Effects of long-term administration of clozapine on body weight and food intake in rats.

Previous reports have shown that long-term administration of typical and atypical neuroleptics induced obesity in female but not in male rats. It has been suggested that impaired ovarian steroidogenesis related to neuroleptic-induced hyperprolactinemia is necessary to observe the body weight changes. This hypothesis was tested with clozapine, an atypical neuroleptic that produces in rats a shorter increase in serum prolactin levels than do other neuroleptics. The effects of clozapine on body weight and food intake were assessed in female and male rats under treatment with any of the following doses: 0.5, 1, 2.5, 5, 10, and 20 mg/kg IP for 21 days. Vaginal cycle under clozapine treatment, as an indirect indicator of ovarian steroidogenesis, was also assessed. Obesity was not observed in any group. By contrast, clozapine at the doses of 10 and 20 mg/kg significantly decreased body weight and feeding in male rats. Clozapine at the doses of 5 and 10 mg/kg IP induced permanent diestrus. The failure of clozapine to induce obesity in female rats, despite impaired vaginal cycle, can be considered indirect evidence that drug-induced hyperprolactinemia is not sufficient to observe neuroleptic-induced obesity in rats.