The effect of ziprasidone on body weight and energy expenditure in female rats

Ziprasidone, a novel antipsychotic agent with a unique receptor-binding profile, has been reported to have lower propensity for weight gain compared with other atypical antipsychotics. Here, we examined the effects of ziprasidone on resting energy expenditure, physical activity, thermogenesis, food intake, and weight gain in female Sprague-Dawley rats. Ziprasidone (20 mg/kg) or vehicle was administered once daily for 7 weeks; and body weight, food intake, resting energy expenditure, locomotor activity, colonic temperature on cold exposure, and abdominal fat were measured. Compared with control animals, ziprasidone-treated rats gained significantly less weight (P =.031), had a lower level of physical activity (P =.016), showed a higher resting energy expenditure (P <.001), and displayed a greater capacity for thermogenesis when subjected to cold (P <.001). In addition, ziprasidone-treated rats had a lower level of abdominal fat than did controls, although the difference was not significant. Ziprasidone had no effect on food intake. Our results indicate that, in female Sprague-Dawley rats, a 7-week treatment regimen of ziprasidone induces a significant decrease in weight gain by increasing resting energy expenditure without decreasing food intake and even with a lower level of physical activity. Further studies are needed to elucidate the precise mechanism of lower propensity of weight gain of ziprasidone.