Investigation into the influence of a high fat diet on antipsychotic-induced weight gain in female rats

Atypical antipsychotic drug therapy may result in substantial weight gain, increased adiposity and the promotion of metabolic abnormalities. The mechanism(s) which underlie such effects remain unclear. Previous studies in our laboratory have demonstrated significant weight gain in female rats maintained on a standard laboratory diet after sub-chronic administration of olanzapine and risperidone, but not ziprasidone. The aim of this paper is to investigate the effect of antipsychotic drugs on body weight, ingestive behaviour and adiposity in female rats with access to a high fat diet. Adult female rats given free access to a high fat diet received either olanzapine ( 2 mg/kg), risperidone ( 0.5 mg/kg), ziprasidone (2.5 mg/kg) or vehicle for 28 days. Body weight, food and water intake in addition to intra-abdominal fat deposition were assessed. Olanzapine initially increased body weight but by the end of the study olanzapine animals appeared to have lost weight compared to the vehicle-treated group. Olanzapine-induced reductions in body weight were accompanied by a significant hypophagia during weeks 3 and 4. Risperidone increased body weight during week 1 only and reduced intake of a high fat diet during weeks 3 and 4. Ziprasidone was without effect on indices of body weight and ingestive behaviour. There were no effects of antipsychotic drugs on intra-abdominal fat deposition. Access to a diet high in fat attenuated weight gain induced by olanzapine and risperidone in female rats.