to development of feeding disturbances. The goal of this research was to evaluate gustatory consequences of bilateral streptozotocin microinjection into the mediodorsal prefrontal cortex of male Wistar rats during conditioned taste avoidance (CTA) acquisition, as well as during taste reactivity tests. Bilateral streptozotocin microinjection failed to impair CTA learning, tested in a saccharin CTA paradigm. However, taste reactivity deficit was found by a modified version of the protocol introduced by Grill and Norgren. The streptozotocin treated animals displayed significantly poorer ingestive reactions to pleasant taste stimuli than did rats of the control group. The unpleasant taste stimuli elicited ingestive and rejective taste reactivity patterns in a comparable manner in rats of the STZ vs. vehicle microinjected groups. The glucose-monitoring neurons of the mdPFC and their distinct role in the gustatory perception may have particular significance in the adaptive control of feeding.
22698870	Prenatal ethanol significantly heightens later alcohol consumption, but the mechanisms that underlie this phenomenon are poorly understood. Little is known about the basis of 'this effect of prenatal ethanol on the sensitivity to ethanol's reinforcing effects. One possibility is that prenatal ethanol exposure makes subjects more sensitive to the appetitive effects of ethanol or less sensitive to ethanol's aversive consequences. The present study assessed ethanol-induced second-order conditioned place preference (CPP) and aversion and ethanol-induced conditioned taste aversion (CTA) in infant rats prenatally exposed to ethanol (2.0 g/kg) or vehicle (water) or left untreated. The involvement of the κ opioid receptor system in ethanol-induced CTA was also explored. When place conditioning occurred during the ascending limb of the blood-ethanol curve (Experiment 1), the pups exposed to ethanol in utero exhibited greater CPP than untreated controls, with a shift to the right of the dose-response curve. Conditioning during a later phase of intoxication (30-45 min post-administration; Experiment 2) resulted in place aversion in control pups exposed to vehicle during late gestation but not in pups that were exposed to ethanol in utero. Ethanol induced a reliable and similar CTA (Experiment 3) in the pups treated with vehicle or ethanol during gestation, and CTA was insensitive to κ antagonism. These results suggest that brief exposure to a moderate ethanol dose during late gestation promotes ethanol-mediated reinforcement and alters the expression of conditioned aversion by ethanol. This shift in the motivational reactivity to ethanol may be an underlying basis of the effect of prenatal ethanol on later ethanol acceptance.
22529783	Taste memory depends on motivational and post-ingestional consequences; thus, it can be aversive (e.g., conditioned taste aversion, CTA) if a novel, palatable taste is paired with visceral malaise, or it can be appetitive if no intoxication appears after novel taste consumption, and a taste preference is developed.The nucleus accumbens (NAc) plays a role in hedonic reactivity to taste stimuli, and recent findings suggest that reward and aversion are differentially encoded by the activity of NAc neurons. The present study examined whether the requirement for N-methyl-D-aspartate (NMDA) receptors in the NAc core during rewarding appetitive taste learning differs from that during aversive taste conditioning, as well as during retrieval of appetitive vs. aversive taste memory, using the taste preference or CTA model, respectively. Bilateral infusions of NMDA (1 μg/μl, 0.5 μl) into the NAc core were performed before acquisition or before retrieval of taste preference or CTA. Activation of NMDA receptors before taste preference training or CTA acquisition did not alter memory formation. Furthermore, NMDA injections before aversive taste retrieval had no effect on taste memory; however, 24 h later, CTA extinction was significantly delayed. Also, NMDA injections, made before familiar appetitive memory retrieval, interrupted the development of taste preference and produced a preference delay 24 h later. These results suggest that memory formation for a novel taste produces neurochemical changes in the NAc core that have differential requirements for NMDA receptors during retrieval of appetitive or aversive memory.
22385266	Diacetyl (DA), a natural butter flavorant, is a causative agent for the lung disease obliterative bronchiolitis. Mutagenic properties of 1,2-dicarbonyls have previously been empirically linked to their possible interaction with DNA nucleobases. This study for the first time identifies chemically the adduct of DA with 2-deoxyguanosine. Selective reactivity of DA with 5'-TTTGTTTTT-3' over 5'-TTTTTTTTT-3' indicated its propensity to modify specifically the guanosine residue. Treatment of plasmid DNA, pBR322, with DA induced changes in electrophoretic mobility that are typical of ternary structure disruption. Such DNA nucleobase interaction of DA translated into increased apoptosis in DA-treated SH-SY5Y cells in a dose-dependent manner (IC(50) = 0.114 ± 0.0421 mM). The traditional carbonyl scavengers metformin, 2-thiobarbituric acid, and d-penicillamine protected cells from DA toxicity in proportion to their rates of reaction with DA, with d-penicillamine causing a maximal increase in the IC(50) to 5.23 ± 0.0992 mM when co-incubated with DA.
22349334	Nanotechnologies are finding a growing range of applications in the food sector. Nanoparticles are used notably to add vitamins and other nutrients to foods and beverages without affecting taste and color. They are also used to develop new tastes, preserve food texture, control the release of flavors, improve the bioavailability of compounds such as antioxidants and vitamins, and monitor freshness with nanosensors. Crosslinked gelatin nanoparticles are a component of nano-sized carriers for nutrient and supplement delivery in foods and related products. This paper describes the production and characterization of polyclonal antibodies against gelatin nanoparticles. Two immunization schemes were investigated: subcutaneous injection with and without a first intravenous injection. Two enzyme-linked immunosorbent assay formats were used to characterize the antibodies: an inhibition format with an antigen-coated plate for detection of the immune response and a sandwich format for development of the method. The antibodies showed good sensitivity with an IC50 equal to 0.11 ng mL(-1) using indirect ELISA format and a good specificity for the nanomaterials, without significant cross-reactivity against native gelatin. The limit of detection was determined-0.42, 0.27, 0.26, and 0.24 μg mL(-1) for apple, orange juice, milk, and soft drink matrices, respectively. ELISA technology offers rapid, low-cost assays for screening foods, feeds, and beverages. We have studied a prototype ELISA for detection of gelatin-based nanocarrier systems. Fruit juices, milk, and a soft drink were the matrices selected for assay development.
22326670	Sodium deficiency reliably produces a robust intake of saline in rats, which is associated with an increased preference for sodium solutions at hypertonic concentrations that would normally be avoided. The mechanisms underlying the shift to an increased preference for sodium in the deficient state are not well understood. The current experiments examined the role of opioids on changes of behavioral responses that are modified as a function of body sodium status by studying the intake of 0.3 M saline in a free access drinking test and by characterizing the changes in orofacial-related behaviors in response to intra-orally delivered 0.3 M NaCl. In intake tests, systemic treatment with morphine and naltrexone respectively, enhanced and attenuated intake of 0.3 M saline in sodium depleted rats. In taste reactivity tests systemic treatment with morphine significantly decreased negative responses to 0.3 M saline infusions in both sodium replete and sodium depleted rats. Systemically administered naltrexone significantly decreased positive hedonic responses to 0.3 M saline infusions only in sodium depleted rats. These results indicate that peripheral administration of opioid agonists and antagonists alter both hypertonic saline ingestion in a free access situation and taste reactivity responses to hypertonic saline under sodium replete and deplete conditions. The results indicate that endogenous opioids alter the processing of central information to affect hedonic mechanisms that influence behaviors related to sodium consumption and palatability.
22315167	The chorda tympani (CT) nerve innervates lingual taste buds and is susceptible to damage during dental and inner ear procedures. Interruption of the CT results in a disappearance of taste buds, which can be accompanied by taste disturbances. Because the CT usually regenerates to reinnervate taste buds successfully within a few weeks, a persistence of taste disturbances may indicate alterations in central nervous function. Peripheral injury to other sensory nerves leads to glial responses at central terminals, which actively contribute to abnormal sensations arising from nerve damage. Therefore, the current study examined microglial and astrocytic responses in the first central gustatory relay, the nucleus of the solitary tract (nTS), after transection of the CT. Damage to the CT resulted in significant microglial responses in terms of morphological reactivity and an increased density of microglial cells from 2 to 20 days after injury. This increased microglial population resulted primarily from microglial proliferation from 1.5 to 3 days, which was supplemented by microglial migration within subdivisions of the nTS between days 2 and 3. Unlike other nerve injuries, CT injury did not result in recruitment of bone marrow-derived precursors. Astrocytes also reacted in the nTS with increased levels of glial fibrillary acidic protein (GFAP) by 3 days, although none showed evidence of cell division. GFAP levels remained increased at 30 days, by which time microglial responses had resolved. These results show that nerve damage to the CT results in central glial responses, which may participate in long-lasting taste alterations following CT lesion.
22260873	The Fischer 344 (F344) and Lewis (LEW) inbred rat strains differ on a host of biochemical, neuroanatomical, immunological and behavioral endpoints. One behavioral difference of interest is their differential reactivity to the aversive effects of morphine as indexed by the conditioned taste aversion preparation (aversions acquired by F344 rats are significantly greater than those acquired by the LEW strain). This differential effect appears to be specific to opioids that work primarily on the mu opioid receptor. Given that morphine works systemically, it is unknown whether these differential effects in F344 and LEW animals are centrally or peripherally mediated. To address this issue, the present study investigated the ability of the peripherally acting mu preferring opioid agonist loperamide to induce differential taste aversions in F344 and LEW animals. Both F344 and LEW animals acquired dose-dependent taste aversions to the loperamide-associated solution with no difference between them. Additionally, control animals initially injected with vehicle during aversion training with loperamide and subsequently conditioned with morphine displayed the typical aversive profile to morphine (F344>LEW). Although the basis for the present data is unknown, their relation to morphine-induced taste aversions and the role of the interaction of stimulus effects of drugs that produce differential abuse liability were discussed.
22167254	Amygdala-related circuitry helps translate learned Pavlovian associations into appetitive and aversive motivation, especially upon subsequent encounters with cues.We asked whether μ-opioid stimulation via microinjections of the specific agonist D-Ala(2), N-MePhe(4), Gly-ol)-enkephalin (DAMGO) in central nucleus of amygdala (CeA), or the adjacent basolateral amygdala (BLA) would magnify sucrose or sex "wanting", guided by available cues.	CeA or BLA DAMGO enhancement of cue-triggered "wanting" was assessed using Pavlovian to instrumental transfer (PIT). Unconditioned food "wanting" was measured via intake, and male sexual "wanting" for an estrous female was measured in a sexual approach test. Sucrose hedonic taste "liking" was measured in a taste reactivity test.	CeA (but not BLA) DAMGO increased the intensity of phasic peaks in instrumental sucrose seeking stimulated by Pavlovian cues over precue levels in PIT, while suppressing seeking at other moments. CeA DAMGO also enhanced food intake, as well as sexual approach and investigation of an estrous female by males. DAMGO "wanting" enhancements were localized to CeA, as indicated by "Fos plume"-based anatomical maps for DAMGO causation of behavioral effects. Despite increasing "wanting", CeA DAMGO decreased the hedonic impact or "liking" for sucrose in a taste reactivity paradigm.	CeA μ-opioid stimulation specifically enhances incentive salience, which is dynamically guided to food or sex by available cues.	
22136568	We present a case of an unusual clinical manifestation of Guillain-Barre syndrome following a pre-existing herpes virus infection. Although there have been several reports describing the co-existence of herpes virus infection and Guillain-Barre syndrome, we undertook a more in-depth study of the cross-reactivity between herpes viruses and recommend a follow-up study based on serology tests.A 39-year-old healthy Caucasian man with Guillain-Barre syndrome presented to our facility initially with sensory disturbance, followed by an atypical descending pattern of clinical progression. On physical examination, our patient showed hot and cold temperature sensory disturbance under the T4 vertebrae level, symmetrically diminished muscle power mainly to his lower limbs, blurred vision, a loss of taste and paresis and diminished reflexes of his lower limbs. Serology test results for common viruses on hospital admission were positive for cytomegalovirus immunoglobulin M, cytomegalovirus immunoglobulin G, herpes simplex virus immunoglobulin M, herpes simplex virus immunoglobulin G, Epstein-Barr virus immunoglobulin M, and varicella zoster virus immunoglobulin G, borderline for Epstein-Barr virus immunoglobulin G and negative for varicella zoster virus immunoglobulin M. At one month after hospital admission his test results were positive for cytomegalovirus immunoglobulin M, cytomegalovirus immunoglobulin G, herpes simplex virus immunoglobulin G, Epstein-Barr virus immunoglobulin G, varicella zoster virus immunoglobulin G, borderline for herpes simplex virus immunoglobulin M and negative for Epstein-Barr virus immunoglobulin M and varicella zoster virus immunoglobulin M. At his six month follow-up, tests were positive for cytomegalovirus immunoglobulin G, herpes simplex virus immunoglobulin M, herpes simplex virus immunoglobulin G, Epstein-Barr virus immunoglobulin G and varicella zoster virus immunoglobulin G and negative for cytomegalovirus immunoglobulin M, Epstein-Barr virus immunoglobulin M and varicella zoster virus immunoglobulin M.	The clinical manifestation of Guillain-Barre syndrome in our patient followed a combined herpes virus infection. The cross-reactivity between these human herpes viruses may have a pathogenic as well as evolutionary significance. Our patient showed seroconversion at an early stage of Epstein-Barr virus immunoglobulin M to immunoglobulin G antibodies, suggesting that Epstein-Barr virus might have been the cause of this syndrome. Even if this case is not the first of its kind to be reported, it may contribute to a better understanding of the disease and the cross-reaction mechanisms of herpes virus infections. This case report may have a broader clinical impact across more than one area of medicine, suggesting that cooperation between different specialties is always in the patient's best interest.	
22129513	Alcohol activates orosensory circuits that project to motivationally relevant limbic forebrain areas that control appetite, feeding and drinking. To date, limited data exists regarding the contribution of chemosensory-derived ethanol reinforcement to ethanol preference and consumption. Measures of taste reactivity to intra-orally infused ethanol have not found differences in initial orofacial responses to alcohol between alcohol-preferring (P) and alcohol-non-preferring (NP) genetically selected rat lines. Yet, in voluntary intake tests, P rats prefer highly concentrated ethanol upon initial exposure, suggesting an early sensory-mediated attraction. Here, we directly compared self-initiated chemosensory responding for alcohol and prototypic sweet, bitter and oral trigeminal stimuli among selectively bred P, NP and non-selected Wistar (WI) outbred lines to determine whether differential sensory responsiveness to ethanol and its putative sensory components are phenotypically associated with genetically influenced alcohol preference. Rats were tested for immediate short-term lick responses to alcohol (3-40%), sucrose (0.01-1 M), quinine (0.01-3 mM) and capsaicin (0.003-1 mM) in a brief-access assay designed to index orosensory-guided behavior. P rats exhibited elevated short-term lick responses to both alcohol and sucrose relative to NP and WI lines across a broad range of concentrations of each stimulus and in the absence of blood alcohol levels that would produce significant post-absorptive effects. There was no consistent relationship between genetically mediated alcohol preference and orosensory avoidance of quinine or capsaicin. These data indicate that enhanced initial chemosensory attraction to ethanol and sweet stimuli are phenotypes associated with genetic alcohol preference and are considered within the framework of downstream activation of oral appetitive reward circuits.
22063718	Cannabinoid receptor agonists are known to stimulate feeding in humans and animals and this effect is thought to be related to an increase in food palatability. On the other hand, highly palatable food stimulates dopamine (DA) transmission in the shell of the nucleus accumbens (NAc) and this effect undergoes one trial habituation. In order to investigate the relationship between the affective properties of tastes and the response of NAc shell DA we studied the effect of delta-9-tetrahydrocannabinol (THC) on behavioral taste reactivity to intraoral infusion of appetitive (sucrose solutions) and aversive (quinine and saturated NaCl solutions) tastes and on the response of in vivo DA transmission in the NAc shell to intraoral sucrose. Rats were implanted with intraoral cannulae and the effect of systemic administration of THC on the behavioral reactions to intraoral infusion of sucrose and of quinine or saturated NaCl solutions were scored. THC increased the hedonic reactions to sucrose but did not affect the aversive reactions to quinine and NaCl. The effects of THC were completely blocked by the CB1 receptor inverse agonist/antagonist rimonabant given at doses that do not affect taste reactivity to sucrose. In rats implanted with microdialysis probes and with intraoral cannulae, THC, made sucrose effective in raising dialysate DA in the shell of the NAc. As in the case of highly palatable food (Fonzies, sweet chocolate), the stimulatory effect of sucrose on shell DA under THC underwent one trial habituation. Altogether, these findings demonstrate that stimulation of CB1 receptors specifically increases the palatability of hedonic taste without affecting that of aversive tastes. Consistent with the ability of THC to increase sucrose palatability is the observation that under THC pretreatment sucrose acquires the ability to induce a release of DA in the shell of the NAc and this property undergoes adaptation after repeated exposure to the taste (habituation). This article is part of a Special Issue entitled 'Central Control of Food Intake'.
21849633	Cross-sectional studies in both humans and animals have demonstrated associations between obesity and altered reward functions at the behavioral and neural level, but it is unclear whether these alterations are cause or consequence of the obese state. Reward behaviors were quantified in male, outbred Sprague-Dawley (SD) and selected line obesity-prone (OP) and obesity-resistant (OR) rats after induction of obesity by high-fat diet feeding and after subsequent loss of excess body weight by chronic calorie restriction. As measured by the brief access lick and taste-reactivity paradigms, both obese SD and OP rats "liked" low concentrations of sucrose and corn oil less, but "liked" the highest concentrations more, compared with lean rats, and this effect was fully reversed by weight loss in SD rats. Acute food deprivation was unable to change decreased responsiveness to low concentrations but eliminated increased responsiveness to high concentrations in obese SD rats, and leptin administration in weight-reduced SD rats shifted concentration-response curves toward that seen in the obese state in the brief access lick test. "Wanting" and reinforcement learning as assessed in the incentive runway and progressive ratio lever-pressing paradigms was paradoxically decreased in both obese (compared with lean SD rats) and OP (compared with OR rats). Thus, reversible, obesity-associated, reduced "liking" and "wanting" of low-calorie foods in SD rats suggest a role for secondary effects of the obese state on reward functions, while similar differences between select lines of OP and OR rats before induction of obesity indicate a genetic component.
21803064	Bilateral injections of moxonidine, an α2-adrenoceptor and imidazoline receptor agonist, into the lateral parabrachial nuclei (LPBN) enhance sodium appetite induced by extracellular dehydration. In the present study, we examined whether LPBN moxonidine treatments change taste reactivity to hypertonic NaCl solution administered into the mouth by intra-oral (IO) cannula. Male Holtzman rats prepared with IO and bilateral LPBN cannulas received subcutaneous injections of furosemide (FURO; 10 mg/kg) and captopril (CAP; 5 mg/kg) to induce hypovolemia with mild hypotension and an accompanying salt appetite and thirst before testing the taste reactivity to oral infusions of 0.3 M NaCl (1.0 ml/min). In the first experiment 45 min after subcutaneous injections of FURO+CAP or vehicle, moxonidine was bilaterally injected into the LPBN, and then 15 min later both bodily and oral-facial ingestive and rejection responses to 0.3 M NaCl delivered through the IO cannula were assessed. Both LPBN vehicle and moxonidine treated rats showed increased ingestive and decreased rejection responses to the IO hypertonic solution. The IO 0.3 M NaCl infusion-evoked ingestive and rejection taste related behaviors were comparable in the LPBN vehicle- vs. the LPBN moxonidine-injected groups. In a second experiment, rats received the same FURO+CAP treatments and LPBN injections. However, beginning 15 min after the LPBN injections, they were given access to water and 0.3M NaCl and were allowed to consume the fluids for most of the next 60 min with the free access intake being interrupted only for a few minutes at 15, 30 and 60 min after the fluids became available. During each of these three brief periods, a taste reactivity test was conducted. On the three taste reactivity tests rats that received LPBN vehicle injections showed progressive declines in ingestive responses and gradual increases in rejection responses. However, in contrast to the LPBN vehicle treated rats, animals receiving bilateral injections of LPBN moxonidine maintained a high number of ingestive responses and a low number of rejection responses throughout the test period even in spite of evidencing substantial water and 0.3 M NaCl consumption during the periods of free access. The results suggest that after α2-adrenoceptor agonist delivery to the LPBN the acceptance of 0.3 M NaCl is sustained and the negative attributes of the solution are minimized. The maintained positive rewarding qualities of 0.3 M NaCl are likely to account for why LPBN moxonidine treated rats show such a remarkable salt appetite when assayed by the volume of hypertonic 0.3 M NaCl consumed.
21770456	Recent studies led to the identification of umami-enhancing (S)-N(2)-(1-carboxyethyl)- and (S)-N(2)-(1-alkylamino)carbonylalkyl)guanosine 5'-monophosphates that, together with their sensorially inactive (R)-stereoisomers, were found to be formed upon Maillard-type glycation of guanosine 5'-monophosphate (5'-GMP) with 1,3-dihydroxyacetone or glyceraldehyde, respectively. As the efficiency of this Maillard-type procedure to generate the amidated derivatives is limited by the low solubility and reactivity of long-chain alkyl amines as well as by the tedious separation of the diastereomers formed, a versatile synthesis for the (R)- and (S)-configured amides of N(2)-carboxyalkylated guanosine 5'-monophosphate was developed. Sensory evaluation of a series of N(2)-(1-alkylamino)carbonylalkyl)guanosine 5'-monophosphates revealed β-values for umami enhancement between 0.1 and 7.7 and identified a strong influence of the stereochemistry as well as the chain length of the N(2)-substituent on the umami-enhancing activity. The observed sensory impact of the (S)-configured isomers was confirmed by recording the enhancing effect of these nucleotides on the l-glutamate-induced response of the functionally expressed T1R1/T1R3 umami receptor in a cell-based assay, thus underscoring the stereospecifity of the umami taste receptor binding site.
21697523	The neural control of feeding involves many neuromodulators, including the endogenous opioids that bind μ-opioid receptors (MORs). Injections of the MOR agonist, Damgo, into limbic and hypothalamic forebrain sites increase intake, particularly of palatable foods. Indeed, forebrain Damgo injections increase sucrose-elicited licking but reduce aversive responding (gaping) to quinine, suggesting that MOR activation may enhance taste palatability. A μ-opioid influence on taste reactivity has not been assessed in the brain stem. However, MORs are present in the first-order taste relay, the rostral nucleus of the solitary tract (rNST), and in the immediately subjacent reticular formation (RF), a region known to be essential for consummatory responses. Thus, to evaluate the consequences of rNST/dorsal RF Damgo in this region, we implanted rats with intraoral cannulas, electromyographic electrodes, and brain cannulas aimed at the ventral border of the rNST. Licking and gaping elicited with sucrose, water, and quinine were assessed before and after intramedullary Damgo and saline infusions. Damgo slowed the rate, increased the amplitude, and decreased the size of fluid-induced lick and gape bouts. In addition, the neutral stimulus water, which typically elicits licks, began to evoke gapes. Thus, the current results demonstrate that μ-opioid activation in the rNST/dorsal RF exerts complex effects on oromotor responding that contrast with forebrain effects and are more indicative of a suppressive, rather than a facilitatory effect on ingestion.
21649644	Strategies designed to enhance cerebral cAMP have been proposed as symptomatic treatments to counteract cognitive deficits. However, pharmacological therapies aimed at reducing PDE4, the main class of cAMP catabolizing enzymes in the brain, produce severe emetic side effects. We have recently synthesized a 3-cyclopentyloxy-4-methoxybenzaldehyde derivative, structurally related to rolipram, and endowed with selective PDE4D inhibitory activity. The aim of the present study was to investigate the effect of the new drug, namely GEBR-7b, on memory performance, nausea, hippocampal cAMP and amyloid-β (Aβ) levels.To measure memory performance, we performed object recognition tests on rats and mice treated with GEBR-7b or rolipram. The emetic potential of the drug, again compared with rolipram, was evaluated in rats using the taste reactivity test and in mice using the xylazine/ketamine anaesthesia test. Extracellular hippocampal cAMP was evaluated by intracerebral microdialysis in freely moving rats. Levels of soluble Aβ peptides were measured in hippocampal tissues and cultured N2a cells by elisa.	GEBR-7b increased hippocampal cAMP, did not influence Aβ levels and improved spatial, as well as object memory performance in the object recognition tests. The effect of GEBR-7b on memory was 3 to 10 times more potent than that of rolipram, and its effective doses had no effect on surrogate measures of emesis in rodents.	Our results demonstrate that GEBR-7b enhances memory functions at doses that do not cause emesis-like behaviour in rodents, thus offering a promising pharmacological perspective for the treatment of memory impairment.	
21573842	Condensed tannins are a major class of plant polyphenols. They play an important part in the colour and taste of foods and beverages. Due to their chemical reactivity, tannins are not stable once extracted from plants. A number of chemical reactions can take place, leading to structural changes of the native structures to give so-called derived tannins and pigments. This paper compares results obtained on native and oxidized tannins with different techniques: depolymerization followed by high-performance liquid chromatography analysis, small-angle X-ray scattering (SAXS) and asymmetric flow field-flow fractionation (AF4). Upon oxidation, new macromolecules were formed. Thioglycolysis experiments showed no evidence of molecular weight increase, but thioglycolysis yields drastically decreased. When oxidation was performed at high concentration (e.g., 10 g L(-1)), the weight average degree of polymerization determined from SAXS increased, whereas it remained stable when oxidation was done at low concentration (0.1 g L(-1)), indicating that the reaction was intramolecular, yet the conformations were different. Differences in terms of solubility were observed; ethanol being a better solvent than water. We also separated soluble and non-water-soluble species of a much oxidized fraction. Thioglycolysis showed no big differences between the two fractions, whereas SAXS and AF4 showed that insoluble macromolecules have a weight average molecular weight ten times higher than the soluble ones.
21524757	Current methods of assessing children's physiological "stress reactivity" may be confounded by psychomotor activity, biasing estimates of the relation between reactivity and health. We examined the joint and independent contributions of psychomotor activity and challenge reactivity during a protocol for 5- and 6-year-old children (N = 338). Measures of parasympathetic reactivity (respiratory sinus arrhythmia [RSA]) and sympathetic reactivity (preejection period [PEP]) were calculated for social, cognitive, sensory, and emotional challenge tasks. Reactivity was calculated relative to both resting and a paired comparison task that accounted for psychomotor activity effects during each challenge. Results indicated that comparison tasks themselves elicited RSA and PEP responses, and reactivity adjusted for psychomotor activity was incongruent with reactivity calculated using rest. Findings demonstrate the importance of accounting for confounding psychomotor activity effects on physiological reactivity.
21401101	The iso-α-acids or isohumulones are the major contributors to the bitter taste of beer, and it is well-recognized that they are degraded during beer aging. In particular, the trans-isohumulones seem to be less stable than the cis-isohumulones. The major radical identified in beer is the 1-hydroxyethyl radical; however, the reactivity between this radical and the isohumulones has not been reported until now. Therefore, we studied the reactivity of isohumulones toward the 1-hydroxyethyl radical through a competitive kinetic approach. It was observed that both cis- and trans-isohumulones and dihydroisohumulones are decomposed in the presence of 1-hydroxyethyl radicals, while the reactivities are comparable. On the other hand, the tetrahydroisohumulones did not react with 1-hydroxyethyl radicals. The apparent second-order rate constants for the reactions between the 1-hydroxyethyl radical and these compounds were determined by electron paramagnetic resonance (EPR) spectroscopy and electrospray ionization-tandem mass spectrometry [ESI(+)-MS/MS]. It follows that degradation of beer bitter acids is highly influenced by the presence of 1-hydroxyethyl radicals. The reaction products were detected by liquid chromatography-electrospray ionization-ion trap-tandem mass spectrometry (LC-ESI-IT-MS/MS), and the formation of oxidized derivatives of the isohumulones was confirmed. These data help to understand the mechanism of beer degradation upon aging.
21384879	Analysis of wines from different grape varieties marked by sometimes intense aromatic nuances of fresh mushroom was performed by gas chromatography coupled with olfactometry. This analysis has led to the identification of several odoriferous zones, which were recalling a fresh mushroom odor. Two trace compounds responsible for these odoriferous zones, 1-nonen-3-one and 1-octen-3-one, have been identified and their content has been determined by using either a multidimensional gas chromatography technique coupled to olfactometry and mass spectrometry detection (in the case of 1-nonen-3-one) or the preparation of the derivative with O-2,3,4,5,6-pentafluorobenzylhydroxylamine hydrochloride in the presence of the deuterated form, as the internal standard (in the case of 1-octen-3-one), then gas chromatography coupled to mass spectrometry detection. The assays allowed the quantification of these compounds at concentration levels sometimes well above their detection and recognition olfactory threshold. We show that adding nitrogen compounds to the altered wines, such as an amino acid (glycine) or a tripeptide (glutathione), led to lower concentrations of 1-octen-3-one in wines and diminished smell of fresh mushrooms. The study of the reaction in a model medium, whose composition is close to wine, by liquid chromatography coupled to mass spectrometry demonstrated the formation of adducts between 1-octen-3-one and glycine, and 1-octen-3-one and glutathione characterized by NMR.
21243485	The interaction between two non-psychotropic cannabinoids, cannabidiol (CBD) and cannabigerol (CBG), which have been reported to act as a 5-hydroxytryptamine 1A (5-HT(1A)) agonist and antagonist, respectively, was evaluated.To evaluate the potential of CBG to reverse the anti-nausea, anti-emetic effects of CBD.	In experiment 1, rats were pre-treated with CBG (0.0, 1, 5, and 10 mg/kg, ip), 15 min prior to being treated with CBD (experiment 1a: VEH or 5 mg/kg, ip) or 8-OH-DPAT (experiment 1b: VEH or 0.01 mg/kg, ip). Thirty minutes later, all rats received a pairing of 0.1% saccharin solution and LiCl (20 ml/kg of 0.15 M, ip). Seventy-two hours later, the rats received a drug-free taste reactivity test with saccharin to evaluate the effects of the treatments on the establishment of conditioned gaping reactions (a model of nausea). As well, conditioned saccharin avoidance was measured. In experiment 2, Suncus murinus were injected with CBG (5 mg/kg, ip) or VEH 15 min prior to CBD (5 mg/kg) or VEH and 30 min later were injected with LiCl (60 ml/kg of 0.15 M, i.p.), and the number of vomiting episodes were measured.	CBD (5 mg/kg) suppressed conditioned gaping in rats and vomiting in shrews, which were reversed by pre-treatment with all doses of CBG. CBG also prevented the anti-nausea effects of 8-OH-DPAT.	Interactions between moderate doses of CBG and CBD may oppose one another at the 5-HT(1A) receptor in the regulation of nausea and vomiting.	
21236281	Food reward is neurologically and psychologically divided into at least two properties; 'liking' and 'wanting'. Although umami taste enhances food palatability, the liking and wanting properties of umami taste, and the underlying neural mechanisms for these properties are not clear. Here, we compared sucrose (0, 10, 30, 120 and 480 mM) and monosodium l-glutamate (MSG; 0, 10, 30, 60 and 120 mM) solutions using a taste reactivity test to evaluate liking, and fixed/progressive-ratio operant licking tasks to evaluate wanting. To determine the underlying neural mechanisms, we also conducted systemic blockade of opioid receptors in both tests. In the taste reactivity test, the hedonic reactions to 30, 60 and 120 mM MSG were greater than those to water (0mM) but lower than those to 480 mM sucrose. In the operant task, the intake, number of licks, and breakpoint to MSG reached peaks at around 60mM but they were lower than those to 30-480 mM sucrose. The systemic naloxone treatment decreased the hedonic responses to MSG and sucrose, and reduced the incentive salience of MSG but not sucrose. These findings indicate that the hedonic response and incentive salience of MSG is lower than those of sucrose when compared at the maximum response and that the incentive salience of MSG is lower than sucrose even where the hedonic response is similar. The present study also suggest that the hedonic response and incentive salience of umami compound is modulated by brain opioid signaling.
21208169	In the last decades, the goal of creating a unique and complete model of alcohol use and alcoholism has been replaced by a myriad of different animal models, each addressing a specific feature of problematic alcohol consumption. This mini-review highlights selected findings in the field of alcohol abuse and dependence, as found through the use of animal models. There are models (e.g., drinking in the dark, drinking after alcohol adulteration or alcohol deprivation) in which animals self-administer alcohol, that are useful to analyze determinants and consequences of binge drinking, progression from casual to problematic alcohol use and relapse or loss of control over alcohol drinking. In other models (e.g., conditioned place preference, conditioned taste aversion, ethanol-induced behavioral sensitization) alcohol dosing is precisely controlled by the experimenter. These models are useful to study motivational (i.e, appetitive, aversive and negative reinforcing) effects of alcohol and neuroadaptive changes that occur after repeated alcohol exposure. The study of age-related differences in reactivity to alcohol provides yet another avenue for analyzing alcohol's acute and chronic consequences. Ethanol interacts with several neurotransmitter (dopaminergic, glutamatergic, opioidergic and cannabinoid) and neuromodulators and these interactions are involved in the development and maintenance of alcohol self-administration. The findings described in the review, however, indicate a key role of the endogenous opioid system, notably in the mediation of alcohol's postitive rewarding effects. The Review also highlights the need to further assess the inter-relationship between different indices of ethanol's motivational effects as well as their association with alcohol intake and preference.
21198990	Glutamatergic inputs to the nucleus accumbens (NAc) modulate both appetitive and fearful motivation. It has been suggested that pathological disturbances of glutamate signaling in NAc contribute to motivation disorders, ranging from excessive desire in drug addiction to paranoia in schizophrenia. Metabotropic glutamate receptors are of special interest, as metabotropic Group II receptor (mglu2/3) agonists have been proposed as potential treatments for both addiction and schizophrenia. Here we tested whether local mglu2/3 receptor blockade in the medial shell of the rat NAc can generate intense distortions of motivation or affect, which might model clinical dysfunction. We found that microinjection of the mglu2/3 antagonist LY341495 at sites throughout medial shell suppressed appetitive motivation to eat and drink. Simultaneously, LY341495 microinjections generated fearful motivation in the form of defensive treading or burying. To assess whether the valence shift extended into a parallel hedonic shift from affective 'liking' to 'disliking' we employed the taste reactivity test, which measures affective orofacial reactions to the sensory pleasure or displeasure of tastes. We found that LY341495 microinjections reduced positive 'liking' reactions to sucrose and enhanced 'disliking' reactions. Overall, mglu2/3 antagonism at most shell sites produced a similar valence shift from positive to negative. This pattern comprised (i) generation of fearful behaviors, and (ii) induction of aversive affective reactions, together with (iii) loss of appetitive ingestion and (iv) loss of 'liking' for rewards. These results are discussed in terms of implications for clinical disorders and the influence of corticolimbic glutamate inputs to NAc in the generation of motivation and affect.
21147152	The Lewis (LEW) and Fischer 344 (F344) inbred rat strains react differentially to acute morphine administration for a variety of behavioral and neurochemical measures. Investigations into effects of chronic morphine are less common, and investigations assessing dependence have been limited to those utilizing antagonist-precipitated withdrawal. The present experiment extended these assessments by examining spontaneous withdrawal in the LEW and F344 strains. In this preparation, males of the LEW, F344 and the outbred Sprague-Dawley (SD) strain were made dependent on morphine. Following this, opiate administration was terminated and animals were examined for spontaneous withdrawal by the acquisition of a withdrawal-associated taste aversion, changes in body weight loss and the display of several behaviors characteristic of opiate withdrawal. Although all morphine-treated subjects decreased body weight and avoided consumption of the withdrawal-associated solution, indicating successful induction of dependence, no difference between the strains emerged in these indices of withdrawal severity. The only strain difference to appear in the behavioral indicators of withdrawal was with diarrhea (LEW>F344). That the strains differ in acute reactivity to opioids, but not in the overall severity of withdrawal, was discussed in relation to the need to examine the relationship between neurochemical and behavioral data in a variety of neural systems and behavioral endpoints.
21111837	Huntington disease (HD) is caused by an expansion of CAG repeat in the Huntingtin gene. Patients demonstrate a triad of motor, cognitive and psychiatric symptoms. A transgenic rat model (tgHD rats) carrying 51 CAG repeats demonstrate progressive striatal degeneration and polyglutamine aggregates in limbic structures. In this model, emotional function has only been investigated through anxiety studies. Our aim was to extend knowledge on emotional and motivational function in symptomatic tgHD rats. We subjected tgHD and wild-type rats to behavioral protocols testing motor, emotional, and motivational abilities. From 11 to 15 months of age, animals were tested in emotional perception of sucrose using taste reactivity, acquisition, extinction, and re-acquisition of discriminative Pavlovian fear conditioning as well as reactivity to changes in reinforcement values in a runway Pavlovian approach task. Motor tests detected the symptomatic status of tgHD animals from 11 months of age. In comparison to wild types, transgenic animals exhibited emotional blunting of hedonic perception for intermediate sucrose concentration. Moreover, we found emotional alterations with better learning and re-acquisition of discriminative fear conditioning due to a higher level of conditioned fear to aversive stimuli, and hyper-reactivity to a negative hedonic shift in reinforcement value interpreted in term of greater frustration. Neuropathological assessment in the same animals showed a selective shrinkage of the central nucleus of the amygdala. Our results showing emotional blunting and hypersensitivity to negative emotional situations in symptomatic tgHD animals extend the face validity of this model regarding neuropsychiatric symptoms as seen in manifest HD patients, and suggest that some of these symptoms may be related to amygdala dysfunction.
20971936	The nucleus accumbens (NAc) plays a role in hedonic reactivity to taste stimuli. Learning can alter the hedonic valence of a given stimulus, and it remains unclear how the NAc encodes this shift. The present study examined whether the population response of NAc neurons to a taste stimulus is plastic using a conditioned taste aversion (CTA) paradigm. Electrophysiological and electromyographic (EMG) responses to intraoral infusions of a sucrose (0.3 M) solution were made in naïve rats (Day 1). Immediately following the session, half of the rats (n = 6; Paired) received an injection of lithium chloride (0.15 M; i.p.) to induce malaise and establish a CTA while the other half (n = 6; Unpaired) received a saline injection. Days later (Day 5), NAc recordings during infusions of sucrose were again made. Electrophysiological and EMG responses to sucrose did not differ between groups on Day 1. For both groups, the majority of sucrose responsive neurons exhibited a decrease in firing rate (77% and 71% for Paired and Unpaired, respectively). Following conditioning, in Paired rats, EMG responses were indicative of aversion. Moreover, the majority of responsive NAc neurons now exhibited an increase in firing rate (69%). Responses in Unpaired rats were unchanged by the experience. Thus, the NAc differentially encodes the hedonic value of the same stimulus based on learned associations.
20725924	The manuscript reviews beneficial aspects of food processing with main focus on cooking/heat treatment, including other food-processing techniques (e.g. fermentation). Benefits of thermal processing include inactivation of food-borne pathogens, natural toxins or other detrimental constituents, prolongation of shelf-life, improved digestibility and bioavailability of nutrients, improved palatability, taste, texture and flavour and enhanced functional properties, including augmented antioxidants and other defense reactivity or increased antimicrobial effectiveness. Thermal processing can bring some unintentional undesired consequences, such as losses of certain nutrients, formation of toxic compounds (acrylamide, furan or acrolein), or of compounds with negative effects on flavour perception, texture or colour. Heat treatment of foods needs to be optimized in order to promote beneficial effects and to counteract, to the best possible, undesired effects. This may be achieved more effectively/sustainably by consistent fine-tuning of technological processes rather than within ordinary household cooking conditions. The most important identified points for further study are information on processed foods to be considered in epidemiological work, databases should be built to estimate the intake of compounds from processed foods, translation of in-vitro results to in-vivo relevance for human health should be worked on, thermal and non-thermal processes should be optimized by application of kinetic principles.
20654704	Overindulgence in easily available energy-dense palatable foods is thought to be an important factor in the current obesity epidemic but the underlying neural mechanisms are not well understood. Here we demonstrate that mu-opioid receptor signaling in the nucleus accumbens may be important. Protracted suppression of endogenous mu-opioid receptor signaling focused on the nucleus accumbens shell for several days by means of microinjected beta-funaltrexamine (BFNA) diminished both "liking" of sucrose, as indicated by fewer positive hedonic orofacial responses, and the incentive reinforcement value ("wanting") of a food reward, as indicated by lower completion speed and increased time being distracted in the incentive runway. BFNA-treatment also decreased responding to sucrose and corn oil in the brief access lick paradigm, a test measuring a combination of mainly taste-guided "liking" and low-effort "wanting", as well as 4 h intake of sucrose solution. These effects were not due to nonspecific permanent neuronal changes, as they were fully reversible. We conclude that endogenous mu-opioid signaling in the nucleus accumbens is necessary for the full display of palatable food-induced hyperphagia through mechanisms including hedonic, motivational, and reinforcement processes. Development of obesity could be the result of predisposing innate differences in these mechanisms or overstimulation of these mechanisms by external factors.
20628734	Melanin-concentrating hormone (MCH) is involved in regulation of appetitive behaviors as well as emotional reactivity and reward, behavioral domains relevant to alcohol addiction.We evaluated the effects of the non-peptide MCH1 receptor antagonist, GW803430 [6-(4-chloro-phenyl)-3-[3-methoxy-4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-3H-thieno[3,2-d]pyrimidin-4-one; 3-30 mg/kg, i.p.] on alcohol-related behaviors in Wistar rats.	Ex vivo binding experiments demonstrated that the GW803430 dose range used resulted in high central MCH1 receptor occupancy. Alcohol self-administration was dose-dependently and potently suppressed, by approximately 80% at the highest dose. Reinstatement of alcohol-seeking induced by alcohol-associated cues was essentially eliminated. In contrast, reinstatement induced by footshock stress was not significantly altered. Taste preference for a quinine/saccharin solution, locomotor activity, and alcohol elimination were unaffected.	Together, these observations support a specific involvement of the MCH system in mediating alcohol reward and cue-induced relapse to alcohol seeking. MCH1-R antagonism may constitute an attractive treatment target for alcohol use disorders.	
20546167	Anorexia nervosa is a complex psychiatric disorder posing a rapidly increasing burden on modern societies. Our purpose was to clarify perceptual-motivational aspects of gustatory disturbances in the disease.A taste reactivity test, with the use of all five primary qualities in two concentrations, was performed in restrictive-type anorexic patients, and their hedonic evaluations were compared to those of age-matched healthy control subjects.	The patients gave significantly lower pleasantness scores for pleasant taste stimuli compared with controls. The differences were the greatest for the lower concentration sucrose, umami and sodium chloride. Ratings given for the aversive taste stimuli were similar in both experimental groups.	Our findings contribute to a better understanding of complex symptoms of anorexia nervosa, and may also help to develop more effective cognitive-behavioral therapies.	
20528084	Recent evidence suggests that liking and wanting of food rewards can be experimentally dissociated (e.g., Berridge, 1996); this dissociation extends to attenuated neophobia in the present study. Rats tend to eat less of a novel food than a familiar food, a phenomenon called neophobia. The present experiments evaluated whether attenuation of neophobia by prior exposure reflects enhanced liking of the flavor using the Taste Reactivity (TR) test. In Experiment 1, rats given five 10-s TR trials with water or various concentrations of saccharin solution (0.1%, 0.2%, 0.5%) did not show a change in the number of hedonic reactions displayed across trials. However, in a subsequent consumption test from a bottle containing 0.25% saccharin solution, rats with no prior saccharin exposure (group water) consumed less than rats with prior saccharin exposure; that is they displayed neophobia. In Experiment 2, whether rats received five 10-s TR trials with water or 0.5% saccharin solution, they did not display a difference in hedonic reactions to 0.25% saccharin solution in two 5-min TR test trials. These results suggest that the attenuation of neophobia is evidenced as an increase in the tendency to approach a bottle containing the flavored solution (wanting), but not as an enhanced liking of that solution.
20451634	Increased stress reactivity has repeatedly been reported in patients suffering from psychiatric diseases including schizophrenia and major depression. These disorders also have other symptoms in common, such as cognitive deficits and psychotic-like behavior. We have therefore investigated if increased stress reactivity is associated with these phenotypic endpoints in an animal model of affective disorders. The stress reactivity mouse model used in this study consists of three CD-1-derived mouse lines, that have been selectively bred for high (HR), intermediate (IR) or low (LR) stress reactivity. Male mice from these three breeding lines were subjected to a reversal learning task and latent inhibition (Li) was assessed using a conditioned taste aversion paradigm. Furthermore, as the dopaminergic system is involved in both Li and reversal learning, the dopamine 1 receptor (D1R), dopamine 2 receptor (D2R) and dopamine transporter (DAT) mRNA expression levels were assessed in relevant brain areas of these animals. The results demonstrate that HR mice show perseveration in the reversal learning task and have disrupted Li. Furthermore, compared to LR mice, HR mice have decreased D2R mRNA levels in the ventral tegmental area, as well as decreased D1R mRNA levels in the cingulate cortex, and an increased expression of D2R mRNA in the nucleus accumbens. Taken together, these results demonstrate that the HR mice display cognitive deficits associated with psychotic-like behavior, similar to those observed in patients suffering from schizophrenia and major depression and could be utilized in the search for better treatment strategies for these symptoms of psychiatric disorders.
20400737	The present experiments, using the latent inhibition (LI) paradigm, evaluated the effect of nonreinforced exposure to saccharin on the acquisition of an LiCl-induced saccharin aversion as measured by conditioned disgust reactions in the taste reactivity test and conditioned taste avoidance in a consumption test. When rats were preexposed to saccharin by bottle exposure (Experiments 1 and 3), LI was evidenced only by conditioned taste avoidance (bottle testing), but not by conditioned disgust reactions (intraoral [IO] testing). On the other hand, when rats were preexposed to saccharin by IO infusion (Experiments 2 and 3), LI was evidenced only by conditioned disgust reactions, but not by conditioned taste avoidance. Experiment 4 showed that LI of conditioned disgust reactions does not appear to be affected by a context shift from preexposure to testing phases. These results show that the expression of LI of both conditioned taste avoidance and conditioned disgust reactions depends critically on a common method of flavor exposure during preexposure and testing.
20352411	A large proportion of smokers consolidate their smoking patterns during young adulthood, and it is possible that the high rates of drinking found in this age group may facilitate the transition from nondaily to daily cigarette use.The primary aim of this study was to examine how alcohol alters the subjective effects of smoking in heavy-drinking young adults (age 21-25) who are still at an experimental stage of smoking but show recent increases in their smoking behavior.	Using a within-subject design, we examined whether alcohol or the expectation of receiving alcohol increased either subjective responses to smoking or the amount smoked. Subjects participated in three sessions, in which they received alcohol (0.08 g/dL targeted blood alcohol level), a taste-masked placebo presented as alcohol, or a mixer beverage not presented as alcohol. Measures included positive and negative subjective reactivity (e.g., satisfaction, nausea, craving relief, and enjoyment of airway sensations) associated with smoking a single cigarette and subsequent ad lib smoking behavior.	Both conditions in which the subjects expected to receive alcohol increased positive effects of smoking (satisfaction, calm, and taste), compared to the mixer beverage. Alcohol, compared to the placebo and mixer beverages, decreased negative effects (nausea) associated with smoking a cigarette and increased subsequent smoking.	This initial study has implications for understanding how alcohol and the expectation of alcohol improves the experience of smoking in nondaily smokers who are still at an experimental stage of smoking.	
20127941	To test the construct validity and discriminative validity of the widely used Dutch Eating Behavior Questionnaire's (DEBQ) External Eating (EE) subscale.After being exposed to food cues or not participants completed a bogus taste test. Subjective cue reactivity during food exposure and actual food intake after food exposure were measured.	EE scores were unrelated to food intake. A robust main effect of food cue exposure was found but contrary to what was predicted, low EE scorers ate more after food cue exposure than without whereas high EE scorers did not. The actual eating behavior of high and low scorers on the other DEBQ subscales - emotional and restrained eating - demonstrated that the EE also lacks discriminative validity.	The EE showed no predictive validity and no discriminative validity. The usefulness of the distinction of different types of concerned eaters is questioned.	
20039021	Responding for a drug- or sucrose-paired cue increases over forced abstinence (incubation of craving). If the incentive value of a cue depends on the incentive value of the primary reward, devaluing the primary reward should reduce cue reactivity.We investigated whether conditioned taste aversion (CTA) to sucrose would transfer to a sucrose-paired cue after 1 or 30 days of forced abstinence and whether CTA after 1 day of forced abstinence would affect incubation of craving.	Rats self-administered 10% sucrose paired with a tone + light cue for 10 days. After 1 (Exp.1) or 30 (Exp.2) days of forced abstinence, rats received two home-cage pairings of sucrose with either LiCl (65 mg/kg, IP) to produce CTA or saline as a control. Two days later, rats responded for the cue alone. The following day, sucrose consumption was assessed in the same operant conditioning chamber. Exp.1 rats were tested again 1 month later to determine if CTA would affect incubation of craving.	Exp.1: CTA after 1 day of forced abstinence did not attenuate cue reactivity when tested immediately after CTA, nor did the treatment affect incubation of craving or incubation of sucrose consumption. Exp.2: CTA after 1 month of forced abstinence resulted in a significant reduction in cue reactivity.	The incentive values of sucrose and the conditioned representation of sucrose increase over an extended period of forced abstinence. This incubation appears to facilitate the transfer of an aversion to the primary reward to the conditioned cue.	
20026412	Animals develop robust learning and long lasting taste aversion memory once they experience a new taste that is followed by visceral discomfort. A large body of literature has supported the hypothesis that basolateral amygdala (BLA) plays a critical role in the acquisition and extinction of such conditioned taste aversions (CTA). Despite the evidence that BLA is crucially engaged during CTA training, it is unclear how BLA neural activity represents the conditioned tastes. Here, we incorporated a modified behavioral paradigm suitable for single unit study, one which utilizes a sequence of pulsed saccharin and water infusion via intraoral cannulae. After conditioning, we investigated BLA unit activity while animals experience the conditioned taste (saccharin). Behavioral tests of taste reactivity confirmed that the utilized training procedure produced reliable acquisition and expression of the aversion throughout test sessions. When neural activity was compared between saccharin and water trials, half of the recorded BLA units (77/149) showed differential activity according to the types of solution. 76% of those cells (29/38) in the conditioned group showed suppressed activity, while only 44% of taste reactive cells (17/39) in controls showed suppressed activity during saccharin trials (relative to water trials). In addition, the overall excitability of BLA units was increased as shown by altered characteristics of burst activity after conditioning. The changes in BLA activity as a consequence of CTA were maintained throughout test sessions, consistent with the behavioral study. The current study suggests that the neuronal activity evoked by a sweet taste is altered as a consequence of CTA learning, and that the overall change might be related to the learning induced negative affect.
