Characterization of olanzapine-induced weight gain in rats
Characterization of olanzapine-induced weight gain in rats
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DOI：
10.1177/026988110201600402
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发表时间：
2002-12-01
影响因子：
4.1
通讯作者：
Halford, JCG
中科院分区：
文献类型：
--
作者：
Goudie, AJ;Smith, JA;Halford, JCG
新型抗精神病药物（APD）与“典型”APD相比具有增强的治疗作用。然而，临床研究表明，一些诱导显着的体重增加。我们试图在雌性Wistar大鼠中建立这种效应的模型，这些大鼠长期给予4 mg/kg b.i.d（注射间隔4.5 h）奥氮平。这些大鼠显示出显著的体重增加，仅在一天的治疗后就具有统计学显著性，尽管在治疗10天后体重增加达到平台期。停止治疗导致体重迅速下降，停药一天后体重下降明显。观察到的体重增加的特征在于显著的个体差异。由于一些临床报告表明，新型APD诱导的体重增加在体重最低的患者中最为明显，因此我们检查了体重增加与基线体重之间的关系。然而，我们观察到基线体重和体重增加之间没有显著关系。奥氮平可诱导大鼠体重迅速增加的观察结果，以及体重增加的显著个体差异的观察结果表明，有发生体重增加风险的患者可能在治疗早期就可检测到。此外，体重增加可迅速逆转的发现表明，有体重增加风险的患者可改用诱导体重增加趋势不太明显的APD。啮齿类动物APD诱导的体重增加的研究可能会为临床上新的APD诱导的体重增加的性质，原因和治疗提供见解。然而，啮齿类动物模型模拟临床情况的程度以及我们观察到的体重增加所涉及的机制是否与这些药物的临床应用。
Novel antipsychotic drugs (APDs) have enhanced therapeutic actions compared to 'typical' APDs. However, clinical studies indicate that some induce marked weight gain. We attempted to model this effect in female Wistar rats given olanzapine chronically at 4 mg/kg b.i.d (4.5 h between injections). Such rats showed marked weight gain, which was statistically significant after only a single day of treatment, although weight gain increased up to a plateau after 10 days of treatment. Cessation of treatment led to rapid weight loss, which was significant after a single day of withdrawal. The weight gain observed was characterized by marked individual differences. As some clinical reports suggest that novel APD-induced weight gain is most pronounced in patients with the lowest body weight, we examined the relationship between weight gain and baseline body weight. However, we observed no significant relationship between baseline body weight and weight gain. The observation that olanzapine can induce weight gain rapidly in rats, in conjunction with the observation of marked individual differences in weight gain, suggests that patients at risk of developing, weight gain might be detectable early in treatment. Furthermore, the finding that weight gain is rapidly reversible suggests that patients at risk of weight gain could be switched to APDs with less pronounced tendencies to induce weight gain. The study of APD-induced weight gain in rodents may provide insights into the nature, causes, and treatments for, novel APD-induced weight gain in the clinic. However, it remains to be determined how closely rodent models mimic the clinical situation and whether the mechanism(s) involved in the weight gain we have observed are the same as those involved in the.,clinical use of these drugs.