Standardizing Ketamine-Induced Psychosis in Mice: A Comparative Study of Acute and Chronic Administration

Psychosis is a complex mental illness, characterised by positive, negative and cognitive symptoms. NMDA receptor antagonists have been established to induce behavioural as well as biochemical changes in rodents similar to psychotic patients. The aim of the present study was to investigate the effective dose and treatment period of ketamine to induce some behavioural changes. The results suggest that acute treatment of ketamine (50 and 100 mg/kg, i.p.) induced hyperlocomotor activity and reduced step down latency time in passive avoidance test, whereas in effective in forced swim test. Further, with the chronic administration of ketamine (50 and 100 mg/kg, i.p.) effective to produced hyperlocomotor activity, reduced the step down latency time in passive avoidance test and enhanced the immobility duration in forced swim test. Moreover, these behavioural changes persisted for 7 days after the treatment period. Thus, our findings suggest that the chronic administration of Ketamine (50 and 100 mg/kg, i.p.) potential to produce behavioural changes, would serve as an effective tool to screen antipsychotic drugs.

Keywords: Ketamine, NMDA receptor, psychosis, animal models.

Psychosis is a complex, debilitating mental disorder that affects large number of population1. Usually, psychosis is categorized into three main symptoms, positive, negative and cognitive symptoms2,3. Bizzare behaviour, delusions, hallucinations and loss of contact from reality collectively come under positive or bizarre symptom of psychosis4,5. Alogia, anhedonia, avolition, flat affect or social withdrawal or loss of emotion are negative symptom of psychosis6,7. Cognitive symptoms represents as loss of concentration and lack of learning or memory process8. Animal models are used to under the exact mechanism of action as well as for screening of new test drugs9,10,11. The limited research on psychosis has been the main reason of lack of appropriate animal model that mimics the clinical symptoms of psychosis12. Several chemicals or drugs, used to induce psychosis in rodents are not capable to imitate the symptoms seen in human. N-methyl d-aspartate (NMDA) receptor antagonists such as dizocilpine, Ketamine and phencyclidine are used to produce psychosis in rodents as well as in human13. Ketamine, an arylcyclohexylamine derivative of phencyclidine is noncompetitive NMDA receptor antagonist and stimulates psychotic symptoms14. It has also been observed that