20014225	With infant rats, unlike with adults, increased intake of a taste after mere exposure to this stimulus is not consistently found; this has sometimes been interpreted as a failure by the immature subject to recognize tastes as familiar. We studied the effect of preexposure to a tastant, measuring taste reactivity and intake in 14-day-old rats. Familiarity increased hedonic response to sucrose, but also increased aversive response to quinine and ethanol. With the sucrose-quinine compound, familiarity increased both the hedonic and the aversive reaction to the stimulus. In no case was a differential reactivity to water observed. Significant increased intake after familiarization was only found with quinine or the sucrose-quinine compound. Results indicate that in infant rats, and with the present parameters, taste familiarity enhances responsiveness to these stimuli, an effect not always accompanied by detectable changes in intake.
19951296	Acute naltrexone treatment in rats produces significant alterations in ethanol palatability (increase in the aversiveness of the solution) and ethanol consumption during tests of restricted access (decrease in consumption). The effects of chronic naltrexone exposure, accomplished by implantation of osmotic mini-pumps, were examined in the present study.Rats were surgically implanted with intraoral fistulae for taste reactivity testing. The animals were given 2 bottles (distilled water and 10% ethanol, v/v) for 3, 2-week phases: Pre-Drug, Drug, and Post-Drug. After the Pre-Drug phase, rats were assigned to groups (counterbalanced based on ethanol intake) and implanted with a mini-pump containing saline, 7.5 mg/kg/d naltrexone, or 15 mg/kg/d naltrexone. The pumps were removed 2 weeks later. During each 2-week phase, taste reactivity tests with 10% ethanol were conducted at 1, 7, and 14 days (a total of 9 reactivity tests).	The 7.5 mg/kg/d dose produced only minor effects on 10% ethanol reactivity and consumption during the Drug phase. The 15 mg/kg/d naltrexone dose generally shifted taste reactivity responding to 10% ethanol in a negative direction and produced a transient decrease in ethanol consumption. The 15 mg/kg/d group significantly increased ethanol consumption beyond the level of consumption by the Saline group when the pumps were removed, although the increase was delayed 48 hours. By the end of the Post-Drug period, this naltrexone group returned to control levels of ethanol consumption.	Chronic naltrexone treatment at 15 mg/kg/d significantly decreased the palatability of a 10% ethanol solution, an effect seen even after drug withdrawal. Naltrexone had a minor effect on ethanol consumption during treatment but did decrease overall levels of fluid consumption. The significant increase in ethanol consumption postdrug by the high-dose naltrexone group, presumably due to receptor up-regulation during treatment, is important and understanding this effect and developing means of overcoming it within a clinical practice would be useful goals.	
19915733	A high incidence of sensory processing difficulties exists in children with Autism Spectrum Disorder (ASD) and children with Sensory Modulation Disorder (SMD). This is the first study to directly compare and contrast these clinical disorders. Sympathetic nervous system markers of arousal and reactivity were utilized in a laboratory paradigm that administered a series of sensory challenges across five sensory domains. The Short Sensory Profile, a standardized parent-report measure, provided a measure of sensory-related behaviors. Physiological arousal and sensory reactivity were lower in children with ASD whereas reactivity after each sensory stimulus was higher in SMD, particularly to the first stimulus in each sensory domain. Both clinical groups had significantly more sensory-related behaviors than typically developing children, with contrasting profiles. The ASD group had more taste/smell sensitivity and sensory under-responsivity while the SMD group had more atypical sensory seeking behavior. This study provides preliminary evidence distinguishing sympathetic nervous system functions and sensory-related behaviors in Autism Spectrum Disorder and Sensory Modulation Disorder. Differentiating the physiology and sensory symptoms in clinical groups is essential to the provision of appropriate interventions.
19904949	There has been a growing interest in the use of differential sensing for analyte classification. In an effort to mimic the mammalian senses of taste and smell, which utilize protein-based receptors, we have introduced serum albumins as nonselective receptors for recognition of small hydrophobic molecules. Herein, we employ a sensing ensemble consisting of serum albumins, a hydrophobic fluorescent indicator (PRODAN), and a hydrophobic additive (deoxycholate) to detect terpenes. With the aid of linear discriminant analysis, we successfully applied our system to differentiate five terpenes. We then extended our terpene analysis and utilized our sensing ensemble for terpene discrimination within the complex mixtures found in perfume.
19784742	To elucidate the cellular distribution of osteopontin (OPN) in normal human tissues, we undertook immunohistochemistry using two site-specific OPN antibodies. The 10A16 monoclonal antibody was raised against the amino acid sequence just downstream of the thrombin cleavage site, while the O-17 polyclonal antibody was raised against the N-terminal peptide. Each antibody has been confirmed previously to react with both whole OPN and its relevant fragments. The expression pattern for these two antibodies was similar in distribution. In addition, we also identified expression in Ebner's gland, type II pneumocytes, Kupffer cells, cells of the endocrine organs, anterior lens capsule and ciliary body, synovial type A cells, mesothelia, adipocytes, and mast cells. Neurons and glia in the central nervous system and spinal cord, cranial and peripheral nerve sheaths, ganglion cells in the sympathetic ganglion, intestinal plexuses, retina, and choroid plexus also regularly exhibited OPN positivity. Testicular germ cells, pancreatic exocrine cells, and follicular dendritic cells reacted with 10A16 only, whereas lutein cells and taste bud cells exhibited O-17 reactivity alone. These minor differences were hypothesized to reflect the state of OPN in the cells; that is, whether OPN was in its whole molecule or fragmented form. In conclusion, we demonstrate that OPN is widely distributed in normal human cells, particularly those comprising the central and peripheral nervous systems.
19675517	To investigate if the increased pain threshold in women with bulimia nervosa (BN) may be due to chronic stress-induced analgesia.We measured thermal pain threshold latency, blood pressure and heart rate in 21 women with BN and 21 healthy women (HW) under six consecutive conditions: rest I, mental arithmetic task, rest II, eating sweet food, rest III, cold-pressor test.	Thermal pain threshold latency was longer in BN than in HW in all six conditions. It increased during mental arithmetic test and remained increased during the rest of the experiment in both groups. In the BN group, the increase of pain threshold during mental arithmetic was positively correlated with illness duration. The differential modulation of pain threshold by stress in BN and HW could not be explained by autonomic system reactivity. In HW, the pain threshold increased more during eating and blood pressure increased more during mental stress; in BN, the pain threshold was highest in the mental stress condition and blood pressure was most increased during eating. During the cold pressor test, women with BN showed smaller blood pressure increase and tolerated the cold for shorter time than HW.	The observed marked modulation of pain threshold by experimental stress suggests that stress-induced analgesia is unlikely to account for baseline pain insensitivity in BN. Increased pain threshold in BN is a stable yet incompletely understood phenomenon, which may be related to the predisposition to or maintenance of the disorder.	
19597155	It generally is assumed that a common neural substrate mediates both the palatability and the reward value of nutritive events. However, recent evidence suggests this assumption may not be true. Whereas opioid circuitry in both the nucleus accumbens and ventral pallidum has been reported to mediate taste-reactivity responses to palatable events, the assignment of reward or inventive value to goal-directed actions has been found to involve the basolateral amygdala. Here we found that, in rats, the neural processes mediating palatability and incentive value are indeed dissociable. Naloxone infused into either the ventral pallidum or nucleus accumbens shell blocked the increase in sucrose palatability induced by an increase in food deprivation without affecting the performance of sucrose-related actions. Conversely, naloxone infused into the basolateral amygdala blocked food deprivation-induced changes in sucrose-related actions without affecting sucrose palatability. This double dissociation of opioid-mediated changes in palatability and incentive value suggests that the role of endogenous opioids in reward processing does not depend on a single neural circuit. Rather, changes in palatability and in the incentive value assigned to rewarding events seem to be mediated by distinct neural processes.
19576896	Estrogen receptor activation has been shown to reduce body weight and produce a conditioned reduction in food intake in male rats that is putatively mediated by estradiol's suggested aversive effects. Evidence has shown that the selective estrogen receptor modulator tamoxifen used in the prevention and treatment of breast cancer may also produce changes in food intake and body weight, which are known to impact cancer development and survival. The purpose of the present study was to examine whether tamoxifen produces a conditioned reduction in intake similar to estradiol by producing a conditioned aversion. A one bottle lickometer test was used to examine conditioned changes in sucrose drinking, while the taste reactivity test was used to measure rejection reactions, which serve to index aversion in rats. A backward conditioning procedure that consisted of 3 conditioning days and one vehicle test day was used to examine conditioned changes in 0.3 M sucrose intake and taste reactivity. Our results show that tamoxifen produced a conditioned reduction in sucrose drinking in a one bottle fluid intake test that was similar to the effects produced by estradiol (positive control); however, no active rejection reactions were produced by either tamoxifen (1 and 10 mg/kg) or estradiol. The present results suggest that tamoxifen, at the doses used in the present study, acts as an estrogen receptor agonist to regulate food intake and that the conditioned reduction in intake produced by tamoxifen and estradiol reflects conditioned taste avoidance rather than conditioned taste aversion.
19573540	Vasopressin V1a receptors in the rat brain have been studied for their role in modulating aggression and anxiety. In the current study blood-oxygen-level-dependent (BOLD) functional MRI was used to test whether V1a receptors modulate neural processing in the maternal brain when dams are exposed to a male intruder. Primiparous females were given an intracerebroventricular (ICV) injection of vehicle or V1a receptor antagonist ([beta-Mercapto-beta,beta-cyclopentamethylenepropionyl(1), O-me-Tyr(2),Arg(8)]-Vasopressin, [corrected] 125 ng/10 microL) 90-120 min before imaging. During fMRI, awake dams were presented with a male intruder threat to pups using a specialized chamber that contained separate compartments for pups and a male intruder. Our results indicate that the number of activated voxels was reduced in the cortical amygdala with V1a receptor blockade, while an increase was observed in the anterior olfactory nucleus and other areas. Dams treated with V1a antagonist showed significantly greater BOLD responses in the anterior olfactory nucleus, infralimbic prefrontal cortex, gustatory cortex, somatosensory cortex, and substantia innominata when presented with a novel male intruder. BOLD responses were reduced in the cortical amygdala and ventromedial hypothalamus. The V1a receptor sensitive areas play roles in the processing of smell, taste and touch and emotional reactivity. Thus one interpretation of the present fMRI data is that vasopressin, acting through V1a receptors, may modulate sensory processing and perhaps coordinate this effect with changes in visceromotor activity during the initial stages of maternal aggressive motivation and/or anxiogenic responses.
19549546	The present study was designed to test the hypothesis that sensitivity of ingestive behavior of infant rat to the pharmacological effects of ethanol changes between postnatal (P) days 9 and 12. The intake of 0.1% saccharin and water, general motor activity, and myoclonic twitching activity were assessed following administration of three doses of ethanol (0, 0.25, and 0.5 g/kg) while fluids were free available to the animals. The 0.5 g/kg dose of ethanol attenuated saccharin intake in P9 pups and enhanced saccharin intake in P12 rats. On P12 some sex-related differences emerged at 0.5 g/kg of ethanol, with saccharin intake being higher in females than in their male counterparts. Taste reactivity probe revealed that 0.5 g/kg of ethanol increased taste responsiveness to saccharin on P12 but only to infusions presented at a high rate. The results of the present study indicate that ontogenetic changes in sensitivity to the effects of ethanol on ingestive behavior occur during the second postnatal week, with P9 animals being more sensitive to the inhibitory (sedative) effects on saccharin intake and P12 rats being more sensitive to the stimulatory effects of ethanol. We suggest that acute ethanol enhanced saccharin intake via sensitization of oral response to appetitive taste stimulation.
19540830	Despite tobacco being highly addictive, it is unclear if nicotine has significant affective properties. To address this, we studied taste reactions to gustatory stimuli, palatable sucrose and unpalatable quinine, which are believed to reflect ongoing affective state. Taste reactivity was assessed during chronic nicotine administration and spontaneous withdrawal and the role of the endogenous cannabinoids was also investigated. C57BL6J mice were implanted with intraoral fistula to allow passive administration of solutions. In the first study, taste reactivity was tracked throughout chronic vehicle or nicotine (12 mg/kg/day) infusion via osmotic minipumps and spontaneous withdrawal following removal of minipumps. In the second study, the endocannabinoid CB1-receptor antagonist AM251 (1, 3 and 10mg/kg, intraperitoneal) or vehicle was acutely administered before taste reactivity measurement during chronic nicotine administration. Chronic nicotine treatment and spontaneous withdrawal did not influence taste reactions to sucrose or quinine. AM251 decreased positive reactions to sucrose and increased negative reactions to quinine. The effects of AM251 were respectively attenuated and enhanced in nicotine infused mice. These results suggest chronic nicotine exposure and withdrawal has no apparent affective sequelae, as probed by taste reactivity, and thus may not explain the difficulty tobacco-users have in achieving abstinence. In contrast, endocannabinoids elevate affective state in drug-naïve animals and changes in endogenous endocannabinoid tone may underlie compensations in affective state during chronic nicotine exposure.
19505346	Taste is a major determinant of children's food preferences, but its development is incompletely known. Thus, exploring infants' acceptance of basic tastes is necessary. The first objective was to evaluate the acceptance of tastes and their developmental changes over the first year. The second objective was to compare acceptance across tastes. The third objective was to evaluate global taste reactivity (within-subject variability of acceptance across tastes). Acceptance of sweet, salty, bitter, sour and umami tastes was assessed in three groups of forty-five 3-, 6- and 12-month-old infants using observations based on ingestion and liking scored by the experimenter. For each taste, four bottles were presented (water, tastant, tastant, water). Acceptance of each taste relative to water was defined using proportional variables based on ingestion or liking. Acceptance over the first year only evolved for sweet taste (marginal decrease) and salty taste (clear increase). At each age, sweet and salty tastes were the most preferred tastes. Reactions to umami were neutral. Sour and bitter tastes were the least accepted ones but rejected only when considering liking data. Ingestion and liking were complementary to assess taste acceptance. However, congruency between these measures rose during the first year. Moreover, with increasing age, reactions were more and more contrasted across tastes. Finally, during the first year, inter-individual variability increased for all tastes except salty taste. By enhancing knowledge of the development of taste acceptance the present study contributes to understand better food behaviour in infancy, the foundation of food behaviour in adulthood.
19485574	Fragile X syndrome, a form of mental retardation caused by inadequate levels of fragile X mental retardation protein (FMRP), is characterized by extreme sensitivity to sensory stimuli and increased behavioral and hormonal reactivity to stressors. Fmr1 knockout mice lack FMRP and exhibit abnormal responses to auditory stimuli. This study sought to determine whether Fmr1 knockout mice on an F1 hybrid background are normal in their response to footshock. Knockout mice were also examined for signs of hyperexcitation across an extended trial range, and serum corticosterone levels were evaluated in response to various stressors. The ability to acquire conditioned taste aversion was also assessed. Knockout mice exhibited no impairment in associative aversive learning or memory, since they successfully expressed conditioned taste aversion. Footshock-sensitivity, freezing behavior, and corticosterone response to various stressors did not differ between knockout and wild-type mice. However, knockout mice exhibited significantly increased responses during the extended test. The knockout mice's increased responsiveness to footshock in the extended test may be an indication of increased vulnerability to stress or enhanced emotional reactivity.
19477193	Paroxetine is prescribed to treat depression, but it also produces nausea. The potential of animal models to detect nauseating, antidepressant-like, and rewarding/aversive effects of paroxetine were assessed. In Experiments 1 (spaced conditioning trials) and 3 (massed conditioning trials), a dose of 30 mg/kg, but not lower doses (3 and 10 mg/kg) of paroxetine produced conditioned gaping reactions (reflective of nausea) in the Taste Reactivity (TR) test. In Experiment 2, when administered 23.5, 5 and 1 h prior to a 5 min forced swim test (FST) a dose as low as 3 mg/kg of paroxetine increased swimming and decreased immobility (reflective of antidepression) compared to controls. In Experiment 3, neither 10 nor 30 mg/kg of paroxetine produced a conditioned floor preference/aversion, but both doses decreased activity during conditioning trials. These results suggest that paroxetine produced an antidepressant-like effect at a lower dose (3 mg/kg) than that necessary to produce nausea (30 mg/kg). The TR test may be beneficial for assessing the side effect of nausea in preclinical tests of new compounds.
19264093	Adolescents have been hypothesized to exhibit an age-related partial anhedonia that may lead them to seek out natural and drug rewards to compensate for this attenuated hedonic sensitivity. In the present series of experiments, taste reactivity (TR) and 2 bottle choice tests were used to assess hedonic reactions to sucrose. In Exp 1, total positive taste responses to 10% sucrose solution were significantly higher in adolescent than adult rats during the infusion period. In Exp 2, adolescent animals exhibited a concentration-effect shift that was consistent with a greater hedonic sensitivity compared to adults. Conversely, adolescents exhibited fewer negative responses to quinine. Using a shortened infusion period, adolescents in Exp 3 exhibited a trend for greater positive TR than adults in response to 10 and 34% sucrose. Consistent with the TR results of Exp 1-3, adolescents consumed significantly more sucrose solution (ml/kg) than adults, although no significant age difference in sucrose preference rates emerged. The results of the current series of experiments do not support the hypothesis that adolescents exhibit an age-related, partial anhedonia, with adolescent animals, under a number of test circumstances showing greater positive taste reactivity and reduced negative responding.
19174448	The "waist" area (W) of the parabrachial nucleus contains neurons that receive orosensory input and play a role in the initiation of oromotor behaviors. Immunohistochemical data indicate that neurons in W receive glutamatergic input and express glutamate receptors, but a behavioral role for glutamate neurotransmission within W has not been investigated. To determine the role of specific glutamate receptors in taste reactivity behaviors, glutamate receptor blockers were delivered into W by reverse microdialysis during intraoral infusion of 0.1 M sodium chloride, 0.1 M sucrose, 0.03 M hydrochloric acid, and 0.003 M quinine hydrochloride. Blocking alpha-amino-3-hydroxy-5-methyl-isoxazolepropionate (AMPA)/kainate ionotropic glutamate receptors in W with 6-cyano-7-nitroquinoxaline-2,3-dione disodium (CNQX) reduced ingestive taste reactivity behaviors to each tastant by 72-85% compared with baseline levels (P's < 0.05). Blocking N-methyl-D-aspartate receptors as well as type 1 and group III metabotropic glutamate receptors had minor effects on taste reactivity responses to the tastants. These data provide strong evidence for a behavioral role of glutamatergic neurotransmission in W in conscious rats.
19138695	Previous studies show that the opioid peptide nociceptin stimulates food intake. Here, we studied nociceptin receptor knockout (NOP KO) mice in various behavioral paradigms designed to differentiate psychological and physiological loci at which endogenous nociceptin might control feeding. When presented a choice under food restriction, NOP KO mice displayed reduced preference for high sucrose diet, but lower intake of high fat diet under no-choice conditions. These responses were absent under ad libitum feeding conditions. Conditioned place preference to high fat diet under food-deprived conditions was unaltered in NOP KO mice, suggesting no difference in reward responses. Furthermore, operant food self-administration under a variety of conditions showed no genotype-dependent differences, suggesting no differences in the motivational properties of food. Taste reactivity to sucrose was unchanged in NOP KO mice, though NOP KO mice had altered aversive reactions to quinine solutions under ad libitum feeding, suggesting minor differences in the affective impact of palatable and unpalatable tastants. Although NOP KO mice re-fed following food-deprivation showed normal increases in plasma glucose and insulin, multidimensional scaling analysis showed that the relationship between these measures, body weight and plasma leptin was substantially disrupted in NOP KO, particularly in fasted mice. Additionally, the typical positive relationship between body weight and plasma leptin was considerably weaker in NOP KO mice. Together, these findings suggest that endogenous nociceptin differentially modulates diet preference depending on macronutrient content and homeostatic state, independently of the motivating, rewarding or orosensory properties of food, but may involve metabolic or postingestive processes.
19103649	Pavlovian conditioning is one of the major neurobiological mechanisms of placebo effects, potentially influencing the course of specific diseases and the response to a pharmacological therapy, such as immunosuppression. In our study with behaviorally conditioned rats, a relevant taste (0.2% saccharin) preceded the application of the immunosuppressive drug cyclosporin A (CsA), a specific calcineurin (CaN) inhibitor. Our results demonstrate that through pavlovian conditioning the particular pharmacological properties of CsA can be transferred to a neutral taste, i.e., CaN activity was inhibited in splenocytes from conditioned rats after reexposure to the gustatory stimulus. Concomitant immune consequences were observed on ex vivo mitogenic challenge (anti-CD3). Particularly, Th1-cytokine, but not Th2-cytokine, production and cell proliferation were impeded. Appropriate pharmacological and behavioral controls certify that all these changes in T-lymphocyte reactivity are attributable to mere taste reexposure. Furthermore, the underlying sympathetic-lymphocyte interaction was revealed modeling the conditioned response in vitro. CaN activity in CD4(+) T lymphocytes is reduced by beta-adrenergic stimulation (terbutaline), with these effects antagonized by the beta-adrenoreceptor antagonist nadolol. In summary, CaN was identified as the intracellular target for inducing conditioned immunosuppression by CsA, contributing to our understanding of the intracellular mechanisms behind "learned placebo effects."
19063906	C57BL/6J (B6) and DBA2/J (D2) mice differ markedly in voluntary consumption of tastants and responses to abused drugs. In particular, compared to D2 mice, B6 mice avidly drink ethanol and sucrose solutions, but avoid quinine solutions. In the first study, we compared taste reactivity in B6 and D2 mice to determine the extent to which differences in drinking patterns depend on orosensory processing. Both strains showed concentration-dependent increases in positive reactions to sucrose (0.01 to 1 M). Quinine (0.03 to 3 mM) elicited concentration-dependent aversive reactions in B6 mice, whereas all reactions to quinine were virtually indistinguishable from reactions to water in D2 mice. In contrast, D2 mice reacted with relatively strong aversive responses to ethanol (5 to 30%). In the second study, we evaluated the effect of subcutaneous morphine (1 to 4 mg/kg) and methamphetamine (0.5 to 2 mg/kg) on taste reactivity to sucrose. Morphine generally decreased reactions to sucrose in both strains, suggesting a general motor depressant effect. Methamphetamine shifted sucrose responses towards aversion in both strains; particularly in D2 mice. These results suggest that strain-dependent differences in voluntary ethanol and quinine drinking depend at least partially on differences in orosensory responses. However, differences in voluntary sucrose intake may relate solely to genetic differences in post-ingestive factors. Finally, as has been suggested by previous place conditioning studies, methamphetamine appears to induce a dysphoric state in D2 mice, which may be reflected in fewer positive and more negative taste reactions to sucrose in the current study.
18958188	It is well established that Egr1/zif268, a member of the Egr family of transcription factors, is critical for the consolidation of several forms of memories. Recently, the Egr3 family member has also been implicated in learning and memory. Because Egr family members encode closely related zinc-finger transcription factors sharing a highly homologous DNA binding domain that recognises the same DNA sequence, they may have related functions in brain. Another Egr family member expressed in brain, Egr2/Krox20 is known to be crucial for normal hindbrain development and has been implicated in several inherited peripheral neuropathies; however, due to Egr2-null mice perinatal lethality, its potential role in cognitive functions in the adult has not been yet explored. Here, we generated Egr2 conditional mutant mice allowing postnatal, forebrain-specific Cre-mediated Egr2 excision and tested homozygous, heterozygous and control littermates on a battery of behavioural tasks to evaluate motor capacity, exploratory behaviour, emotional reactivity and learning and memory performance in spatial and non-spatial tasks. Egr2-deficient mice had no sign of locomotor, exploratory or anxiety disturbances. Surprisingly, they also had no impairment in spatial learning and memory, taste aversion memory or fear memory using a trace conditioning paradigm. On the contrary, Egr2-deficient mice had improved performance in motor learning on a rotarod, and in object recognition memory. These results clearly do not extend the phenotypic consequences resulting from either Egr1 or Egr3 loss-of-function to Egr2. In contrast, they indicate that Egr family members may have different, and in certain circumstances antagonistic functions in the adult brain.
18835436	There is much debate on how immune activation affects cognitive processing. Research has shown that stimulation of the immune system can significantly impair, have no adverse effects, or enhance learning and memory processes in animals. The present experiment evaluated the effects of the bacterial endotoxin, lipopolysaccharide (LPS) on the acquisition of a rapidly acquired conditioned taste aversion using a toxin-containing food. Male Long Evans rats were fitted with intraoral cannulae and habituated to the taste reactivity procedure. Rats received two conditioning days, 72 h apart, in which they were injected systemically with LPS (200, 100, or 50 microg/kg) or NaCl (0.9% vehicle) and 90 min later placed in the taste reactivity test chamber. Rats were given 5 brief (1 min) intraoral infusions of either a LiCl-adulterated sucrose solution (0.15M LiCl+0.3M sucrose) or NaCl-sucrose solution (0.15M NaCl+0.3M sucrose) across a 1h period. On the test day (72 h after the last conditioning trial), rats were given a 2 min intraoral infusion of the respective taste in a drug-free state. Individual taste reactivity responses were recorded and analyzed. Results demonstrate that rats treated with LPS dose-dependently increased ingestive responding to the LiCl-sucrose flavor while at the same time showing reduced rejection response frequency on the two conditioning days. LPS treatment did not alter taste reactivity responding to the NaCl-sucrose solution. On the test day, the LPS groups again displayed a dose dependent increase in ingestive responses and a decrease in rejection responses to the LiCl-sucrose taste. The present results suggest that LPS-induced immune system activation, significantly impairs the rapid acquisition of a conditioned taste aversion.
18835293	Rolipram, a phosphodiesterase-4 (PDE4) inhibitor, is of current interest as a cognitive enhancer and as a treatment for inflammatory diseases. Originally developed as an anti-depressant, rolipram's efficacy was limited due to its side effects of nausea and vomiting. The experiments reported here evaluated the potential of rolipram to produce conditioned gaping (a selective measure of nausea in rats) to a flavor in the taste reactivity test (Experiment 1) and to a context (Experiment 2). In Experiment 1, rats were intra-orally infused with 17% sucrose solution prior to being injected with rolipram (Vehicle, 0.03, 0.1 or 0.3 mg/kg). Following 3 conditioning trials, rats conditioned with 0.3 mg/kg rolipram displayed conditioned gaping reactions during the infusion of sucrose. In Experiment 2, rats received 4 conditioning trials in which they were injected with 0.3 mg/kg rolipram and placed into a distinctive chamber. At test, when returned to the chamber rats displayed conditioned gaping. These results demonstrate the ability of the conditioned gaping model to detect the nauseating properties of a rolipram-paired flavor (Experiment 1) and rolipram-paired context (Experiment 2), further validating the potential use of the conditioned gaping model as a pre-clinical screening tool to evaluate the side effect of nausea produced by newly developed drugs.
18778149	The terms conditioned taste avoidance and conditioned taste aversion are often used interchangeably in the literature; however, considerable evidence indicates that they may represent different processes. Conditioned taste avoidance is measured by the amount that a rat drinks in a consumption test that includes both appetitive phases and consummatory phases of responding. However, conditioned taste aversion is more directly assessed using the taste reactivity (TR) test that includes only the consummatory phase of responding. Rats display a conditioned taste aversion as conditioned disgust reactions (gapes, chin rubs, and paw treads) during an intraoral infusion of a nausea-paired flavored solution. Only treatments that produce nausea produce conditioned disgust reactions, but even rewarding drugs produce conditioned taste avoidance. Furthermore, treatments that alleviate nausea prevent the establishment and the expression of conditioned disgust reactions, but they do not necessarily modify conditioned taste avoidance. Considerable evidence exists indicating that these two measures can be independent of one another. The potential of a compound to produce conditioned disgust reactions is a reflection of its nausea-inducing properties. Taste avoidance may be motivated by conditioned fear rather than conditioned nausea, but conditioned disgust is motivated by conditioned nausea.
18690102	A positive relationship between the consumption of sweetened dietary substances (e.g. saccharin and sucrose) and drug abuse has been reported in both the human and other animal literature. The proposed genetic contribution to this relationship has been based on evidence from behavioral, neurobiological, and linkage studies in heterogeneous and homogeneous animal populations. Initial work in several laboratories indicated that rodents that are selected for high alcohol consumption also display an increased preference for sweets compared with low alcohol-consuming animals. More recently, Sprague-Dawley rats have been selectively bred based on high saccharin (HiS) or low saccharin (LoS) consumption, and these lines represent an ideal opportunity to determine whether a reciprocal genetic relationship exists between the consumption of sweetened substances and self-administration of drugs of abuse. The purpose of this review is to examine a series of studies on the HiS and LoS rats for drug-seeking and drug-taking behavior using laboratory animal models that represent critical phases of drug abuse in humans. The data support the hypothesis that sweet consumption and drug self-administration are closely related and genetically influenced. Other characteristics of HiS and LoS rats are discussed as possible mediators of the genetic differences such as activity, impulsivity, novelty reactivity, stress, and emotionality. The interaction of sweet preference with biological variables related to drug abuse, such as age, sex, and hormonal influences, was considered, as they may be additive vulnerability factors with consumption of sweet substances. In the studies that are discussed, the HiS and LoS lines emerge as ideal addiction-prone and addiction-resistant models, respectively, with vulnerability or resilience factors that will inform prevention and treatment strategies for drug abuse.
18672009	The ventromedial hypothalamic nucleus (VMH) is a central site of action of interleukin-1beta (IL-1beta) induced feeding disturbances. This study was designed to elucidate taste-related perceptual and motivational processes potentially contributing to the anorexia and adipsia seen after bilateral IL-1beta microinjection into the VMH. A saccharin conditioned taste aversion (CTA) paradigm was tested after the central IL-1beta administration. To further investigate whether gustatory deficits are involved in development of the feeding alterations, IL-1beta induced changes of taste responsiveness were also studied in taste reactivity tests. Administration of the cytokine into the VMH did not cause the development of CTA. During taste reactivity tests, however, IL-1beta treated rats displayed significantly poorer ingestive reactions to pleasant taste stimuli than did animals of the control group. In addition, the aversive responses of IL-1beta injected rats to pleasant tastes were significantly more robust than those of control animals. The cytokine treated animals also showed stronger aversion than ingestion to hedonically positive tastes. The present findings indicate that (1) anorexigenic and adipsogenic consequences of IL-1beta microinjection into the VMH are not due to development of cytokine induced CTA; and (2) hedonic responsiveness to palatable tastes is processed by IL-1beta mediated neural mechanisms in the VMH.
18538914	Exposure to stress can lead to either increased stress vulnerability or enhanced resiliency. Laboratory rats are a key tool in the exploration of basic biobehavioral processes underlying individual differences in the effect of stress on subsequent stressors' impact. The Occidental low (LoS) and high (HiS) saccharin-consuming rats, which differ in emotional reactivity, are useful in this effort. In the present study, footshock affected acoustic startle amplitude 4 h later among LoS but not HiS rats. Surprisingly, shock attenuated startle rather than sensitizing it, a finding not previously reported for male rats exposed to shock. Attenuation was blocked by administering the anxiolytic drug alprazolam prior to stress, implicating anxiety in the effect. Preliminary tests provided no evidence of mediation by adenosine or corticosterone. This novel result encourages further study of the stressor and dispositional variables that modulate the timecourse of effects of stress on startle and identification of its mechanisms.
18494184	The rationale for investigating the gustatory reactivity as influenced by personality dimensions was suggested by some prior findings of an association between extraversion and acuity in other sensory systems. Detection thresholds for sweet, salty, and bitter qualities of taste were measured in 60 young healthy male and female volunteers using a two-alternative forced-choice technique. Personality of the responders was assessed using the Eysenck Personality Inventory. Multivariate analysis of variance failed to demonstrate a statistically significant interaction between an extraversion-introversion score, neuroticism score, smoking, gender and age. The only reliable negative association was found between the body mass index (BMI) and taste sensitivity (Roy's largest root = 0.05, F(7436.5) = 8.34, P = 0.003). Possible reasons for lack of differences between introverts and extraverts in the values of taste detection thresholds were discussed.
18470507	Many studies support the validity of the chronic mild stress (CMS) model of depression in rodents. However, most of them focus on analysis of reactivity to rewards during the CMS and/or depressive-like behavior shortly after stress. In this study, we investigate acute and long-term effects of CMS and antidepressant treatment on depressive, anxiety-like behavior and learning.Mice (C57BL/6) were exposed to CMS for 6 weeks and anhedonia was evaluated by weekly monitoring of sucrose intake. Paroxetine (10 mg kg(-1)day(-1) i.p.) or saline were administered the last 3 weeks of CMS and continued for 2 weeks thereafter. Behavioral tests were performed over the last week of CMS (acute effects) and 1 month later (long-term effects).	Mice exposed to CMS displayed both acute and long-term decreased sucrose intake, increased immobility in the forced swimming test (FST) and impaired memory in the novel object recognition test. It is interesting to note that a correlation was found between the cognitive deficits and the helpless behavior in the FST induced by CMS. During the CMS procedure, paroxetine treatment reverted partially recognition memory impairment but failed to prevent the increased immobility in the FST. Moreover, it decreased on its own sucrose intake. Importantly, the long-term effects of CMS were partially prevented by chronic paroxetine.	CMS leads to a long-term altered behavioral profile that could be partially reverted by chronic antidepressant treatment. This study brings novel features regarding the long-term effects of CMS and on the predictive validity of this depression animal model.	
18410179	The precise role played by serotonin (5-HT) in taste--an issue of great interest given the involvement of serotonin in human sensory and eating disorders--is a matter of considerable debate, perhaps because of the variety of methodologies that have been brought to bear by different researchers. Here, we use multiple methods to reveal the motivational mechanism whereby 5-HT(1A) receptor activation modulates drinking behavior. Subcutaneous injections of the selective 5-HT(1A) agonist 8-hydroxy-2-di-n-propylamino-tetralin (8-OH-DPAT), a drug that reduces 5-HT release by acting on presynaptic autoreceptors, dose-dependently increased consumption of 0.45 M NaCl in a one-bottle test. In a two-bottle test, however, 8-OH-DPAT-treated animals (30 microg/kg/ml) demonstrated decreased NaCl preference--although our detection of this effect was obscured by adaptation to the drug across days. Rats' performance in a brief access test confirmed that 8-OH-DPAT decreased preference for saline by both increasing water consumption and decreasing NaCl consumption. Finally, taste reactivity tests demonstrated that the latter result does not reflect decreased NaCl palatability. Overall, the results suggest that 8-OH-DPAT-induced 5-HT hypofunction increases thirst without substantially affecting the palatability of NaCl.
18386901	The effect of lipids on the formation of the Strecker aldehyde phenylacetaldehyde during wort boiling was studied to determine the role that small changes in the lipid content of the wort have in the production of significant flavor compounds in beer. Wort was treated with 0-2.77 mmol per liter of glucose, linoleic acid, or 2,4-decadienal and heated at 60-98 degrees C for 1 h. After this time, the amount of the Strecker aldehyde phenylacetaldehyde increased in the samples treated with linoleic acid or decadienal but not in the samples treated with glucose. Thus, the amount of phenylacetaldehyde produced in the presence of linoleic acid was 1.1-2.5 times the amount of the Strecker aldehyde produced in the control wort, and this amount increased to 3.6-4.6 times when decadienal was employed. The higher reactivity of decadienal than linoleic acid for this reaction decreased with temperature and was related to the oxidation of linoleic acid that occurred to a higher extent at higher temperatures. The above results suggest that lipids can contribute to the formation of Strecker aldehydes during wort boiling and that changes in the lipid content of the wort will produce significant changes in the formation of Strecker aldehydes in addition to other well-known consequences in beer quality and yeast metabolism. On the other hand, because of the high glucose content in wort, small changes in its content are not expected to affect the amount of Strecker aldehydes produced.
18341996	The motivation to seek cocaine comes in part from a dysregulation of reward processing manifested in dysphoria, or affective withdrawal. Learning is a critical aspect of drug abuse; however, it remains unclear whether drug-associated cues can elicit the emotional withdrawal symptoms that promote cocaine use. Here we report that a cocaine-associated taste cue elicited a conditioned aversive state that was behaviorally and neurophysiologically quantifiable and predicted subsequent cocaine self-administration behavior. Specifically, brief intraoral infusions of a cocaine-predictive flavored saccharin solution elicited aversive orofacial responses that predicted early-session cocaine taking in rats. The expression of aversive taste reactivity also was associated with a shift in the predominant pattern of electrophysiological activity of nucleus accumbens (NAc) neurons from inhibitory to excitatory. The dynamic nature of this conditioned switch in affect and the neural code reveals a mechanism by which cues may exert control over drug self-administration.
18248119	In two experiments, rats received minimal (16) pairings of one auditory conditioned stimulus (CS) cue with a sucrose reinforcer, and extensive (112) pairings of another auditory CS with that reinforcer. After sucrose was devalued by pairing it with lithium chloride in some rats (Devalue groups) but not others (Maintain groups), taste reactivity (TR) and other responses to unflavored water were assessed in the presence of the auditory CSs alone. The minimally trained CS controlled substantially more evaluative TR responses than the extensively trained CS. Those TR responses were hedonic (positive) in the Maintain groups, but aversive (negative) in the Devalue groups. By contrast, food cup entry and other responses thought not to reflect evaluative taste processing were controlled more by the extensively trained cue. These responses were reduced by sucrose devaluation comparably, regardless of the amount of training. The results suggest rapid changes in the content of learning as conditioning proceeds. Early in training, CSs may be capable of activating preevaluative processing of an absent food reinforcer that includes information about its palatability, but that capability is lost as training proceeds.
18234713	To understand the functional similarities of fly and mammalian taste receptors, we used a top-down approach that first established the fly sweetener-response profile. We employed the fruit fly Drosophila melanogaster, an omnivorous human commensal, and determined its sensitivity to an extended set of stimuli that humans find sweet. Flies were tested with all sweeteners in 2 assays that measured their taste reactivity (proboscis extension assay) and their ingestive preferences (free roaming ingestion choice test). A total of 21 sweeteners, comprised of 11 high-potency sweeteners, 2 amino acids, 5 sugars, 2 sugar alcohols, and a sweet salt (PbCl2), were tested in both assays. We found that wild-type Drosophila responded appetitively to most high-potency sweeteners preferred by humans, even those not considered sweet by rodents or new world monkeys. The similarities in taste preferences for sweeteners suggest that frugivorous/omnivorous apes and flies have evolved promiscuous carbohydrate taste detectors with similar affinities for myriad high-potency sweeteners. Whether these perceptual parallels are the result of convergent evolution of saccharide receptor-binding mechanisms remains to be determined.
18162068	Rat pups demonstrate high levels of immediate acceptance of ethanol during the first 2 weeks of postnatal life. Given that the taste of ethanol is most likely perceived by infant rats as a combination of sweet and bitter, high intake of ethanol early in ontogeny may be associated with age-related enhanced responsiveness to the sweet component of ethanol taste, as well as with ontogenetic decreases in sensitivity to its bitter component. Therefore, the present study compared responsiveness to ethanol and solutions with bitter (quinine) and sweet (saccharin) taste in terms of intake and palatability across the first 2 weeks of postnatal life.Characteristic patterns of responsiveness to 10% (v/v) ethanol, 0.1% saccharin, 0.2% quinine, and water in terms of taste reactivity and fluid intake were assessed in rat pups tested on postnatal day (P) 4, 9, or 12 using a new technique of on-line monitoring of fluid flow through a two-channel intraoral cannula. Taste reactivity included analysis of ingestive and aversive responses following six intraoral infusions of the test fluids. This taste reactivity probe was followed by the intake test, in which animals were allowed to voluntarily ingest fluids from an intraoral cannula.	Pups of all ages showed more appetitive responses to saccharin and ethanol than to water or quinine. No age-related differences were apparent in taste responsiveness to saccharin and ethanol. However, the age-related pattern of ethanol intake drastically differed from that of saccharin. Intake of saccharin increased from P4 to P9 and decreased substantially by P12, whereas intake of ethanol gradually increased from P4 to P12. Intake of ethanol was significantly lower than intake of saccharin on P9, whereas P12 pups took in more ethanol than saccharin.	The findings of the present study indicate ontogenetic dissociations between taste reactivity to ethanol and saccharin and intake of these solutions, and suggest that high acceptance of ethanol early in ontogeny may not be associated with its orosensory properties but rather with the pharmacological effects of ethanol.	
17962740	Phenolic compounds form one of the main classes of secondary metabolites. They display a large range of structures and they are responsible for the major organoleptic characteristics of plant-derived-foods and beverages, particularly color and taste properties and they also contribute to the nutritional qualities of fruits and vegetables. Phenolic compounds are also highly unstable compounds which undergo numerous enzymatic and chemical reactions during postharvest food storage and processing thus adding to the complexity of plant polyphenol composition. Among these compounds flavonoids constitute one of the most ubiquitous groups of all plant phenolics. Owing to their importance in food organoleptic properties and in human health, a better understanding of their structures, their reactivity and chemical properties in addition to the mechanisms generating them appears essential to predict and control food quality. The purpose of this work is an overview of our findings concerning the hemisynthesis, the reactivity and the enzymatic oxidation of some flavonoids and shed light on the mechanisms involved in some of these processes and the structures of the resulting products. The free radical scavenging activity of some of the synthesized compounds is also presented and a structure-activity relationship is discussed. The first part of this review concerns the synthesis and structural characterization of modified monomeric flavanols. The use of these compounds as precursor for the preparation of natural and modified dimeric procyanidin derivatives was then explored through different coupling reactions. The full characterization of the synthesized compounds was achieved by concerted use of NMR and ESI-MS techniques. The free radical scavenging activity of some of the synthesized compounds was investigated. The second part of this review concerns the enzymatic oxidation of several flavonols by Trametes versicolor laccase. Most of the major oxidation products have been isolated as pure compounds and their structures unambiguously established through spectroscopic methods. Correlation between the structure of the oxidation product and the substitution pattern of the starting materials allows mechanistic features of this transformation to be elucidated.
17761543	Through associative learning, cues for biologically significant reinforcers such as food may gain access to mental representations of those reinforcers. Here, we used devaluation procedures, behavioral assessment of hedonic taste-reactivity responses, and measurement of immediate-early gene (IEG) expression to show that a cue for food engages behavior and brain activity related to sensory and hedonic processing of that food. Rats first received a tone paired with intraoral infusion of sucrose. Then, in the absence of the tone, the value of sucrose was reduced (Devalue group) by pairing sucrose with lithium chloride (LiCl), or maintained (Maintain group) by presenting sucrose and LiCl unpaired. Finally, taste-reactivity responses to the tone were assessed in the absence of sucrose. Devalue rats showed high levels of aversive responses and minimal appetitive responses, whereas Maintain rats exhibited substantial appetitive responding but little aversive responding. Control rats that had not received tone-sucrose pairings did not display either class of behaviors. Devalue rats showed greater FOS expression than Maintain rats in several brain regions implicated in devaluation task performance and the display of aversive responses, including the basolateral amygdala, orbitofrontal cortex, gustatory cortex (GC), and the posterior accumbens shell (ACBs), whereas the opposite pattern was found in the anterior ACBs. Both Devalue and Maintain rats showed greater FOS expression than control rats in amygdala central nucleus, GC, and both subregions of ACBs. Thus, through associative learning, auditory cues for food gained access to neural processing in several brain regions importantly involved in the processing of taste memory information.
17651789	Although genetic and early environmental factors interact to affect drug abuse in humans, surprisingly few tractable laboratory animal models have been developed. Using reciprocal cross-fostering of the inbred Fischer and Lewis rat strains, we recently reported significant gene-environment interaction effects on responses to the aversive properties of 32 mg/kg subcutaneous cocaine, but only in females [Roma PG., Davis CM, Riley AL. Effects of cross-fostering on cocaine-induced conditioned taste aversions in Fischer and Lewis rats. Dev Psychobiol 2007;49:172-9]. The present study describes a follow-up analysis tracking the extinction of the equally acquired cocaine aversions in the adult male Fischer and Lewis rats raised by either Fischer or Lewis dams (n=11-12/group). Based on mean consumption, after eight saccharin-saline pairings, the in-fostered Fischer rats never extinguished while the Lewis animals fully extinguished; however, the cross-fostered Fischer rats partially extinguished, while extinction was completely suppressed in the cross-fostered Lewis animals. Based on documented strain differences in avoidance behavior and stress reactivity, the data were interpreted in terms of differential sensitivity to conditioned aversive stimulation. These data join other examples of cross-fostering effects on physiology and behavior in these strains and further support the use of the Fischer-Lewis model for exploring gene-environment interaction in drug-induced phenotypes.
17640625	When subjects receive a taste stimulus (conditioned stimulus, CS) that is paired with malaise, they acquire conditioned taste aversion (CTA). It is thought that the taste CS changes from appetitive to aversive after acquisition of CTA. Previous studies have suggested that the ventral pallidum (VP) is involved in the hedonics of taste stimuli, therefore the present study investigated whether the VP is a neural substrate for the shift in preference of the CS after CTA acquisition. In the first experiment, CTA-learned rats received microinjections of the GABA(A) receptor antagonist bicuculline into the VP just before presentation of the CS (saccharin or quinine) in a single-bottle test. The bicuculline-injected rats showed higher intake of the saccharin CS than the vehicle-injected rats. To test whether these results were due to a change in taste preference for the CS, in the second experiment, we examined the effects of bicuculline on the affective aspects of the saccharin CS using a taste reactivity test, which is a useful tool for evaluating taste palatability. The bicuculline-injected rats showed higher appetitive and lower aversive responses to the saccharin CS than the vehicle-injected group. These results suggest that the higher saccharin intake observed in the first experiment was at least partly due to the bicuculline injection, which changed the perceived palatability of the taste CS (saccharin) from aversive to appetitive. The GABAergic system in the VP may play an important role in hedonic-based ingestive behaviors after CTA.
17560720	Increased blood pressure and sweet taste are often associated with decreased pain sensitivity. Animal research suggests that endogenous opioids are involved in both these relationships. Fifty-eight healthy young adults (36 male, 22 female) participated in two sessions receiving a placebo tablet or 50mg of naltrexone on counterbalanced days. On each day, three cold-pressor tests were administered while the participant held a sweet solution, water, or nothing in their mouth when their hand was in the water. 2 Drug x 3 Solution x 2 Gender x Pre-Drug Resting Blood Pressure general linear models (GLM) were conducted separately for systolic (SBP) and diastolic (DBP) pressure. Consistent with previous research, significant main effects of SBP were observed in GLMs of pain tolerance and pain unpleasantness ratings. A main effect of solution on tolerance was seen in the GLM with DBP, which was qualified by an interaction of solution by blood pressure. Sweet taste increased pain tolerance among those with lower DBP across drug conditions. This suggests some overlap between mechanisms of sweet taste and blood pressure analgesia, without implicating opioid activity in sweet taste analgesia. However, the GLM of tolerance also produced a significant drug by DBP interaction suggesting that blood pressure-related analgesia is at least partially opioid-mediated. Also participants with higher DBP showed dampened mood reactivity to the experiment, which was partially reversible by naltrexone. These results are consistent with findings suggesting that endogenous opioid activity may contribute to generally reduced pain sensitivity, and perhaps mood reactivity, in those with higher BP.
17524600	Reviewing the development of nociceptive circuits provides the rationale behind the need to modify and reduce premature painful experiences, especially during the "plastic" neonatal phase. Indeed, if physiological mechanisms of the functional nociceptive system follow a harmonious and predetermined development, it is the individual personal experience, intrinsically random, which will shape the final reactivity of this system and the later painful experience. If pain would not have been the organism's alarm system, we could have simply compared it by analogy to other sensorial systems, which its development depends exclusively on the presence of environmental stimuli. The eyes wait for light, the ears for sound, the skin to be touched, the tongue to taste and the olfactory bulbs to smell. However with pain it is not the quantitative exposure that determines its development, but rather the context-laden aspects of its affliction which in turn create the complex experience and "memory" of pain. Prolonged, but also "unnecessary" exposure to pain transforms it into a futile sensation, which impacts the individual immediately but also resonates into its future. This article reviews recent neurobiological mechanisms (such as neural circuitry, neurotrophins, peripheral and central sensitization, inhibitory pathways) now known to develop during the chronicisation and apprenticing of pain in the growing individual. Its cognizance is vital for a better comprehension of adult pain.
17488745	Olfactory sensory stimulation induces a fast-phase arrest response (FPA-R) of the blowfly heart activity that has been described as a sensitive tool for testing insect reactivity to odor perception. We analyzed FPA-R occurrence to repeated olfactory stimulation with low and high 1-hexanol concentrations that are behaviorally attractant and repellent, respectively, in the blowfly. FPA-R occurrence diminished and ceased with repeated presentations of low and medium odor concentrations, according to dynamics inversely related to odor doses. On the other hand, repeated stimulation with higher odor concentrations induced persistent FPA-Rs. Sensory input amplitude to repeated presentations of singly tested odor concentrations did not change throughout stimulation sessions. A spontaneous restoration of FPA-R to olfactory stimulation was recorded 30 min after cessation of FPA-R to a previous olfactory stimulation session. However, a prompt restoration of FPA-R to olfactory stimulation after cessation of FPA-R was obtained following mechano-taste stimulation of labellar sensilla. Our findings show that the FPA-R habituates to olfactory sensory stimulation with low and medium odor concentrations according to dynamics inversely related to odor intensities. On the other hand, the FPA-R does not habituate to higher odor concentrations. Therefore, flies learn to disregard nonaversive odor information, but they cannot ignore iterative detection of a repellent volatile.
17488743	Electrical stimulation of the waist area (W) of the parabrachial nucleus (PBN) in conscious rats elicits stereotypical oromotor behaviors (Galvin et al. 2004). To identify neurons possibly involved in these behavioral responses, we used Fos immunohistochemistry to locate populations of neurons within central gustatory and oromotor centers activated by PBN stimulation. Dramatic increases in the numbers of Fos-like immunoreactive neurons were observed in the ipsilateral PBN, nucleus of the solitary tract (NST), and central amygdala. The increase in neurally-activated cells within the ventral subdivision (V) of the rostral NST is particularly noteworthy because of its projections to medullary oromotor centers. A modest increase in labeled neurons occurred bilaterally within the gustatory cortex. Although there were trends for an increase in Fos-labeled neurons in the gustatory thalamus and medullary reticular formation, most changes in labeled neurons in these areas were not statistically significant. Linear regression analysis revealed a relationship between the number of taste reactivity (TR) behaviors performed during PBN stimulation and the number of Fos-like immunoreactive neurons in the caudal PBN and V of the rostral NST. These data support a role for neurons in W of the PBN and the ventral rostral NST in the initiation of TR behaviors.
