Effects of atypical antipsychotic drugs on intralipid intake and cocaine-induced hyperactivity in rats

Abstract

Clozapine and olanzapine have been shown to acutely stimulate consumption of a fat emulsion (Intralipid) by male Lister hooded rats. We initially investigated the extent of any sex difference in Intralipid hyperphagia associated with olanzapine treatment. We then examined the degree of Intralipid hyperphagia produced by a range of atypical antipsychotic drugs having different associations with human weight gain, and also determined their effects on cocaine-stimulated locomotor activity as a measure of functional dopamine antagonism in vivo. Olanzapine (0.1-1 mg/kg) stimulated Intralipid intake to an equal extent in male and female rats. Quetiapine (10 mg/kg) also stimulated Intralipid intake whereas ziprasidone (0.3-10 mg/kg) or risperidone (0.03-0.3 mg/kg) did not have this effect. All of the compounds, except quetiapine, reduced cocaine-stimulated locomotor activity but the relationship to the degree of Intralipid hyperphagia was variable. Since there was a positive relationship between Intralipid hyperphagia and the reported extent of human body weight gain, we conclude that Intralipid hyperphagia may have predictive value for this drug-associated side effect and is not related to the dopamine antagonist properties of these agents. © 2006 Nature Publishing Group All rights reserved.