Department of Neuroendocrinology, University of Groningen, Groningen, The Netherlands.
Pharmacol Biochem Behav. 2010 Nov;97(1):163-9. doi: 10.1016/j.pbb.2010.05.029. Epub 2010 Jun 4.
Olanzapine is an a-typical antipsychotic drug antagonizing predominantly 5-HT and dopamine, but also histamine, muscarin, and α-adrenergic receptors. In humans, Olanzapine induces weight gain and increases the risk of type 2 diabetes. The underlying mechanisms of Olanzapine-induced weight gain are unclear. To study this we administered Olanzapine (5mg/kg) in female Wistar rats on a medium fat diet for 14 days via a permanent gastric catheter twice a day, just prior to the onset and at the middle of dark phase. Food and water intake, locomotor activity and body temperature were measured. Olanzapine acutely induced hypothermia, markedly decreased locomotor activity and increased body weight during 14 days of treatment. Olanzapine treatment did not result in an alteration of 24h food intake, but diurnal patterns of feeding behavior and body temperature were dramatically changed. We conclude that in female Wistar rats Olanzapine has an acute hypothermic effect, that the effect of Olanzapine on feeding behavior is secondary to the effect on activity, and that Olanzapine-induced weight gain is primarily the result of reduction in locomotor activity.
奥氮平是一种非典型抗精神病药物，主要拮抗 5-HT 和多巴胺，但也拮抗组胺、毒蕈碱和α-肾上腺素能受体。在人类中，奥氮平会导致体重增加，并增加患 2 型糖尿病的风险。奥氮平引起体重增加的潜在机制尚不清楚。为了研究这一点，我们通过永久性胃管每天两次在高脂肪饮食的雌性 Wistar 大鼠中给予奥氮平（5mg/kg），在暗期开始前和中期共 14 天。测量食物和水的摄入量、运动活动和体温。奥氮平急性诱导体温降低，在 14 天的治疗期间，显著降低运动活动并增加体重。奥氮平治疗并没有导致 24 小时食物摄入量的改变，但摄食行为和体温的昼夜节律明显改变。我们得出结论，在雌性 Wistar 大鼠中，奥氮平具有急性降温作用，奥氮平对摄食行为的影响次于对活动的影响，奥氮平引起的体重增加主要是由于运动活动减少所致。