17418693	Naltrexone, a nonspecific opioid antagonist, produces significant changes in ethanol responsivity in rats by rendering the taste of ethanol aversive as well as producing a decrease in voluntary ethanol consumption. The present study investigated the effect of naltrindole, a specific antagonist of delta opioid receptors, on ethanol taste reactivity and ethanol consumption in outbred rats. In the first experiment, rats received acute treatment of naltrexone, naltrindole, or saline followed by the measurement of ethanol consumption in a short-term access period. The second experiment involved the same treatments and investigated ethanol palatability (using the taste-reactivity test) as well as ethanol consumption. Results indicated that treatment with 3 mg/kg naltrexone significantly affected palatability (rendered ethanol more aversive, Experiment 2) and decreased voluntary ethanol consumption (Experiments 1 and 2). The effects of naltrindole were inconsistent. In Experiment 1, 8 mg/kg naltrindole significantly decreased voluntary ethanol consumption but this was not replicated in Experiment 2. The 8 mg/kg dose produced a significant increase in aversive responding (Experiment 2) but did not affect ingestive responding. Lower doses of naltrindole (2 and 4 mg/kg) were ineffective in altering rats' taste-reactivity response to and consumption of ethanol. While these data suggest that delta receptors are involved in rats' taste-reactivity response to ethanol and rats' ethanol consumption, it is likely that multiple opioid receptors mediate both behavioral responses.
17406653	Cannabinoid drugs such as Delta9-THC are euphoric and rewarding, and also stimulate food intake in humans and animals. Little is known about how naturally occurring endogenous brain cannabinoids mediate pleasure from food or other natural sensory rewards. The taste reactivity paradigm measures effects of brain manipulations on affective orofacial reactions to intraorally administered pleasant and unpleasant tastes. Here we tested if anandamide microinjection into medial nucleus accumbens shell enhances these affective reactions to sweet and bitter tastes in rats. Anandamide doubled the number of positive 'liking' reactions elicited by intraoral sucrose, without altering negative 'disliking' reactions to bitter quinine. Anandamide microinjections produced Fos plumes of approximately 0.02-1 mm3 volume. Plume-based maps, integrated with behavioral data, identified the medial shell of accumbens as the anatomical hotspot responsible for hedonic amplification. Anandamide produced especially intense hedonic enhancement in a roughly 1.6 mm3 'hedonic hotspot' in dorsal medial shell, where anandamide also stimulated eating behavior. These results demonstrate that endocannabinoid signals within medial accumbens shell specifically amplify the positive hedonic impact of a natural reward (though identification of the receptor specificity of this effect will require future studies). Identification of an endocannabinoid hotspot for sensory pleasure gives insight into brain mechanisms of natural reward, and may be relevant to understanding the neural effects of cannabinoid drugs of abuse and therapeutic agents.
17175173	Anterior insula and adjacent frontal operculum (hereafter referred to as IFO) are active during exposure to tastants/odorants (particularly disgusting ones), and during the viewing of disgusted facial expressions. Together with lesion data, the IFO has thus been proposed to be crucial in processing disgust-related stimuli. Here, we examined IFO involvement in the processing of other people's gustatory emotions more generally by exposing participants to food-related disgusted, pleased and neutral facial expressions during functional magnetic resonance imaging (fMRI). We then exposed participants to pleasant, unpleasant and neutral tastants for the purpose of mapping their gustatory IFO. Finally, we associated participants' self reported empathy (measured using the Interpersonal Reactivity Index, IRI) with their IFO activation during the witnessing of others' gustatory emotions. We show that participants' empathy scores were predictive of their gustatory IFO activation while witnessing both the pleased and disgusted facial expression of others. While the IFO has been implicated in the processing of negative emotions of others and empathy for negative experiences like pain, our finding extends this concept to empathy for intense positive feelings, and provides empirical support for the view that the IFO contributes to empathy by mapping the bodily feelings of others onto the internal bodily states of the observer, in agreement with the putative interoceptive function of the IFO.
17141813	Based on animal data it has been suggested that an increased sensitivity to bitter tastes is linked with increased emotional reactivity. The present study examined for the first time in humans whether the intensity of experimentally induced negative emotional responses is related to sensitivity to the bitter tasting compound PROP (6-n-propylthiouracil). Normal-weight participants (61 men, 57 women) with a mean age of 24 years were classified into PROP non-tasters (n=54), medium tasters (n=25), or supertasters (n=39), and were shown two film clips to induce negative emotional response patterns: one pattern predominated by anger and tension, and another predominated by sadness and depressed mood. A third film clip was emotionally neutral. Before and after film clip viewing, self-rated emotional responses were obtained. PROP supertasters showed more intense responses than non-tasters or medium tasters after the anger-inducing film clip (increased anger, tension, sadness and fear as well as decreased mood and joy). Significant correlations were found between emotional responses and a continuos measure of PROP sensitivity. Group differences and correlations could not be attributed to personality measures, trait affectivity, or gender. For emotional responses after the sadness-inducing film clip, no differences between taster groups could be detected. PROP sensitivity appears to be related to arousability of emotions, in particular those emotions that are associated with an increased readiness to respond actively to stimuli from the environment, e.g. anger, disgust and fear.
17118412	Here we provide evidence that the cannabinoid agonist, Delta9-tetrahydrocannabinol (Delta9-THC) enhances quinine palatability and the CB1 antagonist/inverse agonist, AM251, reduces sucrose and quinine palatability using the taste reactivity test, which provides a direct measure of palatability independently of appetitive behavior. In Experiment 1, rats were treated with a low dose of Delta9-THC (0.5 mg/kg) or Vehicle 30 min, 60 min, 120 min or 240 min prior to a 5-min intraoral infusion of a highly unpalatable 0.05% quinine solution. Regardless of the post-injection interval, Delta9-THC reduced rejection of quinine. The Delta9-THC-induced palatability shift was reversed by AM251. In Experiment 2, rats were injected with either AM251 (1 mg/kg) or Vehicle prior to receiving a 5-min intraoral infusion of either 32% sucrose or 0.05% quinine solution. AM251 significantly decreased sucrose-elicited hedonic reactions across both time intervals; however, AM251 did not significantly modify the rejection of 0.05% quinine solution. When the concentration of the quinine solution was reduced to 0.01% in Experiment 3, AM251 enhanced quinine aversion. Although the range of concentrations of the solutions tested in the present data is limited, our results suggest that the cannabinoid system may modulate the palatability of ingested substances regardless of the palatability of the ingested substance.
17111174	The endogenous cannabinoid system plays a vital role in the control of nausea and emesis. Because of the rapid breakdown and hydrolysis of endocannabinoids, such as anandamide, the therapeutic effects may be enhanced by prolonging their duration of action.The present experiment evaluated the potential of various doses of URB597, a fatty acid amide hydrolase (FAAH) inhibitor, alone and in combination with systemic administration of anandamide to modulate the establishment of lithium-induced conditioned taste reactivity responses in rats.	In experiment 1, on the conditioning day, rats first received an injection of 0.3 mg/kg URB597, 0.15 mg/kg URB597, or vehicle and then received a second injection of anandamide (5 mg/kg) or vehicle, before a 3-min exposure of 0.1% saccharin by intraoral infusion. Immediately after the saccharin exposure, the rats were injected with lithium chloride. On each of three test days, rats received a 3-min intraoral infusion of saccharin solution, and the taste reactivity responses were videotaped and monitored. In experiment 2, the effects of pretreatment with the CB(1) antagonist, AM-251, on URB597 and anandamide-induced suppressed aversion was evaluated.	Administration of URB597 alone and in combination with anandamide reduced active rejection reactions elicited by a LiCl-paired saccharin solution; both effects were reversed by pretreatment with AM-251, suggesting that they were CB(1) receptor mediated.	The results suggest that prolonging the action of anandamide by pretreatment with the FAAH inhibitor, URB597, suppresses lithium-induced nausea in the rat.	
17082515	The central distribution of QHCl-elicited Fos-like immunoreactivity (FLI) suggests the location of a brain stem circuit that controls the oral rejection response. Although many species display an oral rejection response to bitter stimuli, the distribution of FLI associated with this response has been investigated only in rats. Fos data are minimal for the mouse, a species of increasing importance, due to its use in molecular and transgenic studies and taste-evoked oromotor responses are also only incompletely described in these rodents. We investigated these questions in FVB/NJ mice and a related transgenic strain (FVB-Tg(GadGFP)4507) that expresses green fluorescent protein in a subset of GAD1-containing neurons. QHCl, sucrose, or water delivered through intraoral cannulae yielded behavioral profiles that clearly differentiated QHCl from sucrose. Similar to rat, the number of neurons expressing FLI in the medial third of the solitary nucleus was elevated following QHCl compared with the other stimuli. In mice expressing green fluorescent protein, there was a pronounced distribution of GABAergic neurons in the ventral half of the solitary nucleus. Approximately 15% of solitary neurons expressing Fos were GABAergic, but this proportion did not differ according to stimulus.
17018216	Taste reactivity testing (TRT), which entails infusing a solution into the oral cavity of subjects, is used across a wide range of studies. For laboratories inexperienced in the conventional technique of implanting cheek fistulae, the surgery can be problematic for both the subjects and the experimenter. We have proposed a refined method for fistulae implantation that is less invasive, thereby reducing the pain and distress of the animals. Using this refined technique, we were able to replicate the findings of previous TRT studies, namely that a high dose of lithium chloride produces an increase in aversive and a decrease in ingestive orofacial and somatic responses. Using indices of health, we demonstrate that unlike animals with the conventional method of fistulae implantation, subjects that receive the refined technique regain their pre-surgery body weights rapidly and show no physical signs of discomfort. Additional advantages of the refined technique are discussed.
17013640	The primary aim of this project was to examine the role of alcohol use in smoking lapse behavior, as alcohol consumption is a known risk factor for poor smoking cessation outcomes.We have developed a novel human laboratory model to examine two primary aspects of alcohol-mediated tobacco relapse: (1) Does alcohol facilitate the initiation of the first cigarette? (2) Once the first cigarette is initiated, does alcohol facilitate subsequent smoking? Using a within-subject design, 16 daily smokers who were also heavy social drinkers received a priming drink (0.03 g/dl or taste-masked placebo) and then had the option of initiating a tobacco self-administration session or delaying initiation by 5-min increments for up to 50 min in exchange for monetary reinforcement. Subsequently, the tobacco self-administration session consisted of a 1-h period in which subjects could choose to smoke their preferred brand of cigarettes using a smoking topography system or receive monetary reinforcement for cigarettes not smoked. Alcohol craving, tobacco craving, subjective reactivity to alcohol, and nicotine withdrawal were assessed as secondary outcomes.	Results demonstrated that after consuming the alcohol beverage, subjects were less able to resist the first cigarette and initiated their smoking sessions sooner, and smoked more cigarettes compared to the placebo beverage. These findings have implications for smoking cessation in alcohol drinkers and model development to assess smoking lapse behavior.	
16893301	Here the authors evaluated the effect of the method of conditioning (bottle or intraoral [IO] infusion) on the strength of a flavor-drug association when measured in a standard 1-bottle consumption test or when measured by IO infusion in a taste reactivity test. When tested with the bottle test in Experiment 1, rats conditioned by bottle displayed stronger taste avoidance than those conditioned by IO infusion. When tested for rejection reactions with the taste reactivity test in Experiment 2, rats conditioned by infusion displayed a stronger aversion than did rats conditioned by bottle. The results suggest that when the contextual cues of conditioning are similar at conditioning and testing, a stronger association is evident regardless of the individual specifics of each method. These results may shed light on recent reports that different neural mechanisms are involved in conditioning by active consumption and passive infusion.
16875757	The reinforcing effects of addictive drugs and palatable foods are regulated, at least in part, by a common biological mechanism. The reactivity or sensitivity of these brain reward regions have been found to correlate significantly with the risk for a variety of drug addictions. Sensitivity to Reward (STR) is conceptualised as a psycho-biological personality trait rooted firmly in the availability of dopamine in the mesocorticolimbic ('common reward') pathways, and as such is a good candidate for studying motivational factors and eating behaviours. The purpose of the present study was to examine whether STR was related to behaviours that contribute to excess body weight. Structural equation modelling procedures were used with a sample of healthy adult women (n=151). We hypothesised that STR would positively predict overeating and a preference for foods high in fat and sugar; and that these two behaviour would, in turn, predict a higher Body Mass Index. Results provided an excellent fit of the model to our data confirming our view that a personality trait like STR can only influence a physical condition like body weight indirectly by the way it co-varies with behaviours that contribute directly to variation in the outcome variable.
16862244	Some patients with bipolar disorder experience mood episodes following emotional life events, whereas others do not. There is evidence that orbitofrontal hypoactivity may be related to this, because the orbitofrontal cortex is involved in the regulation of emotional and behavioural responses to external events. The close anatomical and functional connection between the orbitofrontal cortex and olfactory processing suggests that patients with bipolar disorder and heightened emotional reactivity may exhibit altered olfactory function compared with patients with bipolar disorder who do not exhibit this sensitivity.In this pilot study, olfactory function was assessed in patients with bipolar disorder and a history of event-triggered episodes (n = 7) and in patients with bipolar disorder without such a history (n = 9) at the Department of Psychiatry and the Taste and Smell Clinic of the University of Dresden, Germany. Each patient's bipolar disorder was in remission at study entry, and they were on monotherapy with mood stabilizers. Assessment included olfactory event-related potentials (ERP) and psychophysical tests for odour threshold, odour identification and olfactory quality discrimination.	Odour thresholds were lower in patients with bipolar disorder and event-triggered episodes compared with the other patient group. In addition, patients with event-triggered episodes exhibited shorter N1 peak latencies of the olfactory ERP.	Our findings indicate disinhibition of orbitofrontal areas involved in the processing of emotional events in a subset of patients with bipolar illness.	
16857218	This study examined adults' affective and facial reactions to tastes which differ in quality and valence, and the impact of sadness and joy on these reactions. Thirty-six male and female subjects participated voluntarily. Subjects each tasted 6 ml of a sweet chocolate drink, a bitter quinine solution (0.0015 M) and a bitter-sweet soft drink. Following a baseline period, either joy or sadness was induced using film clips before the same taste stimuli were presented for a second time. Subjects rated the drinks' pleasantness and intensity of taste immediately after each stimulus presentation. Facial reactions were videotaped and analysed using the Facial Action Coding System (FACS [P. Ekman, W.V. Friesen, Facial Action Coding System: Manual. Palo Alto, CA: Consulting Psychologists Press; 1978., P. Ekman, W. Friesen, J. Hager, Facial Action Coding System. Salt Lake City, Utah: Research Nexus; 2002.]). The results strongly indicated that the tastes produced specific facial reactions that bear strong similarities to the facial reactivity patterns found in human newborns. The data also suggest that some adults' facial reactions serve additional communicative functions. Emotions modulated taste ratings, but not facial reactions to tastes. In particular, ratings of the sweet stimulus were modulated in congruence with emotion quality, such that joy increased and sadness decreased the pleasantness and sweetness of the sweet stimulus. No emotion-congruent modulation was found for the pleasantness and intensity ratings of the bitter or the bitter-sweet stimulus. This 'robustness' of bitter taste ratings may reflect a biologically meaningful mechanism.
16786882	Extinction of a conditioned palatability shift preceded extinction of conditioned taste avoidance whether rats were tested using a within-subjects design or a between-subjects design. In each of two experiments, consumption of 0.1% saccharin was paired with either 20 ml/kg of 0.15 M LiCl or equi-volume physiological saline on a single trial. In Experiment 1, on each of 10 extinction trials, rats were given a taste reactivity test immediately prior to a consumption test. In Experiment 2, half of the rats were extinguished by taste reactivity testing and half of the rats were extinguished by a consumption test on each of 10 extinction trials. In both experiments, the aversive reactions of gaping and passive dripping were extinguished in a single trial and the suppression of ingestive reactions was extinguished in 2 trials; however, extinction of taste avoidance required 4-5 trials. These results suggest that rats continue to avoid a lithium-paired flavor even when they do not have an aversion to the taste.
16733065	Sensation seeking is frequently observed among drug addicts. This behaviour has been modelled in non-primate animals as novelty seeking. We previously determined that novelty preference did not predict amphetamine-induced place conditioning but was positively correlated with the consumption of a low concentrated amphetamine solution. Here, we studied the relationship between novelty seeking and the vulnerability to rewarding and reinforcing effects of morphine. Wistar rats were selected according to their novelty preference. In this model, animals have free choice between a new compartment and a "familiar" compartment to which they were previously exposed during two 30-min sessions, 24 h apart. We measured oral morphine consumption when this drug was presented in tap water (25 or 50 mg/l) in free choice with water or when it was presented (50 mg/l) in a 5% (w/v) sucrose solution in free choice with a sucrose solution. The oral consumption of quinine was also measured. The rewarding effect of morphine (1.25 and 5 mg/kg; i.p.) was determined in a conditioned place preference paradigm. Whereas high and low novelty seekers did not differ in reactivity to the aversive taste of quinine, preference for novelty was associated with a greater oral morphine consumption as well as an increased conditioned place preference induced by the 5 mg/kg dose of morphine. The present results support the hypothesis that novelty preference predisposes to drug abuse.
16713505	In the present study, the effects of ethanol familiarity on the ability of naltrexone to alter ethanol palatability and consumption were examined. One group of rats was allowed continuous access to 10% vol/vol ethanol and water for 3 weeks. A second group received only water. At the end of this time, the groups were further subdivided and injected with either 3mg/kg naltrexone or saline (total of four groups; n=11-13 per group) before ethanol taste reactivity tests with 10% vol/vol ethanol and ethanol consumption tests. Results showed that naltrexone effectively decreased ingestive responding and increased aversive responding. Further, rats familiar with alcohol made more ingestive responses to 10% vol/vol ethanol. A significant interaction of drug treatment and familiarity was found in the data for aversive responses: naltrexone treatment produced more aversive responses in ethanol-familiar rats, whereas saline treatment resulted in fewer aversive responses in rats familiar with ethanol. Naltrexone treatment clearly reduced consumption of 10% vol/vol ethanol, although its effects were attenuated somewhat by ethanol familiarity. The present data indicate that both alcohol familiarity and naltrexone treatment affect ethanol reactivity and ethanol consumption in outbred rats. The interaction of naltrexone treatment and ethanol familiarity only for aversive reactivity and the lack of such an interaction for the consumption measures suggests that the mechanisms underlying ethanol reactivity and ethanol consumption may be dissociable at the neural level.
16621047	Acetaldehyde, the first metabolite of ethanol, may mediate some ethanol-induced effects. Previous research in our laboratory has shown that D-penicillamine, an inactivation agent for acetaldehyde, is effective in decreasing locomotor stimulation and conditioned place preference induced by ethanol in mice. In the present study, the effects of D-penicillamine on the voluntary consumption of ethanol were assessed. Male rats were offered ethanol under restricted access, without food or water deprivation. Daily availability of ethanol was limited to a 15-min period in the home cages. When the response for 10% ethanol was stable, rats received an intraperitoneal (IP) injection of D-penicillamine (0, 25, 50 or 75 mg/kg) over a 5-day period, given 30 min before exposure to ethanol. In a second study we determined the specificity of D-penicillamine effects (50 mg/kg) on voluntary sucrose consumption (3%). Another study was conducted to evaluate whether IP D-penicillamine (50 mg/kg) alters taste reactivity responses. In the final experiment, rats were treated with intracerobroventricular (ICV) infusions of D-penicillamine (75 microg) for 5 days before drinking ethanol or sucrose. D-Penicillamine was found to reduce ethanol intake in a dose-dependent manner. Sucrose consumption was also affected by this thiol amino acid. We also demonstrated that D-penicillamine produced changes in the ingestive and flavor properties of sucrose and ethanol, measured by means of a taste reactivity test. When D-penicillamine was administered ICV, only voluntary ethanol consumption was modified. These findings indicate that the central inactivation of acetaldehyde blocks ethanol intake in rats, and suggest that acetaldehyde plays a key role in the motivational properties of ethanol.
16553623	The nucleus accumbens and its related circuitry have been shown to play an important role in promoting the intake of hedonically desirable food. A previous report has demonstrated that the blockade of GABAA receptors in the ventral pallidum (VP), a target of GABAergic projection from the nucleus accumbens, greatly increases food, but not water, intake in satiated rats [Stratford et al. (1999)Brain Research, 825, 199-203]. The present study examined which neurotransmission in the VP is specifically involved in the intake of normally preferred taste stimuli. Microinjections of the GABAA antagonist bicuculline selectively increased the intake of saccharin solution but not that of water and quinine solution in water-deprived rats. In contrast, the facilitation of GABAA receptors by microinjections of muscimol in the VP generally suppressed the intake of saccharin, water and quinine. The same injections induced strong aversive taste reactivity responses to oral stimulation with not only quinine but also water and saccharin. The local administration of D-Ala2,N-Me-Phe4,Glyol5-enkephalin, a selective micro-opioid receptor agonist, into the VP had time-dependent effects, decreasing saccharine intake early and increasing intake late. Microinjections of SCH-23390, a dopamine D1 receptor antagonist, in the VP suppressed the intake of saccharin but not water or quinine. Microinjections of sulpiride, the dopamine D2 receptor antagonist, and 6-cyano-7-nitroquinoxaline-2,3-dione, the AMPA/kainate glutamate receptor antagonist, had no effect on fluid intake. These results reveal that GABA, opioid and D1 receptors in the VP are involved in the consumption of hedonically positive taste stimuli.
16492132	To examine the role of incentive sensitization in the potentiation of salt appetite by prior depletions, the authors assessed the motivation to obtain salt ("wanting") and the palatability of salt ("liking") independently in salt-sensitized rats. Breakpoint on a progressive ratio reinforcement schedule was used to measure salt wanting and taste reactivity was used to measure salt liking in rats with and without a history of Na+ depletion. Salt-sensitized rats displayed higher breakpoints relative to controls. However, a history of Na+ depletion was not associated with a greater positive shift in taste reactivity measures. The data suggest that these components of reward are separable in this model and support the general proposition that sensitization may alter wanting but not liking.
16472715	Withdrawal severity and voluntary alcohol consumption are inversely related in rats and mice. The present study demonstrated this empirical relation and extended it in two ways. First, the rats were selectively bred for low (LoS) and high (HiS) saccharin intake, a phenotype that correlates positively with ethanol intake and inversely with emotional reactivity. Withdrawal has not yet been studied in these rats. Second, proclivity to consume ethanol was measured as conditioned preference for an ethanol-paired flavor. After 2 weeks of forced exposure to ethanol and a period of abstinence, LoS rats showed elevated acoustic startle; HiS rats did not (Exp. 1). When ethanol- and no-ethanol solutions were available freely during conditioning, both LoS and HiS rats preferred a flavor paired with 4% ethanol, but only HiS rats preferred a flavor paired with 10% ethanol (Exp. 2A); when exposure to the two solutions was controlled, all groups except LoS males preferred flavors paired with 4% or 10% ethanol (Exp. 2B). Thus, as predicted, withdrawal was more severe in the line with less ethanol proclivity (LoS). These results implicate basic associative and affective processes in individual differences in patterns of alcohol use.
16445991	To maintain nutritional homeostasis, external food-related stimuli have to be evaluated in relation to the internal states of hunger or satiety. To examine the neural circuitry responsible for integration of internal and external determinants of human eating behaviour, brain responses to visual and complex gustatory food-related stimuli were measured using functional magnetic resonance imaging in 18 healthy non-smokers (10 women, 8 men). Each individual was studied on two occasions, the order of which was counterbalanced; after eating as usual and after 24 h fasting. Raised plasma free fatty acids and lower insulin and leptin concentrations confirmed that participants fasted as requested. When fasted, participants reported more hunger, nervousness and worse mood and rated the visual (but not gustatory) food-related stimuli as more pleasant. The effect of fasting on hunger was stronger in women than in men. No circuitry was identified as differentially responsive in fasting compared to satiety to both visual and gustatory food-related stimuli. The left insula response to the gustatory stimuli was stronger during fasting. The inferior occipito-temporal response to visual food-related stimuli also tended to be stronger during fasting. The responses in the occipito-temporal cortex to visual and in the insula to gustatory stimuli were stronger in women than in men. There was no interaction between gender and fasting. In conclusion, food reactivity in modality-specific sensory cortical areas is modulated by internal motivational states. The stronger reactivity to external food-related stimuli in women may be explored as a marker of gender-related susceptibility to eating disorders.
16412500	Lewis (LEW) and Fischer (F344) rat strains differ on a variety of physiological and behavioral endpoints, including reactivity to drugs of abuse. Although they differ in drug reactivity, such assessments are generally limited to morphine and cocaine. To determine if these differences generalize to other drugs, the present study examined these strains for their reactivity to the affective properties of nicotine, specifically their sensitivity to nicotine in the conditioned taste aversion preparation. For four or five conditioning cycles given every other day, rats from both strains were allowed access to saccharin and injected with nicotine (0.1, 0.4, 0.8 mg/kg) or vehicle. On intervening days, all rats were given access to water and injected with vehicle. Under this one-bottle training and testing procedure, neither strain displayed aversions at the lowest dose of nicotine (0.1 mg/kg). Aversions were evident for both strains at 0.4 and 0.8 mg/kg, although the F344 rats acquired the aversions at 0.4 mg/kg faster and displayed a significantly greater aversion at 0.8 mg/kg than subjects from the LEW strain. For both strains, aversions were evident at all doses (and in a dose-dependent manner) when subjects were given access to saccharin and water in a two-bottle test. There were, however, no strain differences on this test. Differences between the two strains in their acquisition of nicotine-induced taste aversions were discussed in the context of aversion assessments with other compounds as well as in relation to differences in the self-administration of nicotine in the two strains.
16386277	Anhedonia, a core symptom of clinical depression, refers to the loss of interest in normally rewarding stimuli; the chronic mild stress paradigm, an animal model of depression, was designed with this as an underlying feature. The procedure consists of the administration of a variety of ecologically relevant stressors over long durations. Its effects have been thoroughly investigated in male but not female rats. This study examines the appropriateness of stressors designed to evaluate the development and progression of depression in two strains of female rats, the effectiveness of two measures of anhedonia, and the relationship between stress reactivity and the estrous cycle. Changes in hedonic status were indexed for three weeks following a three week baseline period using two standard behavioral measures of anhedonia: sucrose intake and preference and thresholds for brain stimulation reward. Decreases in 24 h sucrose intake were observed in both strains during the first week of stress manipulations, and continued to decline thereafter for the remainder of the stress phase; in contrast, sucrose preference was unaffected by the stressors, indicating an overall reduction in fluid intake. No changes in the thresholds for brain stimulation reward were observed. The cyclical pattern of estrous was altered in both strains with a significant reduction in the number of regular cycles as a consequence of both the stressors and brain stimulation reward. Furthermore, cyclicity was not reinstated in many animals even six weeks after stress manipulations and behavioral tests had ceased. While the physiological measures suggest that the mild stressors are disruptive to female rats, the results of the behavioral tests are not consistent with the notion that the stressors induce an anhedonic state.
16266733	It has been suggested that reward "wanting" and "liking" are mediated by separable brain systems. To facilitate neuropharmacological and neurophysiological research on this issue we developed a behavioral task with putative measures of reward "wanting" and "liking" available on a trial-by-trial basis. We were able to test whether our measures were sensitive to changes in thirsty rats' "wanting" and "liking" of liquid reward by manipulating its delay, taste and volume. We found that three of our putative "wanting" measures (anticipatory errors, reaction time and reward collection latency) were affected by upcoming reward delay and/or taste and our putative "liking" measure (post-reward licking) was sensitive to variations in reward taste and volume. To cross-validate our measures with previous pharmacological work we tested rats following acute, systemic administration of drug compounds that globally enhance serotonin and noradrenaline (imipramine), dopamine (GBR 12909) and opioid (morphine) function. Imipramine augmented the effects of delay and taste on reward "wanting", GBR 12909 attenuated the effects of delay on reward "wanting" and the effects of taste on reward "liking", and morphine reduced the effect of delay on a measure of reward "wanting". Since morphine failed to affect reward "liking" but has been previously found to enhance reward "liking" in taste reactivity tests, our measure requires further pharmacological validation. However, this task shows potential to assess the specific neural mechanisms that contribute to the impact of reward parameters on "wanting" and "liking".
16257045	Previous studies have shown that prenatal exposure to a moderate dose of ethanol (2 g/kg) during the last days of gestation of the rat (17-20) not only increases postnatal intake of the drug but also enhances the palatability of ethanol's taste when measured with a taste reactivity test. Prenatal administration of the opioid antagonist naloxone, together with ethanol, reduces ethanol intake. The aim of the present study was to analyze whether this decreased intake of ethanol after the administration of naloxone is accompanied by a reduction in ethanol's palatability. Results show that preweanling rats exposed prenatally to ethanol alone displayed more ethanol intake and more ingestive responses in reaction to its taste than non-exposed pups. Simultaneous prenatal administration of naloxone with ethanol prevented both the increased intake of ethanol and the higher amount of appetitive responses to its taste. These results indicate that the opioid system plays an important role in the effect of enhanced palatability of ethanol's taste after its prenatal exposure. Results also support the hypothesis of a conditioned response established in utero as a consequence of the association between ethanol's chemosensory and reinforcing aspects, the latter mediated by the opioid system.
16249011	Dietary and body fat are essential for life. Fatty acids modulate fat detection, ingestion, digestion, absorption and elimination. Though direct effects occur throughout the body, much of this regulation stems from signals originating in the oral cavity. The predominant orosensory cue for dietary fat is textural, but accumulating electrophysiological, behavioral and clinical evidence supports olfactory and gustatory components. Orosensory stimulation with long-chain unsaturated, but possibly also saturated, fatty acids elicits an array of cephalic phase responses including release of gastric lipase, secretion of pancreatic digestive enzymes, mobilization of lipid stored in the intestine from the prior meal, pancreatic endocrine secretion and, probably indirectly, altered lipoprotein lipase activity. Combined, these processes influence postprandial lipemia. There is preliminary evidence of marked individual variability in fat "taste" with uncertain health implications. The possibility that fat taste sensitivity reflects systemic reactivity to fat warrants further evaluation.
16246529	The neurosteroid allopregnanolone may increase feeding by altering food palatability; however, it may also increase feeding by reducing anxiety (neophobia). Moreover, it is unclear whether this induced hyperphagia is selective to safe, palatable foods only. Male rats were injected with allopregnanolone 20 min prior to behavioral testing. The taste reactivity test was used to examine possible shifts in the palatability of a 0.3 M sucrose solution. A lickometer was used to monitor intake and licking of either a sucrose or sucrose-quinine solution. Sucrose palatability was not enhanced; however, allopregnanolone significantly increased sucrose intake and licking on Test Day 1 when the solution was novel, but not on Test Day 2 when the solution was familiar. Sucrose-quinine intake was not enhanced. Allopregnanolone-induced hyperphagia is not a result of altered sucrose palatability, but rather reflects a reduction in the neophobia elicited by a novel solution; an effect that further seems to be selective to safe, palatable foods.
16214027	Activation of the immune system with lipopolysaccharide (LPS) has been shown to result in decreased consumption of normally preferred substances while at the same time not affecting palatability. The present study examined the effects LPS administration on both intake and palatability of a relatively unpalatable bitter-sweet taste. Bitter is thought to signal a danger cue to an animal representing a potential toxin-containing food. Using a one-bottle consumption test, voluntary intake of a sucrose-quinine (0.15 M sucrose + 0.00015 M quinine; S-Q) solution was assessed in rats on two conditioning days (days 1 and 4) after a systemic injection with LPS, LiCl, or NaCl. On the test day (day 7), rats were given 1h access to the same solution in the absence of any injection. In a separate experiment, rats fitted with intraoral cannulae received similar testing schedules, however, the solution was delivered intraorally, activating only the consummatory responses of the animal. During conditioning, rats received 5 brief (1 min) intraoral infusions of the taste across a 1h period following injections of LPS, LiCl or NaCl. Individual taste reactivity responses were recorded and analyzed. Both LPS and LiCl resulted in decreased consumption of the unpalatable taste relative to controls on the test day, suggesting typical conditioned taste avoidance. When the consummatory responses were examined, LPS-treatment produced an increase in active oral rejection relative to NaCl- and LiCl-treated groups on both conditioning days. The present study demonstrates that although both LPS- and LiCl-treatment result in similar conditioned avoidance using an intake measure, they do not elicit similar patterns of taste reactivity responding to intraoral infusions of the bitter-sweet taste. Furthermore, the present results suggest that immune activation with LPS-treatment results in increased rejection of a mildly aversive stimulus and supports the hypothesis that reorganization of behavioral priorities occurs during bacteria-induced sickness.
16185725	The taste reactivity test was employed to determine the effect of pre-treatment with Delta9-Tetrahyrdrocannabinol THC on sucrose palatability. In Experiment 1, on each of 9 trials, rats were injected with THC or Vehicle prior to receiving a 5 min intraoral infusion of sucrose solution. The concentration of sucrose (2%, 10% or 32%) and the interval between the injection and the sucrose infusion (30, 60 or 120 min) were varied in a within-subjects design. THC enhanced the frequency of ingestion reactions only when administered 120 min prior to the taste reactivity test, regardless of sucrose concentration. In Experiment 2, the CB1 antagonist, SR141716, reversed the enhanced sucrose palatability produced by THC. These results suggest that the increased intake of palatable food 2 h, but not earlier, following administration of a low dose of THC may be the result of enhanced palatability and that this effect is the result of action of THC at the CB1 receptor.
15961147	Opioid agonists and benzodiazepine agonists each increase food intake. Both also increase hedonic 'liking' reactions to sweet tastes in rats. Do opioids and benzodiazepines share overlapping mechanisms of hedonic impact? Or are benzodiazepine and opioid effects on hedonic impact mediated by independent mechanisms? The present study examined whether blockade of opioid receptors prevents benzodiazepine-induced enhancement of taste palatability, as assessed by the affective taste reactivity test. Rats were implanted with oral cannulae, and prior to an oral infusion of bittersweet quinine-sucrose solution, all received i.p. injections of either vehicle, or diazepam alone (5 mg/kg diazepam+0 mg/kg naltrexone), naltrexone alone (1 mg/kg naltrexone+0 mg diazepam), or both diazepam plus naltrexone (5 mg/kg diazepam+1mg/kg naltrexone). Videotaped hedonic ('liking') and aversive ('disliking') orofacial reactions elicited by sucrose/quinine taste were compared across drug conditions. Diazepam administration alone more than doubled hedonic 'liking' reactions to the bittersweet taste, while reducing 'disliking' in half, compared to vehicle levels. Naltrexone by itself had little effect on taste-elicited affective reactions, and only marginally increased aversive gapes. However, naltrexone completely blocked diazepam's enhancement of positive hedonic 'liking' reactions, and naltrexone similarly disrupted diazepam-reduction of aversive 'disliking' taste reactions. These results indicate that endogenous opioid neurotransmission may be crucial to benzodiazepine enhancement of hedonic 'liking' for natural taste reward.
15948012	A growing body of evidence suggests that cannabinoid CB1 receptor antagonists have potential therapeutic utility as appetite suppressants. However, the specific mechanisms underlying the reduction in food intake produced by these drugs are not well understood.Considering the known antiemetic and motor-suppressive effects of CB1 agonists, the present studies were conducted to determine if the reductions in food intake induced by the CB1 antagonist AM 251 could result from nausea or impairments in intake-related motor control, rather than solely from appetite suppression.	Three experiments were conducted to examine the effects of AM 251 (2.0, 4.0, or 8.0 mg/kg or vehicle) on detailed parameters of food intake, on the development of conditioned taste avoidance, and on taste reactivity.	In the first experiment, acute administration of AM 251 dose-dependently decreased food intake; nevertheless, feeding rate (grams consumed per time spent eating) and food handling were unaffected, which suggests that food intake was not reduced because of severe motor impairments. In the second experiment, AM 251 dose-dependently reduced intake of a flavor with which it had previously been associated, indicating that conditioned taste avoidance had developed. Lastly, AM 251 was found to induce conditioned rejection reactions in a dose-dependent manner.	The CB1 antagonist AM 251 may reduce food intake in part by inducing nausea or malaise, but not because of incoordination or motor slowing related to feeding.	
15935458	Effects of the anxioselective anxiolytic abecarnil, a beta-carboline benzodiazepine-receptor agonist, on initial licking responses for a 3% sucrose solution and on taste reactivity responses were evaluated in adult male rats. The rats' behaviour was video recorded, and analysed according to a frame-by-frame procedure to generate the durations of categorized fixed action patterns, and the number and rate of licking responses. The results indicated that abecarnil (0.3-3.0 mg/kg, i.p.) significantly increased the number of licks in the first continuous sample of licking, while significantly reducing the lick rate (licks/s). Additionally, abecarnil selectively enhanced positive ingestive responses, but had no effect on either neutral or aversive response categories in taste reactivity measures. On the basis on this pattern of results, we conclude that abecarnil can enhance taste palatability selectively, and that it may act as an agonist at GABA(A) benzodiazepine receptor subtypes which mediate drug effects on ingestive behaviour.
15862524	In conditioned taste aversion (CTA), the animals learn to avoid a taste substance (conditioned stimulus, CS) which was previously associated with visceral distress (unconditioned stimulus, US). The present study examined the effects of administration of midazolam (MDZ), a benzodiazepine agonist, after the acquisition of CTA on the expression of CTA. After ingestion of 0.5 M sucrose (CS) was paired with an intraperitoneal (i.p.) injection of 0.15 M LiCl (US), control rats showed strong CTA to the CS. However, a systemic injection of MDZ (1.5 mg/kg, i.p.) before the retention test prevented conditioned animals from rejecting the CS, but in the subsequent retention tests where the drug was not administrated, those animals again showed strong aversions to the CS. Aversive taste reactivity patterns to the intraorally infused sucrose and 0.3 M dl-alanine in the conditioned animals were also diminished by the similar injection of MDZ, but not by a serotonergic anxiolytic agent, buspirone (2.5 or 5.0 mg/kg, i.p.). General taste sensory deficit might not be induced by MDZ because the drug injection did not impair conditioned aversions to 0.2 M NaCl and 0.01 M HCl. Infusion of MDZ into the basolateral nucleus of the amygdala (BLA) also attenuated conditioned aversions to sucrose. These results suggest that systemic or intra-BLA administrations of MDZ impair the expression of CTA selectively to sweet-tasting substances, implying that a transient MDZ-induced CTA expression deficit is due to the enhancement of palatability of CSs with preferable tastes rather than general anxiolytic or amnesic effects of MDZ.
15806925	During the last two decades it has been established that Greenland Eskimos living on their traditional diet, have a lower incidence of coronary heart disease (CHD) than when living in Denmark on a western diet. These findings have been attributed to their diet, particularly the high amounts n-3 polyunsaturated fatty acids. The Eskimo diet consists mainly of meat and blubber of seal and whale and relatively small amounts of fish. Another aspect of the Eskimo diet, still not fully explored, is that the Eskimos consume the bulk of their food raw or dried, seldom boiled or exposed to excessive heat. The main task of modern processes is to make edible and stable products. Removal of molecules that cause off-flavours or taste to improve sensory attributes may, for instance, destroy potent antioxidants. Modern meal preparing techniques may also lower the content of biologically active components. The objective of our experiments has been, by mimicking in part the traditional Eskimo diet, to explore the beneficial effects of raw food items on parameters related to development of CHD. Reduced tendency of developing arteriosclerosis has been related to the lower reactivity of platelets and less production of proinflammatory products, e.g. cytokines, prostaglandins and leukotrienes. In our study, healthy volunteers ingested raw or heat processed marine materials (smoked versus heat processed salmon muscle, cold pressed versus refined marine oils).
15770108	Previous studies have shown that prenatal exposure during gestational days 17 to 20 to low or moderate doses of ethanol (1 or 2 g/kg) increases alcohol intake in infant rats. Taking into account that higher consumption does not necessarily suggest a preference for alcohol, in the present study, the hedonic nature of the prenatal experience was analyzed further with the use of a taste reactivity test.General activity, wall climbing, passive drips, paw licking, and mouthing in response to intraoral infusions of alcohol, water, and a sucrose-quinine solution (which resembles alcohol taste in rats) were tested in 161 preweanling 14-day-old rat pups that were prenatally exposed to 0, 1, or 2 g/kg of alcohol during gestational days 17 to 20. Consumption of those substances was measured during the taste reactivity test and on postnatal day 15.	Pups that were prenatally exposed to both doses of ethanol displayed lower levels of general activity and wall climbing than controls in response to ethanol. Infant rats that were treated prenatally with both doses of ethanol showed higher intake of the drug and also more mouthing and paw licking in response to ethanol taste. Only pups that were exposed to the higher ethanol dose in utero generalized those responses to the sucrose-quinine compound.	These results seem to indicate that for the infant rat, the palatability of ethanol is enhanced after exposure to the drug during the last days of gestation.	
15763581	Decrease in food intake is one of the most documented non-specific symptoms of inflammatory processes. However, attention has been mainly focused on quantitative analysis. The present paper reports studies undertaken to test the possible contribution of changes in taste processes in inflammatory-induced alteration of feeding behavior. In a first experiment, the effects of lipopolysaccharide-induced sickness were assessed on preference for saccharin and aversion for quinine in rats using the two-bottle test paradigm. In a second experiment, effect of lipopolysaccharide (LPS) on the behavioral reactivity to palatable, unpalatable and mixed solutions was analyzed using the taste-reactivity paradigm. Our results show that LPS decreased total fluid intake but did not change taste responses to unpalatable or palatable substances. However, LPS increased aversive reactions and decreased hedonic responses to mixed taste. These LPS-induced changes are interpreted as an increase in finickiness and are discussed in regard to their potential role in the adaptation of individuals to sickness.
15708786	Calcium-deprived rats have elevated intakes of CaCl2, other calcium salts, and some non-calcium compounds. We used taste reactivity to examine the effects of calcium deprivation on the palatability of CaCl2 and other solutions. Nine male Sprague-Dawley rats were calcium-deprived by maintenance on a low-calcium diet, and eight replete rats were used as controls. All rats were videotaped during intraoral infusion of the following solutions: 30 and 300 mM CaCl2, 30 mM calcium lactate, 100 and 600 mM NaCl, 30 mM MgCl2, 1 mM quinine.HCl, 2.5 mM sodium saccharin, and deionized water. We counted individual orofacial and somatic movements elicited by the infusions and used them to calculate total ingestive and aversive scores. Relative to controls, calcium-deprived rats gave a significantly larger number of tongue protrusions and had higher total ingestive scores for CaCl2, calcium lactate, NaCl, and MgCl2. Our results suggest that CaCl2, calcium lactate, NaCl, and MgCl2 taste more palatable to rats when they are calcium-deprived than replete, and this may be responsible for the increased intake of these solutions following calcium deprivation.
15652396	Lithium chloride (LiCl) and morphine both produce a conditioned taste avoidance response, while only LiCl is able to elicit a conditioned rejection response (taste reactivity), indicating that the effects of conditioning are drug and preparation dependent. The present experiments extend this assessment to another behavioral preparation, schedule-induced polydipsia (SIP), by examining the ability of LiCl and morphine to produce conditioned suppression of nonregulatory drinking. In Experiment 1, schedule-induced saccharin consumption was followed by LiCl or morphine (at doses comparably effective in conditioning taste avoidance under water deprivation) or by the distilled water vehicle. Although both LiCl and morphine suppressed SIP, morphine produced a significantly weaker suppression than did LiCl. Using a massed feeding design in which animals received all their food pellets in a single meal, Experiment 2 determined that LiCl and morphine were equally effective in suppressing consumption, indicating that the differential effects seen under SIP were due to the schedule of spaced food pellet deliveries. The basis for the differential effects of LiCl and morphine on SIP may be a function of an increase in the reinforcing properties of drugs of abuse (such as morphine) within this procedure that mask the acquisition and/or display of the conditioned suppression. If so, then this procedure may be useful in assessing the reinforcing properties of such drugs.
15617317	Saliva is an essential body fluid. It is important in maintaining oral health, taste acuity, mastication, deglutition and digestion, oral flora regulation, oral cleansing, voice acuity, and speech articulation. Saliva is composed largely of water but also contains minerals, electrolytes, buffers, enzymes, growth factors, cytokines, immunoglobulins, proteins, and metabolic waste products, with the concentrations and compositions of these components varying by individual. Many systemic disorders can affect salivary function, greatly compromising oral health. One such disorder is Sjögren's Syndrome (SS), an autoimmune exocrinopathy characterized by oral and ocular dryness with or without impairment of other organ systems. SS can cause substantial serologic autoimmune reactivity and in some instances is associated with other connective-tissue autoimmune disorders, such as rheumatoid arthritis, scleroderma, or systemic lupus erythematosus. SS increases the risk for developing malignant non-Hodgkin's lymphoma. Treatment of this syndrome consists of a combination of multiple agents, depending on the degree of symptomatology: cholinergic agonists, artificial salivary substitutes, nonsteroidal anti-inflammatory agents, antirheumatic drugs, and biologic agents. This article describes saliva and salivary function, the pathogenesis of SS, the current treatment of xerostomia, and quality of life issues related to salivary dysfunction.
15607993	Preclinical studies indicate that dopaminergic transmission in the basal ganglia may be involved in processing of both pleasant and unpleasant stimuli. Given this, the aim of the present study was to assess taste responses to sweet, bitter, sour, and salty substances in patients with Parkinson's disease (PD).Rated intensity and pleasantness of filter paper discs soaked in sucrose (10-60%), quinine (0.025-0.5%), citric acid (0.25-4.0%), or sodium chloride (1.25-20%) solutions was evaluated in 30 patients with PD and in 33 healthy controls. Paper discs soaked in deionised water served as control stimuli. In addition, reactivity to 100 ml samples of chocolate and vanilla milk was assessed in both groups. Taste detection thresholds were assessed by means of electrogustometry. Sociodemographic and neuropsychiatric data, including cigarette smoking, alcohol consumption, tea and coffee drinking, depressive symptoms, and cognitive functioning were collected.	In general, perceived intensity, pleasantness, and identification of the sucrose, quinine, citric acid, or sodium chloride samples did not differ between the PD patients and controls. Intensity ratings of the filter papers soaked in 0.025% quinine were significantly higher in the PD patients compared with the control group. No inter-group differences were found in taste responses to chocolate and vanilla milk. Electrogustometric thresholds were significantly (p = 0.001) more sensitive in the PD patients.	PD is not associated with any major alterations in responses to pleasant or unpleasant taste stimuli. Patients with PD may present enhanced taste acuity in terms of electrogustometric threshold.	
15596426	The aim of the present study was to evaluate the effects of acute and chronic exposure to alcohol on taste responses to a prototypic umami substance, monosodium glutamate (MSG).The rated intensity and pleasantness of MSG taste (0.03-10.0%) was compared in chronic male alcoholics (n = 35) and control subjects (n = 25). In a separate experiment, the effects of acute exposure of the oral mucosa to ethanol rinse (0.5-4.0%) on MSG taste (0.3-3.0%) were studied in 10 social drinkers.	The alcoholic and control group did not differ in terms of the rated intensity and pleasantness of MSG taste. Electrogustometric thresholds were significantly (P < 0.01) higher, i.e. worse, in the alcohol-dependent subjects. The difference remained significant after controlling for between-group differences in cigarette smoking and coffee drinking. Rinsing with ethanol did not alter either intensity or pleasantness of MSG taste in social drinkers.	The present results suggest that: (i) neither acute nor chronic alcohol exposure modifies taste responses to MSG; (ii) alcohol dependence may be associated with deficit in threshold taste reactivity, as assessed by electrogustometry.	
15528928	Spices are the most attractive ingredients to confer an authentic taste to food. As they are derived from plants, they harbour allergenic potency and can induce symptoms ranging from mild local to severe systemic reactions. Due to the content of pharmacologically active substances of spices, the diagnosis of allergy and the differentiation from intolerance reactions may be difficult. Association with inhalative allergies via IgE cross-reactivity, but also direct gastrointestinal sensitization plays a role. This article is a botanical and allergological overview of the most important spices and molecules responsible for eliciting IgE-mediated reactions or cross-reactions. As no curative treatments are known at present, strict avoidance is recommended and, therefore, accurate labelling of pre-packed food is necessary.
15506891	Three experiments examined the effect of acute naltrexone treatment on both taste reactivity and consumption of ethanol in high ethanol-preferring rat lines: Alko Alcohol-Accepting (AA) rats (Experiments 1 and 2) and Alcohol-Preferring (P) rats (Experiment 3). A 3.0 mg/kg naltrexone dose was ineffective at altering ethanol palatability for either line, whereas 7.5 mg/kg was effective at reducing palatability of 10% ethanol for AA, but not P, rats, as reflected by both a decrease in ingestive responding and an increase in aversive responding. The effects of naltrexone on ethanol consumption were quite consistent: At both dosages, acute naltrexone treatment significantly decreased consumption of 10% ethanol. Termination of naltrexone resulted in an immediate increase in ethanol consumption to control levels. Results show that ethanol palatability and consumption can be dissociated in the rat and that the organization of opioidergic mechanisms that mediate ethanol responses may vary between rat lines.
15451656	Animal studies suggest that induction of depression-like states may alter preference for sweet tastants. A major goal of the present study was to search for correlations between depressive symptoms measured by the Beck Depression Inventory (BDI) and taste responses to sweet and bitter substances. Thirty-three nonclinical volunteers rated intensity and pleasantness of chocolate and vanilla milk as well as of sucrose- and quinine-soaked filter paper disks. Reactivity to citric acid (sour) and sodium chloride (salty) was also tested with the paper disk methodology. Taste detection thresholds were assessed by means of electrogustometry. A weak inverse relationship was found between the BDI scores (range: 3-33) and rated intensity of paper disks soaked in 60% sucrose. No correlations were found between depressive symptoms and intensity, pleasantness or identification of the other samples. Similarly, there was no relationship between the BDI scores and responses to chocolate and vanilla milk. BDI scores were not associated with electrogustometric thresholds. These data suggest that depressive symptoms may not influence taste reactivity in nonclinical population.
15371751	The effects of lipopolysaccharide (LPS) and LiCl on conditioned taste aversion acquisition using intraoral infusions as the method of taste delivery was examined. Rats received two pairings of an intraorally delivered sucrose (5 ml) taste with the effects of a systemic injection of LPS, LiCl or NaCl. The magnitude of conditioning was quantified by scoring taste reactivity responses to a brief intraoral infusion of sucrose in the absence of any drug injection. Rats previously conditioned with LiCl or LPS displayed clear evidence of conditioned aversion with increased oral rejection responses relative to saline controls. Our results suggest activation of the immune system with LPS can condition consummatory aspects of ingestion when this conditioning involves intraoral fluid presentation.
15313030	The present experiment examined the individual and combined effects of systemic injection and oral ingestion of lithium chloride (LiCl) on both within and across session shifts in palatability. Male rats fitted with intraoral cannulae received two conditioning days in which they were injected with either LiCl or sodium chloride (NaCl) and were then presented with brief intraoral infusions of a sucrose plus LiCl or NaCl solution. The individual taste reactivity responses during the intraoral infusions were videotaped and later analyzed for response frequency. Forty-eight hours after the second conditioning day the same sucrose plus salt solution was presented again in the absence of any injection. The present results demonstrate that systemic injections of LiCl result in profound within session and across session decreases in ingestive responding accompanied by increased active and passive aversive responses. Animals receiving LiCl by injection as well as ingestion demonstrated an exaggerated response. Rats which received LiCl only through intraoral infusions produced the same pattern of decreased ingestive responding to the sucrose plus salt flavored tastant on each test trial suggesting little or no across session conditioning effects. A two process model by which animals may regulate toxicosis is discussed.
