Investigation into the effects of the novel antipsychotic ziprasidone on weight gain and reproductive function in female rats

Weight gain and sexual dysfunction are serious side effects of certain antipsychotic drugs. Ziprasidone, a novel antipsychotic with a unique receptor binding profile, is reported to have a low propensity for such side effects. Previous results from this laboratory have demonstrated substantial weight gain following sub-chronic treatment with olanzapine and risperidone. Risperidone induced weight gain and markedly impaired reproductive function while olanzapine induced weight gain, without affecting reproductive function. The aim of this study was to investigate effects of ziprasidone on weight gain and reproductive function in female rats. Ziprasidone (1 and 2.5 mg/kg i.p.) or vehicle was administered once daily for 28 days and body weight, food and water intake measured, in addition to histological examination of vaginal lavage to determine the stage of the oestrous cycle. On day 28, the rats were sacrificed and the uterine weights recorded, intra-abdominal fat weight and plasma prolactin levels measured. Ziprasidone failed to induce significant weight gain during weeks 1-3, however, significant weight gain was observed on day 28 at 2.5 mg/kg (p < 0.05). Ziprasidone had no effect on food intake at any time point. A significant reduction in water intake (p < 0.05) was observed during the first week of treatment with 2.5 mg/kg ziprasidone. Ziprasidone had no effect on intra-abdominal fat weight, wet or dry uterine weight or plasma prolactin levels. All ziprasidone treated animals displayed a normal four-day oestrous cycle. This study is the first to report that ziprasidone is without effect on reproductive function or ingestive behaviour in the rat.