Chronic treatment with olanzapine via a novel infusion pump induces adiposity in male rats

Aims: Clinical use of olanzapine has been suggested to be associated with weight gain and adiposity in schizophrenic patients. While studies in experimental animals have noted weight gain in olanzapine-treated female rats, these findings have yet to be replicated in males. This study investigated the effect of chronic subcutaneous infusion of olanzapine in male rats via a recently developed electrical microinfusion pump. Main methods: An electrical microinfusion pump was subcutaneously implanted in male Sprague-Dawley rats who were then chronically administered olanzapine. Plasma olanzapine concentration and body weight were monitored, and fat pads were weighed after six weeks' olanzapine treatment. Key findings: Plasma olanzapine concentration plateaued within 4 h of commencement of chronic olanzapine 1.5 mg/animal/day infusion and remained constant until day 21. Six-week infusion of olanzapine at 1.5 but not 1 mg/animal/day induced significant adiposity in subcutaneous, epididymal, and retroperitoneal fat. Body weight and food intake values did not differ between olanzapine- and vehicle-treated rats throughout the experiment. Significance: The present study demonstrated that chronic infusion of olanzapine induced adiposity in male rats without inducing weight gain or hyperphagia, even with sufficient plasma concentration. This report is the first to provide information about adiposity-inducible plasma concentration of olanzapine in male rats. (C) 2011 Elsevier Inc. All rights reserved.