15302133	Newborn humans are known to show specific facial expressions in response to various kinds of taste stimuli and are presumed to be able to discriminate those kinds of tastes from just after birth. As the closest relatives to humans, the taste reactivity (threshold, preference and taste-elicited facial expression) of non-human primates has long been of great interest. To date, however, there have been few investigations in newborn non-human primates. In the present study, we investigated the facial expressions elicited in response to four basic taste stimuli, sweet, salty, sour and bitter, in the newborns of two non-human primate species, rhesus macaques and chimpanzees. The taste-elicited facial expressions were compared among the kinds of taste stimuli and between the two species. Rhesus macaques of less than 7 days old showed different patterns of facial expressions for water/sweet than for bitter, and chimpanzees less than 30 days old did so for sweet and bitter. The differences between these two species were evident in the presence and absence of certain facial expressions and the emerging patterns of certain components for each stimulus. In particular, chimpanzee response patterns to the bitter stimulus resembled to those of humans rather than rhesus macaques. Overall, rhesus macaques and chimpanzees responded differently to the same kinds of tastes, presumably reflecting differences in their evolutionary backgrounds.
15219332	Nicotine and alcohol may have common neurobiological mechanisms of reinforcement. Therefore, withholding one substance might result in compensatory increases in self-administration of the other. This laboratory study investigated the effects of brief tobacco deprivation on alcohol cue-elicited urges to drink, corresponding psychophysiological reactions, and alcohol consumption. Young adults (N=78) who were moderate to heavy smokers and drinkers were stratified and randomized to a 2 x 2 design. Participants were either deprived of tobacco for 5 h or not deprived and then exposed to in vivo alcohol or control beverage cues. Subsequently, participants engaged in a taste-rating task as an unobtrusive measure of alcohol consumption. Tobacco deprivation resulted in increased urge to smoke and decreased cardiovascular responses but did not increase alcohol urges or alcohol consumption. Results indicate that brief tobacco deprivation does not result in compensatory increases in alcohol consumption among young moderate to heavy drinkers.
15135013	This study was aimed at investigating the coping style of mice subjected to a subchronic unpredictable mild stress procedure and its relationship to initial emotional reactivity. Two inbred strains of mice, the BALB/c ByJ and the C57BL/6 J, known to exhibit distinct emotionality, have been used. They were first observed in the elevated plus-maze and the free exploratory paradigm, each provides a separation of the population in high and low emotional mice. Half of the mice of each strain were then confronted to a 2-week subchronic unpredictable mild stress and tested for their responses in different behavioural situations (consumption of a palatable food, physical state, grooming behaviours and reactivity to a conflict situation). Mice were also tested in the light/dark procedure to assess the effect of the subchronic stress on emotional reactivity. First, a relationship between initial emotional reactivity in the elevated plus-maze and behavioural coping style in response to stress was found, high emotional mice (i.e., BALB mice) displaying inhibited behaviours and less emotional mice (i.e., BL/6 mice) exhibiting few behavioural changes. Furthermore, emotional reactivity was increased in stressed mice compared with nonstressed ones.
15078563	Rab proteins are small GTPases involved in intracellular trafficking. Among the 60 different Rab proteins described in mammals, Rab3a is the most abundant in brain, where it is involved in synaptic vesicle fusion and neurotransmitter release. Rab3a constitutive knockout mice (Rab3a(-/-)) are characterized by deficient short- and long-term synaptic plasticity in the mossy fiber pathway and altered circadian motor activity, while no effects on spatial learning have been reported so far for these mice. The goals of this study were to analyse possible behavioral consequences of the lack of synaptic plasticity in the mossy fiber pathway using a broad battery of sensitive behavioral measures that has been used previously to analyse the behavior of Gdi1 mice lacking a protein thought to regulate Rab3a. Rab3a(-/-) mice showed normal acquisition but moderately impaired platform reversal learning in the water maze including reference memory and episodic-like memory tasks. A mild deficit in spatial working memory was also observed when tested in the radial maze. Analysis of explorative behavior revealed increased locomotor activity and enhanced exploratory activity in open field, O-maze, dark/light box and novel object tests. Spontaneous activity in normal home cage settings was unaffected but Rab3a(-/-) mice showed increased motor activity when the home cage was equipped with a wheel. No differences were found for delayed and trace fear conditioning or for conditioned taste aversion learning. Congruent with earlier data, these results suggest that Rab3a-dependent synaptic plasticity might play a specific role in the reactivity to novel stimuli and behavioral stability rather than being involved in memory processing. On the other hand, the phenotypic changes in the Rab3a(-/-) mice bore no relation to the behavioral changes as observed in the Gdi1 mice. Such divergence in phenotypes implies that the putative synaptic interaction between Gdi1 and Rab3a should be reconsidered and re-analysed.
15001020	A robust finding in eating research is the so-called counterregulation in restrained eaters. This means that while normal subjects eat less during a taste test, after they consumed a preload, restrained eaters consume more. An explanation is that food exposure causes stronger physiological preparatory reactivity in the restrained eaters. This reactivity is experienced as craving and leads to an increased food intake. To test this theory, 46 high and low restrained eaters were exposed to food or soap, while physiological measurements were made. Afterwards, the subjects performed a taste test, during which food intake was secretly measured. Unrestrained eaters showed an increase in heart rate, gastric activity, and saliva during food exposure; however, restrained eaters did not. Gastric activity significantly correlated with food intake. Group or exposure type did not influence food intake. It can be concluded that unrestrained eaters prepared for food intake, whereas the restrained eaters did not. A possible explanation is that restrained eaters used cognitive suppression to block physiological responding, thereby controlling their food intake.
15000982	Overweight is becoming more common in children, but we know nearly nothing about the eating behavior of overweight children. Learning theory predicts that overeating follows from learned associations between the smell and taste of palatable food on the one hand and intake on the other hand. It was tested whether overweight children overeat after confrontation to these cues. They indeed failed to regulate food intake after both the exposure to the intense smell of tasty food (without eating it) and after eating a small preload of appetizing food, whereas normal-weight children decreased their intake after both cues. Overweight children are thus more vulnerable to triggers of overeating. Their overeating was not related to psychological factors like mood, body esteem, and a restrained eating style, but it was related to cue-elicited salivation flow. Apart from supporting the cue reactivity model of overeating, the data point to an interesting satiety phenomenon in normal eaters after prolonged and intense smelling palatable food without eating it.
14994885	Upper removable appliances (URA), as well as full dentures, are known to be the cause of various complaints related to oral handling of food and beverages, phonation and vocalization, in addition to general discomfort. To test the hypothesis that taste and flavour perception might also be affected by URA, 22 young orthodontic patients (10 males and 12 females aged 11.5 +/- 1.7 years; experimental group) wearing URA and 17 subjects (seven males and 10 females aged 11.6 +/- 2.0 years; control group) not wearing any orthodontic appliances were presented with a battery of eight intra-oral gustatory and three retro-nasal flavour stimuli. The subjects in the experimental group were tested on three different occasions and those in the control group on two occasions. All participants were required to label verbally the perceived taste and flavour sensations, as well as to estimate the palatability and intensity of the perceived sensation on a 100 mm visual analogue scale (VAS). Means and standard deviations were calculated from the individual values and then compared between the two groups and among the different testing times. Statistical significance was assessed with a level of confidence set at 0.025. The results revealed no significant difference between the indicative values chosen to represent taste and flavour reactivity, neither between the groups nor among different dates of testing within each group. Orthodontists should therefore encourage patients to also use the URA during meals, without any detrimental effect on taste and/or flavour perception.
14757501	The aim of this study was to prepare and to investigate acetaminophen taste-masked granules obtained in a high-shear mixer using three different wet granulation methods (method A: water granulation, method B: granulation with a polyvinylpyrrolidone (PVP) binding solution and method C: steam granulation). The studied formulation was: acetaminophen 15%, alpha-lactose monohydrate 30%, cornstarch 45%, polyvinylpyrrolidone K30 5% and orange flavour 5% (w/w). In vitro dissolution studies, performed at pH 6.8, showed that steam granules enabled the lower dissolution rate in comparison to the water and binding solution granules; these results were then confirmed by their lower surface reactivity (D(R)) during the dissolution process. Moreover, the results of the gustatory sensation test performed by six volunteers confirmed the taste-masking effects of the granules, especially steam granules (P<0.001). Morphological, fractal and porosity analysis were then performed to explain the dissolution profiles and the results of the gustatory sensation test. Scanning electron microscopy (SEM) analysis revealed the smoother and the more regular surface of steam granules with respect to the samples obtained using methods A and B; these results were also confirmed by their lower fractal dimension (D(s)) and porosity values. Finally, differential scanning calorimetry (DSC) results showed a shift of the melting point of the drug, which was due to the simple mixing of the components and not to the granulation processes. In conclusion, the steam granulation technique resulted a suitable method to comply the purpose of this work, without modifying the availability of the drug.
14749139	In the present study, young (5-month-old (mo)) and aged (24 mo) adult male Fischer-344 (F344) rats were assigned to experimental groups based upon their performance of a reference memory task in the Morris water maze and reactivity to a novel palatable taste in a gustatory neophobia task. Levels of norepinephrine (NE) and its metabolite 3-methoxy-4-hydroxy-phenylglycol (MHPG) were assayed via high performance liquid chromatography (HPLC) in brain regions associated with the locus coeruleus (LC)-hippocampus-cortex system and A1/A2-hypothalamic system. Binding of ligands specific for alpha-1, alpha-2, beta-1, and beta-2 receptors was assessed in hippocampus and cortex with receptor autoradiography. Impaired acquisition and retention of the water maze task and gustatory neophobia in aged rats was primarily associated with decreased NE activity in cingulate cortex (CC) as indicated by a significant reduction in the MHPG/NE ratio coupled with increased NE content. No significant changes in adrenergic receptor binding were detected in any region sampled. The results suggest that an aging-related reduction in cortical NE neurotransmission is associated with the expression of increased neophobia and deficits in spatial learning and memory performance occurring with advanced age in rats.
14714932	The Short Sensory Profile was used to assess parental report of sensory reactivity across four groups of young children (n = 102). Groups were autism (n = 26), fragile X syndrome (n = 20), developmental disabilities of mixed etiology (n = 32), and typically developing children (n = 24). Groups were comparable on overall mental age (x = 22 months), and clinical groups were comparable on chronological age (x = 31 months). Significant differences were detected at alpha <.01 for tactile sensitivity [F(3,99) = 10.01], taste/smell sensitivity [F(3,99) = 11.63], underreactive/seeks stimulation [F(3,99) = 4.56], auditory filtering [F(3,99) = 19.67], and low energy/weak muscles [F(3,99) = 14.21]. Both children with fragile X syndrome and children with autism had significantly more sensory symptoms overall than the two comparison groups, and children with autism did not differ significantly from children with fragile X syndrome. Both groups were more impaired than developmentally delayed and typically developing children in tactile sensitivity and auditory filtering. Children with autism were more abnormal in responses to taste and smell than all other groups. Children with fragile X syndrome were more abnormal than all other groups in low energy/weak muscles. Sensory reactivity of children with developmental delays was comparable to mental age-matched typically developing toddlers. Correlational analyses indicated that neither overall developmental level nor IQ was related to abnormal sensory reactivity in children with autism or general developmental disorders. However, abnormal sensory reactivity had a significant relationship with overall adaptive behavior.
14684243	Feeding and drinking typically involve both appetitive and consummatory behaviors. Appetitive behaviors include those behaviors produced by an animal prior to the actual consumption, such as approach movements, whereas consummatory behaviors (such as licking and chewing) are involved in the actual consumption of food. The present research compared the gustatory conditioning effects of bacterial lipopolysaccharide (LPS) and lithium chloride (LiCl) in two different paradigms, conditioned taste avoidance and conditioned taste aversion which differentially affect the appetitive and consummatory components of feeding. Male rats were implanted with intraoral cannulae and habituated to a water deprivation schedule and afterwards received two conditioning days (Days 1 and 4). Each conditioning day consisted of 1 h access to a novel sucrose solution (0.3 M) immediately followed by a systemic injection of LPS (200 microg/kg), LiCl (0.15 M, 3 meq) or NaCl vehicle. Conditioned taste aversion was assessed using the taste reactivity test on Day 7, where orofacial and somatic responses were videotaped and analyzed during 3 brief (1 min) exposures to the sucrose solution. Conditioned taste avoidance was assessed on Days 8 and 9 using a two-bottle preference test (sucrose versus water). Animals conditioned with LiCl displayed typical aversive-like responses in the taste reactivity paradigm evidenced by significant reductions in positive ingestive responses (P<0.05) and an increase in active aversive responses (P<0.05) relative to controls. Furthermore, LiCl treatment resulted in conditioned avoidance of sucrose in the two-bottle preference test characterized by a decreased sucrose preference (P<0.05). Conditioning with LPS produced a reduced sucrose preference (P<0.05) relative to controls, comparable to the avoidance seen in LiCl-treated rats. In contrast, conditioning with LPS resulted in similar positive ingestive responses to intraorally infused sucrose as seen in controls. The present results demonstrate that LPS treatment produces conditioned avoidance but not aversion and suggest that LPS can selectively condition the appetitive aspects of feeding whereas the consummatory behaviors remain unaffected.
14561867	What is the role of dopamine in natural rewards? A genetic mutant approach was taken to examine the consequences of elevated synaptic dopamine on (1) spontaneous food and water intake, (2) incentive motivation and learning to obtain a palatable sweet reward in a runway task, and (3) affective "liking" reactions elicited by the taste of sucrose. A dopamine transporter (DAT) knockdown mutation that preserves only 10% of normal DAT, and therefore causes mutant mice to have 70% elevated levels of synaptic dopamine, was used to identify dopamine effects on food intake and reward. We found that hyperdopaminergic DAT knockdown mutant mice have higher food and water intake. In a runway task, they demonstrated enhanced acquisition and greater incentive performance for a sweet reward. Hyperdopaminergic mutant mice leave the start box more quickly than wild-type mice, require fewer trials to learn, pause less often in the runway, resist distractions better, and proceed more directly to the goal. Those observations suggest that hyperdopaminergic mutant mice attribute greater incentive salience ("wanting") to a sweet reward in the runway test. But sucrose taste fails to elicit higher orofacial "liking" reactions from mutant mice in an affective taste reactivity test. These results indicate that chronically elevated extracellular dopamine facilitates "wanting" and learning of an incentive motivation task for a sweet reward, but elevated dopamine does not increase "liking" reactions to the hedonic impact of sweet tastes.
13129831	Considerable evidence suggests that the mesolimbic dopaminergic system is an important substrate for the rewarding effects of ethanol consumption. Previous data have demonstrated that pharmacological agents that alter dopamine signaling also influence the self-administration of ethanol. The present experiments were designed to assess the role of the dopamine-3 receptor (D3-R) on voluntary ethanol consumption in C57BL/6 mice. Mice with targeted disruption of the D3-R gene (D3-R - /-) were compared to wild-type controls in an ethanol intake paradigm. In Experiment 1, mice had 24-hour access to ethanol each day in a two-bottle choice paradigm for a period of 7 days per concentration. The concentrations tested were 3, 6, 10 and 15%. In Experiment 2, mice had I hour of access to ethanol each day in a two-bottle paradigm for a period of 7 days per concentration. The same concentrations in Experiment I were compared in Experiment 2. In Experiment 3 we sought to test the development of a conditioned taste aversion (CTA) after receiving an intraperitoneal (ip.) injection of 2.0 g/kg ethanol. In Experiment 4, blood ethanol levels where assessed following a 2.0 g/kg ip.injection of ethanol. Experiment 5 assessed taste preference for saccharine and quinine in wild-type and D3-R -/- mice. Contrary to our predictions, both D3-R -/- and wild-types on a CS57BL/6 background had similar intakes of ethanol, at all concentrations tested, in the 24-hour and 1-hour intake paradigms. Wild-type and D3-R -/- mice respond to injected ethanol similarly by developing a conditioned taste aversion. Metabolic analysis revealed mutant mice are slower in metabolizing a bolus injection of ethanol. Lastly, wild-type and D3-R -/- mice showed similar consumption to increasing concentration of both sweet and bitter tastes. These data suggest that deletion of the D3-R gene does not increase ethanol consumption above that found on the C57BL/6 genetic background. Furthermore, the D3-R -/- mice adequately learn a CTA to ethanol and do not ham differing taste reactivity to saccharin or quinine. However, D3-R -/- mice do appear to have a slower rate of ethanol metabolism.
12972953	The aim of this study was to analyse the genetic basis of excessive ethanol consumption and its relationship with emotional reactivity. The high-ethanol preferring line of rats used is characterized by a: (i) high voluntary consumption of alcohol; (ii) high sensitivity to taste reinforcement (saccharine, quinine); (iii) high locomotor activity in a novel environment; and (iv) low emotional reactivity, these features being opposite in the Wistar-Kyoto (WKY) rat strain. The F2 population demonstrated a very large variability in these behavioural traits, and factor analysis revealed that these characteristics appear to be largely unrelated to each other. The molecular bases for these differences were investigated by quantitative trait loci (QTL) analysis. For this purpose, the 196 F2 rats were genotyped with regularly distributed markers on the whole genome, and genetic linkage maps were generated for all subsequent QTL analyses. A locus with a maximum LOD score of 7.6 and accounting for approximately 61% of the genetic variance of the trait in the F2 population was detected on chromosome 4 for alcohol drinking. In the same region, we found a QTL related to the reinforcement properties of saccharin, with a significant LOD score of 4.9 and explaining 46% of the variance of the trait. Other significant QTL were found for plus maze behaviour and open field activity on chromosome 1. Current research aims to identify the gene(s) involved.
12931785	QTL search in a segregating F2 intercross between HEP (High-Ethanol Preferring line) and wistar-kyoto (WKY, a low-alcohol consuming strain) rats identified a locus on chromosome 4 linked to the consumption of a 5% alcohol solution offered as a free choice with water (Terenina-Rigaldie et al. submitted). In order to confirm and analyse the influence of this locus, F2 rats were selected according to their genotype at the markers flanking the QTL and bred in order to obtain two groups of rats homozygous HEP/HEP ('HIGH' line) or WKY/WKY ('LOW' line) at the QTL, the rest of the genome being randomly inherited from one or the other founder strain. These two groups of animals displayed large differences in emotional reactivity (open field, elevated-plus maze), sensitivity to taste reinforcers (saccharin, quinine) and alcohol consumption (either forced or as a free choice with water). These results confirm the influence of this locus on alcohol intake and emotional reactivity traits, and suggest a pleiotropic effect of the gene(s) involved. Current research aims at the identification of this (these) gene(s).
12882375	The terms conditioned taste avoidance and conditioned taste aversion are often used interchangeably in the literature; however, considerable evidence indicates that they may represent different processes. Conditioned taste avoidance is measured by the amount that a rat consumes in a consumption test that includes both appetitive phases and consummatory phases of responding. However, conditioned taste aversion is more directly assessed with the taste reactivity test, which includes only the consummatory phase of responding. Rats display a conditioned taste aversion as conditioned rejection reactions (gapes, chin rubs, and paw treads) during an intraoral infusion of a nausea-paired flavored solution. Treatments that produce nausea are not necessary for the establishment of taste avoidance, but they are necessary for the establishment of taste aversion. Furthermore, treatments that alleviate nausea modulate neither the establishment nor the expression of taste avoidance, but they interfere with both the establishment and the expression of taste aversion. Considerable evidence exists indicating that these two measures are independent of one another. Taste avoidance may be motivated by conditioned fear rather than conditioned nausea, but taste aversion (as reflected by rejection reactions) may be motivated by conditioned nausea.
12815759	In transgenic neurotrophin-3 lacZ-neo (NT-3(lacZneo)) mice, in which the coding region for NT-3 is replaced by Eschericia coli lacZ, the expression of beta-galactosidase faithfully mimics the expression of NT-3 (Vigers AJ, Baquet ZC, Jones KR [2000], J Comp Neurol 416:398-416). During embryonic and early postnatal development, beta-galactosidase is detected in the olfactory system, beginning at embryonic day 11.5 in the nasal epithelium and at embryonic day 16.5 in the olfactory bulb. Levels of beta-galactosidase rise with age, reaching a peak during the second postnatal week, when beta-galactosidase reactivity is visible in up to 50% of the glomeruli. As the animal matures, the beta-galactosidase levels decline, but staining remains present in axons and cell bodies of a specific subset of olfactory receptor neurons (ORNs) projecting to a limited subset of glomeruli. The heavily labeled ORNs do not follow the typical OR expression zones in the epithelium but appear similar to the "patch" expression pattern of mOR37 receptors. The most heavily reactive glomeruli exhibit a striking reproducible pattern in the ventral olfactory bulb (OB). Some glomeruli of the OB contain calcitonin gene-related peptide (CGRP)-immunoreactive fibers of the trigeminal nerve. However, double-label immunocytochemistry for CGRP and beta-galactosidase rendered no correlation between trigeminal innervation and the degree of innervation by NT-3-expressing ORNs. Thus, the timing and presence of beta-galactosidase in a subset of ORNs suggests that NT-3 plays a role in synaptogenesis and/or synapse function in a specific subset of ORNs within the olfactory bulb.
12772172	The interaction between taste sensitivity and emotionality in rats provides a provocative view of hyperactivity. Rats that have been bred selectively for their reactivity to saccharin exhibit characteristic emotionality. When placed on restrictive diets, these rats exhibit excessive activity levels, relative to rats that are not sensitive to saccharin. Because humans who are highly arousable (i.e., reactive to environmental stimuli) also exhibit an increase in sensitivity to saccharin's bitterness, the current study evaluated whether women who are highly arousable, currently dieting, and sensitive to saccharin's bitterness engage in excessive exercise.Participants completed a questionnaire packet, which assessed emotionality, eating patterns, and exercise patterns. On another occasion, they completed a body contour drawings handout, and their weight and height were measured. They also rated saccharin's bitterness and sweetness following a stressful event.	As hypothesized, sensitivity to saccharin's bitterness predicted overactivity in highly arousable female dieters, which reveals the multidimensionality of activity anorexia.	
12713649	Non-adaptive activation of dopamine transmission in the nucleus accumbens shell by drugs of abuse has been attributed a fundamental role in the mechanism of drug addiction. In order to test this hypothesis, we compared in the same subject the effect of an addictive drug (ethanol) and of taste stimuli, including ethanol's own taste, on dialysate dopamine in the nucleus accumbens shell as an estimate of dopamine transmission and on taste reactivity as an expression of motivational valence. Ethanol was also monitored in the dialysates. In naive rats, intraoral infusion of a 20% sucrose + chocolate solution elicited a monophasic increase of dialysate dopamine immediately after the intraoral infusion. In contrast, intraoral infusion of 10% ethanol, 10% ethanol + 20% sucrose or 10% ethanol + 20% sucrose + chocolate solutions elicited a biphasic increase of nucleus accumbens dopamine with an early taste-related rise and a late rise related to dialysate ethanol. Pre-exposure to the ethanol solutions 24 h before resulted in the absence of the early dopamine rise and permanence of the late dopamine rise. This late dopamine rise was actually increased as compared with that of the nonpre-exposed group when sucrose-containing ethanol solutions were tested. The results indicate that single trial pre-exposure to the ethanol solutions differentially affects the responsiveness of nucleus accumbens shell dopamine to the direct intracerebral action of ethanol and to the effect of its taste with potentiation, or no change of the first and abolition of the second. These observations point to the existence of major differences in the adaptive regulation of nucleus accumbens dopamine transmission in the shell after drug as compared with taste reward. These differences, in turn, are consistent with a role of nucleus accumbens shell dopamine in the mechanism of the behavioural effects of addictive drugs.
12623544	Changes in palatability of tastes and flavours as a result of flavour preference conditioning were examined. In Experiment 1, when tastes were paired with glucose in a reverse-order differential conditioning paradigm, rats acquired conditioned preferences for CS(+) and displayed more hedonic responses to CS(+) than to CS(-) in a postconditioning taste reactivity test. In Experiment 2, rats that received oral infusions of flavours as CSs during a reverse-order conditioning procedure expressed both palatability shifts and conditioned preferences for CS(+). Rats that received a forward conditioning procedure acquired a preference for CS(+), but the palatability of CS(+) was unchanged. In Experiment 3, hungry rats drank mixtures of a flavour CS and a calorific or sweet tasting reinforcer in a long-exposure conditioning paradigm. When tested hungry, rats preferred CS(+) whether they had acquired flavour-calorie or flavour-taste associations. However, CS(+) became more palatable only for rats that acquired flavour-calorie associations. These results suggest that acquisition of flavour preferences, as measured by 2-bottle tests, may not always be accompanied by enhanced palatability.
12619913	Pairing a novel taste with provocative vestibular stimulation results in conditioned taste aversions in both rats and humans. Vestibular system involvement in gustatory conditioning was examined in sham-lesioned or labyrinthectomized rats. Three conditioning trials consisted of 30 min access to asaccharin (0.1%) solution followed by 30 min of rotation (70 rpm) or sham rotation. In a taste reactivity test with saccharin, rotated sham-lesioned rats, but not labyrinthectomized rats, exhibited increased oral rejection reactions compared with control rats. When conditioned with lithium chloride, both labyrinthectomized and sham-lesioned rats displayed robust conditioned rejection reactions. The finding that normal vestibular function is necessary in obtaining rotation-induced conditioned taste aversions supports the face and construct validity of a rat model of motion sickness.
12605071	This article presents the proceedings of a symposium at the 2002 RSA/ISBRA Meeting in San Francisco, California, co-organized by Julie A. Mennella and Alexander A. Bachmanov of the Monell Chemical Senses Center. The goal of this symposium was to review the role that chemosensory factors (taste, smell, and chemical irritation) play in the perception, preference, and consumption of alcohol. The presented research focused on both humans and laboratory animals and used a variety of approaches including genetic, developmental, pharmacological, behavioral, and psychophysical studies. The presentations were as follows: (1) Introduction and overview of the chemical senses (Julie A. Mennella and Alexander A. Bachmanov); (2) Taste reactivity as a measure of alcohol palatability and its relation to alcohol consumption in rats (Stephen W. Kiefer); (3) Early learning about the sensory properties of alcohol in laboratory animals (Juan Carlos Molina); (4) Early learning about the sensory properties of alcohol in humans (Julie A. Mennella); (5) Genetic dissection of the ethanol-sweet taste relationship in mice (Alexander A. Bachmanov and Michael Tordoff); and (6) Human genetic variation in taste: connections with alcohol sensation and intake (Valerie B. Duffy and Linda M. Bartoshuk). The symposium concluded with a general discussion.
12576130	In order to determine the respective roles of conditioned food aversion, satiety and palatability, we studied behavioral responses to a 50% total milk protein diet, compared with those to a normal protein diet containing 14% total milk protein. Different paradigms were employed, including meal pattern analysis, two-choice testing, flavor testing, a behavioral satiety sequence (BSS) and taste reactivity. Our experiments showed that only behavioral and food intake parameters were disturbed during the first day when an animal ate the high-protein (P50) diet, and that most parameters returned to baseline values as soon as the second day of P50. Rats adapted to P50 did not acquire a conditioned taste aversion (CTA) but exhibited satiety, and a normal BSS. The initial reduction in high-protein diet intake appeared to result from the lower palatability of the food combined with the satiety effect of the high-protein diet and the delay required for metabolic adaptation to the higher protein level.
12576119	Eating is influenced by both the hedonic preferences and reinforcing value of food. Incentive salience theory predicts these are separate influences. This study tested whether hedonics reliably change as a function of increasing the reinforcing value of food by deprivation in 17 non-obese, non-dietary restrained females. Baseline measures of hedonics for pleasant (chocolate milk), unpleasant (lemon juice) and neutral (water) tastes were determined under deprived conditions. Participants were then randomly assigned to fed or maintained in deprived conditions, and after food consumption, a second determination of hedonics was obtained, followed by assessing the reinforcing value of food. Hedonics was measured by subjective ratings and behavioral observations in a taste reactivity paradigm. Results showed food was more reinforcing for the deprived than the fed group, but no influences of group were observed for the subjective or objective hedonic measures. These results suggest that hedonics and the reinforcing value of food are separate processes in humans, and they may independently influence eating behavior.
12576114	Nutrient-conditioned flavors preferences are thought to involve an increase in flavor palatability (hedonic evaluation). Consistent with this view is the recent finding that a sweet flavor paired with intragastric glucose infusions elicited more hedonic taste reactivity (TR) responses than did an alternative sweet flavor paired with intragastric water. The generality of this finding was examined by conditioning preferences for inherently avoided nonsweet flavors. Rats were trained in 20 h/day and then 30 min/day sessions with a CS+ flavor (sour citric acid or bitter sucrose octaacetate) paired with intragastric 16% glucose infusion, and the opposite flavor (CS-) paired with intragastric water. Glucose conditioning increased the CS+ acceptance in one-bottle tests and produced a 95% CS+ preference in two-bottle sessions. Yet, TR responses to brief intraoral infusions of the two CS flavors did not differ, even after extensive testing. Subsequent choice tests revealed that a 1% fructose solution was preferred to the CS-, whereas the CS+ was preferred to 1% and 2% fructose and equally preferred to 4%, 8%, and 16% fructose. These results indicate that strong nutrient-conditioned flavor preferences are not always associated with increased flavor palatability as measured by TR tests. Therefore, nonhedonic processes, perhaps increased incentive salience, appear to mediate the enhanced preference and acceptance conditioned by postingestive nutrient actions.
12573685	Research on reactivity to alcohol cues yielded conflicting results. While some authors report differences in subjective or physiological responses to drug-related stimuli between addicts and healthy controls, other researchers found no group differences in response patterns. Moreover, a dissociation of self-report and psychophysiological measures of cue reactivity is often observed. To some extent, this might be due to confounding stimulus type (neutral vs. drug-related) and stimulus intensity in cue reactivity research. The purpose of the present study is to match alcoholic and nonalcoholic stimuli according to their empirically assessed intensity. Stimulus intensity is estimated by magnitude estimation. Results clearly indicate that alcohol-related cues differ considerably from water and other neutral stimuli with respect to perceived intensity. Moreover, estimation of stimulus intensity depends on mode of presentation (smell vs. combined smell and taste). Results of previous cue reactivity studies in the alcohol field might have been affected in different degrees by confounding stimulus type and intensity.
12501929	Most of the factors initiating food or fluid intake have already been studied, but much less is known about those terminating ingestion. We have hypothesised that discomfort originating from the gastrointestinal system may be one of those factors. Gut distension cause pain if the intestinal volume changes but merely discomfort if only the tension of the gut wall increases. It seems that mild unpleasantness (i.e. discomfort) arising from the gut as a result of moderate (quasi-isometric) distension, among and in concordance with other factors, may significantly reduce intake and hence contribute to physiological satiety. The arising discomfort can be detected by measuring the amount and rate of the ingestion, by recording and analysing ingestive behavior by taste-aversivity and taste-reactivity tests, etc. Conclusions of all experiments point to the same direction: tension increase in the gut wall causes discomfort and results in decrease of intake, i.e. satiety.
12397512	Corticotropin-releasing factor (CRF) plays an integral role in mediating stress responses and anxiety. However, little is known regarding the role of CRF in ethanol consumption, a behavior often associated with stress and anxiety in humans.The present study sought to determine the role of CRF in ethanol consumption, locomotor sensitivity and reward by examining these behaviors in C57BL/6J x 129S mice with a targeted disruption in the gene encoding the CRF prohormone.	Male wild-type and CRF-deficient mice were given concurrent access to ethanol and water in both limited and unlimited-access two-bottle choice paradigms. Taste reactivity (saccharin or quinine vs water) was examined in a similar manner under continuous-access conditions. Blood ethanol levels and clearance were measured following limited ethanol access as well as a 4-g/kg i.p. injection of ethanol. Locomotor stimulant effects of ethanol were measured in an open-field testing chamber, and the rewarding effects of ethanol were examined using the conditioned place preference paradigm.	CRF-deficient mice displayed normal body weight, total fluid intake, taste reactivity and blood ethanol clearance, but consumed approximately twice as much ethanol as wild types in both continuous- and limited-access paradigms. CRF-deficient mice failed to demonstrate a locomotor stimulant effect following acute administration of ethanol (2 g/kg i.p.), and also failed to demonstrate a conditioned place preference to ethanol at 2 g/kg i.p., but did display such a preference at 3 g/kg i.p.	CRF deficiency may lead to excessive ethanol consumption by reducing sensitivity to the locomotor stimulant and rewarding effects of ethanol.	
12167557	It has been shown repeatedly that opioid dependence is associated with increased consumption of refined sugars. It is possible that this association results from altered taste reactivity in opioid-dependent subjects. Thus, in the present study, we compared taste responses to sweet, bitter, sour and salty solutions in methadone-maintained opioid-dependent men and healthy control subjects. The two groups did not differ in terms of rated intensity or pleasantness of sucrose (1-30%), quinine (0.001-0.005%), citric acid (0.02-0.1%) and sodium chloride (0.18-0.9%) solutions. Proportions of 'sweet-likers', i.e. subjects rating a 30% sucrose (0.88 M) solution as the most pleasant, were also similar in both groups. In line with the previous findings, the methadone-maintained subjects reported adding more table sugar to caffeinated beverages. The results of the present study suggest that changes in taste reactivity may not be responsible for altered dietary choices in opioid addicts.
12124755	Cholecystokinin (CCK), neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), and galanin all are known to have central effects on food intake. Immunocytochemistry was used to examine the presence of these substances within the primary gustatory nuclei of the goldfish, including the vagal lobe, which is a large, laminated structure composed of discrete sensory, fiber, and motor layers. The vagal lobes receive primary afferent input from the gustatory portion of the vagus nerve and contain reflex circuitry involved in the ingestion or rejection of potential food items. Immunohistochemistry indicates a heavy concentration of CCK-, CGRP-, NPY-, and galanin-immunoreactive fibers in the capsular fiber layer as well as in deeper sensory layers of the vagal lobe. CGRP immunoreactivity throughout the sensory layers and capsular immunoreactivity for CCK are greatly reduced 1-2 weeks following vagus nerve transection, indicating that the majority of these fibers are primary sensory afferents. In contrast, NPY and galanin immunoreactivity in the capsular fiber layer and reactivity for CCK, NPY, and galanin in the deeper sensory and fiber layers are relatively unaffected by vagus transection. CCK-, NPY-, and galanin-immunoreactive fibers and puncta also were present in the motor layers, as were CGRP-immunoreactive motor somata. CCK-immunoreactive cell bodies are present in layer III and layer VII/VIII of the vagal lobe and in the superficial granular layer of the lateral subnucleus of the commissural nucleus of Cajal, which is caudally contiguous with the vagal lobe.
12106830	Naltrexone, an opioid antagonist, has been shown to reduce the palatability of 10% alcohol solutions in rats, as measured by taste reactivity. In the present study, the effect of acute naltrexone treatment on taste reactivity to a variety of taste solutions and concentrations was tested to determine whether naltrexone has generalized effects on taste responsiveness. Thirty minutes before a taste reactivity test, rats were injected with either naltrexone (3 mg/kg; n = 15) or saline (n = 15). On separate days, rats were tested with distilled water and three concentrations each of sucrose (0.1, 0.5, and 1.0 M), sodium chloride (0.06, 0.10, and 0.30 M), quinine hydrochloride (0.0005, 0.001, and 0.005 M), and alcohol [10%, 20%, and 40% (vol./vol.)]. In Experiment 1, naltrexone consistently reduced the palatability of alcohol and sodium chloride solutions (across concentrations), as reflected by a decrease in ingestive responding and an increase in aversive responding. Naltrexone increased aversive responding for sucrose but did not affect ingestive responding for these solutions. Finally, there was no significant effect of naltrexone on responding to quinine hydrochloride. A second experiment with naive rats and five concentrations of sucrose (0.01, 0.05, 0.1, 0.5, and 1.0 M) replicated the initial data: Across concentrations, naltrexone produced a significant increase in aversive responding but did not alter ingestive responding. In Experiment 3, naive rats were tested with five concentrations of quinine hydrochloride (0.00001, 0.00005, 0.0001, 0.0005, and 0.005 M). Results indicated that naltrexone significantly altered taste reactivity to the bitter solutions (less ingestive responding and more aversive responding), particularly at the lower concentrations. The results indicate that naltrexone treatment has significant effects on taste reactivity to some aqueous solutions (alcohol, sodium chloride), regardless of solution concentration. The effects of naltrexone on sucrose and quinine reactivity are more difficult to describe because the drug effects seemed to be dependent on the specific measure examined (ingestive vs. aversive responses) and the concentration of the solution. These results support the suggestion that naltrexone has a fairly generalized effect on taste reactivity to taste solutions; specifically, naltrexone seems to make solutions more aversive, as revealed by a decrease in ingestive responding and an increase in aversive responding.
12076722	A review of previous results and the new data in this report show clearly that the Falk model of adjunctive behavior is an adequate analogue of human alcoholism and can be applied to induce excessive ethanol consumption. New data on the consumption of sweet flavored ethanol solutions and, especially, sweet alone solutions during brief periods of ethanol withdrawal provide some significant insights concerning the possible physiological basis for cravings in humans. Because voluntary consumption of ethanol is the normal process by which alcoholism develops, a general set of environmental and other experimental conditions that produce behavioral excess; adjunctive behavior, electrical stimulation of the brain, and salt arousal of drinking are discussed in some detail. Neuronal circuits of the lateral hypothalamus are important because some of the cells are chemosensitive and monitor osmolality of the blood and initiate drinking in the normal regulation of body fluids. Alcohol in very small amounts has a direct effect on these cells that also project to lower spinal motor neurons and modulate the level of excitability in spinal reflexes and thereby reactivity to environmental stimulation. Taste and other sensory information from the mouth arrives in presynaptic endings on these same cells by a multitude of indirect multisynaptic pathways. A theoretical model is developed to explain how tactile and taste sensory information and what is initially a nonspecific general state of motor arousal interact together to produce an excessive consumption or craving for ethanol.
12062321	Intraventricular infusion of neuropeptide Y (NPY) decreases the amount female rats ingest during intraoral infusion (consummatory behavior) of a 1-M solution of sucrose at a rate of 0.5 ml/min and simultaneously increases the number of times the rats visit a bottle filled with sucrose (appetitive behavior). In this study, we investigated if the suppression of consummatory behavior was dependent upon the increase of appetitive behavior. The shift from consummatory to appetitive ingestive behavior was attenuated by adding 3-mM quinine HCl (QHCl) to the sucrose solution in the bottle. However, the intraoral intake of the sucrose solution was still decreased in NPY-treated rats. NPY did not modify taste reactivity as measured by aversive responses during continuous intraoral infusion of sucrose or ingestive and aversive responses to brief intraoral infusion of sucrose (0, 0.3 or 1 M) or QHCl (0, 0.3 or 3 mM). NPY stimulated visits to a bottle and intake from the bottle and inhibited sexual behavior in male rats but had no effect on the sexual behavior in the absence of a bottle. The visits and the intake were suppressed, but sexual behavior was not activated by adding QHCl (3 mM) to the solution in the bottle. Obstructing appetitive ingestive behavior, therefore, does not indiscriminately facilitate consummatory behavior. Male rats showed aversive or ingestive behavior and sexual behavior simultaneously during intraoral infusion of QHCl or condensed milk. It is suggested that NPY decreases intraoral intake and increases appetitive ingestive behavior via partially separable mechanisms that are independent of taste aversion.
11989853	From the 38th developmental stage of the tadpole of Rana esculenta the process of tongue formation consists in the fast growth of the lining of the oral cavity floor anteriorly and faucially. This process is accompanied by the development of taste organs on the dorsal side of the tongue. At developmental stages 39-42 taste disc anlages are covered by a layer of ordinary epithelial cells. At these stages, in some cells of a taste disc single synaptic-like vesicles with an electron-dense core appear. Apart from that, as early as at stage 42 differentiation of the cells of a taste disc can be observed at the ultrastructural level. It is only at the 44th stage that all cell types characteristic for the mature TD can be distinguished in TEM (i.e., taste cells, basal cells and three kinds of associate cells: mucous, wing and sustentacular). Starting from that stage changes in the cell membrane can be observed indicating the presence of afferent synaptic junctions. The antibody used in the experiment was raised against neuron-specific enolase (NSE). At each of the developmental stages investigated (38, 42, 45) nerve fibres within the connective tissue beneath the epithelium of a taste disc anlage were immunopositive for NSE. From stage 42 onwards neural elements present in the basal part of the epithelium of a taste disc anlage were also NSE-positive. Basal cells did not show immuno-reactivity for NSE at any of the developmental stages investigated.
11958946	The opioid antagonist naltrexone, at doses of 1 and 3 mg/kg, has been shown to decrease the palatability and consumption of 10% ethanol in rats. However, a dose of 0.5 mg/kg of naltrexone has produced equivocal results. The purpose of the present study was to clarify the effects of low doses of naltrexone (0.0 [control], 0.25, 0.50, 0.75, and 1.0 mg/kg) on palatability and consumption of 10% ethanol. Sixty-four, male, Long-Evans hooded rats were divided into five groups matched for ethanol consumption. Each rat was injected over four consecutive days with one of five doses of naltrexone exactly 30 min before taste reactivity testing with 10% ethanol. When reactivity testing was completed, rats were acclimated to drink during a period of restricted access to fluid under conditions of mild fluid deprivation. Then, on four consecutive test days, rats were injected with naltrexone 10 min before 10% ethanol was made available for 30 min. Although each dose of naltrexone decreased ingestive responding to 10% ethanol over four days, this effect was not statistically reliable. However, all doses of naltrexone produced significant increases in aversive responding to the ethanol solution. Naltrexone, at the three highest doses, produced significant decreases in consumption of 10% ethanol. These results were consistent with the interpretation that naltrexone, even at low doses, reliably reduces palatability and consumption of 10% ethanol.
11925064	The present study examined the relationship between ethanol-induced conditioned taste aversion (CTA) and ethanol oral self-administration (OSA) in male and female rats (N = 183) from three related strains not genetically selected for their ethanol preference and differing in their emotional reactivity profile. The strains used were the Wistar Kyoto (WKY), Spontaneously Hypertensive (SHR) and Wistar Kyoto Hyperactive (WKHA). We hypothesized that differences between strains in sensitivity to the aversive properties of alcohol could explain the different propensities to drink alcohol solutions.All animals were given three conditioning trials consisting of 20-minute access to saccharin solution followed by saline or ethanol injections (0.5, 1 or 1.5 g/kg, intraperitoneally). Animals subsequently had free access to ethanol OSA for 3 weeks, followed by two CTA trials.	Ethanol injections produce a dose-dependent reduction of saccharin consumption in all animals; moreover, the strength of the CTA is gender- and strain-dependent. Taste avoidance induced by ethanol injections disturbed the initiation of ethanol OSA in two strains (WKY and WKHA) but did not change subsequent long-term ethanol consumption in either strain. In addition, voluntary alcohol drinking experience does not attenuate ethanol-induced CTA, and no association was found between ethanol-induced CTA and ethanol OSA.	The data confirm the large variation among strains and between genders in alcohol drinking and taste-aversion learning, but suggest that there is no relationship between the sensitivity to the aversive properties of alcohol and alcohol drinking.	
11897257	These experiments sought to distinguish whether increased calcium intake during pregnancy and lactation in the rat is due to arousal of a specific calcium appetite, with altered taste hedonics, as occurs with sodium depletion, to reduced taste sensitivity, or to the hyperdipsia of reproduction. We find that, during pregnancy and lactation, CaCl(2) intake is not increased more (in fact less) than intakes of control tastants, MgCl(2) and quinine HCl, and multiparous dams do not have a greater calcium intake than primaparous dams. Changes in taste reactivity to CaCl(2) and to NaCl do not correlate with changes in intake of these minerals during pregnancy or lactation, suggesting that alterations in hedonics or sensitivity do not explain the increased intake of these minerals. Taken together with the increased intake of all the tastants, it may be that the increased intakes of calcium and sodium during reproduction are not due to respective specific appetites or to a general mineral appetite but rather to the reproduction-increased ingestion that may meet all the dam's increased mineral and nutrient requirements. Differences in the degree of increased intakes of tastes may be due to specific alterations in their transduction during reproduction.
11890958	Rats selectively bred on the basis of saccharin intake also differ on some measures of emotional reactivity. The present studies were designed to contribute to our understanding of this association. Rats selectively bred for relatively high (HiS) versus low (LoS) saccharin intake were tested in two paradigms useful in assessing the ability to respond adaptively to internal perturbations of metabolic regulation or to external events that may produce metabolic challenges. The first study concerned slow-onset (regular insulin) and rapid-onset (2-deoxy-D-glucose [2-DG], fast-acting insulin) glucoprivation and resultant feeding behavior. LoS and HiS lines did not differ in response to saline or slow-onset challenges, but LoS rats ate less in the first half hour after rapid-onset challenges; the line differences were eliminated by pretreatment with caffeine. The second study revealed significantly higher plasma corticosterone (CORT) among LoS rats relative to HiS rats, both in the light and in the dark. Preliminary assessments after a single stressor and a single dose of dexamethasone showed, respectively, CORT elevation and suppression that was comparable in the two lines. These results add further support to the ideas that voluntary consumption of saccharin is related to the expression of classically defined emotional behaviors, and that responsiveness to diverse metabolic challenges may share a common basis, such as genetic pleiotropism.
11862377	When paired with morphine, rats suppress their intake of saccharin solution, but not a less palatable salt solution. The reward comparison hypothesis argues that when a taste is paired with morphine, intake of the solution is expected to decrease as the palatability of the taste increases. Therefore, morphine should more effectively suppress intake of salt solution in rats that are conditioned in a sodium-deprived state than in rats that are conditioned in a sodium-replete state.The present experiments evaluated the effect of furosemide-induced sodium deprivation on morphine and lithium-induced salt (experiment 1) and saccharin (experiment 2) avoidance and salt taste reactivity (experiment 4).	Rats were injected with furosemide or saline 21 h prior to access to salt solution (experiments 1 and 3) or saccharin solution (experiment 2). Immediately following access to the solution, the rats were injected with saline, morphine or lithium chloride solution. In experiments 1 and 2, a two-bottle test measured the strength of the taste preference/avoidance. In experiments 3 and 4, the taste reactivity test evaluated the furosemide-induced unconditional palatability changes for salt solution (experiment 3) and the conditional palatability changes for salt previously paired with morphine or lithium (experiment 4).	Sodium depletion induced by furosemide pretreatment conditionally enhanced subsequent preference for salt solution using both the taste avoidance test (experiment 1) and the taste reactivity test (experiment 4). Salt-lithium associations, but not salt-morphine associations, suppressed salt preference. However, the salt-morphine (40 mg/kg) association enhanced salt preference (in both experiments 1 and 4) when rats were conditioned in a sodium-deprived state. In experiment 2, morphine-saccharin associations resulted in conditioned saccharin avoidance regardless of pretreatment condition.	When the palatability of salt was enhanced by sodium depletion, morphine produced a mild conditioned salt preference in both a two-bottle preference test and enhanced ingestion reactions in the taste reactivity test, but morphine produced conditioned saccharin avoidance.	
11790409	Rats learn to prefer a flavor that is paired with intragastric (IG) glucose infusion, which may represent a learned shift in the hedonic evaluation or palatability of the flavor. The present study used the taste reactivity (TR) test to infer nutrient-conditioned changes in flavor palatability. Rats were first conditioned in 20-h/day and then 30-min/day sessions to associate a flavored saccharin solution (the CS+) with IG infusions of 16% glucose, and a different flavored saccharin solution (the CS-) with IG water infusions. They strongly preferred the CS+ to the CS- in two-bottle intake tests. When next tested with brief intraoral (IO) infusions of the CS flavors, the rats exhibited significantly more hedonic TR responses to the CS+ flavor than the CS- flavor, which indicates an enhanced hedonic evaluation. A subsequent series of two-bottle tests established that the CS- flavor was equally preferred to 3% fructose, whereas the CS+ flavor was equally preferred to 16% fructose. In addition, the difference between the TR responses to 3% and 16% fructose paralleled the difference between the TR responses to CS- and CS+. These findings support the idea that pairing flavored saccharin with the postingestive effects of glucose produces a learned shift in palatability comparable to that produced by increasing the concentration of a sugar solution.
11790398	The aim of this work was to study the negative effects of the intestinal stimulation by a method that is sensitive to assess internal malaise and discomfort. Effects of volumetric and "isometric" gut distension on the behavior were compared in the small and the large intestines, respectively. Chronically separated (Thiry-Vella) intestinal loops prepared from the upper jejunum and/or from the uppermost segment of the colon were stimulated with a rubber balloon. Conditioned taste aversion (CTA) series were accompanied with recording satiety and aversive behavioral indexes. Both isometric and volumetric stimuli elicited taste aversion. No essential differences between the two intestinal parts were found. Behavioral indices supported intake data: satiety indexes were similar to each other, whereas aversive indexes were high during stimulation and lower during testing. Data were consistent over conditions and time, proving the reliability of the method. Results are compared to earlier taste reactivity records.
11704264	We have reported that a diazepam binding inhibitor (DBI)-like peptide is released by the aversive quinine stimuli 'Chem. Senses 25 (2000) 739'. To determine the effect of DBI on the fluid intake, we injected a DBI peptide fragment into the fourth ventricle in mice. DBI suppressed the intake of 5% sucrose, water and 0.9 mM quinine-HCl and the preference for 0.05% saccharin. Administration (i.p.) of flumazenil, a benzodiazepine receptor antagonist, 20 min before the injection of DBI (i.c.v.) antagonized the suppressive effect of DBI on the intake and the preference for saccharin. We also studied the dose dependency of the effect of DBI on the intake of 5% sucrose. Injection of DBI in excess of 3 microg suppressed the intake of 5% sucrose in mice. Furthermore, injection of DBI (i.c.v.) increased the aversive response to 0.9% NaCl in the taste reactivity in mice. These results suggest that DBI affect the preference to food.
11684058	Rats in which a ligation of the bile duct (BDL) was paired with a saccharin taste developed a persistent conditioned taste aversion in both preference and taste reactivity tests. All BDL animals regardless of pairing had increased c-Fos-like immunoreactivity (FLI) in the area postrema and the nucleus of the solitary tract. This FLI may reflect the illness associated with BDL, but there was no evidence of conditioned FLI.
