Antipsychotic drug-induced weight gain:: development of an animal model
Antipsychotic drug-induced weight gain:: development of an animal model
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DOI：
10.1038/sj.ijo.0802928
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发表时间：
2005-06-01
影响因子：
4.9
通讯作者：
Allison, DB
中科院分区：
文献类型：
--
作者：
Cope, MB;Nagy, TR;Allison, DB
目的：体重增加是大多数非典型抗精神病药物（AAPD）的一个突出效应;然而，其机制尚未完全了解，也没有建立良好的小鼠模型来研究其机制。因此，我们开发了一种小鼠模型来评估AAPD对进食、体重（BW）和身体组成的影响。方法：雌性C57 BL/6 J小鼠用于测试奥氮平、奎替鲁、齐拉西酮和利培酮。使小鼠适应单独圈养，随意获得食物和水，用安慰剂花生酱丸给药1周，然后每天用AAPD掺杂的花生酱丸给药4周。每周的食物摄入量和体重进行了测量，并在每个实验结束时测定身体成分。结果：治疗4周后，奥氮平，奎替鲁，齐拉西酮，利培酮引起显着的体重增加，但只有奥氮平和奎替鲁与显着增加的食物摄入量。身体组成数据显示，奥氮平治疗的小鼠有更多的相对脂肪质量和利培酮治疗的小鼠有更多的相对瘦体重比对照组小鼠。奎替鲁肽和齐拉西酮并没有显着影响相对身体组成，即使BW increased.CONCLUSIONS：口服AAPD给药导致雌性小鼠BW增加。我们的AAPD诱导体重增加的小鼠模型类似于人类对这些药物的反应，并将用于研究体重增加和脂肪积累的机制。国际肥胖杂志（2005）。
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. International Journal of Obesity (2005).