Body weight gain is one of the most serious side effects associated with clinical use of
antipsychotics. However, the mechanisms by which
antipsychotics induce
body weight gain are unknown, and no reliable animal models of
antipsychotics-induced
weight gain have been established. The present studies were designed to establish male rat models of
weight gain induced by chronic and acute treatment with
antipsychotics. Six-week chronic treatment with
olanzapine (5, 7.5, and 10mg/kg/day) in male Sprague-Dawley rats fed a daily diet resembling a human macronutrient diet, significantly increased
body weight gain and weight of fatty tissues. In contrast,
ziprasidone (1.25, 2.5, and 5mg/kg/day) administration caused no observable adverse effects. We then investigated feeding behavior with acute
antipsychotic treatment in male rats using an automated food measurement apparatus. Rats were allowed restricted access to normal laboratory chow (4h/day). With acute
olanzapine (0.5, 1, and 2mg/kg, i.p.) treatment in the light phase, food intake volume and duration were significantly increased, while treatment with
ziprasidone (0.3, 1, and 3mg/kg, i.p.) did not increase food intake volume or meal time duration. Findings from the present studies showed that chronic treatment with
olanzapine in male rats induced
body weight gain, and acute injection induced
hyperphagia, suggesting that
hyperphagia may be involved in the
weight gain and
obesity-inducing properties of chronically administered
olanzapine. These animal models may provide useful experimental platforms for analysis of the mechanism of
hyperphagia and evaluating the potential risk of novel
antipsychotics to induce
weight gain in humans.