Antipsychotic drug-induced weight gain: development of an animal model.
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.
Cope
M B
MB
Department of Nutrition Sciences, Clinical Nutrition Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Nagy
T R
TR
Fernández
J R
JR
Geary
N
N
Casey
D E
DE
Allison
D B
DB
D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001569:Benzodiazepines / Q000009:adverse effects; D001824:Body Constitution; D001835:Body Weight; D003987:Dibenzothiazepines / Q000009:adverse effects; D004435:Eating; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009765:Obesity / Q000139:chemically induced*; D000077152:Olanzapine; D010879:Piperazines / Q000009:adverse effects; D000069348:Quetiapine Fumarate; D018967:Risperidone / Q000009:adverse effects; D013844:Thiazoles / Q000009:adverse effects
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D010879:Piperazines; D013844:Thiazoles; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; C092292:ziprasidone; D018967:Risperidone; D000077152:Olanzapine