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.
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Acknowledgements
This research was supported in part by NIH grant P30DK56336, DK68261 grants from the NARSAD Foundation and Eli Lilly & Co., and the Veteran Affairs Medical Research Program. We thank Dr Steve Barnes, Dr Donald Muccio, Ms Grace Walton, and Dr Benjamin Davis for their contributions to the manuscript. We received technical assistance from Pfizer Pharmaceutical.
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Cope, M., Nagy, T., Fernández, J. et al. Antipsychotic drug-induced weight gain: development of an animal model. Int J Obes 29, 607–614 (2005). https://doi.org/10.1038/sj.ijo.0802928
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DOI: https://doi.org/10.1038/sj.ijo.0802928
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