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Neuropsychopharmacology (2006) 31, 19381945

and Cocaine-Induced Hyperactivity in Rats[notdef]

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[notdef]Abegale W Hartfield1, Nicholas A Moore2 and Peter G Clifton*,11Department of Psychology, University of Sussex, Brighton, UK; 2Eli Lilly & Co, Erl Wood Manor, Windlesham, UKClozapine 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 thenexamined the degree of Intralipid hyperphagia produced by a range of atypical antipsychotic drugs having different associations withhuman weight gain, and also determined their effects on cocaine-stimulated locomotor activity as a measure of functional dopamineantagonism in vivo. Olanzapine (0.11 mg/kg) stimulated Intralipid intake to an equal extent in male and female rats. Quetiapine(10 mg/kg) also stimulated Intralipid intake whereas ziprasidone (0.310 mg/kg) or risperidone (0.030.3 mg/kg) did not have this effect.All of the compounds, except quetiapine, reduced cocaine-stimulated locomotor activity but the relationship to the degreeof Intralipid hyperphagia was variable. Since there was a positive relationship between Intralipid hyperphagia and the reported extentof human body weight gain, we conclude that Intralipid hyperphagia may have predictive value for this drug-associated side effect andis not related to the dopamine antagonist properties of these agents.Neuropsychopharmacology (2006) 31, 19381945. doi:10.1038/sj.npp.1300949; published online 2 November 2005Keywords: antipsychotic; weight gain; hyperphagia; food intake; locomotor activity; rat; olanzapineINTRODUCTIONIn humans, treatment with some atypical antipsychotic

drugs is associated with weight-gain (Hemphill et al, 1975;

Claus et al, 1992; Beasley et al, 1996; Kraus et al, 1999).

Allison et al (1999) performed a meta-analysis of published

data suggesting that clozapine and olanzapine are associated with the greatest weight-gain, followed by quetiapine

and risperidone; while haloperidol treatment produces only

modest weight gain and ziprasidone appears to be weight

neutral in most patients. Similar conclusions have been

reached in reviews by Taylor and McAskill (2000) and

Wetterling (2001); specifically that the rank order for

weight-gain liability in humans is, highest first: clozapine

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Effects of Atypical Antipsychotic Drugs on Intralipid Intake and Cocaine-Induced Hyperactivity in Rats

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