Technion-Israel Institute of Technology, Haifa, Israel.
J Psychopharmacol. 2012 Sep;26(9):1244-51. doi: 10.1177/0269881112450783. Epub 2012 Jun 21.
Blockade of opioidergic neurotransmission contributes to reduction in body weight. However, how such blockade affects body weight gain (BWG) attributed to second generation antipsychotic agents (SGAs) has not yet been established. Here we examined the effects of an opioid receptor antagonist, naltrexone (NTX), on food intake and BWG associated with an SGA, olanzapine (OL). Four groups of Wistar Han IGS rats were treated for 28 days with either OL (2 mg/kg twice daily, intraperitoneal (IP)), a combination of OL (2 mg/kg twice daily, IP) + extended-release NTX (50 mg/kg, one-time, intramuscular (IM)), extended-release NTX (50 mg/kg, one-time, IM) or vehicle and their food intake and body weight were measured daily for the first nine days and every other day thereafter. Food intake and BWG that were increased by OL were decreased by the added NTX while NTX alone had no significant effects on food intake or on BWG. Plasma leptin concentrations were significantly elevated in the three groups receiving pharmacological agents, but did not differ among each other, suggesting that changes in leptin secretion and/or clearance alone would not explain the food intake and the body weight findings. Our results extend prior reports on anorexigenic effects of opioid antagonists by demonstrating that such effects may generalize to food intake increases and BWG arising in the context of OL pharmacotherapy.
阿片能神经传递的阻断有助于减轻体重。然而，这种阻断如何影响第二代抗精神病药物（SGAs）引起的体重增加（BWG）尚未确定。在这里，我们研究了阿片受体拮抗剂纳曲酮（NTX）对与 SGA 奥氮平（OL）相关的食物摄入和 BWG 的影响。四组 Wistar Han IGS 大鼠分别用 OL（2 mg/kg 每日两次，腹腔内（IP））、OL （2 mg/kg 每日两次，IP）+ 延长释放 NTX（50 mg/kg，一次，肌内（IM））、延长释放 NTX（50 mg/kg，一次，IM）或载体治疗 28 天，并在第 1 至第 9 天每天测量其食物摄入量和体重，此后每两天测量一次。OL 引起的食物摄入量和 BWG 增加被添加的 NTX 减少，而 NTX 单独对食物摄入量或 BWG 没有显著影响。接受药物治疗的三组大鼠的血浆瘦素浓度显著升高，但彼此之间没有差异，这表明瘦素分泌和/或清除的变化本身不会解释食物摄入和体重的变化。我们的结果通过证明这种作用可能推广到 OL 药物治疗中出现的食物摄入增加和 BWG，扩展了先前关于阿片拮抗剂的厌食作用的报告。
