Paper
International Journal of Obesity (2005) 29, 607–614. doi:10.1038/sj.ijo.0802928 Published online 29 March 2005
Antipsychotic drug-induced weight gain: development of an animal model
M B Cope1, T R Nagy1, J R Fernández1,2, N Geary3, D E Casey4 and D B Allison1,2
- 1Department of Nutrition Sciences, Clinical Nutrition Research Center, University of Alabama at Birmingham, Birmingham, AL, USA
- 2Department of Biostatistics, Section on Statistical Genetics, University of Alabama at Birmingham, Birmingham, AL, USA
- 3Bourne Laboratory, Department of Psychiatry, Weill Medical College of Cornell University, White Plains, NY, USA
- 4Mental Illness Research Education & Clinical Center (MIRECC) VISN 20 and Mental Health Division, and Departments of Psychiatry and Neurology, Oregon Health & Science University, Portland, OR 97239, USA
Correspondence: Dr DB Allison, Ryals Public Health Building, Suite 327, University of Alabama at Birmingham, 1665 University Boulevard, Birmingham, AL 35294, USA. E-mail: Dallison@UAB.edu
Received 4 August 2004; Revised 7 January 2005; Accepted 16 January 2005; Published online 29 March 2005.
Abstract
OBJECTIVE:
Weight gain is a prominent effect of most atypical antipsychotic drugs (AAPDs); yet, the mechanisms are not fully understood and no well-established mouse models exist for investigating the mechanisms. Thus, we developed a mouse model to evaluate the effects of AAPDs on eating, body weight (BW), and body composition.
METHODS:
Female C57BL/6J mice were used to test olanzapine, quetiapine, ziprasidone, and risperidone. Mice were acclimated to individual housing, given ad libitum access to chow and water, dosed with placebo peanut butter pills for 1 week, and then dosed daily with AAPD-laced peanut butter pills for 4 weeks. Weekly food intakes and BWs were measured, and body compositions were determined at the end of each experiment.
RESULTS:
After 4 weeks of treatment, olanzapine, quetiapine, ziprasidone, and risperidone caused significant weight increases, but only olanzapine and quetiapine were associated with significantly increased food intake. Body composition data revealed that olanzapine-treated mice had more relative fat mass and risperidone-treated mice had more relative lean mass than did control mice. Quetiapine and ziprasidone did not significantly affect relative body composition even though BW was increased.
CONCLUSIONS:
Oral AAPD administration causes increased BW in female mice. Our mouse model of AAPD-induced weight gain resembles the human response to these medications and will be used to investigate the mechanisms for weight gain and fat accumulation.
Keywords:
atypical antipsychotics, weight gain, hyperphagia
