olanzapine and 3-(2-hydroxy-4-(1-1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol

Some atypical antipsychotics clinically used to treat schizophrenia induce weight gain by unknown mechanisms. The dorsal vagal complex (DVC) of the brainstem and the endogenous cannabinoid system are implicated in the regulation of appetite signalling and food intake. We investigated whether antipsychotic drugs alter cannabinoid receptor-binding density in the DVC. Female Spraguewk (short-term) or 120.83, p=0.01). In addition, only chronic olanzapine treatment increased food intake. These results show that olanzapine, an antipsychotic with a high risk of weight gain as a side-effect, significantly decreased cannabinoid receptor binding in the DVC, whilst aripiprazole and haloperidol, antipsychotics with a low risk of weight gain had little or no effect on binding. These results suggest that a mechanism for antipsychotic-induced weight gain may be through the modulation of cannabinoid receptors in the DVC.

Topics: Animals; Antipsychotic Agents; Autoradiography; Benzodiazepines; Binding, Competitive; Cyclohexanols; Female; Immunosuppressive Agents; Medulla Oblongata; Olanzapine; Protein Binding; Rats; Rats, Sprague-Dawley; Receptors, Cannabinoid; Tritium; Weight Gain