Olanzapine affects locomotor activity and meal size in male rats

Olanzapine is an antipsychotic drug that frequently induces weight gain accompanied by increased fat deposition as a side effect. To investigate how olanzapine affects different aspects of energy balance, we used male rats to determine effects on meal patterns, food preference, locomotor activity and body temperature. In two short-term experiments olanzapine was administered via osmotic minipumps. In the first experiment, we offered rats standard lab chow only. In the second experiment, we offered rats free choice between chow, sucrose and saturated fat. In a third experiment, olanzapine was chronically administered via the drinking water to determine effects on body composition. In each experiment olanzapine decreased locomotor activity and altered meal patterns. Olanzapine caused an increase in average meal size accompanied by reduced meal frequency, without clearly affecting food preference. In the chronic experiment body composition was altered, favoring adipose tissue over lean muscle mass, despite reductions in overall body weight gain. The increase in average meal size implies that the primary effect of olanzapine on feeding is an impairment of the normal satiation process. Furthermore, energy balance is clearly affected by a reduction in locomotor activity. Thus, the effects of olanzapine on adiposity do not depend solely on the presence of hyperphagia.