Studies on modulation of feeding behavior by atypical antipsychotics in female mice.

The aim of this study was to examine the effects of different doses of typical antipsychotics, chlorpromazine (0.25-1 mg/kg) and haloperidol (0.25-1 mg/kg), and atypical antipsychotics, clozapine (0.5-2 mg/kg), olanzapine (0.25-1 mg/kg), risperidone (0.5-2 mg/kg), sulpiride (10-40 mg/kg) and dopamine D1 antagonist, SCH 23390 (0.25-1 mg/kg) on feeding behavior at different time intervals after acute administration. The study further investigated the central dopamine and serotonergic receptor involvement in clozapine-induced hyperphagia using SKF 38393, quinpirole and quipazine. Then, the authors also examined the effect of subchronic treatment for 21 days with fluoxetine on clozapine-induced hyperphagia and modulation of body weight and fat pad weights. The feeding behavior was assessed in nondeprived mice by presenting the palatable chow to different groups of mice in glass petri dishes and recording the food consumed at different time intervals. After acute administration, significant (P<.05) increase in food intake was observed at different time intervals with different doses of both typical and atypical antipsychotics. Further, clozapine-induced hyperphagia was significantly (P<.05) reversed after treatment with SKF 38393 (dopamine D1 agonist), quinpirole (dopamine D2 agonist) and quipazine (5-HT1B, 5-HT2 and 5-HT3 agonist). In subchronic study, treatment with fluoxetine (10 mg/kg) significantly (P<.05) antagonized the increase in body weight and food intake induced by clozapine (2 mg/kg). The current investigations underscore the reported increases in food intake and body weight gain observed with antipsychotics. The study further confirms the involvement of dopamine D1, D2 and serotonergic receptor involvement in clozapine-mediated hyperphagia. Further, the serotonergic agents may prove useful to counteract antipsychotic-induced obesity.