Naltrexone does not prevent the weight gain and hyperphagia induced by theantipsychotic drug sulpiride in rats

Few pharmacological tools are currently available to counteract the excessi ve body weight gain often observed during prolonged administration of antip sychotic drugs. Most antipsychotic drugs block dopamine receptors, and both the brain dopaminergic and opioid systems appear to be involved in initiat ion and maintenance of feeding behavior, respectively. We evaluated whether the opioid antagonist naltrexone (NAL, 0.5-16 mg/kg/ip for 21 days) (a) af fects body weight and food intake in gonadally-intact and drug-free female rats, (b) prevents obesity, hyperphagia, hyperprolactinemia and vaginal cyc le disruption induced by long-term administration of the antipsychotic drug sulpiride (SUL, 20 mg/kg/ip for 21 days), or (c) reverses the acute hyperp hagia induced by SUL (15 mu g bilaterally), when directly applied in the pe rifornical lateral hypothalamus (PFLH). In drug-free rats, only NAL doses a bove 4 mg/kg, significantly decreased weight gain and food intake. Even tho ugh NAL (1 and 8 mg/kg) significantly attenuated SUL-induced hyperphagia an d hyperprolactinemia, it did not reverse at any dose the weight gain and pe rmanent diestrous induced by SUL. In addition, local NAL did not prevent th e hyperphagia and polidypsia observed after acute intrahypothalamic SUL. Un expectedly, the cumulative and 24 h food intake in SUL-treated rats was sig nificantly increased by NAL. Collectively, these results do not support a r ole for endogenous opiates in the neural and endocrine mechanisms involved in weight gain during prolonged antipsychotic drug administration in rats. (C) 2000 Academic Press.