11517277	The involvement of dopamine (DA) in conditioned taste aversion (CTA) learning was studied with saccharin or sucrose as the conditioned stimulus (CS) and intraperitoneal lithium as the unconditioned stimulus (US). The dopamine D(1) antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH 23390) (12.5-50 microg/kg, s.c.), given 5 min after the CS, impaired the acquisition of CTA in a paradigm consisting of three or a single CS-lithium association. SCH 23390 failed to impair CTA acquisition given 45 min after, 30 min before, or right before the CS. (-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5a-benzo-(d)-naphtho-(2,1b) azepine (SCH 39166) (12.5-50.0 microg/kg, s.c), a SCH 23390 analog that does not bind to 5HT(2) receptors, also impaired CTA. No significant impairment of CTA was obtained after administration of the specific D(2)/D(3) antagonist raclopride (100 and 300 microg/kg, s.c.). The ability of SCH 23390 to impair CTA learning was confirmed by its ability to reduce the conditional aversive reactions to a gustatory CS (sweet chocolate) as estimated in a taste reactivity paradigm. SCH 39166 impaired CTA also when infused in the nucleus accumbens (NAc) shell 5 min after the CS. No impairment was obtained from the NAc core or from the bed nucleus stria terminalis. The results indicate that D(1) receptor blockade impairs CTA learning by disrupting the formation of a short-term memory trace of the gustatory CS and that endogenous dopamine acting on D(1) receptors in the NAc shell plays a role in short-term memory processes related to associative gustatory learning.
11487423	To investigate the role of sensitivity to reward in mediating social drinkers' reactivity to alcohol cues.A standard cue-reactivity paradigm was employed. Two groups of social drinkers (heavy and light) were assessed after exposure to the sight, smell and taste of a neutral cue (water) and then an alcohol cue (glass of beer).	Sessions were conducted in a laboratory based environment.	Twenty heavy (12 males, eight females) and 18 light social drinkers (seven males, 11 females) were recruited; mean age was 23.6 years.	The Card Arranging Reward Responsivity Objective Test (CARROT), assessing behavioural responsiveness to a monetary incentive; urge to drink; positive affect; and the BAS scales, assessing sensitivity to reward.	Heavy drinkers displayed a significant increase in responsivity to rewards (i.e. CARROT) and self-reported urge to drink, but not positive affect, after exposure to alcohol. For the heavy drinkers, heightened sensitivity to reward (i.e. BAS scales) was significantly related to cue-elicited urge to drink and positive affect.	The results are consistent with a conditioned appetitive motivational model of alcohol use and suggest that Gray's theory of personality may be of some benefit in explaining variation in reactivity responses.	
11396520	Altered motivation for drugs of abuse is a central feature of most definitions of drug dependence and the impact of drug-related cues on motivation is of current interest. However, since most studies of cue-reactivity have not used behavioural measures of motivation, their results are often difficult to interpret in motivational terms. In the current paper we describe two experiments in which a behavioural technique, based on multiple variable interval (VI) schedules of reinforcement, was used to study motivation for alcohol in human subjects. In both experiments, subjects attended for several sessions and, during each session, were exposed to a 6-ply VI schedule (values ranged from 1 to 720 s), during which they earned points that were later exchanged for a preferred beer or lager. In Experiment 1 the procedure was validated by showing that changes in the magnitude of reinforcement altered behaviour appropriately. In Experiment 2 we found evidence that the presence of an alcohol-related cue increased the value of alcohol rewards. The results are discussed with reference to a model for the behavioural effects of drug-related cues in triggering relapse and a number of problems we found in using the multiple variable interval schedule procedure.
11348834	Studies have shown that animals prenatally exposed to ethanol (E) exhibit deficits in conditioned taste aversion as well as displaying hypothalamic-pituitary-adrenal (HPA) hyperresponsiveness during exposure to stressors. In contrast, postnatal handling has been shown to attenuate both emotional and HPA reactivity under certain conditions. The present study tested the hypothesis that handling could attenuate adverse effects of prenatal ethanol exposure on consummatory behavior and HPA activity in a conditioned taste aversion task. We found that both prenatal ethanol exposure and handling independently increased saccharin consumption over 5 days of pretoxicosis exposure, suggesting that neophobia decreased at a faster rate in these animals. When conditioned aversion was assessed in handled animals under nondeprived conditions, E animals showed increased consumption compared to controls. Furthermore, across prenatal groups, lower corticosterone (CORT) levels were found in handled compared to nonhandled animals during reexposure under food-deprived conditions, emphasizing the importance of assessing both behavior and HPA function when examining an animal's response to a task and indicating that handling may not be effective at attenuating some deficits in E animals.
11344340	Foods produced through agricultural biotechnology, including such staples as corn, soybeans, canola, and potatoes, are already reaching the consumer marketplace. Agricultural biotechnology offers the promise to produce crops with improved agronomic characteristics (eg, insect resistance, herbicide tolerance, disease resistance, and climatic tolerance) and enhanced consumer benefits (eg, better taste and texture, longer shelf life, and more nutritious). Certainly, the products of agricultural biotechnology should be subjected to a careful and complete safety assessment before commercialization. Because the genetic modification ultimately results in the introduction of new proteins into the food plant, the safety, including the potential allergenicity, of the newly introduced proteins must be assessed. Although most allergens are proteins, only a few of the many proteins found in foods are allergenic under the typical circumstances of exposure. The potential allergenicity of the introduced proteins can be evaluated by focusing on the source of the gene, the sequence homology of the newly introduced protein to known allergens, the expression level of the novel protein in the modified crop, the functional classification of the novel protein, the reactivity of the novel protein with IgE from the serum of individuals with known allergies to the source of the transferred genetic material, and various physicochemical properties of the newly introduced protein, such as heat stability and digestive stability. Few products of agricultural biotechnology (and none of the current products) will involve the transfer of genes from known allergenic sources. Applying such criteria provides reasonable assurance that the newly introduced protein has limited capability to become an allergen.
11282139	Estrogen treatment can suppress the intake of a previously presented gustatory conditioned stimulus (CS). This finding has been interpreted as an estrogen-induced conditioned taste aversion. However, a distinction must be made between taste aversion and taste avoidance. In particular, tastes are only considered aversive if they elicit a stereotypic behavioral response, otherwise the reduction in intake is classified as an avoidance. Although aversive orofacial responses have been reported in male rats after taste-estrogen pairings, they have not been examined in ovariectomized female rats. The goal of the present investigation, then, was to use similar procedures to determine whether conditioned aversion also mediates the estrogen-induced reduction of intake in female rats. Animals were introduced to a novel 0.1% saccharin solution and immediately thereafter were given a subcutaneous injection of vehicle or estradiol benzoate (10 microg). Responses were assessed using a two-bottle preference test, a one-bottle acceptance test, and a taste reactivity (TR) test. The results confirmed previous reports of a reduced preference for saccharin after saccharin-estradiol pairing using the two-bottle test. The reduction in intake during the one-bottle test, however, was not accompanied by stereotypic aversive responses, such as gaping. Surprisingly, a similar reduction in intake also occurred when using a backward conditioning procedure in which estrogen was injected before, rather than after, CS access. Thus, the present results show that the suppressive effects of estrogen reflect an avoidance, rather than aversion and, moreover, that the reduced intake may be due to an unconditioned, rather than a conditioned, response.
11195999	The mechanisms of naltrexone's effects on urges to drink during abstinence are unclear. Naltrexone may suppress either urges to drink specifically or appetitive responses in general. The effects of naltrexone on cue reactivity to alcoholic and sweet nonalcoholic beverages were investigated. Alcohol-dependent men (N = 53) in treatment received naltrexone (50 mg) or placebo. Four hours later, they received baseline assessment, exposure to fruit juice, and exposure to their usual alcoholic beverage in 3-min trials. Naltrexone reduced urge to drink and self-reported attention to the alcohol cues, not at the initial exposure but after repeated exposures to alcohol cues. Naltrexone reduced negative affect across baseline and alcohol trials. No effects of naltrexone on responses to the nonalcoholic appetitive beverage cues were found, suggesting that general appetite suppression does not mediate the effects of naltrexone on urges.
11117512	Previous research has shown that acute corticosterone treatment can have rapid effects on learning and memory. Using the taste reactivity test (TRT), the present study examined the effect of acute administration of corticosterone on sucrose palatability and the development of LiCl-induced rapid gustatory conditioning. On each of two conditioning days rats were injected with either a low dose of lithium chloride (LiCl; 0.75 mEq, i.p.) or saline (NaCl; 0.9%, i.p.) and 10 min later, received a second injection of either corticosterone (5 mg/kg, i.p.) or cyclodextrin vehicle. Rats were then placed in the TRT chamber, where 1 min intraoral infusions of sucrose (0.3 M) were delivered every 10 min. Taste reactivity responses were videotaped and later analyzed for frequency of occurrence. Rats treated with both LiCl and corticosterone showed enhanced aversive responding and reduced ingestive responding relative to control rats treated with LiCl and vehicle. The implication that corticosterone may have a rapid enhancing effect on gustatory conditioning is discussed.
11114149	The hedonic dimension of the taste sensation plays a crucial role in the control of many taste-mediated responses related to food ingestion or rejection. The purpose of this study was to evaluate the emotional reactivity associated with each primary taste (sweet, salty, sour and bitter) through analysis of the variations of autonomic nervous system (ANS) parameters. Thirty-four healthy non-smoker volunteer subjects (17 males and 17 females, mean age = 28 years) participated in the experiment. Taste stimuli were solutions of 0.3 M sucrose (sweet), 0.15 M NaCl (salty), 0.02 M citric acid (sour) and 0.00015 M quinine sulfate (bitter). Evian mineral water was used as the diluent and control (neutral taste). Throughout the test, five ANS parameters (skin potential and skin resistance, skin blood flow and skin temperature, and instantaneous heart rate) were simultaneously and continuously recorded. Results of the ANOVA evidenced a significant effect of primary taste on skin resistance amplitude (P: < 0.001) and duration (P: < 0.0001), skin temperature amplitude (P: < 0.001), skin blood flow amplitude (vasoconstriction) (P: < 0.0001) and instantaneous heart rate increase (P: < 0.0001). Skin resistance and cardiac responses were the most relevant ANS parameters to distinguish among the taste solutions. The four primary tastes could be associated with significantly different ANS responses in relation to their hedonic valence: the pleasantly connoted and innate-accepted sweet taste induced the weakest ANS responses whereas the unpleasant connoted tastes (salty, sour and bitter) induced stronger ANS responses, the innate-rejected bitter taste inducing the strongest ones. Such a neurovegetative characterization of each primary taste could provide references for the hedonic analysis of the more complex gustative sensation attached to foods.
11108436	Cow's milk protein hydrolyzed formulas appeared in the 1940s with the aim of decreasing or eliminating the allergenicity of cow's milk proteins, in addition to reducing the risk of sensitization. In recent years, the so-called "hypoallergenic" formulas have been developed. The use of such hydrolyzed formulas is based on the premise that predigested proteins, when fed as amino acids and peptides, provide nutrients in a nonantigenic form. Thus, protein hydrolyzed formulas have been classified as hypoallergenic. These formulas are processed by heat and enzymatic hydrolysis, and the conformational and sequential structures are more or less changed. The formulas contain peptides of lower molecular weight than the native protein source, which are thought to be less immunogenic. Hydrolyzed formulas appear to be nutritionally adequate and infants generally gain weight until they refuse the formula because of its bad taste. However, caution should be taken when such formulas are given for prolonged periods since no data are available on nutritional assessment of infants exclusively fed hydrolyzed formulas for several months. In this paper we report and discuss more than 202 reactions to different hydrolyzed formulas, including cases of anaphylactic shock and apparent life-threatening events. The cross-reactivity between different hydrolyzed formulas and cow's milk proteins, and the potential immunogenicity of such formulas are discussed. We conclude that none of the hydrolyzed formulas are nonallergenic, both for allergic children and for high-risk babies. Moreover, we suggest that double-blind placebo-controlled food challenge studies in larger cohorts of babies evaluated with well-defined and well-validated diagnostic methods may establish a more reliable prevalence of allergy to hydrolyzed formulas.
11070333	To date, there are few known predictors of stress-induced eating. The purpose of this study was to identify whether physiological and psychological variables are related to eating after stress. Specifically, we hypothesized that high cortisol reactivity in response to stress may lead to eating after stress, given the relations between cortisol with both psychological stress and mechanisms affecting hunger. To test this, we exposed fifty-nine healthy pre-menopausal women to both a stress session and a control session on different days. High cortisol reactors consumed more calories on the stress day compared to low reactors, but ate similar amounts on the control day. In terms of taste preferences, high reactors ate significantly more sweet food across days. Increases in negative mood in response to the stressors were also significantly related to greater food consumption. These results suggest that psychophysiological response to stress may influence subsequent eating behavior. Over time, these alterations could impact both weight and health.
11069950	The peripheral, central, and behavioral consequences of glossopharyngeal nerve transection (GLX), regeneration, and the prevention of regeneration on the quinine-elicited responses of adult rats were concurrently examined. Oromotor taste reactivity (TR) was videotaped during intraoral infusion of 7 ml of either quinine (3 mm) or distilled water at 17, 52, or 94 d after surgery. We confirmed previous findings by showing that 17 d after neurotomy, (1) the number of circumvallate (CV) and foliate taste buds, (2) gapes (a characteristic aversive TR response), and (3) the number of Fos-like immunoreactive (FLI) neurons in the gustatory NST (gNST), particularly in the medial portion (subfield 5) of the rostral central subdivision (RC), were all severely attenuated in GLX rats. We extended these findings by showing that these lesion-induced effects were enduring when the GL did not regenerate (up to 94 d). In contrast, when the GL regenerated, as few as 52 d were sufficient to re-establish quinine-elicited TR, especially gaping, and FLI expression in RC, particularly within subfield 5, to values comparable with quinine-stimulated sham-operated rats. Evidently, the gNST maintains its potential to restore accurately the organization of neural activity that is disrupted by nerve injury, as assessed by FLI, ultimately leading to the return of normal protective oromotor responses, provided the nerve regenerates. This recovery was complete despite the reappearance of a reduced population of CV taste buds ( approximately 75% control values) and may relate to peripheral and/or central changes that occur in tandem with regeneration of the GL.
11056879	Conditioned rejection reactions displayed in the taste reactivity test are exclusively produced by treatments that elicit nausea. The present experiments demonstrate that pretreatment with the antinausea agent ondansetron interferes with both the establishment and the expression of conditioned rejection reactions. Ondansetron did not interfere with lithium-induced taste avoidance in either a 1-bottle or a 2-bottle test. In fact, when rejection reactions were measured during a consumption test, ondansetron selectively attenuated rejection reactions, with only a slight modification of consumption. These results suggest that conditioned rejection reactions, but not conditioned taste avoidance, reflect nausea in rats that can be attenuated by ondansetron pretreatment.
11050134	Amphetamine microinjection into the nucleus accumbens shell enhanced the ability of a Pavlovian reward cue to trigger increased instrumental performance for sucrose reward in a pure conditioned incentive paradigm. Rats were first trained to press one of two levers to obtain sucrose pellets. They were separately conditioned to associate a Pavlovian cue (30 sec light) with free sucrose pellets. On test days, the rats received bilateral microinjection of intra-accumbens vehicle or amphetamine (0.0, 2.0, 10.0, or 20.0 microgram/0.5 microliter), and lever pressing was tested in the absence of any reinforcement contingency, while the Pavlovian cue alone was freely presented at intervals throughout the session. Amphetamine microinjection selectively potentiated the cue-elicited increase in sucrose-associated lever pressing, although instrumental responding was not reinforced by either sucrose or the cue during the test. Intra-accumbens amphetamine can therefore potentiate cue-triggered incentive motivation for reward in the absence of primary or secondary reinforcement. Using the taste reactivity measure of hedonic impact, it was shown that intra-accumbens amphetamine failed to increase positive hedonic reaction patterns elicited by sucrose (i.e., sucrose "liking") at doses that effectively increase sucrose "wanting." We conclude that nucleus accumbens dopamine specifically mediates the ability of reward cues to trigger "wanting" (incentive salience) for their associated rewards, independent of both hedonic impact and response reinforcement.
10986343	Benzodiazepines have been reported to induce eating when administered into the brainstem of rats (either the fourth ventricle or the parabrachial nucleus). Benzodiazepines in the brainstem also have been reported to enhance the hedonic impact of taste, as measured by hedonic/aversive taste reactivity patterns, when administered to the fourth ventricle. The present study examined whether the parabrachial nucleus in particular is a brainstem site of the benzodiazepine-produced enhancement of eating and palatability. Food intake (cereal mash) was measured after brainstem microinjections of midazolam or vehicle (0.0, 7.5, and 15.0 microg) into the parabrachial nucleus, the nucleus of the solitary tract, the pedunculopontine tegmental nucleus, or the fourth ventricle (60 microg). We used the taste reactivity paradigm to measure hedonic/aversive affective reactions elicited from rats by oral infusions of a bittersweet solution (7% sucrose-0.01% quinine). Positive hedonic reactions and negative aversive reactions to sucrose-quinine were also measured after microinjections of midazolam (0.0, 7.5, and 15 microg) into the parabrachial nucleus. Midazolam increased food intake and selectively enhanced positive hedonic taste reactivity patterns to the bittersweet solution when microinjections were delivered to the parabrachial nucleus. When administered to the other brainstem sites at the same doses, however, midazolam had no effect. We therefore conclude that the parabrachial nucleus can mediate the benzodiazepine-induced enhancement of the hedonic impact of taste as well as mediating the enhancement of eating behavior.
10962767	To assess the responsiveness of questionnaire measures of desire to drink and alcohol outcome expectancies.A subjective alcohol cue-reactivity paradigm (alcohol cue: sight, smell, taste) was used with a 2 x 2 between-subject design (n = 88), drink type (soft/alcoholic) and order of assessment (desire-expectancy/expectancy-desire). Covariance analysis controlled for quantity of recent alcohol consumption.	A quiet alcohol research suite.	Eighty-eight male and female social drinking students, recruited for a 'taste preference' survey.	Three composite measures using questionnaire totals and subscales: of desire (DAQ), positive expectancy (AEQ) and negative expectancy (NAEQ). Timeline Follow-back procedure for recent consumption.	Subjective cue-reactivity was found for the DAQ total score and the subscales 'strong intentions and desires' and 'negative reinforcement'. Expectancies did not demonstrate alcohol cue-reactivity.	The DAQ and subscales are sensitive measures of alcohol cue-reactivity in social drinkers. Potential uses of the subjective cue-reactivity procedure with multi-factorial representations of cue reaction are identified.	
10944506	Glossopharyngeal nerve (GL) transection in rats is known to markedly reduce gaping, a stereotypical aversive oromotor behavior, in response to intraorally delivered quinine. In this experiment we tested whether GL transection would reduce gaping in response to an otherwise palatable stimulus (sucrose) but conditioned to be aversive. Sprague-Dawley rats were implanted with intraoral cannulae. Five received bilateral transection of the GL and five served as sham-operated controls. Water-deprived rats were presented with 0.3 M sucrose for 15 min immediately followed by an injection of 0.15 M LiCl on three occasions. Rats were then habituated to the taste reactivity chamber and intraoral fluid infusion for 3 days, and tested on day 4 with a 1 ml infusion (1 min) of 0.3 M sucrose. All rats drank negligible amounts of sucrose by the third conditioning session and there were no differences in sucrose intake between the groups. There were no significant differences in gapes, or any other measured oromotor response, to sucrose between GL-transected and sham-operated rats. These results show that the GL is not a necessary afferent limb for gaping in response to conditionally aversive taste compounds.
10906399	The present study is aimed at finding taste reactivity patterns in domestic cats (Felis silvestris catus) which reflect 'liking' or perceived palatability. Three groups of nonstressed cats living in households were formed which a priori were expected to differ in motivational state for eating food items (more or less hungry), and which were offered two different food items differing in general taste properties (more or less flavourful food, MFF and LFF, respectively) around the time that they were fed their normal food. Analysis of the amount of food eaten showed that MFF was consumed regardless of hunger level and that LFF was consumed depending on the hunger level of cats: the more hungry cats ate more of LFF than the less hungry cats. Analysis of post-meal behavioural sequences showed that the 'MFF consumption sequence' differed from the 'LFF refusal sequence' and that the 'LFF consumption sequence' strongly resembled the 'MFF consumption sequence' but also contained elements of the 'LFF refusal sequence'. Subsequent analysis of the frequencies and total durations of behavioural patterns showed that two kinds of patterns existed, possibly reflecting two 'palatability dimensions': hedonic taste reactivity patterns (lick/sniff feeding bowl, lip lick and groom face) and aversive taste reactivity patterns (lick/sniff food and lick nose). These dimensions may be combined to obtain a single palatability score.
10896758	The current study investigated responsivity to individualized food cues consisting of binge/favourite foods in 17 women with bulimic nervosa (BN) and 17 women with no history or current symptoms of eating disorders (C). The hypothesis that increasing cue salience would be associated with an increase in responsivity was tested by comparison of self reported urges, affective responses and salivation to the sight and smell (SS) and the sight, smell and taste (SST) of a binge/favourite food compared to a neutral stimulus (lettuce leaf). As predicted, the BN group reported a greater urge to binge and higher levels of stress/arousal to selected binge/favourite food cues compared to the C group. The BN group also reported lower confidence to resist the urge to binge and control over food intake compared to the C group. Further, a series of planned comparisons in the BN group found that the urge to binge, stress, and loss of control were greater when participants were exposed to the SST cue than to the SS cue. There was no difference between the groups in salivary responsivity to food cues. These results are discussed in terms of a conditioning model of cue reactivity.
10880683	It was determined whether ethanol palatability in rats could be changed by manipulating the reinforcement experienced during limited access consumption. During the first 3 days of the experiment, initial taste reactivity (TR) testing to distilled water (1 day) and 10% alcohol (2 days) was performed. Following the establishment of baseline TR, separate groups of animals received bilateral microinjections (0.5 microl/side) into the nucleus accumbens of either the nonspecific dopamine agonist d-amphetamine sulfate (20 microg, n = 10), the D(2) antagonist raclopride (1.0 microg, n = 8), or physiological saline (n = 5). The injections occurred at the same time each day for 5 consecutive days. Five minutes after the microinjection, the fluid-deprived rats were given 30-min access to 10% ethanol. Over the 3 days following drug administration, TR to distilled water and 10% alcohol was repeated. After this, the rats were once again given 30 min of access to 10% ethanol for 5 consecutive days, but without drug microinjection prior to alcohol access. A final TR exposure (the same as the others) was performed over the final 3 days of the study. Both raclopride and d-amphetamine administration produced reductions in ethanol consumption (in comparison to saline treatment). However, treatment with d-amphetamine and raclopride during ethanol consumption did not cause significant, conditioned changes in palatability as measured by the taste reactivity procedure. These results suggest that dopamine plays a role in the motivation to consume ethanol but this neurotransmitter is not involved in evaluating its incentive value.
10869506	The chronic supracollicular decerebrate (CD) rat fails to increase meal size in response to systemic/metabolic aspects of food deprivation. Here we asked whether or not deprivation increases immediate oral motor responding to taste stimuli (taste reactivity) in CD rats, as it does in neurologically intact controls. The responses of CD rats were evaluated as functions of glucose concentration and deprivation state, with taste reactivity responses recorded myographically during 15-s intraoral infusions and during 45-s post-infusion periods. Five glucose concentrations (0, 3.2, 6. 25, 12.5, 25%) were each presented three times during each test session. The rats were tested when not-deprived (i.e. receiving their full complement of gavage feedings), deprived (23.5 h) of food and water, and deprived of food but not water. The number of oral motor responses emitted increased monotonically with stimulus concentration; during oral infusions the increase was greatest over the lower half of the concentration range, whereas responding increased linearly with concentration in the post-infusion period. This CD response profile resembled that obtained previously with neurologically intact rats tested according to the same protocols. In contrast to results obtained in intact rats, deprivation did not influence the CD's response to glucose at any concentration or for any observation period. Although the caudal brainstem may receive and process information associated with deprivation state, neural interactions between forebrain and brainstem structures appear necessary for the behavioral expression of deprivation effects on meal size or, as we can now conclude, on immediate oral motor responses to taste stimuli.
10780304	In rodents, exposure to chronic mild stress (CMS) is known to induce unresponsiveness to environmental stimuli, as well as sleep disturbances, suggesting some analogies between this syndrome and human depression. Furthermore, numerous studies reported a decrease in nocturnal melatonin concentration in depressed patients, compared with controls. The present study was conducted to test a possible preventative action of daily treatment with melatonin on behavioural alterations induced in C3H/He mice by CMS exposure. In addition to daily spontaneous locomotor activity and preference for sucrose solution, the emotional behaviour of mice was examined in a stressful situation (light/dark choice test), as well as in a situation devoid of constraining components (free-exploratory paradigm), after three weeks of CMS. The results showed that the behaviour of C3H/He mice was disrupted after CMS. Stressed mice exhibited blunted emotional reactivity in both the light/dark choice test and the free-exploratory situation. While unstressed mice presented no variation in their preference for a sucrose solution, stressed mice presented a decrease in such preference towards the end of the CMS exposure. Furthermore, daily spontaneous locomotor activity of the mice was reduced after CMS. Daily treatment of stressed mice with melatonin was able to prevent several CMS-induced disturbances, except in the light/dark choice test, where melatonin was ineffective. Compared to the effects of 10 mg/kg of fluoxetine, which completely prevented CMS-induced dysregulation of behaviour, melatonin was less effective. The present results support the idea that melatonin may be implicated in an homeostatic system which protects animals from disruptions induced by chronic stress.
10773195	Microinjection of opioid agonists, such as morphine, into the nucleus accumbens shell produces increases in eating behavior (i.e. 'wanting' for food). This study (1) reports direct evidence that activation of accumbens opioid receptors in rats also augments food 'liking', or the hedonic impact of taste, and (2) identified a neural site that definitely contains receptors capable of increasing food intake. Morphine microinjections (0.5 microgram) into accumbens shell, which caused rats to increase eating, were found also to cause selective increases in positive hedonic patterns of behavioral affective reaction elicited by oral sucrose, using the 'taste reactivity' test of hedonic palatability. This positive shift indicated that morphine microinjections enhanced the hedonic impact of food palatability. The accumbens site mediating morphine-induced increases in food 'wanting' and 'liking' was identified using a novel method based on local expression of Fos induced directly by drug microinjections. The plume-shaped region of drug-induced increase in Fos immunoreactivity immediately surrounding a morphine microinjection site (Fos plume) was objectively mapped. A point-sampling procedure was used to measure the shape and size of 'positive' plumes of Fos expression triggered by microinjections of morphine at locations that caused increases in eating behavior. This revealed a functionally 'positive' neural region, containing receptors directly activated by behaviorally-effective drug microinjections. A subtraction mapping procedure was then used to eliminate all surrounding regions containing any 'negative' Fos plumes that failed to increase food intake. The subtraction produced a conservative map of the positive site, by eliminating regions that gave mixed effects, and leaving only a positive region that must contain receptors capable of mediating increases in food intake. The resulting mapped 'opioid eating site' was contained primarily within the medial caudal subregion of the nucleus accumbens shell, and did not substantially penetrate either into the accumbens core or into other subregions of the shell. Several other structures outside the nucleus accumbens (such as rostral ventral pallidum), immediately medial and adjacent to the shell, also appeared to be included in the functional site. Opioid receptors within this site thus are capable of mediating morphine-induced increases in eating, in part by enhancing the hedonic reward properties of food.
10760484	Lipopolysaccharide (LPS) and cholecystokinin (CCK) have been shown to have anorectic properties in a variety of species. The present study examined the effects of LPS and CCK, both alone and in combination, on two different aspects of water ingestion, water intake and palatability. On test days, animals were first injected intraperitoneally (i.p.) with either LPS (200 microg/kg) or NaCl vehicle, and 2 h later received a second injection of either CCK (8 microg/kg) or NaCl vehicle. In Experiment 1, water intake was monitored for 1 h on 3 separate test days 72 h apart; while in Experiment 2, water palatability was assessed using the taste reactivity test (TRT), on two separate test days 72 h apart. Both LPS and CCK significantly (p<0.05) reduced water intake, with the effects of combined LPS with CCK being more pronounced than either agent injected alone. Rats developed a rapid tolerance to the effects of LPS on water intake on subsequent exposures to LPS. Results from the TRT indicated that LPS enhanced water palatability (p<0.05), as evidenced by a high level of ingestive responding, whereas CCK produced a pattern of responding indicative of satiety. LPS plus CCK reduced ingestive responding on the first test day, but these responses were significantly increased on the second test day (p<0.05). These results demonstrate that although LPS reduces water intake, it enhances water palatability. The results further underscore the necessity for examining palatability changes in addition to intake measures when studying the regulation of feeding and drinking.
10716554	Rats avoid a diet that is deficient in one or more essential amino acids (EAAs). This phenomenon is thought to involve the development of a "learned aversion" for the sensory properties or spatial placement associated with the deficient diet. The dietary self-selection technique has been widely used to show this avoidance of the deficient diet. Because avoidance does not necessarily imply taste aversion, we used the Taste Reactivity Test initially created by Grill and Norgren (1978) to analyze the affective reactivity pattern of rats that ingested a threonine-deficient diet. The results showed that there was an increase in the aversive responses when ingesting the threonine-deficient (Thr-Dev) diet, compared to a control diet, without changes in the hedonic responses. The aversive reactions were mainly gaping, and to a lesser extent chin rubbing and head shaking. This asymmetrical shift in the Thr-Dev diet palatability is consistent with a two-dimensional hypothesis of palatability, indicating that the aversive palatability of the deficient diet was increased while the positive palatability did not change. Further evidence indicates that rats do not develop a normal behavioral satiety sequence after ingesting the threonine-deficient diet. These results indicate that a true aversion is formed to the taste of a diet that is deficient in an essential amino acid.
10716221	The present study examined the effects of repeated injections of lipopolysaccharide (LPS) and cholecystokinin (CCK) on both sucrose palatability and body weight. Rats received repeated injections of LPS (200 microg/kg), CCK (8 microg/kg) and/or NaCl on days 1, 4, 7 and 10. Body weight was monitored on each test day and sucrose palatability was assessed using the taste reactivity test (TRT) on days 7 and 10. Rats treated with LPS developed a rapid tolerance to the reductions in body weight; however, this tolerance did not affect sucrose palatability. Furthermore it was found that repeated exposures to LPS and CCK attenuated the typical satiety related behaviors produced in the TRT by administration of CCK. This desensitization to CCK with repeated exposures to LPS may be one of the mechanisms that could account for the rapid development of tolerance to LPS-induced hypophagia.
10714382	The hedonic impact of taste is reflected in affective facial reactions made by human infants, other primates, and even rats. Originally studied in human infants, affective reactions to taste have also been used by affective neuroscience to identify hedonic brain systems in studies of animals (via application of neural stimulation, pharmacological activation, and neural lesion manipulations). The chief limitation of measuring affective reactions is that it is difficult for experimenters to know how to interpret them, and therefore how to interpret changes produced by brain manipulations. This paper notes guidelines to interpretation. It examines the phylogenetic continuity between humans, other primates, and rats in terms of the microstructure of taste-elicited affective reactions. It reviews evidence that affective taste reactivity patterns truly reflect a 'core hedonic process' of palatability or affect, rather than being an ingestion measure, consummatory behavior measure, or a sensory reflex measure. It reviews affective neuroscience studies of taste reactivity that have identified true hedonic brain substrates, and discriminated them from false hedonic brain substrates. It considers the neural bases of incentive 'wanting' versus 'liking'. Finally, it notes the difference between human subjective affective ratings of pleasure and 'core hedonic processes' reflected by behavioral affective reactions.
10686370	Previous research shows that dependent drinkers respond more strongly to alcohol-related cues and suggests that alcohol cue-reactivity may be relevant to understanding dependence liability. However, a significant weakness in many studies is the fact that cue-reactivity is studied without actually conditioning subjects; responses to alcohol-related cues are simply assumed to be conditioned responses. The current report attempts to overcome this weakness by studying alcohol cue-reactivity following a flavour-conditioning procedure. A statistical model of individual differences in cue-reactivity was constructed using previous alcohol exposure, alcohol tolerance, and personality as predictor variables. Although there was no evidence for overall differences in subjective and psychophysiological responses to alcohol and soft-drink paired flavours, there were marked individual differences in responding to the different flavours. The statistical model showed that reward sensitivity (high extroversion, high neuroticism), heavier levels of drinking, and higher levels of tolerance to the intoxicating effects of alcohol were associated with lower levels of skin conductance in the presence of alcohol paired flavours.
10676446	The regulation of salt intake is achieved through the coordination of behavioral and physiological responses. Brain neuropeptides, such as the tachykinins, play an important role in orchestrating both of these responses. Intraventricular injections of NK3 receptor agonists, such as senktide, are potent in suppressing salt intake. Experimental results show that intraventricular injections of senktide that suppress salt intake have no effect on the ingestion of other tastes, such as sucrose. The means by which senktide suppresses salt intake was investigated in a series of experiments. Taste reactivity and lick rate analyses suggest that the activation of NK3 receptors reduces salt intake by modulating the oral-stimulating property of salt taste.
10552643	A new method for the "one-pot" synthesis of S-methyl thioesters has been developed by reacting methyl chlorothiolformate with carboxylic acids. The resulting "flavor library" contained all the intended thioesters and a single major impurity, identified by GC-MS as S, S-dimethyldithiocarbonate. Quantification of individual compounds present in the library was performed by GC analysis using two independent methods of detection, SCD and FID. It was shown that apart from S-methyl thioacetate (0.8 mol %), molar concentrations of other thioesters varied in a relatively narrow range from 4.2 mol % for S-methyl thiopropionate to 14.1 mol % for S-methyl thiohexanoate. In general, medium chain S-methyl thioesters were present in slightly higher molar concentrations than those prepared from short or long chain carboxylic acids. This variation was attributed to partial loss of the most volatile components during extraction and the lower reactivity of higher homologues. The library was used for the characterization of some physicochemical parameters of thioesters. In particular, lipophilicity coefficients (log k(w)) and thioester retention in 10, 20, and 33% triolein (used as a model lipid phase) were determined directly by reverse-phase HPLC and extrapolated from the respective data. This analysis illustrates that substantial information can be generated using a library containing a relatively large number of compounds in effectively the same way as is necessary for the analysis of a single sample.
10556695	Hazelnuts are widely used in the food industry owing to their nutritive value and taste. The amount of hazelnut present in a recipe is usually considered as a mark of quality. On the other hand, contamination of foods that normally do not contain hazelnuts is a threat for patients with a hazelnut allergy. For this reason, the availability of a method for the detection and quantification of hazelnuts in foods would be desirable. The objective of this study was to develop a method for the detection and quantification of minor amounts of hazelnut protein in food products that is potentially applicable for the food industry. Several immunochemical methods, e.g., immunoblotting and enzyme-linked immunosorbent assay (ELISA), were developed with antibodies from both hazelnut-sensitized patient sera and the sera of rabbits hyperimmunized with hazelnut protein. Immunoblotting appeared to be non-specific when the sera of patients were used as a source of antibodies. Using immunopurified antibodies from rabbits immunized with hazelnuts, immunoblotting became specific, but the sensitivity of this method was limited. Inhibition of IgE binding is a generally used test in clinical laboratories to establish contamination with hazelnuts. This approach is sensitive and specific, but not readily accessible for the food industry since patient serum is needed. Similar results in terms of sensitivity and specificity were obtained with a sandwich ELISA constructed with an immunopurified antibody from rabbits sensitized to hazelnuts. No substantial cross-reactivity with other nuts, legumes or other food constituents was observed, and concentrations as low as 5 ng/ml, corresponding to 1 ppm in food products, were detected. In a field test, several consumer products regarded to be free of hazelnuts were shown to contain traces of hazelnut. This sandwich ELISA constructed with immunopurified antibodies from rabbits sensitized with hazelnut protein is a sensitive and specific method to detect and quantify hazelnut and is useful in detecting trace contamination with hazelnut in various consumer products. Since this test does not require serum from patients, it is appropriate for use in the food industry.
10497960	The present article analyzed the dramatic increase in alcohol ingestion that is known to occur in laboratory rats subjected to food restriction. In the first experiment, we wished to know when during the day food restricted animals consume the "extra" alcohol ration. Determinations of ethanol drinking at 3-h intervals throughout the day revealed that although food-restricted animals drink much ethanol at all times of the day, they retain a definite daily rhythm such that peak intake occurs during the dark hours. The second experiment tested the hypothesis that chronic food restriction is accompanied by positive alliesthesia for the taste of alcohol. To answer this question, we employed the taste reactivity method to measure hedonic and aversive reactions to 6% ethanol as a function of nutritional status. It was found that two weeks of food restriction, which approximately doubled the voluntary intake of ethanol, was associated with a significant increase in the hedonic response elicited by intraoral infusions of ethanol. Alcohol also elicited fewer aversive responses in food restricted subjects. Because chronic food restriction increases adrenal corticosterone secretion, we used the corticosterone synthesis inhibitor metyrapone as a tool to assess the importance of adrenal corticosterone secretion for the increased palatability of alcohol observed during food restriction. The third experiment demonstrated that attenuation of corticosterone synthesis significantly reduced the hedonic taste reactions to alcohol observed in food-restricted rats; this drop in alcohol taste reward was accompanied by a nonsignificant increase in the aversive reaction to alcohol. The final experiment investigated the effect of prolonged exposure to exogenous corticosterone on the taste reactivity to ethanol in freely fed subjects. Adrenalectomized animals bearing corticosterone implants for 3 weeks found the taste of alcohol more pleasant than did intact or adrenalectomized rats implanted with blank pellets. Taken together, the present results suggest that food restriction is associated with an apparent increase in the sensory reward--positive alliesthesia--derived from alcohol; this effect appears to be mediated by increased adrenal corticosterone secretion.
10484487	The differential effects of CCK and lipopolysaccharide (LPS) on sucrose intake and palatability were examined. Rats were injected with LPS (200 microg/kg ip) or NaCl (0.9%, vehicle) and 2 h later received a second injection of either CCK (8 microg/kg ip) or NaCl. In experiment 1, sucrose (0.3 M) intake was monitored for 1 h on three different test days 72 h apart, while in experiment 2, palatability was assessed by means of the taste reactivity test (TRT) on two separate days (72 h apart). In the TRT, orofacial and somatic responses to brief (30 s) intraoral infusions of sucrose were recorded and analyzed for response frequency. Singly, LPS and CCK reduced sucrose intake, with a more pronounced effect from combined LPS and CCK. LPS by itself did not alter sucrose palatability, as evidenced by continuous high levels of ingestive responding. In contrast, CCK-treated rats displayed a pattern of responding indicative of satiety, as did the combined LPS-CCK-treated rats. These results suggest that LPS does not induce hypophagia by altering palatability.
10460323	Exploring subjective alcohol cue reactivity in non-clinical samples should assist understanding in clinical samples where additional problems muddy the water. However, exploration is stalled through using insensitive, single-item representations.The effect of alcohol cues and a priming dose of alcohol on a new multi-factorial representation of cue reactivity is sought (DAQ, Desire for Alcohol Questionnaire).	Prime and Cue exposure are variables in a standard 2x2 between subjects design set within a stooge taste-evaluation experiment. The DAQ was administered after a Prime and Cue exposure phase.	Main effects for Cue exposure but not Prime were found for the DAQ total and the subscales Mild desires (positively reinforcing items) and Strong desires/intentions but not Negative reinforcement (negatively reinforcing items) and Controllability; however, there was no interaction.	The DAQ is a sensitive measure of subjective cue reactivity in social drinkers and its potential in the evaluation of pharmacological interventions is proposed.	
10456567	Alcohol-preferring rats (Alko alcohol or AA) were tested for taste reactivity to water, sucrose, quinine, and a range of alcohol concentrations (5-40%) both before and after a period of continuous alcohol access. The alcohol-avoiding line of rats (Alko nonalcohol or ANA) was also tested for comparison. It was found that AA rats displayed greater ingestive reactivity to alcohol compared to ANA rats both before and after a three-week period of continuous access to 10% alcohol (during which time AA rats drank significantly more alcohol than ANA rats). AA rats also made significantly more ingestive responses to a 0.3 M sucrose solution and a 0.0005 M quinine solution. Differences between AA rats and ANA rats in aversive reactivity appeared only after the alcohol consumption tests; AA rats made significantly fewer aversive responses to the 30% and 40% concentrations after continuous alcohol access. AA rats also made significantly more aversive responses to the quinine solution. The results suggest that line differences between AA rats and ANA rats in the reactivity response to alcohol solutions have been selected in association with the original selection phenotype of alcohol consumption.
10380980	The taste reactivity test was used to evaluate the ability of motion sickness to produce conditioned rejection reactions, a putative measure of nausea in rats. Following three conditioning trials, rats displayed conditioned rejection reactions during an intraoral infusion of a rotation-paired saccharin solution. This is the first demonstration of conditioned rejection produced with a non-pharmacological emetic agent and provides support that the conditioned rejection reaction may serve as a rat model of nausea.
10357445	Discomfort created by intestinal distension may play a role in controlling intake behavior. We analyzed these effects in details by the taste reactivity test in Long-Evans rats. A balloon inserted into a separated Thiry-Vella intestinal loop was distended with different volumes of water (0.05, 0.09, 0.12, and 0.28 mL, respectively). Saccharin solution (0.001 M) was infused into the mouth via an implanted oral cannula nine times for 30 s, with 5-min intertrial intervals. The balloon was distended after the second and released following the seventh trial. Taste reactivity (TR) elements were videotaped and later analyzed for appetitive and aversive responses. The number of appetitive responses decreased after gut distension, whereas aversive elements were infrequent and stable. It is suggested that pleasantness of the taste stimulus decreased independently of the discomfort, which remained mild but steady; that is, sweet taste gradually lost its hedonic value but was not accompanied by an acquired aversion of the same taste. This finding may point to the difference of the motivational and discriminative effects of the internal stimuli.
10341253	Stimulation of T-cells with staphylococcal enterotoxin B (SEB) significantly elevates interleukin-2 (IL-2) and contemporaneous activation of the hypothalamic-pituitary-adrenal (HPA) axis and c-fos in the paraventricular nucleus (PVN) of BALB/cByJ mice. Such neural signaling may promote cognitive and emotional adaptation before or during infectious illness. Because corticotropin-releasing hormone (CRH) is an anxiogenic neuropeptide that may mediate the stressor-like effects of immunological stimuli, we measured neuronal CRH mRNA alterations in mice challenged with SEB. Increased CRH mRNA levels were observed in the PVN and central nucleus of the amygdala (ceA) 4-6 hr after SEB administration. This was associated with plasma ACTH increases, which could be abrogated by the systemic administration of anti-CRH antiserum. Additional experiments did not support a role for IL-2 or prostaglandin synthesis in activating the HPA axis. Behavioral experiments testing for conditioned taste aversion did not confirm that SEB challenge promotes malaise. However, consistent with the notion that central CRH alterations induced by SEB may affect emotionality (e.g., fear), SEB challenge augmented appetitive neophobia in a context-dependent manner, being marked in a novel and stressful environment. It is hypothesized that immunological stimuli generate a cascade of events that solicit integrative neural processes involved in emotional behavior. As such, these data support the contention that affective illness may be influenced by immunological processes and the production of cytokines and are consistent with other evidence demonstrating that autoimmune reactivity is associated with enhanced emotionality.
9929592	Epithelial Na+ channels (ENaCs) are thought to mediate the amiloride-blockable salt taste. The rat vallate papilla does not contribute to amiloride-blockable salt taste, yet the presence of ENaC-mRNA in this tissue has been reported. Is ENaC actually contained in the taste cells, or is it merely present in the supporting lingual epithelium? To avoid contamination by ENaC contained in the lingual epithelium, we physically isolated taste buds from the vallate papilla and used mRNA purification followed by reverse transcriptase polymerase chain reaction (RT-PCR) to investigate the presence of ENaC-type message in the isolated buds. mRNA of alpha-, beta- and gamma-subunits was detected, the alpha-signal being the strongest. These results provide first molecular evidence for the presence of ENaC subunits in taste buds that were isolated from the posterior tongue and were free of epithelial contamination. In addition, we used immunohistochemistry to show ENaC-like reactivity in posterior tongue taste cells. Interestingly, the immunoreactivity was not predominantly apical but was intracellular and close to or at the basolateral membrane. The function of basolateral ENaC-type channels is unknown. Possibly, the channels are normally closed or of very low open probability in the resting state.
9864063	Tachykinin NK-3 receptor agonists reduce alcohol intake in alcohol-preferring rats; the nucleus basalis magnocellularis (NBM) is highly sensitive to their effect. Tachykinins and their receptors are widely distributed in gustatory pathways and NK-3 receptor agonists have been reported to modify taste reactivity to salt solutions in rats. The present study evaluated whether the TK NK-3 receptor agonist aminosenktide (NH2-SENK) influences taste reactivity to ethanol solutions. Genetically selected Marchigian Sardinian alcohol-preferring (msP) rats were employed. In response to the intraoral infusion (0.8 ml in 1 min) of 10, 20, 40, or even 60% ethanol solution, ethanol-naive rats showed a large number of ingestive reactions and a much lower number of aversive reactions. Two min before the intraoral infusion of 10 or 40% ethanol, NH2-SENK was injected either into the lateral ventricle (LV) or into the NBM. Doses of NH2-SENK that markedly reduce alcohol intake, 125 ng/rat into the LV or 5 ng/site into the NBM, did not modify the ingestive reactions and, in some instances, reduced the aversive reactions to ethanol solutions in ethanol-naive rats. Injections of 125 ng/rat into the LV failed to modify taste reactions in ethanol-experienced rats. The present results show that msP rats have an innate hedonic evaluation of ethanol solutions, even of high concentration. Moreover, they indicate that reduction of ethanol intake induced by TK NK-3 receptor agonists in alcohol-preferring rats does not depend on influences on gustatory processes.
9858756	What roles do mesolimbic and neostriatal dopamine systems play in reward? Do they mediate the hedonic impact of rewarding stimuli? Do they mediate hedonic reward learning and associative prediction? Our review of the literature, together with results of a new study of residual reward capacity after dopamine depletion, indicates the answer to both questions is 'no'. Rather, dopamine systems may mediate the incentive salience of rewards, modulating their motivational value in a manner separable from hedonia and reward learning. In a study of the consequences of dopamine loss, rats were depleted of dopamine in the nucleus accumbens and neostriatum by up to 99% using 6-hydroxydopamine. In a series of experiments, we applied the 'taste reactivity' measure of affective reactions (gapes, etc.) to assess the capacity of dopamine-depleted rats for: 1) normal affect (hedonic and aversive reactions), 2) modulation of hedonic affect by associative learning (taste aversion conditioning), and 3) hedonic enhancement of affect by non-dopaminergic pharmacological manipulation of palatability (benzodiazepine administration). We found normal hedonic reaction patterns to sucrose vs. quinine, normal learning of new hedonic stimulus values (a change in palatability based on predictive relations), and normal pharmacological hedonic enhancement of palatability. We discuss these results in the context of hypotheses and data concerning the role of dopamine in reward. We review neurochemical, electrophysiological, and other behavioral evidence. We conclude that dopamine systems are not needed either to mediate the hedonic pleasure of reinforcers or to mediate predictive associations involved in hedonic reward learning. We conclude instead that dopamine may be more important to incentive salience attributions to the neural representations of reward-related stimuli. Incentive salience, we suggest, is a distinct component of motivation and reward. In other words, dopamine systems are necessary for 'wanting' incentives, but not for 'liking' them or for learning new 'likes' and 'dislikes'.
9857212	Salt taste signals from the rat anterior tongue are probably transduced via epithelial sodium channels (ENaCs) residing in the apical cellular pole of taste cells. The signals are blocked by mucosal amiloride in low microM concentrations. In contrast, the rat vallate papilla does not contribute to amiloride-blockable salt taste. Two approaches were used to probe for the three subunits of ENaC in the anterior and posterior tongue of the rats in sodium balance. (a) Immunohistochemistry with antibodies against ENaC subunits and against amiloride binding sites. In the anterior tongue, reactivity for alpha-, beta-, and gamma-subunits was present in taste buds and lingual epithelium. In the posterior tongue vallate papilla, reactivity for alpha-subunit and for amiloride binding sites was easily demonstrable, whereas that for beta-subunit and especially for gamma-subunit was weaker than in the anterior tongue. (b) RT-PCR techniques were used to probe for the presence of ENaC subunit mRNA. In isolated taste buds of the anterior tongue, mRNA of all three subunits was found, whereas in isolated taste buds of the vallate papilla only mRNA of the alpha-subunit was easily detectable. That of beta- and gamma-subunits was much less abundant. RNA of all three subunits was abundant only in taste buds of the anterior tongue. Therefore, subsets of elongated taste cells do express ENaC, but regional differences exist in the transcription and expression of subunits. The regional differences suggest that amiloride-sensitive salt taste, which requires all three subunits, is present in the anterior but not the posterior tongue of rats, as functional studies indicate.
9726288	The taste reactivity test was used to determine the response of outbred mice to orally infused taste solutions. For the initial measures, mice (n = 10) were tested with 3%, 6%, 9%, and 12% (v/v) alcohol and four taste solutions: sucrose, sodium chloride, hydrochloric acid, and quinine hydrochloride (a single concentration of each). A second group of naive mice (n = 16) was tested with 5%, 10%, 20%, 30%, and 40% alcohol. The final set of measures with naive mice (n = 26) was taken with a range of sucrose concentrations: 0.01 M, 0.05 M, 0.1 M, 0.5 M, and 1.0 M. In general, mice made similar reactivity responses to all solutions tested. A predominant component of the mouse response to all infused fluids was forelimb flailing; gaping was also a common response to all solutions. Despite the large number of aversive-type responses, mice rejected very little fluid via passive drip or fluid expulsion. The single, significant difference in responding to the four taste stimuli was that mice made fewer aversive responses to sucrose. Differential responding to the 5 to 40% alcohol concentrations and sucrose concentrations was observed. Mice increased ingestive responding as the concentration of alcohol and sucrose increased. Aversive responding decreased reliably only with increases in the sucrose concentration. Data provide the first reported taste reactivity responses of mice to orally infused taste solutions. These results can be compared with the extant data available in rats and can also be used as a basis for exploring taste factors in genetically defined mouse populations.
9700744	The taste reactivity test was used to examine the effect of CCK-octapeptide (CCK-8) on the palatability of a sucrose solution in ovariectomized rats either receiving hormonal replacement (estradiol and progesterone; OVX + HRT), or treated with vehicle only (OVX + VEH). Statistical analyses revealed that the OVX + HRT rats treated with CCK-8 exhibited a robust decrease in ingestive responses, and an increase in aversive responses and passive drips to the intraoral sucrose infusions, relative to treatment with the NaCl vehicle. In contrast, a weak effect of CCK-8 on ingestive responses, no significant effect on the frequency of aversive responses, and a reduced effect on passive drips was observed in the OVX + VEH rats. These results show that CCK-8 modifies sucrose palatability, and that this effect is modulated by gonadal hormone levels.
