Document Detail

Long term treatment with olanzapine mixed with the food in male rats induces body fat deposition with no increase in body weight and no thermogenic alteration.
MedLine Citation:
PMID:  16551485     Owner:  NLM     Status:  MEDLINE    
Body weight gain is a worrying side effect of many new antipsychotic drugs. The mechanisms by which antipsychotic drugs increase weight in humans are not known. Attempts to model the metabolic effects of antipsychotic drugs in the animal have not been successful. Female rats appear to be sensitive to the effects of antipsychotics, but male rats less, and this does not match the clinical situation in humans. In previous rodent studies, antipsychotics were always given by daily gavage or injections. Antipsychotics have different pharmacokinetics in rodents and humans, and in the present study, we tested the hypothesis that the insensitivity of male rats to the effects of antipsychotics could be related to their mode of administration. Thus, we administered antipsychotic drugs mixed with the food. Animals were treated during 6 weeks with haloperidol (1mg/kg), olanzapine (1mg/kg), ziprasidone (10mg/kg), or a control solution. Animals were allowed to self-select food among three macronutrients (carbohydrates, lipids and proteins). Food selection was measured throughout the study. At the end of the study, body composition was measured by dissection and weighing of the rat's main organs and tissues. Mitochondrial thermogenesis was measured in brown adipose tissue in olanzapine-treated animals. Circulating leptin, insulin, glucose, triglycerides, cholesterol, high-density lipoprotein (HDL) were also assayed at the end of the study. The results show that none of the antipsychotic treatments modified caloric intake, food selection or body weight. Olanzapine did not alter mitochondrial thermogenesis. However, haloperidol and olanzapine induced a significant increase in adiposity and circulating leptin. Ziprasidone produced a moderate fat accumulation. It is concluded that mixing antipsychotic treatments with the food provides a reliable animal model of antipsychotic-induced fat accumulation.
Julie Minet-Ringuet; Patrick C Even; Marc Goubern; Daniel Tomé; Renaud de Beaurepaire
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-03-23
Journal Detail:
Title:  Appetite     Volume:  46     ISSN:  0195-6663     ISO Abbreviation:  Appetite     Publication Date:  2006 May 
Date Detail:
Created Date:  2006-06-19     Completed Date:  2007-01-12     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8006808     Medline TA:  Appetite     Country:  England    
Other Details:
Languages:  eng     Pagination:  254-62     Citation Subset:  IM    
Laboratoire de Psychopharmacologie, Centre Hospitalier Paul Guiraud, 54 avenue de la République, 94806 Villejuif, France.
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MeSH Terms
Adipose Tissue / drug effects,  metabolism*
Animal Feed*
Antipsychotic Agents / administration & dosage,  adverse effects*,  therapeutic use
Benzodiazepines / administration & dosage,  adverse effects,  therapeutic use
Eating / drug effects*
Haloperidol / administration & dosage,  adverse effects,  therapeutic use
Organ Size
Random Allocation
Rats, Sprague-Dawley
Thermogenesis / drug effects,  physiology
Weight Gain / drug effects*
Reg. No./Substance:
0/Antipsychotic Agents; 12794-10-4/Benzodiazepines; 132539-06-1/olanzapine; 52-86-8/Haloperidol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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