The distinct effects of subchronic antipsychotic drug treatment on macronutrient selection, body weight, adiposity, and metabolism in female rats
The distinct effects of subchronic antipsychotic drug treatment on macronutrient selection, body weight, adiposity, and metabolism in female rats
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DOI：
10.1007/s00213-007-0833-9
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发表时间：
2007-10-01
影响因子：
3.4
通讯作者：
Neill, J. C.
中科院分区：
文献类型：
--
作者：
Fell, M. J.;Anjum, N.;Neill, J. C.
简介 使用某些抗精神病药物治疗可能会导致体重过度增加，从而对患者的依从性、发病率和死亡率产生不利影响。本研究的目的是调查非典型抗精神病药物对雌性大鼠饮食常量营养素选择、体重、身体成分和与肥胖相关的生化参数的影响。 材料和方法 40 对成年雌性 hooded-Lister 大鼠（250 +/- 5 g）在笼子里习惯三种主要含有蛋白质、脂肪或碳水化合物的饮食 自选择范式。腹腔注射奥氮平（2 mg/kg）、利培酮（0.5 mg/kg）、齐拉西酮（2.5 mg/kg）或赋形剂，每日一次，持续 22 天；每天记录食物选择、水摄入量和体重，同时在研究结束时分析身体成分和血浆激素（胰岛素、葡萄糖、非酯化游离脂肪酸、总胆固醇、甘油、三酰甘油、瘦素和催乳素）。 结果只有奥氮平显着增加体重和食物摄入量。奥氮平和利培酮治疗后，大量营养素的选择发生了显着变化（蛋白质增加，脂肪偏好减少）。只有奥氮平可以增加胴体脂肪含量。所有治疗组的运动活动均显着降低。奥氮平和利培酮均显着增加血浆催乳素。奥氮平对测量的任何其他生化参数没有影响。齐拉西酮显着降低血浆瘦素，但非显着降低 NEFA，而利培酮则显着降低空腹血糖。 结论 这项研究支持了我们之前的工作，证明了奥氮平引起的体重增加和进食行为增加，并且可能对增强我们对奥氮平和其他非典型抗精神病药在临床中引起体重增加的机制的理解具有重要意义。
Introduction Treatment with some antipsychotic drugs may result in excessive body weight gain which can have detrimental effects on patient compliance, morbidity and mortality. The aim of the present study was to investigate the effect of atypical antipsychotic drugs on dietary macronutrient selection, body weight, body composition and biochemical parameters related to obesity in female rats.Materials and methods Forty pair-housed, adult female hooded-Lister rats (250 +/- 5 g) were habituated to three diets containing principally protein, fat, or carbohydrate in a home cage self-selection paradigm. Olanzapine (2 mg/kg), risperidone (0.5 mg/kg), ziprasidone (2.5 mg/kg), or vehicle was injected intraperitoneally once daily for 22 days; food selection, water intake, and body weight were recorded daily, while body composition and plasma hormones (insulin, glucose, nonesterified free fatty acid, total cholesterol, glycerol, triacylglycerol, leptin, and prolactin) were analyzed at the end of the study.Results Only olanzapine significantly increased body weight and food intake. Macronutrient selection was significantly altered after olanzapine and risperidone treatment (increased protein and decreased fat preference). Only olanzapine increased carcass fat content. Locomotor activity was significantly reduced in all treatment groups. Both olanzapine and risperidone significantly increased plasma prolactin. Olanzapine was without effect on any other biochemical parameter measured. Ziprasidone significantly reduced plasma leptin and nonsignificantly reduced NEFA, while risperidone significantly reduced fasting plasma glucose.Conclusion This study supports our previous work demonstrating weight gain and increased feeding behavior induced by olanzapine and could have important implications for enhancing our understanding of the mechanisms by which olanzapine and other atypical antipsychotics induce weight gain in the clinic.