9682998	This study examined the effect of the benzodiazepine, midazolam, on the consumption and palatability of 6% ethanol in male Wistar rats. In the first experiment, it was found that midazolam (5 mg/kg) increased home cage ethanol drinking 0-2 h after administration. Another intake experiment, in which ethanol was infused directly into the oral cavity through an indwelling catheter, also showed that midazolam (10 mg/kg) stimulated alcohol ingestion. The affective response to intraoral infusions of ethanol (1 ml during 1 min) was subsequently monitored in benzodiazepine-treated rats. Taste reactivity testing showed that midazolam (5-10 mg/kg) significantly increased the occurrence of hedonic orofacial responses and suppressed the number of passive drippings. A similar response pattern was observed following administration of diazepam (5 mg/kg) and chlordiazepoxide (10 mg/kg), but not after exposure to cis(Z)flupentixol (10 mg/kg). Midazolam also increased the incidence of hedonic responses in alcohol-naive rats with no previous access to ethanol in the home cages. Hedonic responsiveness did not appear to diminish with repeated benzodiazepine exposure: the behaviour of rats given five midazolam injections (10 mg/kg every second day) was similar to that shown by rats with no benzodiazepine pre-exposure. The increased hedonic response to ethanol induced by midazolam was blocked by pretreatment with the benzodiazepine receptor antagonist flumazenil (10 mg/kg), the latter drug exerting no effects on its own. The present results suggest that benzodiazepines, by acting on GABA(A) receptors, may facilitate ethanol intake by increasing ethanol's taste hedonic properties.
9590520	Previous animal models testing infantile reactivity to ethanol (EtOH) in maternal milk used EtOH doses that vastly exceeded levels actually encountered in a mildly or moderately intoxicated dam. The present study assessed whether 12- and 16-day-old rats are capable of detecting EtOH in milk at levels actually recorded in an intoxicated dam. Experiment 1 determined representative levels of EtOH in maternal milk as a function of maternal intragastric administration of EtOH (0.5-3.0 g/kg). Experiment 2A assessed generalization of conditioned taste aversions accrued with a high level of EtOH (6%) in either water or milk vehicles towards lower, more representative EtOH levels obtained from Experiment 1. With body weight gain as the dependent measure, conditioned aversions to milk were evident with the milk vehicle, but there was no detection of EtOH at any level at either age. Detection of the high level of EtOH (6%) in milk, however, was observed by 16 day olds within an habituation paradigm (Exp. 2b) via cardiac and behavioral (locomotion, mouthing) indexes. In Experiment 3 application of Experiment 2's more sensitive, behavioral index to assess generalization of the conditioned taste aversions revealed detection of a lower, more representative concentration of EtOH (175 mg%) in milk in 16-day-old rats. Overall the results show that the unweaned rat is capable of detecting very low concentrations of EtOH in milk and can modify their behavior accordingly. The expression of this capability is not, however, homogeneous across different response indexes. In conjunction with prior research it is clear that the infant rat's perception of EtOH in milk, including the very low levels of EtOH found in maternal milk during mild or moderate intoxication, is a relevant experience for generating new responses towards EtOH.
9564805	Hydrolyzed milk formulas (HFs) are given to infants allergic to cow's milk proteins and, for preventive reasons, to atopy-prone newborns for which breast feeding is not feasible. The ultimate properties of HFs are not only a reduced allergenicity but also decreased immunogenic capacity combined with good taste and caloric value. No information is available concerning the capacity of HFs to induce immune responses.We sought to determine the residual immunogenic capacity of partially (pHF) and extensively hydrolyzed milk formula (eHF), and we studied the cellular reactivity of cord blood-derived (n = 71) mononuclear cells induced by 10 different HFs.	To test the effect of HF on T-helper cells, beta-casein-specific T-cell clones (TCCs, n = 21) from individuals allergic to milk were established, and T-cell proliferation and cytokine profiles (interferon-gamma and IL-4) were determined on stimulation with HF.	We found significantly reduced proliferative responses of eHF compared with milk proteins. Whey-based pHF displayed the same proliferative capacity as unmodified milk proteins. As expected, extensively processed whey products displayed lower cellular responses compared with partially hydrolyzed products (pHF whey vs eHF whey, p < 0.0001). No difference in cellular response was found between casein-based pHF and casein-based eHF. Beta-casein-specific TCCs (n = 21) proliferated in response to casein-derived hydrolysates (14% with casein/whey-based pHF, 4% with casein-based pHF, and 0% with casein-based eHF). Whey-based pHF was also found to induce proliferation in beta-casein-specific TCCs, indicating the presence or the generation of peptides displaying cross-reactivity with these whey-derived hydrolysates. TCCs stimulated with whey- or casein-based pHF or eHF produced the same amount of cytokines (IL-4, interferon-gamma) as the same clones stimulated with unmodified products.	Our data indicate that whey- and casein-derived eHFs display highly reduced immunogenic properties at the T-cell level. In contrast, pHFs display residual immunogenic properties detectable at the T-cell level, reflecting a potential for the induction of pathogenetically important T-cell responses.	
9530238	Gonadal hormones (e.g., estradiol) may regulate feeding by producing a shift in the taste or palatability of food items. This study examined the impact of endogenous gonadal hormones on palatability by investigating sex differences in taste responsivity, as well as the effect of the estrous cycle on taste responsivity, in a rodent model. In the taste reactivity test, male and female Long-Evans rats received a brief (1 min) intraoral infusion of one of three tastants: sucrose (0.3 M), quinine (0.0003 M), and a sucrose-quinine mixture (0.3 M sucrose and 0.0003 M quinine). Statistical analyses indicated that female rats tested during diestrus or proestrus produced significantly more ingestive responses than did male rats and fewer aversive responses than did both male rats and female rats tested during estrus or metestrus (P < 0.05). These results indicate a sex difference in taste responsivity in the rat that is modulated by the reproductive status of female rats. This finding implies a role of gonadal hormones in the regulation of taste responsivity in the rat.
9493864	Central injections of the selective tachykinin NK3 receptor agonist senktide (SENK) suppresses salt appetite. Also, following SENK, intraoral infusions of hypertonic NaCl elicit fewer ingestive taste reactivity responses and more aversive responses than following intraventricular injections of isotonic saline. This pattern of taste reactivity results suggest that SENK affects the oral stimulating properties of salt taste. Before accepting this interpretation, however, alternative explanations need to be examined. The following experiments evaluated whether the effects of intraventricular SENK injection on taste reactivity could be due to: 1) a general oral motor impairment that reduces ingestive responding to tastes (Experiment 1) or; 2) SENK having aversive consequences (Experiment 2). In Experiment 1, the effects of intraventricular injections of SENK (200 ng) on taste reactivity responses to 0.5 M NaCl and 0.1 M sucrose were measured in sodium deficient rats. Intraoral infusions of 0.5 M NaCl elicited fewer ingestive taste reactivity responses following SENK than injections of isotonic saline in sodium deficient rats. Sucrose continued to elicit the same high number of ingestive taste reactivity responses following intraventricular injections of isotonic saline and SENK. Thus, SENK did not cause a general decrease in ingestive responding. A conditioned taste aversion test was employed in Experiment 2 to determine if SENK had aversive consequences. Rats were given 30 min access to alanine (0.3 M) and were then administered either lithium chloride (LiCl) or intraventricular injections of SENK (200 ng) on three consecutive days. Rats avoided alanine that was paired with LiCl, but those rats that had alanine paired with SENK showed no avoidance of the taste even after three pairings. These results replicate findings that intraventricular injections of the NK3 agonist SENK decreases the palatability of NaCl (as measured by taste reactivity) and suggest that its effect on NaCl-elicited taste reactivity is not due to the treatment causing a motor impairment or malaise.
9443533	The hedonic properties of chlordiazepoxide (CDP) were examined using the place conditioning and the taste conditioning paradigms. Following four conditioning trials, CDP (5-20 mg/kg) produced a conditioned place aversion in an "unbiased" paradigm in which the chamber paired with CDP was counterbalanced among two equally preferred chambers. In a "biased" place-conditioning paradigm, CDP (5 and 20 mg/ kg) prevented the dissipation of the natural aversion to the nonpreferred chamber. Finally, although CDP unconditionally potentiated sucrose consumption, it produced a sucrose aversion in the taste reactivity test and sucrose avoidance in the taste avoidance test when the taste conditionally preceded injections of CDP. The pattern of findings suggest that, when novel to rats, CDP is hedonically aversive.
9408206	The aversive properties of acute naloxone-precipitated morphine withdrawal were examined in the taste reactivity paradigm. Acute naloxone-precipitated withdrawal paired with sucrose solution established conditioned active rejection of the sucrose solution. Active rejection of sucrose was observed when naloxone was administered both 1 h and 22 h after morphine. When the stimulus properties of morphine were present during the conditioning trial, the conditioned sucrose aversion was only expressed when the rats were tested in the same drug state in which they had learned the aversion. However, when the stimulus properties of morphine were not present during conditioning, the aversion was expressed in the absence of the morphine state. The results suggest that palatability shifts can be conditioned to sucrose paired with acute morphine withdrawal.
9329075	Several "taste reactivity" studies of dopamine and reward have concluded that pimozide suppresses the hedonic reaction patterns normally elicited by sucrose but enhances aversive reaction patterns elicited by quinine. However, other taste reactivity studies have failed to find hedonic/aversive shifts in reaction patterns after dopamine antagonists or dopamine lesions. The divergent conclusions have come from two different laboratories. To resolve the controversy regarding dopamine blockade and palatability, the present study joined the two laboratories to investigate the effect of pimozide on taste reactivity patterns elicited by sucrose and quinine. The results replicated many (but not all) of the earlier findings and identified procedural factors responsible for different outcomes. Overall, the results provide evidence for sensorimotor effects of pimozide on taste reactivity but not for a hedonic shift in palatability. Pimozide suppressed both hedonic and aversive reaction patterns in a gradual sensorimotor fashion when the eliciting taste stimulus was repeated or continued for several minutes. The general suppression typically did not alter the initial reaction to a taste but emerged only after an oral infusion of sucrose or quinine continued for several minutes or trials. Aversive reactions were never enhanced. The balance between hedonic and aversive reaction patterns was not shifted by pimozide. We conclude that pimozide produces a sensorimotor impairment of taste reactivity patterns but does not shift taste palatability toward anhedonia or aversion.
9194917	Acute naltrexone treatments (0.0, 0.5, 1., or 3.0 mg/kg body weight) were administered to separate groups of rats and alcohol taste reactivity and consumption were measured. Rats were given daily naltrexone injections and then tested for taste reactivity to 10% alcohol 30 and 60 min after injection. Each reactivity trial (total of 4) was 60 sec during which 1 ml of fluid was infused. The rats' orofacial and body movements were videotaped and scored later. In the final measure, rats were placed on a restricted fluid access schedule and given naltrexone treatments 10 min before being presented with the 10% alcohol solution in the home case (60-min drinking period). After 4 days of consumption tests under the drug condition, the rats were given 4 more daily tests without the drug. Results indicated that the two highest naltrexone doses significantly decreased ingestive responding and increased aversive responding, particularly at the 30-min test. Both the 1.0 and 3.0 mg/kg body weight doses also significantly decreased alcohol consumption as measured during the free access tests. Alcohol consumption returned to control levels immediately after the drug treatments were stopped. The data show that dosages of naltrexone 1.0 mg or higher significantly alter both alcohol taste reactivity (increased aversiveness and decreased palatability) and alcohol consumption (decreased intake) in outbred rats. These results are discussed in relation to naltrexone treatment as a means for decreasing alcohol use and abuse.
9160799	High, low, and control alcohol-sensitive (HAS, LAS, CAS, respectively) rats were tested for their perception of the taste of alcohol using the taste reactivity test. Reactivity tests with a single concentration of sucrose and quinine were also done. After initial taste reactivity, all rats were tested for alcohol consumption in a standard two-bottle test (water in the second bottle). Postconsumption taste reactivity tests completed the experiment. Results indicated that HAS, LAS, and CAS rats did not differ significantly in their taste reactivity response to a range of alcohol concentrations (5-40%), nor did they differ significantly in response to sucrose or quinine. Reactivity responses were similar for each group before and after the consumption tests. Despite the lack of line differences in taste reactivity, HAS and LAS rats consumed significantly less alcohol than the CAS rats during the two-bottle access tests. The present results are in contrast to research done with rats selectively bred for alcohol consumption (Alcohol Preferring and Nonpreferring rats, High Alcohol Drinking and Low Alcohol Drinking rats), which exhibit clear line differences in patterns of reactivity changes following alcohol access. The selection phenotype of alcohol sensitivity appears to be independent of rats' behavioral response to the taste of alcohol.
9409086	Opiates in general, and heroin in particular, are known to induce compulsive drug-seeking and drug-taking behavior. Addiction is accompanied by psychobiological processes which may distort perception of sensory stimuli. Gustatory and olfactory stimuli are hedonically polarized and therefore most appropriate for the assessment of the organism's reactivity to "useful" and "harmful" chemosensory events. Previous studies revealed that psychophysical self-estimates and reflectory facial expressions mirror with comparable reliability the hedonics of the perceived taste and odor sensations. In the present study both cognitive verbal and reflectory facial expressions of a group of: a) heroin addicts were recorded and compared to those of a group of b) detoxified former addicts and to c) a group of matching controls. Results show that all three groups differentiate between pleasant, indifferent and aversive tastes and odors. Active addicts estimated sweet taste and savory smells as being somewhat more pleasant, and bitter and sour tastes and a putrid odor as less unpleasant than did the other two groups. The reflectory facial displays of addicts were less expressive and discriminative than those of the two other groups. Taste- and odor-induced facial displays are known to be controlled primarily by the brainstem. The findings indicate that heroin-addiction affects brain-mechanisms, which mirror taste- and odor-hedonics. Modulation of the phylogenetically ancient, sensory-motor coordinations was found to be of a different pattern than that of the cortically-controlled cognitive reactions.
9037386	The distribution and origins of nitric oxide (NO)-producing nerves in the dog tongue with reference to calcitonin gene-related peptide (CGRP)-containing sensory fibers were investigated using NADPH-diaphorase (NADPH-d) histochemistry and immunohistochemistry for CGRP and NO synthase combined with retrograde axonal tracing and denervation experiments. The ultrastructural relationships between NADPH-d-positive and CGRP-immunoreactive neuronal elements were also examined electron microscopically. NADPH-d-positive and CGRP-immunoreactive varicose fibers were found within the taste buds and surrounding the epithelia of the fungiform papillae, and they disappeared completely after severance of the lingual nerve. Following injection of fast blue into the subepithelial layer of the anterior two thirds of the tongue, retrogradely labeled neurons possessing NO synthase and/or CGRP immunoreactivities were mainly detected in the trigeminal ganglion. Some of the retrogradely labeled trigeminal cells showed the coexistence of NADPH-d reactivity and CGRP immunoreactivity, but in the geniculate ganglion neither NADPH-d reactivity nor NO synthase immunoreactivity was found instead of retrogradely labeled CGRP-immunoreactive neurons. The lingual artery and its branches, including the arteriovenous anastomoses, showed dense distributions of NADPH-d-positive fibers, most of which were unaffected by the denervation experiments. There were many small ganglia in the tongue, and virtually all ganglionic neurons were NADPH-d reactive. CGRP-immuno-reactive varicose fibers were also found around the vascular walls and within the intralingual ganglia. Ultrastructural analysis revealed a close distribution of NADPH-d-positive and CGRP-immunoreactive varicose fibers within the arterial walls, and synaptic contacts between CGRP-immunoreactive terminals and NADPH-d-positive intralingual ganglionic neurons. These results indicated that the taste buds of epithelia of fungiform papillae in the anterior two thirds of the dog tongue receive NADPH-d-positive and CGRP-immunoreactive sensory fibers from the trigeminal ganglion, and that perivascular NADPH-d-positive fibers mainly originate from intrinsic ganglia in the tongue. The ultrastructural findings suggest an intrinsic peripheral nerve-reflex mechanism in the regulation of the lingual vascular function by NO-producing postganglionic parasympathetic neurons and CGRP-containing sensory fibers.
8981466	Taste avoidances were conditioned in male rats by pairing ingestion of a novel sucrose (0.3 M solution) taste with injections of 17 beta oestradiol (100 micrograms kg-1, s.c.). Following conditioning and prior to a two-bottle choice test (sucrose vs water), taste reactivity responses to three 30 s intraoral sucrose infusions were quantified. A robust conditioned shift in palatability, consisting of reduced ingestive and increased aversive taste reactivity responses, was obtained in the oestradiol group but not the vehicle control group. This conditioned palatability shift was also reflected in subsequent strong avoidance of the sucrose solution in the two-bottle choice test. The findings that oestradiol can condition taste aversions and shift food preferences support a role for oestrogens in the production of anorexia.
8946425	The aim of these experiments was to determine whether impaired retention performance in aversively motivated tasks, induced by blockade of amygdala AMPA receptors, is due to influences on mechanisms underlying memory retrieval or to other influences on performance. Rats received either footshock escape training (1 or 10 trials), or no foot shock, in a two-compartment straight alley and bilateral intra-amygdala infusions of the AMPA receptor antagonist CNQX (0.5 microgram) were subsequently administered prior to inhibitory avoidance retention testing 8 days later. The CNQX impaired, but did not block, inhibitory avoidance retention performance as indicated by the initial latencies to enter the shock compartment. The animals were then retained in the alley until they remained in the starting compartment for 100 consecutive s and entries into the shock compartment were recorded as errors. In both the controls and CNQX-treated groups, increases in amount of original training resulted in fewer errors, indicating memory for the escape training. Furthermore, regardless of the amount of original training (i.e., 0, 1, or 10 trials), CNQX-treated groups made more errors. Other experiments examined intra-amygdala CNQX effects on reactivity to footshock, locomotor activity, and anxiety. CNQX decreased reactivity to footshock, blocked shock-induced decreases in locomotor activity, and had an anxiolytic effect in an elevated plus maze comparable to that induced by midazolam (0.5 microgram). These findings suggest that intra-amygdala infusions of CNQX prior to retention testing affect inhibitory avoidance retention performance following aversive training by altering locomotor activity, reducing sensitivity to footshock, and reducing anxiety. The implications of these findings for hypotheses concerning amygdala function in aversively motivated learning and memory is discussed.
8899901	Our previous studies have shown that i.c.v. injections of the selective tachykinin NK3 receptor agonist [Asp5,6,MePhe8]substance P(5,11), also referred to as NH2-senktide (NH2-SENK), inhibit salt intake in rats in a two-bottle intake test. The present study evaluated the effect of i.c.v. injections of NH2-SENK on intraoral intake and taste reactivity responses elicited by intraoral infusions of water or NaCl solutions (0.03, 0.15, 0.25 and 0.5 M) in sodium-replete rats. The effect of NH2-SENK on the intake of 0.03, 0.15 and 0.25 M NaCl solutions and of water was also evaluated in a two-bottle intake test. In this test, 31 ng/rat of NH2-SENK significantly reduced the intake of 0.15 and 0.25 M NaCl, but not that of water or of 0.03 M NaCl. The dose of 31 ng/rat of NH2-SENK reduced the intraoral intake of 0.25 and 0.5 M NaCl, while 125 ng/rat reduced the intraoral intake of 0.15, 0.25 and 0.5 M NaCl; neither dose reduced the intraoral intake of water or of 0.03 M NaCl. Taken together, these findings indicate that the effect of NH2-SENK on salt intake is dependent on the concentration of the NaCl solution offered; moreover, the intraoral intake data suggest that the effect of NH2-SENK on salt intake may be exerted to a large extent on the consummatory processes of salt ingestion. NH2-SENK, 31 or 125 ng/rat, altered taste reactivity responses shortly after the beginning of the intraoral infusion. The most peculiar effect was an increase in passive dripping during the first min of intraoral infusion of 0.15, 0.25 and 0.5 M, but not of water or of 0.03 M NaCl. This finding suggests that NH2-SENK elicits a prompt alteration of taste mechanisms for salt, which may account for its antinatriorexic action.
8853391	We used conjoint manipulation of taste and physiological state to address the theoretical issue of signal integration. The interaction between taste (glucose concentration) and state (food deprivation) was evaluated using the taste reactivity method in which oral motor responses elicited by direct intraoral infusion are measured. The time frame of the typical taste reactivity paradigm, where observation is limited to the infusion period, was expanded to include the postinfusion interval. In each test session, rats received a series of trials consisting of 15-s intraoral infusions and 45-s postinfusion observation intervals. Two experiments were run in which glucose concentration was varied and rats were run nondeprived and after 24 h food deprivation. In experiment 1, glucose concentrations (0, 3.2, 6.25, 12.5, and 25%) were randomly presented during each test session. In experiment 2, individual glucose concentrations (0, 6.25, or 25%) were presented during separate sessions. For both, a deprivation condition was flanked by nondeprived (baseline) sessions. Concentration-response functions were comparable in both experiments. In each experiment, the shape of the concentration-response function was dramatically different during and after infusions. During infusions, there were no increases in glucose-elicited rhythmic oral responses beyond a very dilute concentration. After infusions, the concentration-response functions appeared linear across the concentration range. In both experiments, deprivation elevated responding only in the after-infusion periods. In experiment 1, the concentration-response function was uniformly elevated (on average, 27%) by deprivation, which if taken at face value would suggest an additive combination of taste and state feedback signals. In experiment 2, however, deprivation increased responding (approximately 30%) for 6.25%, but not for 0 or 25%, suggesting a stimulus specificity of the taste-state integration. Clearly then, the taste-state profiles differed as a function of experimental design. In the GENERAL DISCUSSION, we suggest that the uniform elevation of responding to all glucose concentrations, and to water, seen in experiment 1, may be an artifact of the random presentation of all stimuli during individual sessions. Experiment 2, in which stimuli were presented in a between-sessions design, may provide a truer reflection of the underlying integrative process.
8842379	The hypothesis that benzodiazepine-induced hyperphagia is due to a specific enhancement of the palatability of foods has been supported by previous 'taste reactivity' studies of affective (hedonic and aversive) reactions to taste palatability. Diazepam and chlordiazepoxide enhance hedonic reactions of rats (rhythmic tongue protrusions, etc.) to sweet tastes in a receptor-specific fashion. A role for brainstem circuits has been indicated by a previous demonstration of the persistence of the taste reactivity enhancement by diazepam after midbrain decerebration. The present study examined whether benzodiazepine brainstem receptors are the chief substrates for palatability enhancement even in intact brains. We compared the effectiveness of benzodiazepine microinjections to elicit feeding and enhance hedonic reactions when delivered into either the lateral ventricle (forebrain) or the fourth ventricle (brainstem) of rats. The results show diazepam is reliably more effective at eliciting feeding and enhancing positive hedonic reactions to oral sucrose when microinjections are made in the fourth ventricle than in the lateral ventricle. We conclude that brainstem neural systems containing benzodiazepine-GABA receptors are likely to be the chief substrates for benzodiazepine-induced palatability enhancement.
24213867	Three dependent measures-a taste reactivity test, a two-bottle preference test, and a one-bottle extinction test-were used to investigate the conditioning effects of pairing a taste/taste compound with LiCl-induced illness in rats. Avoidance of saccharin consumption in the one-bottle test was attenuated if saccharin and denatonium were paired during illness training (overshadowing). Also, saccharin was found to be more palatable if paired with denatonium during training as reflected by aversive (but not ingestive) taste reactivity measures. It is argued that overshadowing was reflected mainly by a modulation of aversive taste reactivity behavior with little influence on ingestive taste reactivity. The results are discussed in terms of current palatability issues, and it is suggested that applying taste reactivity tests to phenomena associated with taste avoidance learning (e.g., overshadowing or potentiation) may further our understanding of the mechanisms that guide such learning. 
8888996	The hedonic properties of lysergic acid diethylamide (LSD) were assessed using the place conditioning, taste reactivity, and taste avoidance tests. LSD produced a conditioned place preference, but only at the highest dose tested (0.2 mg/kg). A single preexposure to the conditioning chamber (latent inhibition) prevented the establishment of a place preference. When paired with sucrose, doses of 0.05 to 0.2 mg/kg of LSD produced taste avoidance, but no dose of LSD produced an aversion to the taste as assessed by the taste reactivity test. These results suggest that LSD, like other rewarding drugs, produces taste avoidance by a mechanism other than that produced by emetic drugs.
8737903	The effects of d-fenfluramine on intake and on hedonic responses to taste stimuli in rats were investigated using a modified taste reactivity paradigm. Subjects (n = 15) were first trained to consume a 3% sucrose solution. They were then pretreated with d-fenfluramine (0.3-3.0 mg/kg, i.p.), and tested with access to either 3% sucrose, or a 0.01% quinine HCl solution. In the modified taste reactivity test, chronic oral cannulation was not used; instead, taste reactivity measures were scored during periods of noningestion in a voluntary intake test. d-Fenfluramine reliably reduced both sucrose and quinine consumption, and increased latency to drink at the highest dose. d-Fenfluramine also spared aversive responses to quinine, but reduced positive ingestive responses to sucrose. These results are consistent with an effect of d-fenfluramine to reduce taste palatability, which may, in turn, be an important factor in the effect of this drug on feeding motivation.
8778862	Rats selectively bred for high (HiS) vs. low (LoS) saccharin consumption were compared on taste reactivity responses to 0.1% saccharin before and after continuous access to 0.1% saccharin. The rats were also tested with other saccharin concentrations (0.01-0.3%) before and after the consumption test. Finally, all rats were tested for reactivity to 0.1 M sucrose, 0.0001 M quinine hydrochloride, and a sucrose + quinine mixture. HiS rats ingested more saccharin than did LoS rats, but the groups did not differ in total ingestive or total aversive reactivity on any of the taste tests. When aversive reactivity was analyzed further to distinguish passive drip from other, more active responses, HiS rats made more active responses than LoS rats; the latter showed a consistent tendency to passive drip more than HiS rats. Overall, aversive responding decreased and ingestive responding increased as saccharin concentration rose and from the first to the second concentration series. Because the brain stem-mediated hedonic evaluation of tastes by HiS and LoS rats appears to be similar, the difference in saccharin consumption must be mediated by psychological processes whose neural substrates lie above the brain stem.
8866978	The ability of morphine to modify sucrose palatability was assessed by the taste reactivity test. In Experiment 1, rats were injected with morphine (0.0, 0.5, 2.0, and 10.0 mg/kg, subcutaneously), 30 min before receiving a 10-min intraoral infusion of 2% or 20% sucrose solution. A dose of 2.0 mg/kg morphine enhanced ingestive reactions elicited by both concentrations of sucrose solution. In Experiment 2, the interval between morphine pretreatment and the taste reactivity test was manipulated. Rats given 2.0 mg/kg morphine 30 or 120 min before testing displayed enhanced ingestive reactions elicited by 20% sucrose solution during the first 5 min of a 10-min test. The results support the hypothesis that morphine enhances the hedonic assessment of sucrose solution.
8866948	The ability of individual differences in the strength of conditioned taste avoidance (CTA) to predict strength of place conditioning produced by the same drug was assessed. In Phase 1, rats were assigned to High CTA and Low CTA groups on the basis of their intake of saccharin solution previously paired with morphine, amphetamine, lithium, or fenfluramine. In Phase 2, the rats received place conditioning training with the same drug used during Phase 1. The rats that displayed the strongest amphetamine-induced CTA also displayed the strongest amphetamine-induced place preference, suggesting that a common mechanism mediates both effects. On the other hand, the strength of the CTA was unrelated to the strength of the place preference or place aversion produced by morphine, lithium, or fenfluramine.
8660034	The effects of a reduced energy content of two meals on hunger motivation, physiological variables and reactions to emotional stress were investigated. Healthy normal-weight male students received breakfast and lunch in the laboratory. Half of the subjects (n = 28) received meals with normal energy content (1700 kcal), and half received meals with reduced energy content (260 kcal). Psychological and physiological variables were obtained for 8 h from morning to afternoon, including during a period of emotional stress in the afternoon. Psychophysical state was altered by the reduction of energy in food (e.g. increased subjective motivation to eat, decreased systolic blood pressure). Noise decrease feelings of relaxation in subjects who had received low-energy meals, but not in subjects who had received high-energy meals. This enhanced emotional reactivity after low-energy intake is interpreted as a biologically meaningful consequence of the heightened hunger motivation. Furthermore, subjective hunger motivation was potentiated by stress when energy intake in the preceding hours was low. The latter result may be due to increased emotional reactions and/or an augmentation of deprivation-induced physiological changes by noise-induced emotional stress.
8652067	The rapid acquisition and subsequent retention of lithium-induced conditioned changes in taste reactivity responses to sucrose were examined in rats with the area postrema (AP) either ablated or intact. On 2 conditioning days, a series of brief intraoral sucrose infusions was paired with the effects of LiCl or NaCl injections. Repeated associations of the sucrose taste with the effects of lithium significantly reduced ingestive responses and increased aversive responses only in the AP-intact group. AP-ablated rats treated with LiCl and rats injected with NaCl displayed an ingestive pattern of responses. Only the AP-intact rats, previously injected with LiCl, subsequently displayed evidence of a conditioned taste aversion. We conclude that toxin activation of the AP is required to produce the conditioned shift in taste reactivity responses and subsequent expression of a taste aversion in rats treated with lithium.
8646491	In vivo electrophysiological recordings in the sea catfish, Arius felis, showed that the magnitude of the integrated facial taste responses to binary mixtures of amino acids was predictable with knowledge obtained from previous cross-adaptation studies of the relative independence of the respective binding sites of the component stimuli. Each component from which equal aliquots were drawn to form the mixtures was adjusted in concentration to provide for approximately equal response magnitudes. The magnitude of the taste responses to binary mixtures whose component amino acids showed minimal cross-adaptation was significantly greater than that to binary mixtures whose components exhibited considerable cross-reactivity. There was no evidence for mixture suppression. The relative magnitude of the taste responses in the sea catfish to stimulus mixtures is similar to that previously reported for olfactory receptor responses in the freshwater channel catfish and chorda tympani taste responses in the hamster.
8622814	What are the neural substrates of food reward? Are reward and pleasure identical? Can taste pleasure be assessed in animals? Is reward necessarily conscious? These questions have re-emerged in recent years, and there is now sufficient evidence to prompt re-examination of many preconceptions concerning reward and its relation to brain systems. This paper reviews evidence from many sources regarding both the psychological structure of food reward and the neural systems that mediate it. Special attention is paid to recent evidence from "tasty reactivity" studies of affective reactions to food. I argue that this evidence suggests the following surprising possibilities regarding the functional components and brain substrates of food reward. (1) Reward contains distinguishable psychological or functional components--"liking" (pleasure/palatability) and "wanting" (appetite/incentive motivation). These can be manipulated and measured separately. (2) Liking and wanting have separable neural substrates. Mediation of liking related to food reward involves neurotransmitter systems such as opioid and GABA/benzodiazepine systems, and anatomical structures such as ventral pallidum and brainstem primary gustatory relays. Mediation of wanting related to food reward involves mesotelencephalic dopamine systems, and divisions of nucleus accumbens and amygdala. Both liking and wanting arise from vastly distributed neural systems, but the two systems are separable. (3) Neural processing of food reward is not confined to the limbic forebrain. Aspects of food reward begin to be processed in the brainstem. A neural manipulation can enhance reward or produce aversion but no single lesion or transection is likely abolish all properties of food reward. (4) Both wanting and liking can exist without subjective awareness. Conscious experience can distort or blur the underlying reward process that gave rise to it. Subjective reports may contain false assessments of underlying processes, or even fail at all to register important reward processes. The core processes of liking and wanting that constitute reward are distinct from the subjective report or conscious awareness of those processes.
8577880	The taste reactivity (TR) test was devised as a method to obtain behavioural data in response to gustatory stimuli in neurologically impaired rats, incapable of voluntary feeding. Sapid solutions were infused through surgically implanted intraoral cannulae. Facial and motor responses corresponded well to known hedonic and aversive properties of tastes (e.g., sweet, bitter). TR testing has since proved effective as an adjunct to intake-based methods, in the psychopharmacology of ingestion in the normal rat. We developed a nonsurgical modification of the TR test, in which intact rats sampled stimuli voluntarily. The benzodiazepine receptor agonist midazolam (3.0 mg/kg, IP) was administered to rats first trained to consume a sweet 3% sucrose solution, and later tested with access to a bitter 0.01% quinine solution. Response were videotaped, and TR measures were scored during periods of noningestion using a frame-by-frame playback. Treatment increased ingestion and facilitated ingestive responses in accordance with published data for cannulated rats. Results support a two-component view of response palatability, in which treatment alters feeding motivation, increasing positive palatability and facilitating ingestion of both palatable and unpalatable stimuli.
8548298	Chronic intracerebroventricular (i.c.v.) infusion of 3.2 micrograms/day of nerve growth factor (NGF) in normal rats elevated choline acetyltransferase (ChAT) activity of the striatum, medial septum, and basal forebrain and improved performance of a conditioned taste aversion (CTA) task. Relative to bovine serum albumin (BSA) or Cytochrome C treatments, NGF treatment facilitated acquisition and prolonged extinction of a lithium chloride (LiCl)-induced saccharin aversion. This facilitation was evident at saccharin/LiCl intervals ranging up to 1 h. Also, NGF treatment did not increase reactivity to LiCl-induced illness and neither shifted detection thresholds nor altered hedonic reactions to taste stimuli, indicating that NGF did not produce simple changes in sensory function. NGF treatments that elevate ChAT also facilitate memory of CTA in normal, adult rats.
7501654	The effect of nicotine pretreatment on the palatability of flavored solutions was assessed using the taste reactivity test. In Experiment 1, low doses of nicotine [0.2-0.4 mg/kg, subcutaneously (s.c.)] suppressed the aversive taste properties of quinine and quinine-sucrose mixture and enhanced the hedonic taste properties of sucrose (0.4 mg/kg, s.c.) in rats that were nicotine naive. In Experiment 2, rats were chronically preexposed to nicotine or saline over a period of 21 pretreatment days. Tolerance developed to the ability of nicotine to enhance the palatability of sucrose. Furthermore, rats that were chronically preexposed to nicotine displayed enhanced hedonic evaluation of sucrose 24 h after nicotine was withdrawn. These results confirm human self-reports that withdrawal from nicotine dependency enhances the palatability of sweet-tasting foods.
7667409	The purpose of this study was to determine whether the anorexia following epinephrine and glucose IP injections is due to the activation of mechanisms of satiety. Epinephrine (100 micrograms.kg-1) and glucose (4 g.kg-1) were injected IP in rats. In control sessions for epinephrine test, rats received IP saline, and IM epinephrine. In control sessions for the glucose test, rats received IP NaCl, isoosmotic to the glucose solution. Food intake or taste reactivity to a sucrose solution was recorded after these treatments. Epinephrine and glucose decreased food intake by 75% (p < 0.001), and 49% (p < 0.01), compared to their controls. No change of taste reactivity responses was observed with any of these treatments. Twelve-hour fasting did not modify the general taste reactivity responses when compared to the responses evoked in rats fed ad lib. These results might be explained by the fact that anorexia could be obtained by a suppression of hunger without the activation of the mechanisms of satiety. This in turn would imply a possible dissociation between the signals and physiological pathways normally involved in hunger and satiety.
7667376	Morphine pretreatment attenuates aversive taste reactions elicited by quinine solution when assessed by the taste reactivity test. To determine whether this effect changes across trials, rats were administered morphine (2 mg/kg, subcutaneously) 30 min before a 5-min intraoral infusion of quinine solution (0.05%) on each of eight trials. Neither tolerance nor sensitization developed to morphine-induced attenuation of quinine aversiveness; morphine suppressed quinine-elicited aversive reactions on each trial. In addition, when tested in the absence of morphine, rats displayed a reduced aversion to quinine, suggesting that quinine became conditionally less aversive following previous pairings with morphine.
7625558	High alcohol drinking (HAD) and low alcohol drinking (LAD) rats were tested, in three exposures, for taste reactivity to five concentrations of alcohol (5%, 10%, 20%, 30%, and 40%, v/v), water, and one concentration each of sucrose and quinine. Of the three reactivity exposures, one was done before a 3-week period of continuous access to water and 10% alcohol, the second test was done immediately after the consumption period, and the final reactivity test was done after 1 month of alcohol abstinence. The results showed that the groups did not differ in reactivity on the initial test. After the consumption tests (when the HAD rats consumed significantly more alcohol than the LAD rats), differences in reactivity were found: HAD rats produced significantly more ingestive responses (which promote consumption) and significantly fewer aversive responses (which facilitate fluid rejection) than LAD rats. These differences were maintained even after 1 month of alcohol abstinence. The present data replicate an earlier experiment with alcohol-preferring (P) rats and alcohol-non-preferring (NP) rats, and indicate that the selective breeding process does not produce differences in the innate perception of the taste of alcohol. However, after experience with drinking alcohol, rats selectively bred for high alcohol consumption exhibit a palatability shift reflected by high ingestive responding and little or no aversive responding. Such a shift would clearly contribute to the maintenance of high levels of alcohol consumption.
7753902	The effects of hydrational factors on the ability of cholecystokinin (CCK) to alter taste reactivity responses to intraoral water infusions was assessed in fluid-replete and fluid-deprived rats. Naive male rats were injected with CCK (8 micrograms/kg, IP), or physiological saline (1 ml/kg, IP) and taste reactivity responses elicited by brief (30 s) intraoral water infusions at 2, 4, 6, 8, and 10 min postinjection were measured. One week later and following a 24 h water deprivation period, taste reactivity responses to intraoral water infusions were measured again. Exogenous administration of CCK was found to produce a significant decrease in the frequency of ingestive responses accompanied by a significant increase in passive drip during oral water infusions in fluid-replete rats. In contrast, CCK was found to have no effect on the frequency of taste reactivity responses when rats were subjected to a period of water deprivation. These results demonstrate that the rat's state of hydration interacts with the ability of CCK to alter taste reactivity responses to intraoral water infusions.
7617672	The ability of chlordiazepoxide to modify taste reactions elicited by a saccharin solution that was paired on three occasions with amphetamine (1 or 3 mg/kg), lithium (0.3 or 1.2 mEq/kg), or saline solution was assessed using the taste reactivity test. Chlordiazepoxide enhanced positive ingestive reactions regardless of the conditional properties of the tastant and had no effect on aversive reactions. These results support previous reports that chlordiazepoxide directly modifies the palatability of tastants.
7734082	The hedonic properties of delta-9-tetrahydrocannabinol (THC) were assessed in place and taste conditioning paradigms in both Lewis and Sprague-Dawley rat strains. THC produced place avoidance, taste avoidance, and aversive taste reactivity responses in both strains. The Lewis strain displayed more aversive taste reactions and a stronger taste avoidance when conditioned with lower doses of THC than did the Sprague-Dawley strain of rats. THC is an anomalous drug of abuse that appears to be aversive to rats when assessed by these measures.
8696295	Do centrally-administered opioid agonists stimulate feeding by enhancing the palatability of foods? This hypothesis has been supported by several lines of evidence, including previous 'taste reactivity' studies of the influence of systemic morphine on affective (hedonic and aversive) behavioral reactions to taste palatability. The presents study examined whether opioid agonists enhance palatability by acting centrally on brain palatability systems. Here we report the effect of intraventricular microinjections of morphine (0, 12, 25, 50 nmols) on hedonic taste reactions to a 0.12 M sucrose solution. The effect on feeding was also assessed in order to determine whether feeding and palatability enhancement are linked, as would be required by the hypothesis that feeding is due to enhanced palatability. Both hedonic taste reactivity patterns and feeding were significantly increased together by morphine administration into the lateral ventricle. We conclude that opioid-induced enhancement of the hedonic palatability of food is a centrally mediated effect. Enhancement of food palatability may be an important psychological route by which intracranial administration of opioid agonists induce feeding.
7770201	Conditioned taste avoidances (CTAs) are an important component of behavioral regulation of ingestion. In the laboratory CTAs can be produced by pairing a novel taste stimulus with the physiological feedback produced by a toxin, such as lithium. Such toxins putatively activate a chemosensitive brainstem structure, the area postrema, which ultimately results in the production of a CTA. The present review describes a series of studies which examined conditioned changes in taste reactivity responses (TRRs) when a novel intraoral sucrose taste was paired with the effects of an intraperitoneal (IP) injection of LiCl, and the role of the area postrema in the formation of conditioned palatability shifts. It was first of all necessary to examine the effects of area postrema ablations on TRRs to a range of intraoral sucrose and quinine stimulus intensities. In the first study area postrema lesioned rats exhibited concentration dependent changes in TRRs to these taste stimuli that were very similar to those exhibited by sham lesioned rats. The second study demonstrated that 30 s intraoral infusions of sucrose (0.3 M), presented at 5 or 10 min intervals following an IP injection of LiCl (3.0 meq), resulted in conditioned changes in TRRs. These were characterized by orderly, gradual reductions in ingestive responses and increases in aversive responses. Finally, when area postrema lesioned rats (Study 3) were subjected to this conditioning procedure (brief sucrose presentations paired with the effects of LiCl) no evidence for conditioned or unconditioned changes in TRRs to sucrose were obtained. Lesioned rats injected with LiCl behaved similarly to sham lesioned rats injected with NaCl. These series of studies provide evidence indicating that the chemosensitive area postrema mediates the formation of conditioned palatability shifts induced by treatment with a toxin such as lithium.
7770200	In ingestive taste reactivity analysis, the rhythmic oral motor responses observed during intraoral infusion of fluids normally ingested by rats are categorized and counted. These rhythmic movements can be likened to spout-licking in several respects. Both are emitted in the same frequency range (5-8 Hz), organized in a burst/pause pattern, and serve the function of intraoral transport of fluid into position for swallowing. The parallel suggests that a temporal pattern analysis, based on the spout-licking literature, can be fruitfully applied to the rhythmic movements that attend intraoral infusion. We provide a demonstration of such an analysis using an electromyographic (EMG) recording-based method for automated event detection. Eight rats received a 37.5% glucose solution (1.0 ml/min) in a series of 120 s infusion trials (45 s intertrial intervals) that was extended until the fluid was rejected. Movement counts declined 19.1% from the first to the last complete trial. Parameters derived from the pattern analysis (number of bursts, mean burst duration, pause durations, coefficient of variation for the distribution of within-burst intermovement intervals) were affected to a greater extent. The results indicate the potential value of temporal pattern analysis for various applications of the taste reactivity paradigm.
7770193	The taste reactivity procedure provides a valuable tool for examining issues of palatability of alcohol solutions for rats. Given that alcohol is normally introduced to the internal milieu orally, taste factors must play an important role in the animal's decision to ingest or reject. Extensive studies of rats' reactivity to alcohol solutions have revealed several important variables that appear to affect palatability: solution concentration, alcohol experience, and postingestive consequences. In a recent selective breeding project, it has been found that taste reactivity to alcohol has a high heritability in rats. High ingestive responding and low ingestive responding rats were selected and bred to produce two lines. In the first selected generation, calculation of the realized heritability was 0.43; the cumulative realized heritability using the data from the second selected generation was 0.68. The introduction of the taste reactivity paradigm to the field of behavioral genetics may provide important information for the study of genetics, chemical senses, and alcohol consumption.
7770192	Benzodiazepine agonists stimulate feeding in animals. This paper reviews evidence which indicates that benzodiazepine-induced feeding is due to a specific enhancement of the perceived palatability of food and fluids, and is not a mere secondary consequence of anxiety reduction. In studies of the effect of benzodiazepines on affective reactions that are naturally elicited from rats by tastes, we have shown that (a) benzodiazepines enhance hedonic taste palatability in a receptor-specific fashion; (b) the relevant receptors and the minimal neural circuitry required to mediate benzodiazepine-induced palatability enhancement both exist complete in the decerebrate brain stem; and (c) even in normal brains, receptors in the brain stem, not forebrain, are the primary substrate for the benzodiazepine-induced enhancement of taste palatability. We conclude that a 'benzodiazepine-GABA' neural system in the brain stem constitutes an important component of the neural hierarchy responsible for taste pleasure. The reason why benzodiazepine tranquilizers have not been reported to enhance palatability for humans may be that the appropriate studies have not yet been done, that human doses are low, and that the brain stem palatability system is less responsive to commonly prescribed agonists that are anxiety/arousal benzodiazepine systems. Finally, in keeping with the purpose of the symposium in which this paper was originally presented, we discuss a number of issues regarding the measurement and interpretation of taste reactivity data.
7770191	Taste plays a central role in guiding ingestive behavior and the encoding of taste is affected by manipulations that influence ingestive behavior. In this article, the use of the taste reactivity test to provide a behavioral assessment of how changes in the oral reinforcing properties of a taste may initiate or sustain ingestive behaviors in several contexts are discussed. The affects of the animal's sex, sodium deficiency, exogenous bombesin administration, and the role of central gustatory lesions in mediating taste reactivity responses are discussed. Findings indicate that an enhancement of ingestive taste reactivity responses correlate with an increased preference and intake of taste stimuli for some, but not all situations. Such situations include the bombesin-like peptides that reduce sucrose and sodium chloride intake without influencing taste reactivity responses. Conversely, female rats, compared to males, show an elevated intake and preference for a range of NaCl concentrations and a greater number of ingestive taste reactivity responses to some, but not all of the preferred concentrations. Such mismatches of taste reactivity and intake measures shift attention to the contribution of nongustatory factors (trigeminal, visceral) in the control of intake.
7878095	Bitterness is generally viewed as an undesirable attribute of foods and beverages, yet segments of the population regularly ingest items with a prominent bitter taste. The influence of taste sensitivity, exposure, selected personality traits (i.e., neophobia, variety seeking, sensation seeking) and pharmacological reactivity on alcohol and caffeine consumption, two widely consumed bitter substances, was assessed in 20 healthy adults (10 male, 10 female). Self-reported alcohol use was positively correlated with measured ethanol taste detection threshold and pharmacological reactivity (self-reported behavioral effects). The latter accounted for 23% of the variance in alcohol intake. Caffeine intake was significantly associated with personality traits. Sensation seeking status and self-reported reactivity to caffeine accounted for 46% of the variance in caffeine intake. Pleasantness ratings for novel bitter and sour foods were unaffected by 10 exposures whereas increased ratings were given to sweet and salty items. Variation in the influence of these factors between individuals and across products may explain individual differences in the acceptability and use of foods and beverages containing alcohol, caffeine and other bitter compounds.
7810758	To investigate the hypothesis that peripherally administered cholecystokinin (CCK) reduces food intake by the production of aversive internal cues, we examined the effects of the sulfated, octapeptide form of CCK on taste reactivity responses to oral sucrose infusions in male rats implanted with intraoral cannulas. After injection of CCK (4, 8, or 16 micrograms/kg ip) or 0.15 M saline (1 ml/kg ip), a series of brief (30 s) intraoral infusions of a 0.30 M sucrose solution was administered at 2-min intervals for 10 min. All doses of CCK were found to significantly decrease ingestive responding during the first and subsequent sucrose infusions without promoting a significant increase in aversive responses relative to controls. The lack of a gradual, conditioned shift in taste reactivity responses, from an ingestive to an aversive pattern (which is typically observed after LiCl administration), suggests that the production of nausea-like aversive internal cues was likely not responsible for the observed CCK-induced alterations in taste reactivity responses. It appears that the unconditioned, satiogenic effects of CCK contributed to the selective reduction in ingestive responses observed in the present study.
7734180	The binding site of gurmarin, a peptide inhibiting the sweet-taste sensation, was studied in taste buds in rat circumvallate papillae by means of a histochemical technique. Frozen sections of tongues were incubated with gurmarin conjugated with biotin and thereafter examined with a light microscope. Positive reactivity for the peptide was localized to the taste hairs, the apical projections of taste bud cells. The reaction appeared in about 10% of the circumvallate taste buds examined. As electrophysiological studies indicate that gurmarin suppresses the sweet-taste sensation at the level of reception, the present study suggests that the receptor for sweet taste is located on the taste hairs, and, furthermore, is present only in a certain, limited number of the taste buds.
7533632	Intracerebroventricular (i.c.v.) injections of tachykinin NK3 receptor agonists suppress NaCl intake by sodium deficient rats. The brief exposure, taste reactivity test was used to examine the effect of tachykinins on the immediate, oral reinforcing properties of NaCl (0.5 M) in sodium replete and sodium deficient male rats. In sodium replete rats, intraoral infusions of NaCl elicited a mixed response comprised of a similar number of ingestive and aversive responses following i.c.v. injections of saline and succinyl-[Asp6,N-Me-Phe8]substance P, (6-11), (SENK), a NK3 receptor agonist. When sodium deficient, saline injected rats showed a reliable increase in ingestive and a decrease in aversive taste reactivity responses. Lateral i.c.v. injections of SENK blocked the shift in taste reactivity responses by sodium deficient rats, indicating that concentrated NaCl retained its aversive taste property.
7986371	The researchers performed experiments to evaluate whether the effects of bombesin are selective for the satiation of ingestive behaviors related to energy balance or if ingestive behaviors associated with sodium balance are also suppressed by bombesin. Injections of 4 and 8 micrograms/kg bombesin reliably reduced need-free and sodium deficiency-induced NaCl intake in male rats. The effects of bombesin on the sodium-deficiency-induced change in taste reactivity was assessed. Injections of 4 micrograms/kg and 8 micrograms/kg bombesin had no effect on the sodium deficiency-induced shift in taste reactivity. These data indicate that bombesin suppresses NaCl intake and that bombesin does not appear to interact with gustatory sensibility in exerting its behavior-controlling action.
7972290	The ability of various doses (0, 1.25, 2.5, and 5.0 mg/kg) of fenfluramine to modify the palatability of sucrose and quinine solutions was assessed by means of the taste reactivity test. Although fenfluramine did not modify the positive hedonic ingestive reactions elicited by sucrose solution, it consistently enhanced the negatively hedonic aversive reactions elicited by unpalatable 0.05% quinine solution and moderately palatable 2% sucrose solution. The results suggest that fenfluramine enhances the aversive properties of tastants without suppressing the positive hedonic properties of tastants. The results support a two-dimensional model of palatability.
7945982	The affective mimetic responses of male Wistar rats with prior access to 6% ethanol in their home cages were observed during intraoral infusions of an equivalent alcohol solution. Ethanol preference in the home cage appeared unrelated to measures of aversion and ingestion in the taste reactivity tests in normal rats. Adrenalectomy, which significantly reduced home cage ethanol preference, failed to influence the taste reactions elicited by ethanol or water. On the other hand, treatment of intact rats with the 5-HT1A receptor agonist ipsapirone (2.5 mg/kg), a drug that also decreases ethanol drinking in two-bottle intake tests, did increase the duration of aversive groomings, whereas measures of ingestion remained unaffected. These results suggest that ipsapirone, but not adrenalectomy, may alter the palatability of ethanol; this perceptual change may partly underlie the ability of ipsapirone to reduce home cage alcohol drinking in the rat.
7943654	Naive, male rats (n = 14) were given continuous access to 10% alcohol and water for a period of 6 weeks. Concurrent taste reactivity tests showed a consistent increase in ingestive responding to a range of alcohol concentrations (10%-40%) over the course of alcohol access. The rats also showed a consistent decrease in aversive responding over time. These data suggested that the palatability of alcohol increased with alcohol experience. After a 1-month period of alcohol abstinence, however, ingestive taste reactivity to alcohol returned to the same level as that found when the rats were alcohol naive, whereas aversive responding approached the level seen initially. A separate control group (n = 13) given only water for the same length of time failed to show similar changes in taste reactivity to alcohol solutions.
11224269	Several lines of evidence suggest that the enzyme catalase plays an important role in many of the behavioral and reinforcing effects of ethanol, through its putative role in the central production of acetaldehyde. The role of catalase in the acquisition of voluntary ethanol consumption was examined in the present experiments by administering the catalase inhibitor 3-amino-1,2,4-triazole (aminotriazole) during the presentation of an ascending series of concentrations of either ethanol or saccharin-quinine solutions. Aminotriazole (0.5g/kg) significantly attenuated consumption of both ethanol and saccharin-quinine solutions throughout the acquisition period, and this effect remained during a subsequent maintenance period during which no injections were administered. Drinking did recover, however, when the acquisition procedure was reinstated. These results suggest that the effect of aminotriazole on the consumption of ethanol and saccharin-quinine may be the result of a change in reactivity to taste, or an aversive effect caused by drug administration.
8208759	The effects of low doses of d-amphetamine (0.25-0.5 mg/kg, IP) on taste reactions elicited by quinine solutions in a 5-10-min taste reactivity test were assessed in a series of three experiments. Amphetamine consistently suppressed aversive reactions elicited by quinine solutions. The results suggest that amphetamine, like morphine, attenuates the aversiveness of the taste of quinine solution.
8014254	The existence of a relationship between cardiovascular reactivity to signalled shock and alcohol consumption can be inferred from studies of males at increased familial risk for alcoholism. The present study examined two groups of nonalcoholic men--those with multigenerational histories (MGH) of alcoholism and family--history negative (FH-) controls-to determine whether reactivity was related to voluntary ethanol consumption in the context of a beverage taste test. High reactors, a significant majority of whom were MGH males, drank significantly more vodka and orange juice, rum and coke, and orange juice when asked to rate the flavor of three alcoholic and two nonalcoholic drinks. High reactors also consumed more alcohol on a weekly basis according to their self-report.
8115431	The ability of a rat's reactivity to the aversive taste properties of quinine to predict its' reactivity to the aversive taste properties of a lithium-paired sucrose solution were assessed. In phase 1, all rats were intraorally infused with 0.05% quinine solution over a 2-min taste reactivity (TR) test. On the basis of their composite aversive reactions, rats were divided into high reactors (HiQ) and low reactors (LoQ). In phase 2, rats were given three TR conditioning/testing trials in which they received a 2-min intraoral infusion of 0.5 M sucrose solution immediately followed by an IP injection of either 127.2 mg/kg lithium chloride or physiological saline. Among rats conditioned with lithium during phase 2, the phase-1 quinine HiQs displayed more aversive reactions than did the phase-1 quinine LoQs. This suggests that reactivity to the aversive properties of quinine may predict the strength of conditioned palatability shifts to a lithium-paired sucrose solution.
8155277	Bilateral damage to the central nucleus of the amygdala (CeAX) in the rat blunts need-induced NaCl intake and abolishes daily need-free NaCl intake when measured with a two-bottle test. Such a deficit could be the result of impaired taste function. To assess the taste function of the CeAX rat various taste stimuli were introduced directly into the oral cavity and taste-elicited oral motor responses were measured. Oral motor responses elicited by 0.62 M and 0.13 M sodium chloride, 0.3 M sucrose and 0.01 M citric acid, were similar in control and CeAX rats. Additionally CeAX and control rats acquired a taste aversion for fructose or maltose when either was paired with LiCl. Finally, in CeAX rats, like in control rats, the pattern of oral motor responses to 0.5 M NaCl was dependent on internal state; sodium depletion dramatically altered taste-elicited oral motor behavior. These results suggest that, in the rat, the deficits in NaCl intake behavior that follow CeAX do not appear to be a result of dramatic changes in gustatory function.
8170789	Depressive patients often complain about dullness of taste of previously liked food items as well as of persistent bad taste. Taste and smell experience can be reflected by cognitive (psychophysical) indicators and also by reflectory (facial expressive) responses. In the present study 21 depressed, hospitalized patients and 16 control subjects were exposed to food-related gustatory and olfactory stimuli. Psychophysical and videotaped facial reactions were recorded from both groups. Analysis indicated that cognitive estimates of taste hedonics were similar for depressed and control groups; the former responded to sweet taste with a shorter-lasting facial reaction, involving markedly fewer facial features expressing enjoyment, than did controls. Aversive tastes, in contrast, triggered comparable facial expressive features of disgust in both groups. Facial reactions of depressed patients to acceptable and aversive olfactory stimuli were all significantly shorter and more muted than those of controls. Facial reflexes triggered by chemical cues are known to be controlled primarily by brainstem structures. Present findings suggest a possible influence of the profound anhedonia of severe depression on subcortical processes.
8280397	Daily caloric intake regulation was studied in chronic supracollicular decerebrate rats with a complete transection of the neural axis at the meso-diencephalic juncture and in intact controls. For 1 week, each rat received 3 intraorally delivered meals per day. They were challenged to maintain their 3-meal daily intake over 1 week in which only 2 meals per day were delivered. Intact rats increased meal size to compensate for the lost opportunity to feed, whereas chronic decerebrate rats did not. Results suggest that, although the caudal brainstem, as previously shown (Grill & Kaplan, 1990), is sufficient to modulate ingestive behavior in taste reactivity and single-meal tests, it is not sufficient to regulate daily caloric intake. Although it is possible that chronic decerebrate rats retain a long-term regulatory competence that is somehow masked under the meal omission paradigm, forebrain-hindbrain interactions appear necessary for the coordination of short- and long-term intake control processes.
8279682	The weak ultrasonication (40 kHz, 12 mW, 1 week) of ethanol solutions was found to reduce stimulation of the senses of smell and taste by the ethanol on the basis of blind tests with an aqueous ethanol solution (33.0% w/v) and an immature distilled spirit (25.0% v/v). Experiments on mice also demonstrated that a treated aqueous ethanol solution had a weaker depressant effect on the central nervous system, as evaluated by the relative frequency with which mice regained the righting reflex at a dose of either 4.0 or 4.5 g/kg (p < 0.05 or p < 0.01, respectively) and by the reduction in rectal temperature at a dose of 5.0 g/kg (p < 0.05) soon after ethanol administration. Analyses of both the ethanol concentration by head-space gas chromatography and the free radicals by electron spin resonance spectrometer failed to reveal any chemical changes in aqueous ethanol solutions subjected to weak ultrasonication. However, measurement of the spin-lattice relaxation time (T1) of the 2H of water molecules by 2H-NMR showed that the treatment slightly accelerated the thermal motion of water molecules in the solutions. Treated solutions were also found to have a slightly higher density than untreated ones. These physical data demonstrate that weak ultrasonication induces a structural change, such as a more compact and homogeneous structure by changing the microdynamic behavior of the solution. These biological and physical studies suggest that only a slight structural change in an ethanol solution induces a marked change in the biological reactivity of ethanol without any chemical modification of the solution itself.
8265697	Idebenone (6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone) is a benzoquinone that has been shown to improve cognitive function in animals subjected to cerebral ischemia and in rats with lesions of the basal forebrain cholinergic system. Because the cognitive deficits observed in aged rats have been associated with decreased cerebral blood flow and basal forebrain cholinergic dysfunction, it was hypothesized that IDE might improve cognition in aged animals. In the present study, the effects of idebenone on cognitive function in aged Long-Evans rats were assessed using a battery of tests that evaluated attention, habituation, and spatial learning. Selective attention was assessed using an overshadowing paradigm, where IDE (30 mg/kg, IP) was injected 30 min prior to compound cue exposure. IDE enhanced the overshadowing effect in aged rats. The Morris water maze was used to assess spatial learning, where IDE (3 mg/kg, IP) was injected daily throughout the course of training. IDE did not improve the impaired performance of aged rats in the Morris task. Habituation was tested by measuring recovery from gustatory neophobia. IDE (30 mg/kg, IP) was injected 30 min prior to the first exposure to the novel taste. IDE normalized habituation rate in aged rats. It was concluded that IDE improves some forms of acquisition in aged rats, and may do so by decreasing general reactivity to novel stimuli.
8487545	Physiological responses and self-reported desire for alcohol were compared in heavy (n = 21) and light (n = 29) drinkers under each of two cue conditions. The cues were presented in a counterbalanced order and consisted of the sight, smell and taste of the subject's preferred alcoholic beverage (alcohol cue) and of a nonalcoholic lemon-flavored drink (neutral cue). Heavy drinkers showed a significant linear increase in reported desire for alcohol over time in the presence of the alcohol cue. This persistent increase in desire for alcohol seen in heavy drinkers contrasted with the initial increase shown by light drinkers which dissipated over time. Neither group showed any significant change in desire for alcohol when presented with the neutral cue. Heavy drinkers showed lower levels of skin conductance than light drinkers and all subjects showed changes in heart rate during exposure to both cues. Heart rate was affected differentially in the two groups of drinkers but only when the alcohol cue was presented first. Neither blood pressure nor stress and arousal levels changed significantly from pre- to post-cue presentations. The findings of this study have implications for understanding the nature and time course of cue-elicited desire for alcohol and its potential role in the development and treatment of alcohol dependence.
8447949	The nature of flavor-drug associations produced by a range of doses of the reinforcing agents cocaine (5, 10, 15, 20, or 40 mg/kg sc), phencyclidine (0.5, 2, 10, or 20 mg/kg sc), and methamphetamine (2, 5, or 10 mg/kg ip) were assessed by the taste reactivity (TR) test and the conditioned taste avoidance (CTA) test. Even at the highest doses tested, none of the agents produced aversive TR responding. At doses that produced equivalent-strength CTA, lithium did establish aversive TR responding. These results provide evidence that drugs that serve as reinforcers in other paradigms produce conditioned flavor avoidance that is not motivated by a conditioned dislike for the flavor.
8432680	Toxicity studies commonly include unavoidable environmental differences (experimental history) among test groups, such as chemical taste, odor and irritation. The influence of environmental variables on USEPA guideline neurotoxicity tests was evaluated using an environmental enrichment model. 6-week-old male Fischer 344 rats were housed for 13 weeks in pairs with access to an exercise wheel, trained to run on a rotating rod and handled frequently. Control animals were housed singly, lacked the exercise wheel and rotating rod training, and had only routine interaction with caretakers. At the end of 13 weeks, flash evoked potentials (FEPs), somatosensory evoked potentials (SEPs), auditory brainstem responses (ABRs), grip performance, motor activity (MA), elements of the functional observational battery (activity and reactivity to handling/restraint) and brain histopathology with glial fibrillary acidic protein immunohistochemistry (GFAP IHC) were evaluated. Animals from the enriched group demonstrated changes (P < 0.05) in FEPs, SEPs and grip performance. Enriched animals were more active and reactive to their surroundings, and were highly reactive to physical restraint. Control (unenriched) animals showed little to no exploratory behavior and were more tolerant of restraint. Differences in experimental history can be detected using elements of standard guideline tests and may confound interpretation of such data if not taken into consideration.
8348348	Previous studies have shown that female rats consume significantly more sodium chloride (NaCl) than do age-matched males. The gustatory contribution to this sex difference was examined in the following experiments. In Experiment 1, female rats demonstrated a higher two-bottle preference for NaCl ranging from 0.03 M to 1.0 M than did age-matched males. Next, to determine if the animal's sex modified gustatory sensitivity for NaCl, taste reactivity responses elicited by intraoral infusions (0.8 ml) of NaCl (0.03 M, 0.15 M, 0.3 M, and 1.0 M) were measured in age-matched male and female Sprague-Dawley rats. Intraoral infusions of NaCl were administered in ascending concentration order on successive days. During the intraoral infusion, the animal's oral motor taste reactivity responses were videotaped and subsequently analyzed to determine the number of ingestive and aversive responses. Intraoral infusions of 0.15 M and 0.3 M NaCl elicited reliably more ingestive responses and 1.0 M NaCl more aversive responses in females than in males. Because differences in taste reactivity were not found for all those concentrations for which female rats showed a higher preference than did males, changes in gustatory sensitivity contributes to, but does not appear to fully account for the female rats' preference for NaCl.
1335271	We used the taste reactivity (TR) test, a direct measure of the hedonic properties of a tastant, to assess in Sprague-Dawley rats the ability of morphine (an opiate agonist) and naltrexone (an opiate antagonist) to modify the palatability of a bitter quinine solution and a sweet sucrose solution. Morphine reduced the aversive hedonic properties of both novel and familiar quinine solution (0.05% and 0.1%) but did not modify the palatability of 20% sucrose solution. Naltrexone reduced the positive hedonic properties of sucrose solution (2% and 20%) but did not modify the palatability of 0.05% quinine solution. The pattern of results suggests that the modification of feeding produced by opiate agonists and antagonists may be mediated by an hedonic shift in the palatability of the tastant.
1332732	Alterations in the motivation to ingest sucrose can be quantified by measuring the number and type of oral motor and somatic responses (i.e., taste reactivity [TR]) that are elicited by sucrose. In 2 experiments, rats had intraorally infused sucrose paired with LiCl injections for several trials, or they were injected with LiCl and had sucrose infused every 5 min during the 30-min postinjection period (data from Spector, Breslin, & Grill, 1988). In both experiments, ingestive TR responses decreased, whereas aversive TR responses increased over trials. Individual response components that comprise the ingestive and aversive categories followed the same trends of increase or decrease but changed at different rates as a function of number of trials or exposures. Overall, the array of response components could be projected onto a single unidimensional scale of palatability to capture the motivational states that ranged from acceptance to rejection.
1418662	In two experiments, rats were presented with water and six concentrations of alcohol (0.5%, 3%, 6%, 9%, 12%, and 15%, v/v) under conditions of mild fluid deprivation. Their responses were measured using taste reactivity (fluids infused directly into the mouth), consumption, and lick rate (both in a voluntary drinking situation). Results in both experiments showed that the number of overall ingestive responses was relatively high and consistent across all alcohol concentrations and water; aversive responding was low for all solutions. During one-bottle, 10-min tests, rats consumed the three lowest concentrations of alcohol (0.5%, 3%, and 6%) and water at an equal level. There was an abrupt drop in the amount of alcohol consumed at 9% and a continued decrease at the two highest concentrations. Lick rates for alcohol (measured only in Experiment 2) fell into three general patterns: 0.5%, 3%, and 6% produced almost identical, negatively accelerating curves consistently above that of water which was linear; lick rates for 9% and 12% rose initially but, at approximately 2 min, became flat; the 15% solution produced a low lick rate throughout the 5-min period. There were significant correlations between lick rate and amount consumed but, contrary to expectations, no significant correlations were found between taste reactivity and the other two measures (consumption and lick rate). These results suggest that taste reactivity to alcohol solutions may be reflective of processes different from those that regulate licking behavior or actual consumption.
1489123	We have evaluated the properties of capsaicin as a selective cough-inducing agent in healthy human subjects. Despite frequent coughing, the subjects could inhale repeated breaths of capsaicin aerosol during 60 s without difficulty. Cough started immediately on inhalation and was most intense during the first 30 s. Cough always disappeared promptly when the capsaicin inhalation was terminated. The cough response was well reproducible and concentration-dependent up to 10 microM; at higher concentrations there was a distinct plateau of the cough response. Specific airway conductance was not changed 3 min after 50 microM capsaicin. Capsaicin (> or = 10 microM) had a burning taste, but there were no visual signs of pharyngitis or laryngitis. Citric acid (nebulized solutions 0.125 to 32%) had a choking effect and could be administered only as single breaths. There was no correlation between the cough response to citric acid and to capsaicin. Inhaled lidocaine (20 and 80 mg from nebulized solutions) caused a dose-dependent inhibition of capsaicin-induced cough. Lidocaine suppressed citric acid-induced cough as effectively as capsaicin-induced cough. In conclusion, we have characterized capsaicin-induced cough and demonstrated that it can be a useful tool in the study of cough reactivity and for evaluation of antitussive agents in humans. Capsaicin may be complementary to citric acid and may offer experimental advantages over this traditional tussive stimulus.
1584835	The reinforcing/aversive properties of various doses of naltrexone (0.01, 1, and 10 mg/kg) were assessed in three experiments that employed place conditioning, taste reactivity, and taste avoidance paradigms. Naltrexone produced a place aversion and a taste aversion, but did not produce aversive taste reactivity responses, even at the highest dose (10 mg/kg) tested. This suggests that drugs that produce a place aversion do not necessarily produce a conditional dislike for a flavored solution with which they are paired.
1576537	Two-bottle intake tests and taste reactivity (TR) tests were used to reveal whether changes in ingestive behavior would follow bilateral section of either the chorda tympani (CT) or the glossopharyngeal (GP) nerve. Rats received two-bottle intake tests to compare 24-h ingestion of water to that of NaCl, MgCl2, quinine, or sucrose. Prior to each long-term intake test, rats received a 1 min, 1 ml intraoral infusion of the same chemical stimulus. Ingestive and aversive oral motor responses elicited by these 1 ml infusions were videotaped and subsequently analyzed. GP-section did not alter quinine or sucrose preference; overall, preference of MgCl2 and NaCl was also similar to controls. In contrast, TR tests in GP-sectioned rats revealed that most quinine, MgCl2 and NaCl stimuli elicited significantly fewer aversive oral motor responses. In addition, the latency of aversive responses to these 3 chemical stimuli was increased for these rats. Intake-based preference tests failed to show any difference between rats with CT nerve section and controls. In TR tests, however, CT-sectioned rats displayed significantly fewer ingestive oral motor responses to NaCl, MgCl2, and quinine than controls. Neither sucrose intake nor sucrose-elicited TR were altered by CT or GP nerve section. This report confirms the failure of long-term intake tests to uncover behavioral deficits following the section of gustatory nerves. In contrast, the use of a different behavioral test makes clear for the first time that gustatory nerve section has dramatic consequences on ingestive behavior. The examination of taste elicited oral motor behaviors reveals a coherent and nerve specific pattern of neurological deficit following peripheral nerve section.
1576527	Two-bottle preference and taste-elicited oral motor responses were examined to determine whether the total lingual gustatory denervation that results from combined bilateral chorda tympani (CTX) and glossopharyngeal nerve section (GPX) would (a) alter the ingestive behavior of the rat and (b) if altered, whether the pattern of deficit revealed would be similar to or different from that obtained by sectioning each of the individual nerves separately. Remarkably, intake-based preference was unaffected by an approximately 80% reduction in taste receptors. Lingual gustatory denervation failed to affect the preference for any of the normally-preferred stimuli. Preference for only two of the 8 normally-avoided solutions was increased following the combined nerve cuts. In contrast, examination of oral motor taste-reactivity responses revealed that combined nerve sections significantly reduced the number of ingestive responses elicited by 5 or 6 normally-preferred and 5 of 8 normally-avoided stimuli. In addition, the pattern of deficits in taste-elicited oral motor responses resulting from the combined sections was different from that predicted by summing the effects of the individual nerve sections. We had shown that CTX did not alter aversive behavior to quinine whereas CPX did reduce these responses but did not affect their concentration dependence. Neither CTX nor GPX affected oral motor responses elicited by sucrose. Combined nerve section, by contrast, completely eliminated the concentration-dependent increases in aversive responses to quinine and ingestive responses to sucrose and glycine. In fact, CTX + GPX profoundly reduced the oral motor behavior elicited by all of the chemical stimuli examined.(ABSTRACT TRUNCATED AT 250 WORDS)
1737052	We have developed an enzyme immunoassay method for curculin, a new type of taste-modifying protein. This method can accurately quantify 0.05-20 ng of curculin, a sensitivity about 3000-times that of the psychometric method. The content of curculin in the fruit of Curculigo latifolia increased gradually until 3 weeks after artificial pollination and dramatically at 4 weeks, to finally reach 1.3 mg per fruit. Immunoblot analysis indicated that antiserum to curculin was faintly reactive with miraculin, but not with thaumatin or monellin.
1313241	Control rats rapidly learned to avoid drinking either a sucrose solution (Experiment 1) or a NaCl solution (Experiment 2) when the taste was paired with illness. These rats also produced aversive reactivity to each of these solutions in a taste reactivity test. Rats that lacked gustatory cortex (GC) learned to avoid drinking sucrose and NaCl, albeit at a slower rate than control rats. GC rats failed to display aversive reactivity to these tastes. The GC rats did show normal aversive reactivity to a strong quinine HCl solution during additional tests. It is suggested that the avoidance developed by GC rats did not entail a palatability shift of the conditional stimulus as it did in control rats. This altered learning strategy may account for the consistent learning deficits found in GC rats trained to avoid tastes.
1733338	Intraoral intakes of sucrose (SI; 0.1 M) and distilled water (WI) were measured in tube-fed neurologically intact and tube-fed chronic supracollicular decerebrate (CD) rats after intraperitoneal injections of saline and bombesin (BN) and gastrin-releasing peptide (GRP) in concentrations of 1, 2.5, 5, and 10 micrograms/kg. Also, to determine whether BN and GRP administration interacted with taste processing, oral motor responses during the 1st min of the intraoral infusion were videotaped and subsequently analyzed to determine the number of ingestive and aversive taste reactivity (TR) responses. Injections of greater than or equal to 2.5 micrograms/kg BN reliably suppressed SI similarly in both control and CD rats. In response to GRP, the only group difference was that injections of 1 microgram/kg GRP reliably suppressed SI in control but not CD rats. Administration of greater than or equal to 2.5 micrograms/kg GRP suppressed SI similarly in both control and CD rats. Although SI was suppressed by peripheral administration of BN and GRP, these treatments had no effect on the TR responses elicited by sucrose in either group. To determine whether the effects of BN and GRP were selective for sweet nutritive stimuli, intraoral WI was also measured in control rats after the same treatments. Injections of 5 and 10 micrograms/kg BN and 10 micrograms/kg GRP reliably suppressed WI, but lower doses had no effect. BN and GRP had no reliable effect on the pattern of TR responses elicited by water. Intraoral WI by CD rats was minimal (less than 1 ml) after injections of saline, BN, and GRP, and hence peptide effects could not be reliably assessed.(ABSTRACT TRUNCATED AT 250 WORDS)
1539074	The taste reactivity (TR) test was employed to measure the orofacial, somatic and consummatory CRs elicited by a lithium-paired food. Hungry rats were presented chocolate chips followed immediately by an injection of lithium chloride (CS+ group) or saline (CSc group). During the TR test, the rats' behavioral responses to the chocolate chips were videorecorded. The results demonstrated that rats in the CS+ group did not consume the lithium-paired food, but demonstrated the aversive TR response pattern of chain rubbing, paw treading, and gaping.
1480348	Consumption of a palatable wet mash was examined in rats subjected chronically (4-10 weeks) to unpredictable mild stress. Intake of mash containing 0, 10%, or 20% additional sucrose was normal in stressed animals. In control animals, the addition of 30% or 40% sucrose caused a decrease in the quantity of mash consumed, but increased the rate of eating. Both the increase in eating rate and the decrease in intake, at high sucrose concentration, were markedly attenuated in stressed animals (which therefore had higher intakes of very sweet mash and lower rates of eating, relative to control animals). Like chronic mild stress, the dopamine receptor antagonist pimozide (0.2 mg/kg) also increased the intake of a wet mash with 30% added sucrose, while decreasing the rate of consumption. Stressed animals were relatively insensitive to pimozide, though there were significant additive effects on duration of eating (increased) and on postprandial resting (suppressed). The failure of stressed animals to adapt their intake to increases in sweetness, and the similarities between the effects of chronic mild stress and acute pimozide, are compatible with the hypothesis that animals exposed to chronic mild stress are anhedonic.
1777108	A series of 3 experiments with Sprague-Dawley rats measured taste reactivity (TR) responses elicited by sucrose that was paired on 5 occasions with various doses of d-amphetamine (0, 1, 2, 5, or 10 mg/kg), nicotine (0, 0.4, 0.8, 1.2, or 2.0 mg/kg), or morphine (0, 2, 8, 20, or 80 mg/kg). The TR responses elicited by flavors paired with each of these drugs were compared with those elicited by flavors paired with lithium. The only doses of d-amphetamine and nicotine that effectively conditioned aversive TR responses were high doses that have also been demonstrated to be incapable of producing a place preference. Extremely high doses of morphine were incapable of producing aversive TR responses. It is suggested that aversive TR responses are only produced by doses of agents that are not reinforcing in other paradigms.
1777107	Intake and taste reactivity tests were used to determine the effects of bilateral lesions of the gustatory portions of the nucleus of the solitary tract (NST), the parabrachial nucleus (PBN), and the ventral posteromedial nucleus of the thalamus (VPMpc) on several complex ingestive behaviors. In the 1st experiment, lesions of the PBN and the NST blocked, and VPMpc lesions impaired, the behavioral expression of salt appetite. In the 2nd experiment, alanine was paired with injections of LiCl. Control rats as well as rats with NST and VPMpc lesions acquired the taste aversion, but rats with PBN lesions did not. In the 3rd experiment, all animals increased their food intake after injections of 2 U/kg insulin and 250 mg/kg 2-deoxy-D-glucose, and their food intake was suppressed after nutritive stomach loads.
1667827	Rats were given a single conditioning trial in which 20% sucrose solution was paired with an intraperitoneal (IP) injection of lithium chloride (127.2 mg/kg), d-amphetamine (3 mg/kg) or physiological saline. Thirty min before a subsequent 10-min taste reactivity (TR) test and a 1-h conditioned taste avoidance (CTA) test the rats were injected IP with either the antiemetic agent, trimethobenzamide (5 mg/kg) [corrected] or with physiological saline solution. The lithium-paired, but not the amphetamine- or saline-paired, sucrose solution elicited the aversive TR responses of chin rubs, paw pushes and gapes. Trimethobenzamide suppressed the aversive TR response of chin rubs in the lithium-conditioned group, but not in a group given unconditionally aversive quinine solution. The CTA test was not sensitive to the antiemetic properties of trimethobenzamide, although the drug enhanced sucrose preference overall. The results suggest that chin rub responses may measure conditioned sickness.
1663764	Bilateral electrophysiologically guided lesions were placed in the nucleus of the solitary tract (NST), the parabrachial nucleus (PBN), and the ventral posteromedial thalamic nucleus (VPMpc) of rats, and 15-min intake and taste reactivity (TR) responses elicited by 3 concentrations each of sucrose, NaCl, HCl, and quinine (Q) HCl were subsequently measured. Compared with controls, NST lesions had no significant effects on intake, and rats with PBN lesions consumed significantly more QHCl, sucrose, NaCl, and HCl. Thalamic lesions decreased sucrose intake. Analysis of TR responses showed that the QHCl threshold for aversive responses increased after VPMpc, PBN, and NST lesions. Rats with NST or PBN lesions were unresponsive to increasing sucrose concentration. TR responses elicited by NaCl and HCl were similar across the groups.
1791889	Experimental studies in humans and experimental animals document the acquisition and extinction of classically conditioned alterations of different parameters of humoral- and cell-mediated immune responses. Although the aversive effects of cyclophosphamide in a taste aversion learning paradigm has been the most frequently used model, conditioned immunomodulatory effects are not confined to this conditioning procedure, and they are not limited to cyclophosphamide or, for that matter, the use of immunomodulating drugs as unconditioned stimuli. Conditioned changes in immunologic reactivity have also been found to modulate the progression of spontaneously-developing or experimentally-induced pathophysiological processes in experimental animals. The available data on the immunoregulatory effects of conditioning indicate that the immune system, like other systems operating in the interests of homeostasis, is integrated with other physiological processes and is therefore influenced by and capable of influencing the brain.
1763109	The ability of the neuroleptic agent, pimozide, to modify sucrose palatability was assessed using three 10-min taste reactivity test sessions. Pimozide was found to suppress the ingestive response of tongue protrusions, but enhance the mildly ingestive/neutral response of mouth movements elicited by an intraoral infusion of sucrose solution. Since the pattern of taste reactivity responding shifted from highly ingestive to mildly ingestive/neutral, our results suggest that pimozide pretreatment reduces the palatability of sucrose solution. The temporal pattern of the modification of these taste reactivity responses was predicted by the Anhedonia Hypothesis.
1896509	Taste reactivity, which was first described in the rat, consists of ingestive and aversive response components, the latter seen mostly to bitter-tasting stimuli. The present experiment characterized the hamster's taste reactivity to an array of stimuli (sugars: 1 M sucrose, d-fructose and d-glucose; sodium salts: 1 M NaCl, Na2SO4 and NaNO3; acids: 30 mM HCl, tartaric acid and citric acid; bitter-tasting stimuli: 100 mM quinine hydrochloride and nicotine sulfate and 10 mM denatonium benzoate). These 12 stimuli were chosen to represent 3 examples each of stimuli that taste sweet, salty, sour, or bitter to humans; they were presented in random order via an intraoral fistula, one stimulus each day per animal (n = 10). Infusions of 0.6 ml were delivered over a 1-min period from a syringe pump. Orofacial and somatic motor responses were recorded on videotape for later analysis and were also coded online into a computer. Ingestive responses included forward and lateral tongue protrusions and aversive responses included gaping, chin rubbing, forelimb flailing, fluid rejection, increased locomotion, and aversive posturing. Each stimulus group produced a characteristic pattern of these behaviors, with sugars eliciting only ingestive behaviors and the bitter stimuli evoking predominantly aversive responses. Both sodium salts and acids produced ingestive responses, as seen previously in the rat, although these stimuli also elicited aversive behaviors in the hamster, including apes. The patterns of responses were characterized using multivariate procedures; the stimuli fell into distinct groups that were separated primarily along an hedonic dimension.
2064389	Human judgements of the pleasure of sweetness have been reported to be modulated by caloric hunger, satiety, and sensory-specific satiety. This study examined both hedonic and aversive facial/somatic reactions to taste in the rat, in order to confirm the relation of hunger and satiety to taste affect, and to assess whether affective modulation depends upon the cognitive factors that mediate human self-interpretation of affect. In the first experiment, the affective reactions of rats to sweet, bittersweet, and water tastes were assessed in five states of caloric hunger or satiety. Caloric satiety reduced positive hedonic reactions below normal levels. Conversely, 48-h food deprivation (but not 24-h deprivation) increased hedonic reactivity. Hedonic enhancement by hunger was not restricted to sweet tastes, but also extended to the palatability of water. Only the hedonic reactions to taste were changed by hunger or satiety: taste aversion was not altered. The second experiment compared the magnitude of affective change during sensory-specific satiety and caloric satiety. Taste-reactivity elicited by sucrose solution or milk was assessed after satiating meals of each of those foods. Sensory-specific satiety further reduced hedonic reactions below the level achieved by caloric satiety alone. Both for caloric satiety and for sensory-specific satiety changes in affect were restricted to positive hedonic reactions: no increase in aversion accompanied the hedonic decrements. These results confirm that taste affect is modulated during caloric hunger, caloric satiety, and sensory-specific satiety. In addition they indicate that the modulation of taste affect by hunger and satiety is confined to the positive limb of the two dimensions (hedonic vs. aversive) of palatability.
1821270	Weight gain is considered a frequent consequence of smoking cessation. Several psychological mechanisms may play an important role in weight gain following smoking cessation. The present investigation examined changes in food craving associated with smoking cessation using psychophysiologic (i.e., salivation), self-report, and behavioral (i.e., ad lib consumption) measures of reactivity to food cues in a prospective design. Although quitters (n = 16) evidenced weight gain (approximately 5 lbs.) at 1 week and 5 weeks post quit date and while control groups of smokers (n = 11) and nonsmokers (n = 16) did not, no support was found for increased craving assessed via self-report or salivation. The quitters did show evidence of increased craving as measured by ad lib consumption, while smokers and nonsmokers did not. However, the failure to find a significant Group by Session interaction limits our ability to make a strong statement concerning between-group differences on ad lib consumption.
2261091	Rats were given a series of the conditioning trials during which sucrose solution was paired with ethanol which had previously been experienced on 0, 3, or 9 occasions. On each conditioning trial, the rats received a Taste Reactivity Trial, a Taste Avoidance Trial, and a Place-Conditioning Trial. After the rats had received 4 conditioning trials, they were given a Conditioned Place Preference Test, a Taste Reactivity (TR) Test, and a Conditioned Aversion Extinction Test. Only the group conditioned with novel ethanol demonstrated aversive TR responses, although all CS + groups eventually demonstrated suppressed ingestive TR responses and enhanced neutral TR responses. Familiarization attenuated, but did not eliminate, ethanol-induced CTAs. There was no evidence of place conditioning.
1982355	Previous studies have shown that rats' positive, palatability-dependent consummatory reactions to infused tastes are selectively facilitated by a benzodiazepine agonist (chlordiazepoxide), and that this effect can be blocked by the coadministration of benzodiazepine antagonists (e.g., Ro 15-1788). The purpose of the present study was to determine whether agents acting at other receptor sites (dopaminergic, serotonergic), which have been shown to modulate food consumption, might also modify rats' palatability-dependent reactivity to infused tastes. In this experiment, the benzodiazepine agonist, diazepam, facilitated positive palatability reactions, while dopaminergic agents (haloperidol, apomorphine, amphetamine) had no significant effects on either positive or aversive reactions. The putative 5-HT1A agonists, buspirone and gepirone, had a general inhibitory action on both positive and aversive palatability reactions. These results are surprising in view of the effects of serotonergic and dopaminergic agents on food and fluid intake. Our results suggest that the benzodiazepine receptor system may play a special role in the neural control of appetite through its enhancement of the positive palatability of tastes. Dopamine systems, by contrast, appear to control food intake by modulating processes that are independent of food affect evaluation.
2264601	Taste reactivity tests were used to examine the orofacial responses of alcohol preferring (P) rats and alcohol nonpreferring (NP) rats to the taste of alcohol. In the initial exposure, naive rats were tested for reactivity to five concentrations of alcohol (5%, 10%, 20%, 30%, and 40% v/v), water, and one solution each of sucrose and quinine. A two-bottle consumption test was then given for a 3-week period to allow the rats access to 10% alcohol. After the preference test, a second taste reactivity test was done using the same solutions as in the initial reactivity test. The results indicated no significant differences in taste reactivity between P rats and NP rats on the initial exposure, except that NP rats made significantly more mouth movements. During the two-bottle tests, consumption of alcohol by P rats was consistently higher than that of NP rats across all test days. On the second taste reactivity test, P rats showed an increase in the number of ingestive responses and a decrease in the number of aversive responses to alcohol. NP rats' taste reactivity to alcohol remained unchanged from Exposure 1 to Exposure 2. P rats' and NP rats' responses to sucrose and quinine did not change from Exposure 1 to Exposure 2. It was concluded that there were no innate taste response differences between P and NP rats to alcohol but that following alcohol experience, P rats showed a significant increase in ingestive responses and a concomitant decrease in aversive responses to the taste of alcohol.(ABSTRACT TRUNCATED AT 250 WORDS)
2244985	This study examined the relationship between sensorimotor and motivational functions of the corpus striatum. In rats, excitotoxic lesions of the corpus striatum (neostriatum and globus pallidus) caused by kainic or quisqualic acid can produce both aversive aphagia and a "choreic" sensorimotor syndrome: an exaggerated treading of the forepaws that is triggered by oral sensory stimulation. Experiment 1 used a recovery-of-function approach to show that (a) aphagia induced by ventroposterior striatopallidal lesions was accompanied by an enhancement of aversion (a specific motivational process) to sweet stimuli, which was expressed in taste reactivity measures of affective evaluation; (b) aphagia and enhanced aversion recovered together; and (c) exaggerated treading did not disappear with aphagia-aversion but narrowed the range of its eliciting trigger to sour and bitter stimuli. Experiment 2 used a partial lesion approach to show that this dissociation of enhanced aversion and exaggerated treading could be reproduced by smaller lesions immediately after striatopallidal damage. Experiment 3 used a conditioned aversion procedure to show that the stimulus for exaggerated treading was aversion (natural or conditioned) and not a simple sensory feature of oral stimulation. Three conclusions were made: (a) Exaggerated treading after a small lesion or after partial recovery from a larger one results from a restructuring of a sensorimotor relations that is nested within a system of aversive reaction, (b) exaggerated treading is elicited only by tastes that elicit natural or conditioned aversion, and (c) more extensive lesions potentiate aversion to tastes that are normally palatable and expand the range of treading elicitors to include those tastes. In other words, affective and sensorimotor systems interact in a hierarchial manner in the production of choreic treading. These results demonstrate a specific hierarchical link between motivational and sensorimotor functions mediated by striatopallidal circuits.
2171001	That an aversive property of phenylpropanolamine (PPA) in part contributes to its anorexic capacity is suggested by the demonstration of conditioned taste avoidance to PPA doses ranging from 10-40 mg/kg. In order to further evaluate the putative aversive property of PPA, the present experiment compared the effects of PPA on multiple measures of aversion (chin rubs, gaping) in the taste reactivity (TRT) paradigm with those produced by the classic agent lithium chloride and by amphetamine. Male rats were infused via an intraoral cannula with 0.5 M sucrose followed by injection with either vehicle, 127 mg/kg lithium chloride (LiCl), 1.5 or 3.0 mg/kg amphetamine or by 10, 20 or 40 mg/kg PPA. LiCl and 40 mg/kg PPA induced significant chin rub responses during conditioning but only the aversive response induced by 40 mg/kg PPA persisted during extinction trials. In contrast, lower doses of PPA (10 mg/kg, 20 mg/kg) were not aversive in the TRT paradigm. These results suggest that an aversive component is not contributing to anorexia induced by PPA within the dose range of 10-20 mg/kg, but that higher doses may further suppress appetite via an aversive action.
2377665	The taste reactivity test was employed to assess the effect of pimozide pretreatment on rats' hedonic responsiveness to palatable and unpalatable tastants. Pimozide selectively enhanced the aversiveness of unconditionally unpalatable quinine solution (Experiment 1) and produced the greatest enhancement of aversion at the highest concentration of quinine (0.1%) solution tested (Experiment 3). Pimozide also enhanced the aversiveness of a conditionally unpalatable lithium-paired solution, but only when the dose of pimozide was relatively high and the strength of the baseline aversion was relatively low (Experiment 2). These results are discussed in light of the anhedonia and the sensorimotor deficit hypotheses of neuroleptic effects on reinforced responding.
2357596	The helplessness paradigm is used extensively in basic stress research and is an experimental model of clinical depression. In Experiment 1, exposure to unsignaled, inescapable shock resulted in finickiness about drinking a weak quinine solution, as previously reported. In contrast, exposure to escapable shock resulted in marked individual differences in finickiness that were predicted by prestress body weight. A more sensitive index of finickiness was used in Experiment 2, and a correlation between body weight and finickiness was observed in nonshocked rats. In Experiment 3, measures of quinine reactivity and body weight predicted depressive symptomatology in a nonclinical human sample. Although research in the helplessness paradigm usually focuses on environmental determinants of distress, the paradigm may help identify and explain individual differences in, or intrinsic modulation of, stress and depression.
2385655	Ad lib ingestive behavior and reactivity to water regulatory challenges were examined in rats adapted to citric acid- or to quinine-adulterated fluids. Quinine drinkers were unlike citric acid subjects in being unresponsive to fluid deprivation and to the hypovolemia produced by polyethylene glycol (PEG). The effect during hypovolemia was evident when subjects had access to adulterated physiological saline, a solution more responsive to the PEG-induced need state, and quinine group behavior was not easily explained in terms of the tastes of quinine and saline combined together nor in terms of a posttreatment malaise effect. Substances that degrade the taste of water therefore do not exert uniform effects; bitter quinine appears to have some unique property that remains to be specified.
2359765	Oral motor responses, elicited by the infusion of a taste solution into a rat's mouth, can be changed through association with either other tastes or internal states. Such changes have been well established when ingestive responses, elicited by a normally preferred taste, are changed to aversive responses when the taste signals a LiCl injection. However, the converse has yet to be clearly established; that aversive responses, elicited by a normally avoided taste, can be changed to ingestive responses in a nondeprived animal, as a result of conditioning. We demonstrate here that when a normally avoided taste (quinine or HCl) signals a preferred taste (sucrose), the oral motor responses gradually undergo two types of change as a function of trials. The aversive oral motor responses elicited by the avoided taste decrease over trials and the ingestive responses increase. The two measures, ingestive and aversive responding, were obtained by recording the rat's reactions to the stimuli as they were infused directly into the oral cavity. This taste reactivity method both enabled us to use avoided stimuli in a nondeprived animal and to measure the rat's evaluation of the stimuli's aversiveness. Problems with stimulus sampling may be responsible for the dearth of conditioning experiments which utilize avoided tastes in conditioned preference studies.
2339150	Apomorphine is a positively reinforcing drug at low to moderate doses, but appears to lose its reinforcing properties at higher doses. In Experiment 1, across a range of doses (0.5-15.0 mg/kg, intraperitoneally), apomorphine produced a CTA over 5 conditioning/testing trials which was not dose-dependent by a single bottle test. The rejection taste reactivity responses of chin rubbing and gaping, however, only occurred at the highest dose of apomorphine (15 mg/kg). In Experiment 2, a CTA test which was designed to more effectively discriminate among the different drug dose conditions indicated that the doses of 2.5, 7.5 and 15 mg/kg of apomorphine produce CTAs of equivalent strength. Our results support the contention that CTAs produced by positively reinforcing drugs are not accompanied by a palatability shift.
2328084	The orofacial responses of rats following infusion of taste solutions were examined in two experiments. In the first experiment, naive rats were presented with a 6% alcohol solution and three sucrose mixtures (sucrose combined with quinine hydrochloride, hydrochloric acid, and sodium chloride, respectively) on separate trials and the resulting taste reactivity was examined. The only difference among the solutions was that alcohol elicited a significantly larger number of aversive responses (e.g., gapes, passive drips) than the sucrose mixtures. In the second experiment, naive rats were trained to avoid 6% alcohol using standard conditioned aversion procedures; rats were then tested for reactivity to the three sucrose mixtures and the alcohol solution. With the alcohol solution, trained rats displayed significantly fewer ingestive responses and significantly more aversive responses than control rats. The response of trained rats to the sucrose + quinine solution was similar to that of alcohol: fewer ingestive responses and more aversive responses than control rats. The number of aversive responses to the alcohol and the sucrose + quinine mixture by the trained rats did not differ significantly. Reactivity to the sucrose + hydrochloric acid and sucrose + sodium chloride solutions did not differ between trained rats and control rats. The results suggest that a sucrose + quinine solution has a perceived taste (as revealed by elicited orofacial reflexes) similar to alcohol and that the sucrose mixture is avoided by rats with alcohol aversions because it is unpalatable.
2324313	Primary gustatory neurons and their peripheral and central processes were evaluated histochemically in the geniculate and petrosal cranial nerve ganglia, lingual fungiform taste buds, and the nucleus of the solitary tract (NST) using 1) the plant lectin Griffonia simplicifolia I-B4, which binds specifically to D-galactose residues and selectively labels primarily nonpeptide-containing peripheral somatosensory neurons, and 2) calcitonin gene-related peptide immunoreactivity (CGRP-IR), which labels most peptidergic somatosensory neurons. Lectin reactivity was expressed by the vast majority of geniculate and petrosal ganglion cells, while CGRP-IR labeled very few cells. Peripherally, gustatory intragemmal axons penetrating fungiform taste buds were labeled only by the lectin and were depleted following chorda tympani transection. However, both lectin-labeled and CGRP-IR subpopulations of somatosensory perigemmal axons surrounding the taste buds were observed and were eliminated by section of the lingual nerve. The differing brainstem projection patterns of lectin-reactive vs. CGRP-IR central axons reflected their distinct ganglionic origins and the differential distributions of lectin reactivity and CGRP-IR among taste buds. Central lectin-reactive terminals were found throughout the entire rostrocaudal extent of the NST, including its rostral lateral "gustatory" zone; the extensive lectin-reactive visceral afferent projection can be presumed to have originated mainly from the large proportion of lectin-labeled neurons in the nodose ganglion. The lectin also prominently and selectively labeled the area postrema. CGRP-IR central terminals, however, was relatively sparse and restricted primarily to the caudal and medial "visceral" divisions of the NST. The results are discussed with respect to the possible functional implications of cell surface glycoconjugate expression by gustatory axons innervating taste bud receptor cells of the tongue.
2248110	The following questions, pertaining to cue reactivity in alcoholics, are discussed: (a) What cues are relevant to alcoholics' drinking? Previous research has been concerned with the obvious: bottles, glasses, pub/bar environments, and other visual cues. Presumably more potent cues, that is, smell, taste and internal effects, subtle stimuli like social climate, shifts in conversations, also influence drinking. The effects of mood states on alcoholics' urges and behavior are rarely integrated into experimental studies. (b) What is the CR? Given that drinking is a very complex social behavior, "the drug effect" becomes problematic to disentangle from the effects of other factors, such as bio-medical states, social setting and learning history. This is further complicated by the fact that drugs affect physiological and cognitive systems differently at different dose levels and with rising and falling Blood Alcohol Levels. Moreover, it has been found that alcohol cues may elicit responses that are in the same and in the opposite direction to the drug response. (c) If such responses are reliably tied to alcohol cues (as opposed to novelty of the experimental situation), the impact of the conditioned responses on craving for alcohol and relapse becomes an issue. (d) Another question relates to the analogy between fear in phobias and craving in substance abuse since, unlike phobics, substance abusers do not fear the substance they are responding to. (e) A further issue is the effectiveness of extinction procedures, as opposed to changes in efficacy expectations, as a therapeutic mechanism for the cue exposure paradigm. Examples of recent research at the Hjellestad Clinic are presented.
2610925	To determine what behavioral changes are caused by consumption of Lake Ontario salmon, a 30% diet of Lake Ontario or control Pacific Ocean salmon was fed to rats for 20 days. In Experiments 1 and 2 (preference-for-predictability E-maze test), rats fed Lake Ontario salmon developed a preference for predictable food rewards more quickly than did the control rats. In Experiments 3 (passive avoidance) and 4 (conditioned suppression), rats fed Lake Ontario salmon suppressed responding to food far more after the introduction of mild electric shocks than did control rats. All results supported the hypothesis that ingestion of Lake Ontario salmon, contaminated with polychlorinated biphenyls, mercury, lead, etc., increases the reactivity of rats to aversive events. The results were successfully simulated by DMOD, a mathematical model of learning, using the assumption that rats fed Lake Ontario salmon find unpredictable nonreward and mild shock more aversive.
2610924	Rats were infused intraorally with 4 concentrations of ethanol (3%, 6%, 9%, and 12%), and their subsequent oral, facial, and bodily responses were videotaped and analyzed. Naive rats did not display significant changes in ingestive-type responding over the concentrations tested. A significant increase in aversive responses was noted, with the largest number of aversive responses found with the 12% solution. Initial reactivity failed to predict subsequent consumption when rats were given free access to the same alcohol concentrations during 2-bottle tests. Reactivity testing after the period of alcohol access indicated that only the aversive responding changed significantly from the initial reactivity, with rats showing fewer aversive responses. The results indicated how the taste of alcohol is perceived by naive rats and how this perception is changed after consummatory experience with alcohol.
2665554	This laboratory study examined methods of enhancing physiological and subjective responses of alcoholics to naturalistic alcohol-related stimuli by repeated exposures to a high-dose alcohol drink. Individual subjects participated in five successive daily sessions consisting of randomized-block presentations of gustatory and visual presentation of alcohol, pepper juice (as a control for stimulus taste intensity), or water stimuli. Following the stimulus trial series, all subjects ingested 1.5 oz of alcohol in a shot glass. Twelve subjects next received a 1.7 g/kg alcohol drink ("high dose alcohol group") on Days 1-4 and placebo on Day 5, and 12 subjects received a placebo drink on all study Days (1-5) ("placebo drink group"). On Day 1, alcohol stimuli generally elicited larger heart rate and skin conductance increases and skin temperature decreases than water or pepper juice stimuli. Alcohol stimuli also elicited greater subjective responses than either pepper juice or water. Alcohol availability within the taste trial markedly increased physiological and subjective reactivity to alcohol-related stimuli, perhaps due to the closer approximation to natural drinking behavior. A comparison with previous data from this laboratory suggests that prestudy deprivation from alcohol, instructions to expect alcohol, a conductive drink setting, and the opportunity to drink alcohol within the session may enhance reactivity to alcohol stimuli in alcoholics.
2748936	Previous studies of natural palatability-sensitive reactions, elicited from rats by tastes, have indicated that the taste of concentrated NaCl becomes more palatable during states of body sodium depletion. A training procedure based upon "sensory preconditioning" or "irrelevant incentive" designs was used here to establish gustatory conditioned labels (quinine or citric acid) for either NaCl or fructose while rats were in a normal physiological state. Experiment 1 replicated demonstrations by others that gustatory conditioned labels for salt can attract and act as independent incentives during the salt appetite induced by sodium depletion. Experiment 2 used the taste reactivity measure to show that the enhanced palatability of the taste of NaCl transfers to produce enhanced palatability of the taste of the isolated conditioned label for salt in a state-dependent fashion. These results offer further support for the proposition that conditioned incentives not only predict hedonic events to follow, but themselves become attributed with the hedonic properties of their reinforcers.
2706079	The response of rats to nicotine solutions was examined with the brief-exposure, taste reactivity test and a two-bottle, 24-hr preference test. In Experiment 1, naive nondeprived rats were administered intraoral infusions (0.8 ml infused during 1 min) of distilled water and 1 microgram/ml, 5 micrograms/ml, 10 micrograms/ml, 25 micrograms/ml, 50 micrograms/ml, and 100 micrograms/ml nicotine. The oral motor, taste reactivity (TR) responses of the rats were recorded during the infusion. Nicotine solutions up to a concentration of 50 micrograms/ml elicited a number of ingestive TR responses similar to that by water. Ingestive responses significantly decreased and aversive TR responses significantly increased in response to 100 micrograms/ml nicotine. On the basis of these results, two-bottle preferences for water versus 1 microgram/ml, 5 micrograms/ml, and 0 microgram/ml (water control group) nicotine were measured in three groups of naive rats. Rats initially showed an equal preference for 0 microgram/ml and 1 microgram/ml nicotine. After 16 days of exposure, however, rats developed a significant preference for 1 microgram/ml nicotine. The preference ratio for 5 micrograms/ml nicotine significantly increased during the experiment, but the preference ratio remained significantly less than that for 1 microgram/ml and 0 microgram/ml nicotine solutions. Last, TR responses elicited by intraoral infusions of 1 microgram/ml and 5 micrograms/ml nicotine were then measured in these rats having had the two-bottle experience. Rats showing a two-bottle preference for the 1 microgram/ml nicotine solution displayed significantly more ingestive TR responses to 1 microgram/ml and 5 micrograms/ml nicotine than did the control rats.(ABSTRACT TRUNCATED AT 250 WORDS)
2493791	The deficits in feeding and drinking that result from 6-hydroxydopamine (6-OHDA) lesions of the mesostriatal dopamine system are often explained using either sensorimotor arousal or anhedonia hypotheses. Sensorimotor arousal hypotheses posit that dopamine systems facilitate the capacity of sensory stimuli to activate any motor output. The anhedonia hypothesis suggests that dopamine systems amplify the hedonic impact of positive reinforcers. Natural palatability-dependent ingestive and aversive actions, which are emitted by rats to tastes, provide a sensitive test that can discriminate between these hypotheses: A reduction of sensorimotor arousal should diminish the ability of tastes to elicit any actions, whereas anhedonia should shift the balance between positive and aversive actions. To directly compare these two hypotheses, taste reactivity was examined in rats made aphagic by intranigral 6-OHDA injections. The results did not support either of these predictions: Taste reactivity was essentially unchanged. The persistence of normal taste reactivity argues against both an anhedonia and a global sensorimotor arousal interpretation and provides further evidence that the capacity for hedonics can be neurologically dissociated from motivated appetitive behavior. An incentive attribution hypothesis that can account for the results is discussed, along with its implications for a wide range of phenomena associated with dopamine depletion.

3215010	The Syracuse strains of Long-Evans rats were selectively bred for good (SHA) or poor (SLA) avoidance learning in a two-way shuttle box, which resulted in a phenotypic difference that is correlated with behavior patterns indicative of emotional reactivity, SLA animals showing evidence of greater emotional reactivity than SHA animals. The first three experiments examined conditioned suppression of bar pressing and compared paired and unpaired conditioned- and unconditioned-stimulus presentations to evaluate the influence of conditioning versus primary aversive stimulation on baseline responding. SLA animals acquired conditioned suppression faster than SHA animals and also showed greater suppression of baseline responding than SHA animals. In Experiment 4, SLA animals learned a passive-avoidance task faster than SHA animals. In Experiment 5, SLA animals showed greater stress-induced suppression of drinking a weak quinine solution than SHA animals. These data are consistent with the hypothesis that SLA animals are more emotionally reactive than SHA animals.
3214542	The oral stimulating effects of sucrose and sodium chloride (NaCl) were assessed in chronic decerebrate and pair-fed intact control rats by measuring both oral motor taste-reactivity responses and intraoral intake volume. Taste-reactivity responses were videotaped during the first minute of the intraoral taste infusion. The infusion continued until the taste solution was rejected from the mouth, and the intake volume was computed accordingly. The number of ingestive taste-reactivity responses and the volume of intraoral intake consumed by pair-fed control and decerebrate rats increased with increasing sucrose concentration. Sucrose intake increased as concentration increased to 0.1 M, then plateaued between 0.3, 1.3, and 2.0 M sucrose for both groups. For control rats, intraoral NaCl elicited an inverted U-shaped function for both taste-reactivity responses and intake. Taste-reactivity responses of chronic decerebrate rats varied with NaCl concentration. In contrast to control rats, intake of NaCl did not differ from that of water for decerebrate rats. These data indicate that caudal brain-stem mechanisms are sufficient to control sucrose intake but are not adequate for the concentration dependent intake of NaCl. Second, these data also indicate that it is possible for taste-elicited oral motor responses to be dissociated from intake. The different roles of taste and postingestive factors in sucrose and NaCl intake are discussed.
2850815	Several explanations may account for deficits in the ability of animals to form taste aversions following neural manipulations. These encompass impairments in conditioned stimulus (CS) and unconditioned stimulus (US) processing, conditioned response (CR) measurement, and expression, memory, and taste-visceral integration. A behavioral procedure that aids in the distinction between some of these possibilities is presented. In Experiment 1, 10 rats received seven intraoral (IO) infusions of sucrose (30 s, 0.55 ml) spaced every 5 min starting immediately after the injection of 3.0 mEq/kg of lithium chloride (LiCl). Control rats (n = 12) were treated identically except that they were injected with sodium chloride (NaCl). Oromotor and somatic taste reactivity behaviors were videotaped and analyzed. Lithium-injected rats systematically decreased their ingestive taste reactivity behavior over time, whereas aversive behavior increased. Control rats maintained high and stable levels of ingestive responding and demonstrated virtually no aversive behavior over the 30-min period following sodium injection. Rats were tested several days later for the presence of a conditioned taste aversion (CTA). Rats previously injected with lithium during sucrose infusions demonstrated significantly more aversive behavior than the control group, which demonstrated none. There were no differences in the level of ingestive behavior displayed by the two groups on the CTA test. Experiment 3 revealed that when similarly treated rats were tested for a CTA while in a lithium-induced state, a difference in the ingestive behavior between the two groups was observed. In Experiment 2, naive rats were injected with either NaCl or LiCl but did not receive their first sucrose infusion until 20 min later. These rats also received sucrose infusions at 25 and 30 min postinjection. There were no differences in the taste reactivity behavior displayed by lithium- or sodium-injected rats during any of the sucrose infusions. Collectively, these findings indicate that rats dramatically change their oromotor responses to sucrose during the period following LiCl administration, provided that the infusions start immediately after injection. Furthermore, this time-related behavioral change is predominantly attributable to associative processes. This paradigm can be useful in distinguishing between neural manipulations that affect the establishment of taste-visceral associations from others that affect the animal's ability to retain such associations over the commonly employed 24-hr conditioning-test interval.

2849410	Sprague-Dawley rats drank sweetened (3% dextrose + 0.144% saccharin, w/v) or unflavored water for 18 days and subsequent pain reactivity was assessed using a hot plate. Compared to the rats that consumed unflavored water, the rats that consumed sweet water responded more quickly on the hot plate indicating that their threshold for pain was lowered. Another group of rats given identical exposure to the fluids had their brains prepared for measuring opiate receptor binding using the delta-receptor ligand [3H]D-Ala-D-Leu-enkephalin ([3H]DADLE) and the mu-receptor selective ligand [3H]Tyr-D-Ala-Gly-MePhe-Gly-ol ([ 3H]DAGO). Binding of these opiates to mu- and delta-receptors in the cerebral cortex, striatum, hippocampus, hypothalamus, brain stem, and remaining brain regions was the same for the rats that drank sweet fluids and those that drank unflavored water. These findings suggest that drinking sweet fluids lowers pain thresholds but does not alter mu- and delta-receptors.
24277098	A series of natural drimanes and related synthetic compounds was tested for antifeedant activity against aphids. Polygodial and warburganal were the most active. The synthetic compounds methyl 9α-hydroxydrimenoate and 9α-hydroxydrimenal, although active against lepidopteran larvae, were inactive against aphids. Natural (-)-polygodial and the synthetic (+) isomer showed similar levels of activity as aphid antifeedants and in phytotoxicity, fish toxicity, and human taste tests, but reacted at different rates with enantiomers of 1-phenylethylamine. 
3414837	The taste reactivity test was used to determine whether strain differences in response to NaCl revealed by preference tests were attributable to taste or postoral factors. Taste reactivity data revealed significant differences between sodium-replete Fischer 344 (F-344) and Wistar strains in response to NaCl for both aversive and ingestive oral motor behaviors. Because the taste reactivity test analyzed the immediate response to orally applied chemical stimuli, these data support a strain difference based on taste factors. Taste reactivity data also indicate strain differences in ingestive but not aversive scores to other normally ingested chemical stimuli, water, and two sucrose concentrations. In response to normally avoided quinine, F-344 and Wistar strains did not differ in either ingestive or aversive score. To investigate whether strain differences revealed when rats were tested while sodium replete would persist in the sodium-deficient state, both strains were treated with the diuretic furosemide. Taste reactivity tests revealed that in response to sodium deficiency both F-344 and Wistar strains shift their oral motor response profile to NaCl; strains did not differ in either ingestive or aversive score when sodium deficient. NaCl intake and preference measures also support the fact that both strains demonstrate a sodium appetite. Interpretive limitations based on ceiling and floor effects within taste reactivity and preference data were discussed.
3390698	Previous studies have indicated that the benzodiazepine receptor complex is involved in enhancing taste palatability after chlordiazepoxide (CDP) administration. Positive, palatability-dependent ingestive reactions elicited by orally infused tastes are facilitated in rats by CDP (10 mg/kg), and this effect is reversible by benzodiazepine antagonists. In contrast, the rats' more neutral or aversive reactions are not facilitated by CDP. Because benzodiazepine receptors exist in highest density in the forebrain, it has seemed plausible to posit forebrain structures as the locus of CDP action. However, benzodiazepine receptors do exist in the caudal brainstem (albeit in lesser density), and the isolated decerebrate brainstem has been demonstrated to possess considerable taste processing and response capacity. The present study examined the effects of CDP on taste reactivity in chronic mesencephalic decerebrate rats. The results show that CDP can act on the subdiencephalic brainstem to enhance positive ingestive reactions even in the absence of communications with the forebrain. This indicates that both the relevant benzodiazepine receptors and the minimal neural circuit needed to modulate taste reactivity exist within or below the mesencephalon.
3179508	Previous studies (V. J. Djurić, B. M. Marković, M. Lazarević, & B. D. Janković, 1987, in B. D. Janković, B. M. Marković, & N. H. Spector (Eds.), Neuroimmune interactions, pp. 561-568, New York: New York Acad. Sci.; B. M. Marković, V. J. Djurić, M. Lazarević, & B. D. Janković, 1988, Brain Behav. Immun. 2, 11-23) have shown that rats learn to associate the taste of saccharin with the induction of anaphylactic shock, thus exhibiting conditioned taste aversion (CTA) toward an otherwise preferred saccharin solution. The present experiment investigates the effect of unconditioned stimulus intensity (the amount of antigen used for the induction of shock) on CTA. Rats were sensitized to ovalbumin and subjected to a conditioning trial in which the conditioned stimulus (CS; saccharin solution given orally) signaled the presentation of the unconditioned stimulus (US; shocking doses of ovalbumin ranging from 0.5 to 3 mg given intraperitoneally). Behavioral signs, hematocrit, and rectal temperature were used for evaluation of anaphylactic shock. Twenty-four hours after the conditioning trial, rats were subjected to a two-bottle preference test between saccharin solution and water. Multiple regression statistical analysis revealed significant correlations among saccharin preference ratio, dose of antigen used for the induction of shock, behavioral signs of shock, rise in hematocrit, and fall in rectal temperature. A dose-dependent relation among saccharin preference ratio and physiological indicators of shock suggests that conditioned anaphylactic shock-induced avoidance behavior is functionally related to homeostatic factors involved in immune reactivity.
3259218	In the present study carbohydrate residues in taste buds (TBs) and adjacent epithelial formations of a teleostean fish, a frog and the rabbit were detected by means of lectin histochemistry. Biotinylated lectins from Pisum sativum (PSA), Arachis hypogaea (PNA), Dolichos biflorus (DBA), Triticum vulgaris (WGA and succinylated WGA), Glycine max (SBA) and Ulex europaeus (UEA I) have been applied. The lectins were bound to an avidin-biotin-peroxidase-complex (ABC) and visualized by diaminobenzidine/H2O2. Most intensive reactivity was observed at the taste disc cells of the frog with DBA, S-WGA and SBA. PNA did not bind to the TBs of any of the animals tested. As shown in SBA preparations, sialic acid is present in a nonacylated and an acylated form in the mucosa of the frog's tongue. The TBs of the fish possess all the sugars we looked for except for the disaccharide D-galactose-(1-3)-beta-D-N-acetyl-galactosamine (Gal/GalNAc) and sialic acid. The TBs of the rabbit contain GalNAc, as detected with DBA, but not with SBA; and fucose (Fuc), mannose (Man) and N-acetyl-glucosamine (GlcNAc). As revealed by preincubation of the tissue sections with neuraminidase in TB cells of the rabbit, sialic acid masks Gal/GalNAc and GalNAc. These lectin-binding characteristics show that in the TBs of some selected representatives which belong to different vertebrate classes exist different mucous substances. These substances possess different binding characteristics to specific sugars, and this is possibly of particular interest to chemoreception phenomena.
3249744	A hyperreactivity to the sensory qualities of a food, i.e., finickiness, is a defining feature of the ventromedial hypothalamic (VMH) lesion syndrome. The precise anatomical locus mediating this disturbance has not been determined. This study examines the hypothesis that interruption of amygdalo-hypothalamic connections (either ascending or descending) via the stria terminalis (ST) is involved in VMH lesion-induced finickiness. Taste reactivity was assessed in animals with VMH lesions, ST knife cuts, combined VMH/ST damage, and controls. In sham feeding tests of taste reactivity, ST and VMH rats were equally hyperreactive compared to controls. Rats with combined VMH and ST damage, however, were more reactive than both these groups. None of the brain lesions resulted in an overreactivity to quinine adulteration of the diet. In contrast to sham feeding, ST rats were not hyperphagic when feeding normally, although VMH rats were. In fact, ST damage attenuated VMH-induced hyperphagia and weight gain. We conclude that the taste reactivity changes induced by VMH lesions and ST transections are independent and additive indicating that VMH finickiness does not involve disruption of amygdalo-hypothalamic connections. Nonetheless, disruption of the ST produces a dramatic change in taste reactivity and the properties and origins of this disturbance are discussed.
3237841	Single-unit responses of LH cells and oral reaction were studied in food-deprived animals to intraoral injections of rewarding and aversive tastants differentially cued by tonal stimuli. Correlative tests were carried out with microstimulation. Classification and statistical analysis of task-related neurons in different AP regions of LH revealed two functionally disparate, anatomically segregated groups of cells that may play a role in hedonic reactions to tastants. A rostral group showed strong "excitatory" response to aversive test stimuli and divergent "inhibitory" or minimal response to rewarding test stimuli. More caudal cells displayed maximal excitatory response to rewarding test stimuli, which, in some cases, related to oral behavior. Microstimulation of caudal sites also evoked rhythmical oral movement. Phasic and/or tonic reactivity to taste stimuli were common among LH neurons, but most cells responded differentially to both conditioned stimuli and tastants. Only a few cells reacted selectively to the fluid stimuli.
3741604	Physiological and behavioral concomitants of sodium need were studied in supracollicularly transected and pair-fed intact rats. Chronic decerebrate rats, like intact rats, reduced their urine sodium output when placed on a sodium-deficient diet. Similarly, 24 hr after sodium loading, decerebrate and intact rats excreted comparable levels of the excess sodium. In the 2 hr immediately following the loading, decerebrate rats excreted less sodium. In contrast, behavioral aspects of sodium homeostasis were completely absent in chronic decerebrate rats. In separate experiments, intraoral intake, and taste-reactivity responses, elicited by intraoral infusions of NaCl were measured during sodium-replete and sodium-deficient conditions. In response to oral infusions of NaCl, intact rats consumed significantly more and produced greater numbers of ingestive taste-reactivity responses when they were sodium deficient than when they were sodium replete. The same sodium-depletion treatments in chronic decerebrate rats, however, altered neither the intraoral intake of NaCl nor the frequency of NaCl-elicited ingestive taste-reactivity responses. These results suggest that the behavioral compensatory responses that follow changes in the internal sodium state are dependent upon forebrain mechanisms.
3522452	In order to determine the role of the endogenous opiatergic system in modulation of human pancreatic B-cell function and taste perception, we measured the reactivity of gustatory receptors (electrogustometry), insulin and C-peptide serum concentration (radioimmunoassay) in six normal men (aged 24-26 years) during sham feeding and 0.8 mg of naloxone or placebo (saline) administration. We did not observe any differences in insulin and C-peptide concentrations during tease feeding independently of placebo or naloxone infusion. The verge of electric reactivity of gustatory perception significantly decreased in the period of food presentation and saline administration but did not change under naloxone. Our electrogustometry results support the hypothesis pointing out the role of endogenous opiates in modulation of human taste.
4070397	Previous neurobehavioral investigations have demonstrated that the anterior insular gustatory neocortex (AIGN) mediates taste-illness learning. The present experiment evaluated taste discriminations in rats lacking AIGN. Two groups of rats received distinct surgical treatments. One-half of the animals received bilateral electrolytic lesion placements in the AIGN: Remaining animals received anesthesia and scalp incisions only. Following postoperative recovery animals received standard two-bottle preference tests with various concentrations of sucrose to evaluate gustatory reactivity. Animals thereafter received two-bottle discrimination tests with selected sucrose concentrations. At the conclusion of preference tests and discrimination tests with sucrose, preference tests and discrimination tests were conducted with sodium chloride. Following those tests animals received taste aversion conditioning to determine whether or not AIGN lesions impaired taste-illness learning. Results of two-bottle taste tests indicated that AIGN lesions do not obviously alter taste reactivity nor taste discriminations to preferred concentrations of sucrose and NaCl. Anterior insular lesions did, however, impair normal taste aversion learning. These results, in combination with those of previous investigators, provide further evidence that the AIGN preferentially contributes to taste learning functions.
3040033	Previous neurobehavioral studies have implicated the gustatory thalamocortical relay as a functional substrate of conditioned taste aversion (CTA) learning. These experiments were conducted to examine the involvement of the gustatory thalamic nuclei in fundamental taste reactivity, gastrointestinal reactivity, and CTA learning. In Experiment 1, bilateral electrolytic lesions were produced in the medial ventrobasal thalamic complex (VBm), including the thalamic gustatory nuclei, in one group of rats. A separate group of rats received control lesion placements in the mediodorsal-periventricular (MD-PV) thalamic nuclei. Animals then received preference-aversion taste tests followed by CTA conditioning. At the conclusion of conditioning, lesions were produced in the anterior insular gustatory neocortex (AIGN) to evaluate whether or not the AIGN contributed to CTA learning in animals lacking VBm thalamus. Results of Experiment 1 indicated that control lesions did not disrupt taste reactivity, gastrointestinal reactivity, or CTA learning. Destruction of VBm thalamus attenuated taste reactivity to sucrose, citric acid, and quinine hydrochloride; however, such lesions did not impair normal taste reactivity to sodium chloride. Lesion placements in VBm thalamus also did not reliably impair gastrointestinal reactivity to ingested LiCl. Elimination of VBm thalamus markedly attenuated CTA learning. Results of neocortical lesion manipulations showed that the AIGN contributed to initial CTA learning in animals lacking MD-PV thalamus but that the AIGN did not mediate initial CTA learning in animals lacking VBm thalamus. Whether animals lacking VBm thalamus used olfactory cues associated with drinking solutions to acquire CTAs was evaluated in Experiment 2. Results of Experiment 2 demonstrated that animals lacking VBm thalamus and the olfactory bulbs could not acquire aversions to ingested LiCl following eight conditioning trials. These experiments demonstrate that destruction of VBm thalamus, including the gustatory thalamic nuclei, is sufficient to prevent CTA learning.
3843713	When rats are forced to drink a morphine solution as their only source of fluid, they eventually reverse their initial preference and drink more morphine than water in a two-bottle preference test. The cause of this shift in preference was examined with the taste reactivity test which involves the analysis of fixed action patterns elicited by taste solutions infused into rats' mouths. Three morphine concentrations and two levels of motivation were studied. A greater percentage of ingestive taste reactivity responses occurred to the oral morphine infusion in morphine-raised rats than in water-raised rats. These data argue against the idea that enhanced morphine ingestion is caused by anticipation of positive consequences. Instead, they support the idea that rats come to "like" the flavor of the morphine solution; in other words, the palatability evaluation of the morphine changes, possibly through an association between the flavor and the hedonically positive effects of the morphine.
3967800	Taste reactivity in suckling rat pups was assessed. Five-day-old rats in Experiment I were equipped with tongue cannulae seated 2 mm rostral, 0-3 mm caudal, or 4-6 mm caudal to the intermolar eminence. Either water, 1.4 X 10(-3) QHC1, .50M NH4Cl, or .43M NaCl was delivered in one of three fashions during suckling: (1) continuous: fluid was continuously available from a reservoir connected to the cannula, and could be obtained by exerting suction; (2) discrete: same procedure as above, save that fluid was available for only 30 sec every 3 min of the 30-min test; (3) pulsatile: here, .05 ml fluid was delivered by infusion pump 8-10 sec every 3 min, provided the pups were attached to a nipple. Based on intake, time and behavioral measures, we conclude behavioral reactivity exists especially to NH4Cl and NaCl. As to quinine, Day 5 pups were responsive only when QHCl was delivered in the continuous mode. In Experiment II, rats 10, 15, and 20 days of age received the above solutions by infusions with the cannulae located in one of the three positions. Quinine reactivity developed sequentially in an anterior to posterior direction. NH4Cl disrupted behavior in 5-, 10-, and especially 20-day-old rats. Remarkably, Day 15 rats were not behaviorally reactive to NH4Cl. Sodium chloride, especially in the anterior and middle positions, was treated as an aversive solution during suckling throughout development. Based on existing electrophysiological data, the last finding was unexpected.
6487414	Rats sustaining ablations of gustatory neocortex (GN) at 2, 10, 20, or 60 days of age were compared with control rats in the acquisition and extinction of a learned taste aversion; in addition, these rats were tested for taste preference across five concentrations of sodium chloride solution. Results indicated that GN ablation disrupted aversion acquisition and extinction regardless of age at surgery. Taste response functions for the sodium chloride solutions shown by all GN groups of rats mirrored those of control rats: preference (relative to water baseline) for middle concentrations and rejection of the strongest salt concentration. There was a suggestion that the 20- and 60-day-old GN rats were hyperresponsive to the suprathreshold concentrations of NaCl (except the strongest concentration). The increased response to salt solutions in the 20- and 60-day GN rats may have been related to the significant decreases in water consumption relative to that of normal rats. Water consumption of control rats and GN rats in the 2-day and 10-day groups was essentially equal. It is concluded that infant ablation of the GN does not spare normal taste aversion learning and that rats with GN ablations, regardless of age at surgery, respond in a normal manner to the hedonic aspects of sodium chloride solutions.
6540589	Sterotyped fixed action patterns (FAPs) are elicited in rats by oral infusions of taste solutions. These taste-elicited FAPs can be classified as either ingestive or aversive. They reflect the palatability of the taste and can be modified by learning and by the physiological state of the animal. These studies demonstrated that when the physiological state of the rat is altered by sodium depletion, the pattern of FAPs elicited by oral infusions of 0.5 M NaCl shifts from a mixture of ingestive and aversive components (while sodium replete) to exclusively ingestive ones (while sodium deplete). This shift in taste reactivity occurred the first time the rats were made sodium deplete. A similar shift was not observed to accompany infusions of 0.01 M HCl, a taste solution that also elicited mixed ingestive and aversive FAPs. This result suggests that the shift in response to NaCl is not due to a general change in ingestive bias or to a general taste deficit. On the basis of the change in FAPs, it is concluded that the palatability of highly concentrated salt solutions increases in sodium-deplete rats. Such a shift in salt palatability may be instrumental in directing the appetitive behavior of the animal.
6379262	The examination of 140 normal individuals with a family history of essential hypertension (FHEH) showed a number of differences in their cardiovascular and renin-aldosterone responses as compared to 170 normal subjects of the control group. Two years later the results were analyzed once again with regard to blood pressure changes. It turned out that subjects with a FHEH and an unfavourable pattern of blood pressure changes over two years exhibited elevated response of cutaneous vessels to angiotensin and noradrenaline, a higher threshold of gustatory sensitivity to salt and an increased BP response to psychoemotional stress already during the first examination. It is concluded that the most informative markers of the prehypertension state among the genetically determined features characteristic of healthy individuals with a FHEH are changes in sodium metabolism and regulation which are responsible for the development of vascular hyperactivity.
6670857	A series of experiments was conducted in order to gain additional insight into how endogenous opioids may modulate taste reactivity and, thus, hedonic processes. Using a wide range of saccharin concentrations ranging from mildly preferred to aversive, it was demonstrated that naloxone reduced preference for saccharin over water. This reduction was not dependent upon concentration of saccharin and resulted in a downward displacement of the preference/aversion curve. Naltrexone was shown to result in a greater decrease in intake in animals drinking a mildly aversive quinine solution, as compared to animals drinking tap water. In conclusion, endogenous opioids may serve to broaden the range of food-related stimuli which are avidly accepted, perhaps by inhibiting any aversive component associated with ingestion.
6651967	The hyperphagia/obesity syndrome produced by paraventricular hypothalamic (PVH) lesions and that produced by medial hypothalamic (MH) knife cuts were compared in adult female rats. Each treatment produced hyperphagia and overweight on a chow diet, although the PVH effect was less than the knife-cut effect. Each treatment also produced qualitatively similar ingestive responses to unpalatable quinine- and sucrose octaacetate-adulterated diets and to palatable dextrose and fat diets during the dynamic and static weight-gain phases. The PVH lesions and MH cuts disrupted day/night feeding patterns and elevated water intakes but not water/food intake ratios. However, PVH lesions, unlike MH cuts, did not increase emotional reactivity. The relation of the PVH syndrome to the classic hypothalamic hyperphagia syndrome is discussed. Also considered is the neuroanatomical substrate responsible for the PVH hyperphagic effect.
6657765	In order to compare and contrast hedonic properties of 0.75 M NaCl and 0.5 M sucrose used in behavioral electrophysiology of taste, tests were carried out of evoked patterns of orolingual response and operant licking on a FR-32 schedule to discrete intraoral injections of these stimuli and other basic types of tastants. In tests of taste reactivity, NaCl and sucrose evoked quantitatively similar numbers of orolingual response in excess of those evoked by water. NaCl was also similar to sucrose in amount of operant licking generated at the outset of the test session. Both of these stimuli were more effective than either 0.02 M HCl, 0.01 M QHCl, or water. The NaCl also did not have the suppressant effect of HCl when alternated with sucrose as the reinforcement for licking. NaCl differed from sucrose in sustaining operant licking. While NaCl would appear to share the same basic hedonic value of sucrose, long-term associative processes pertaining to postingestional consequences of fluid input and short-term sensory processes may act to limit behavioral responsivity for concentrated NaCl. Additional information was obtained on operant licking for sodium saccharin.
6318718	Behavioral and physiological studies have shown that the insular neocortex participates in a wide variety of special visceral processes, in particular, the higher-order integration of taste stimuli and the regulation of autonomic activity. The present experiment examined the involvement of the anterior insular (gustatory) neocortex (AIGN) in gastrointestinal reactivity and taste learning in rats by the use of a modified taste aversion training procedure. Normal rats and rats lacking AIGN demonstrated similar "illness thresholds" to the early onset symptoms of ingested LiCl. Conversely, animals lacking AIGN showed significant impairments in taste aversion learning ability. From a consideration of several research findings it is concluded that animals lacking AIGN can normally perceive tastes and illness, but these animals experience reliable impairments in taste aversion learning ability.
6849685	Much of the evidence for the existence of a negative finickiness component in the ventromedial hypothalamic (VMH) syndrome comes from studies comparing the relative reactivities of VMH and normal rats to quinine adulteration. The present experiments addressed two major questions regarding the response of normal and VMH animals to quinine: (a) Do the anorexic properties of quinine depend on quinine's sensory properties (i.e., its bitter taste) or on its postingestive effects; (b) do VMH rats in fact overrespond to quinine adulteration? These issues were examined by comparing the feeding adjustments to quinine by VMH and normal animals in a sham-feeding situation and under normal feeding circumstances, on animals' initial exposure to this drug. The results were consistent with the view that the sensory properties of quinine alone were sufficient to induce large changes of food intake in both groups. In terms of whether lesion rats were more reactive to the taste of quinine, it is argued that previous research had measured reactivity in two dissimilar ways. The present data were used to illuminate how use of these two procedures for measuring reactivity lead to diametrically opposed conclusions regarding the existence of negative finickiness in the VMH syndrome. It is suggested that when the more appropriate measure of reactivity is adopted and when the confound of body weight differences between normal and VMH animals is eliminated, little evidence exists for a conclusion that VMH rats are more reactive than normals to quinine-adulterated foods.
7163398	The effects of the opiate antagonist naloxone (NX) on fluid preference and intake were determined in rats drinking with chronically indwelling gastric fistulas. The subjects were tested both after 22.5 hr fluid deprivation, and no deprivation, with open fistulas (sham drinking), as well as with closed fistulas. Following an injection of either saline or NX (0.5-10.0 mg/kg, administered SC), or no injection, the subjects were given the choice to drink water or 10% sucrose, in a two-bottle test, for 1 hr/day. With open fistulas, and following fluid deprivation, the animals sham drank both sucrose and water, but had a strong preference for sucrose. When not fluid deprived, the same animals sham drank sucrose almost exclusively. NX significantly reduced sucrose intake by the sham drinking animals, in both the deprived and not deprived conditions, but did not modify fluid preference. These data support the idea that NX modifies affective reactivity to palatable solutions, and that NX's antidipsogenic actions are not due to feedback from post-absorptional events.
7182523	Individual differences in responsiveness to bitterness were studied among children with and without histories of accidental ingestion of toxic substances. The oral behaviors of 56 children between the ages of 12 and 41 months were videotaped during two minute test periods with lollipops containing different concentrations of bitter sucrose octaacetate (SOA). Videotapes were scored for mouthing times, numbers of oral contacts and latencies to mouthing for each stimulus. Mouthing time was the most sensitive dependent measure examined. Both groups rejected pops with added SOA, decreasing mouthing times as SOA concentration increased. Mouthing times for children with histories of accidental ingestion were slightly lower overall. These results suggest that lowered reactivity to tastes is not a predisposing factor in accidental ingestions, and that bitter substances have some value as deterrents to ingestion for this age group. Rejection of bitter pops by children closely paralleled ratings of bitterness by adult judges.

7079310	Rats were reared in social isolation or in social groups of 4 or 5 rats per cage from weaning and were fed either a lab chow diet or a diet of 4 palatable foods (cafeteria diet), in addition to the lab chow. The hyperactivity of isolation-reared rats appears to be a reactivity to novel environmental stimuli, since it was seen only in the 0.5 hr tests and not in the near 24 hr test. It was found that hyperactivity and increased body weight can develop within as few as 7 to 10 days in rats reared in isolation from weaning. Cafeteria feeding enhanced activity in isolation-reared rats, but suppressed it in group-reared rats. Isolation-reared rats fed a cafeteria diet had strong, stable preferences for their most preferred food over the 25 days of measurement. Rats reared in isolation had significantly different food preferences, as compared with rats reared in groups. Cafeteria fed rats had a significantly greater calorie intake and body weight than rats fed lab chow. On analysis, cafeteria fed rats had significantly greater carcass energy and an increased amount of parametrial white adipose tissue as compared with rats fed only lab chow. The interscapular brown adipose tissue (IBAT) weights of cafeteria fed rats were also greater. However, as there was no difference between the cafeteria and chow fed rats in the total amount of protein in the IBAT, it was concluded that the increased weight of the IBAT did not reflect a genuine hypertrophy of the tissue.
7272805	Ingestion of palatable and unpalatable solutions was measured in adult mice in which had been administered the common parasite of the dog, Toxocara canis alone, or in combination with lead. In addition, response to hot plate and susceptibility to electroconvulsive seizure were also measured. Results from the palatability test indicated that either lead or Toxocara may alter the mouse's mode of interacting with its environment. However, the two agents in combination interacted in their effects on consummatory behavior. Results from the hot plate and ECS measures were less clear with respect to how lead and/or Toxocara influence temperature reactivity and seizure susceptibility. Histological examination of the CNS in parasite infected animals revealed Wallerian Type degeneration of fiber pathways including the corpus callosum, olfactory tract, and cerebellar penduncles.
7276281	Discretely localized lesions were made in the amygdala to examine how specifically they might alter various measures of feeding behavior in male rats. Behavioral tests included spontaneous intake and body weight regulation, reactivity to saccharin and quinine solutions, conditioned taste aversion, the feeding response to food deprivation, the response to glucose gavage, and teh response to dietary amino acid imbalance. Lesions in virtually all regions of the amygdala disrupted feeding behavior in some respect, but alterations in specific tasks were associated only with highly circumscribed brain damage. Body weight regulation, spontaneous food and water intake, and the responses to glucose gavage and long-term food deprivation were not altered by lesions in the amygdala. The results provide evidence that, in the rat, the amygdala may play a greater role in appetite than in hunger or safety. In particular, amygdaloid nuclei may participate in maintaining a negative bias in the reactivity to all appetitive stimuli.
27942827	Using chronically catheterized, freely moving male Wistar rats, we have shown that the sweet taste of a saccharin solution reliably triggers a rapid cephalic phase insulin response (CPIR), in the absence of any significant change of glycemia. To establish the neural mediation of this reflex response we used rats that were cured from streptozotocin diabetes by intrahepatic islet-transplantation as a denervated B-cell preparation. The complete lack of any saccharin-induced CPIR in these rats suggests that it is indeed mediated by the peripheral autonomic nervous system, and that the insulin-stimulating gastrointestinal hormones are not involved in this response. It was further found that this reflex insulin secretion is not easily extinguishable and thus might have an unconditioned component. To investigate the central neural pathways involved in this reflex response we used both electrophysiological methods in anesthetized and semi-micro CNS manipulations in freely moving rats. On the basis of our preliminary results, and several reports, using the decerebrate rat preparation for measuring behavioral or saliva secretory oral taste reactivity, it appears that CPIR might be organized at the brain stem/midbrain level, receiving strong modulatory influences from the diencephalon. But much further work has to be done to establish the central nervous circuitry. Finally, in two experiments, aiming at the question of how important and physiologically relevant the CPIR might be, we found that, on one hand, its lack can result in pathological oral glucose tolerance and on the other hand its exaggeration might contribute to the behavioral reaction to highly palatable sweet food and the resulting development of dietary obesity.
7014335	Using chronically catheterized, freely moving male Wistar rats, we have shown that the sweet taste of a saccharin solution reliably triggers a rapid cephalic phase insulin response (CPIR), in the absence of any significant change of glycemia. To establish the neural mediation of this reflex response we used rats that were cured from streptozotocin diabetes by intrahepatic islet-transplantation as a denervated B-cell preparation. The complete lack of any saccharin-induced CPIR in these rats suggests that it is indeed mediated by the peripheral autonomic nervous system, and that the insulin-stimulating gastrointestinal hormones are not involved in this response. It was further found that this reflex insulin secretion is not easily extinguishable and thus might have an unconditioned component. To investigate the central neural pathways involved in this reflex response we used both electrophysiological methods in anesthetized and semi-micro CNS manipulations in freely moving rats. On the basis of our preliminary results, and several reports, using the decerebrate rat preparation for measuring behavioral or saliva secretory oral taste reactivity, it appears that the CPIR might be organized at the brain stem/midbrain level, receiving strong modulatory influences from the diencephalon. But much further work has to be done to establish the central nervous circuitry. Finally, in two experiments, aiming at the question of how important and physiologically relevant the CPIR might be, we found that, on one hand, its lack can result in pathological oral glucose tolerance and on the other hand its exaggeration might contribute to the behavioral reaction to highly palatable sweet food and the resulting development of dietary obesity.

7413782	Magnitude-estimation of sucrose pleasantness and sweetness, and feeding behavior, were investigated in female and male college students. The subjects were individually tested five times over a five-week period. Female test intervals were scheduled to include the menses, pre-ovulatory, and luteal phases of the menstrual cycle. The data were analyzed by gender, length of menses, and phase of the menstrual cycle. The results of these analyses were consistent for both the sucrose taste reactivity tests and feeding tests. Male and long-menses females exhibited similar response patterns; and their pattern was significantly different from that of the short-menses females. The mean log pleasantness ratings of the males and long-menses females were significantly smaller than those of the short-menses females. Furthermore, both long-menses females and males behaved similarly in a time-limited surreptitious feeding test. They consumed significantly more food than did short-menses females. Phase of the menstrual cycle did not alter pleasantness reponse patterns, but there was one phase effect in the feeding tests. Luteal phase intake of short-menses females was elevated relative to that of the menses phase. These findings demonstrate that reproductive variables participate in the control of human regulatory behaviors.
456365	The primary structure of the sweet-tasting protein thaumatin has been elucidated. The protein consists of a single polypeptide chain of 207 residues. The sequence of the N-terminal part of the chain was determined by sequenator analysis. As the protein contains only one methionine residue, it was possible to deduce the N-terminal sequence of the C-terminal cyanogen bromide fragment by automatic sequencing of the cyanogen-bromide-cleaved, succinylated protein. To arrive at the sequence of the whole protein tryptic and Staphylococcus protease peptides, together with chymotryptic peptides and a 2-(2-nitrophenylsulfenyl)-3-methyl-3'-bromoindolenine (BNPS-skatole) fragment were also sequenced. Comparing the amino acid sequence of thaumatin with that of the other sweet-tasting protein, monellin, we have located five sets of identical tripeptides. Since immunological cross-reactivity of thaumatin antibodies with monellin has recently been described, one or more of these tripeptides might be part of a common antibody recombination site and possibly be involved in the interaction with the sweet-taste receptor.


630411	The taste reactivity of chronic decerebrate rats is very similar to intact rats although chronic thalamic rats display only the quinine-like rejection sequence. The performance of intact (n = 12), decerebrate (n = 10) and thalamic (n = 10) preparations was further compared across a set of simple behavior tests to more broadly assess the behavioral capacities of the rodent brain stem. Decerebrate rats were immobile. They exhibited no spontaneous activity other than grooming, but often overreacted with well-coordinated movements (i.e., running, jumping and climbing) to seemingly inappropriate activating stimuli such as tail pinch, handling or water squirted on the fur. Decebrates had lower thresholds for elicited attack and grooming behaviors than thalamic or intact rats. The thalamic preparation exhibited a wider range of intact neurological responses than the decerebrate. Cage climbing, resistance to gravity, suspension and muscle tone reactions, rhythmic vibrissae movements and examination of objects with snout and mandible were difficult to distinguish from controls. Decerebrates either did not perform these responses or did so in a clearly different manner. In contrast, grooming behavior in thalamics was much less effective than in decerebrates. Thalamic rats spontaneously executed grooming sequences, but the responses were misdirected and ineffective. Desite their relative immobility, decerebrates coordinated grooming sequences and maintained their fur. No single mechanism appears to account for the constellation of deficits and capacities observed in either chronic thalamic or chronic decerebrate rats.
630410	The taste reactivity test described in the preceding paper was used to begin determining the capacity of brain stem structures to execute and regulate ingestive behavior. Both chronic thalamic and chronic decerebrate rat preparations were examined repeatedly, and their gustatory mimetic responses compared through frame-by-frame videotape analysis with the responses of neurologically normal controls. In response to orally injected taste stimuli, chronic decerebrate rats executed the same mimetic response components, and very similar response sequences observed in intact rats. In contrast, all taste stimuli elicited a quinine-like rejection sequence from chronic thalamic rats. In thalamic rats mimetic responses associated with ingestion were completely absent. Based on the similarities in the ingestion and rejection responses of decerebrate and intact rats, it appears that discriminative responses to taste result from integrative mechanisms complete within, or caudal to, the midbrain. Since decerebrate rats have the capacity to execute both ingestion and rejection response sequences, neural mechanisms rostral to the midbrain in some way suppress ingestion and/or releaser ejection responses in the thalamic preparation.
630409	One or two bottle preference tests, i.e., relative fluid consumption, constitute the primary methodology for determining acceptance or rejection of tastes in animals other than humans. These tests require organisms to initiate and maintain drinking behavior, and, therefore, can not be applied to preparations which do not eat or drink spontaneously. The taste reactivity test, a new method for assessing responses to gustatory stimuli, circumvents this shortcoming. A 50 microliter taste stimulus is injected directly into the oral cavity of a freely moving rat and the immediate response videotaped for frame by frame analysis. Each of the sapid stimuli used (4 concentrations of sucrose, NaCl, HCl, and quinine HCl) generated a stereotyped response derived from a lexicon of 4 mimetic (movements of lingual, masticatory, and facial musculature) and 5 body response components. Responses to taste stimuli were highly consistent within and between rats. For example, sapid sucrose, NaCl and HCl stimuli elicited a response sequence beginning with low amplitude, rhythmic mouth movements, followed by rhythmic tongue protrusions, and then lateral tongue movements. No body movements accompanied these mimetic responses. In contrast, quinine in concentrations at and above 3 X 10(-5) M (1/2 log step above the absolute behavioral threshold for quinine) elicited a response pattern beginning with gaping and proceeding through as many as 5 body responses. These normative data for the intact rat can be directly compared to the taste reactivity of neurally ablated preparations which do not spontaneously feed or drink. Such comparisons can be utlized in determining the neural substrates necessary for the execution and regulation of ingestive behavior.
155939	The epithelial cells in the taste buds of C. jacchus and C.  penicillata show a moderate amount of ribonucleic acid an a concentration of a PAS-positive diastase-resistant material at their apical part. These cells are devoid of UDPG-GT, phosphorylases, G-6-PA, alanyl aminopeptidase, leucine aminopeptidase, cholinesterase and MAO; they present a weak reaction of F-1, 6-P Ald, LDH, SDH, MDH, cytochrome oxidase, beta-OHBDH, nonspecific esterase and acid phosphatase and a stronger reaction to ADH, NADPH2-TR, ATPases, alpha-GPDH, alkaline  phosphatase, 5-nucleotidase and GDH. Although some enzymes (alkaline phosphatase, 5-nucleotidase and ATPases) have an almost uniform reactivity by the several taste buds, the other ones react with a lesser intensity in the smaller uniform reactivity by the several taste buds, the other ones react with a lesser intensity in the smaller taste buds of the fungiform papillae. As a rule the apical part of the cells shows a stronger enzymatic reactivity. The taste buds of the marmosets are penetrated by acetylcholinesterase positive nerve fibers whereas the autonomic ganglia in the connective tissue contain both-acetyl and butyrylcholinesterase.
830734	Is there an age-related decrement in the regulation of calorie intake? The results of Experiment I indicated that there was an age-related decrement in calorie intake and body weight of rats in response to dilution of their diet with non-nutritive cellulose. Was this decrement due to an age-related increase in reactivity to the sensory and hedonic aspects of the adulterated diet? The results of Experiment II indicated that older rats maintained their calorie intake and body weight as well as younger rats in response to dilution of their diet with water but decreased their calorie intake and body weight to a greater degree than younger rats when the water-diet mixture was adulterated by quinine. The results of these experiments suggest that the regulation of calorie intake remains intact over a large segment of the life of the rat, but can be overridden by age-related increases in reactivity to the sensory and hedonic aspects of the diet.
562610	The results of selective breeding for differential impairment of motor activity after alcohol injection is shown for the first 13 generations of the LA and MA rat strains. In F13 rats, the mean decrement of activity after 1.5 g ethanol per kg i/p. is 90% for MA rats and 42% for LA rats, the strain difference significant at a "p" of 1.8 x 10(-11). Blood alcohol levels, body weight, litter size, organ weights and induction of taste aversion to alcohol and lithium chloride are described for these strains in various of the generations. Although strain differences are apparent on some of these measures, none are of a degree or kind which offers more than a speculative explanation of the large difference between the strains in their central nervous system sensitivity to alcohol.
967895	The presence of a single cysteine in the sweet-tasting protein monellin was confirmed by titrations with p-hydroxymercuribenzoate (PHMB) and 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB). The sulfhydryl group in native monellin reacts very slowly with each of these reagents, indicating that the sulfhydryl is relatively inaccessible. In the presence of either 6 M guanidine-HCl, 8 M urea, or 1% sodium dodecyl sulfate, the rate of reaction of the sulfhydryl group with titrant is dramatically increased. Under a variety of conditions, the presence of 1 mole of sulfhydryl per mole of protein (of molecular weight 10,700) was found. Reaction of the sulfhydryl by titration with PHMB or DTNB leads to loss of sweetness. The free sulfhydryl is also lost by carboxymethylation of monellin in the presence of guanidine-HCl, yielding a protein that is not sweet. Exposure to air in the presence of denaturant leads to a decrease in the sweetness of monellin. Sweetness of the PHMB-reacted monellin can be recovered upon treatment of the protein with mercaptoethanol, and the partial loss of sweetness that occurs with air exposure is lessened in the presence of mercaptoethanol. It is postulated that alteration of the single sulfhydryl group of monellin leads to a change in the tertiary structure of the protein and hence its sweet taste.
1020023	Five experiments were performed to evaluate the physiological and behavioral similarities between lesions of the ventromedial hypothalamus (VMH) and injection-produced hyperinsulinemia. It was found that the rate of weight gain and fat deposition in both adult and weanling rats was essentially the same for both VMH and hyperinsulinemic rats. Measures of activity and taste preference measures yielded no differences between hyperinsulinemic rats and intact rats. Electric shock thresholds revealed a decrease in reactivity for hyperinsulinemic rats compared to intact rats. A hypothesis was suggested in which a combination of hypophysectomy, gonadectomy, and hyperinsulinemia might produce most of the physiological effects seen with VMH lesions. It was also suggested that since these physiological alterations radically modify the organism's internal environment, the behavioral effects of VMH lesions may be the results of the attempts of a brain-damaged animal to maintain new physiological conditions.














27744231	Several studies have explored the relationship between C-reactive protein (CRP), serum lipid levels, risk of suicide and alexithymia or impulsivity in mood or anxiety disorders. However, to date, no study has evaluated the effects of anhedonia on these parameters. The aim of the study was to evaluate the relationship between anhedonia, alexithymia, impulsivity, suicidal ideation, recent suicide attempt, C-reactive protein (CRP) and lipid levels in patients with mood or anxiety disorders. One hundred and twenty-two inpatients with mood or anxiety disorders were recruited. Alexithymia and impulsivity were rated by the 20-item Toronto Alexithymia Scale (TAS-20) and the Barratt impulsivity scale (BIS-10), respectively. Anhedonia and depression were rated by the Temporal Experience Pleasure Scale (TEPS) and the Beck Depression inventory (BDI-II). The TEPS contained two subscales rating anticipatory and consummatory anhedonia. From the BDI-II an anhedonia subscale was extracted rating anhedonia-state. Trait consummatory anhedonia and state anhedonia were associated with low levels of total cholesterol or HDL and low levels of triglycerides respectively. Trait anticipatory anhedonia and state anhedonia were associated with suicidal ideations. The difficulty of identifying feelings component of alexithymia was associated with low levels of total cholesterol and LDL. A high level of suicidal ideation was associated with low levels of HDL. Higher levels of CRP were found in inpatients having recently attempted suicide compared with inpatients who had not attempted suicide. In mood and anxiety disorders, anhedonia and the "difficulty of identifying feelings" component of alexithymia (which has previously been found to be associated with suicide risk) could explain the relationship between serum lipid levels and higher suicide risk.
27667317	Social anhedonia, the reduced capacity for social and interpersonal pleasure, often accompanies several forms of psychopathology. The goal of the present study was to validate the Chinese translation of the Anticipatory and Consummatory Interpersonal Pleasure Scale (ACIPS), a promising new tool for the assessment of individual differences in social pleasure. The Chinese versions of the ACIPS, the Temporal Experience of Pleasure Scale (TEPS), and the Schizotypal Personality Questionnaire (SPQ) were administered to 389 nonclinical adults. Factor analysis revealed that a four-factor structure accounted for nearly 53% of the variance, and the factors were consistent with those identified from factor analyses of the ACIPS in Western (U.S.) samples. The ACIPS measure showed high internal consistency as well. Correlational analysis revealed evidence of convergent validity. Individuals who scored high on the ACIPS were more likely to score high on measures of anticipatory and consummatory pleasure. Moreover, ACIPS total scores were inversely associated with scores on the No Close Friends subscale and the Constricted Affect subscale of the Schizotypal Personality Questionnaire (SPQ). Taken together, the findings suggest that the Chinese translation of the ACIPS is a reliable, valid measure that can be used to assess individual differences in the capacity to experience social and interpersonal pleasure in Chinese individuals.
27447103	To date, nearly all self-report measures of anhedonia have been developed for use with adult samples. A valid measure of anhedonia that can be used with adolescents would be useful in order to address key questions about the nature and course of anhedonia during adolescence. This study examined the psychometric properties of an adolescent version of a relatively new measure of social anhedonia, namely, the Anticipatory and Consummatory Interpersonal Pleasure Scale (ACIPS-A). The ACIPS-A was administered to a general, community-derived Spanish adolescent sample of 449 students, including 251 males (55.9%), who ranged in age from 13 to 19 years old. Other measures included the Temporal Experience of Pleasure Scale (TEPS), anhedonia subscales from the Oviedo Schizotypy Assessment Questionnaire (ESQUIZO-Q), and the General Health Questionnaire-12 (GHQ-12). Exploratory factor analysis yielded a four-factor solution (close relationships, casual friendships and relationships, social bonding, and negative affiliation/emancipation). The total ACIPS-A showed excellent internal consistency, with ordinal alpha=0.95. The ACIPS-A total scores were positively correlated with the TEPS-Anticipatory scores (r=0.44, P<0.001) and TEPS-Consummatory scores (r=0.30, P<0.001) but not with total GHQ-12 scores. The ACIPS-A total scores were negatively correlated with social anhedonia subscale scores (r=-0.55) taken from a measure developed for use with adolescents. These results suggest that the ACIPS-A is a valid measure for use with non-clinical adolescents and is likely to prove useful for screening purposes. 
24653714	Anhedonia, the lowered ability to experience pleasure, is one of the non-motor symptoms of Parkinson's disease (PD) that is underdiagnosed and consequently undertreated. Few studies have investigated anhedonia in PD by taking into account the influence of socio-demographic variables and versus a control group composed of patients with a pure motor neurologic disease other than PD. The aim of this study was to investigate hedonic deficits in patients with PD compared to a control group of patients with non-Parkinson motor neurologic disease (OND), matched for age, gender, level of education, and inpatient/outpatient status. Distinctions between anticipatory and consummatory anhedonia and between endogenomorphic and non-endogenomorphic depression were taken into account.The study population comprised 49 PD patients and 40 subjects with OND. Anhedonia was rated by using the anticipatory [Temporal Experience Pleasure Scale (TEPS)-ANT] and consummatory (TEPS-CONS) subscales of the TEPS and two subscales extracted from the revised Physical Anhedonia Scale (PAS), measuring physical anticipatory (PAS-ANT) and physical consummatory (PAS-CONS) anhedonias. The Snaith-Hamilton Pleasure Scale (SHAPS) and the Beck Depression Inventory-II (BDI-II) were also used together with a subscale extracted from the BDI-II (ENDO-BDI-II) for the diagnosis of endogenomorphic depression. Statistical analyses were performed on the whole group and on the PD group.	As hypothesized, several anhedonia scores varied with age and gender in the whole population or in the PD group. On univariate or multivariate analyses, only PAS-CONS was specific for PD and only SHAPS scores differed between depression subtypes in the whole population or the PD group.	This study suggests that physical consummatory anhedonia could be specific to PD subjects.	
21295860	Recent research has distinguished between anticipatory and consummatory pleasure. In the current study, we examined the psychometric properties of the Temporal Experience of Pleasure Scale (TEPS) to determine whether reliability and validity findings reported in previous research replicate in an additional sample of schizophrenia patients. Participants included 86 individuals with schizophrenia and 59 demographically matched healthy controls. Inconsistent with previous research, patients differed from controls in their reports of consummatory (TEPS-CON), but not anticipatory (TEPS-ANT) pleasure. We also failed to replicate some important correlational findings reported in previous research indicating relationships between the TEPS-ANT subscale and external validators. Analyses of the stability of the TEPS subscales were conducted in a sub-group of patients (n=19), and indicated excellent stability for the TEPS-CON (ICC (intraclass correlation coefficient)=0.93), but somewhat lower stability for the TEPS-ANT subscale (ICC=0.74). These findings suggest that additional studies are needed using the TEPS, as well as other measures, to determine the nature of anhedonia in individuals with schizophrenia.