Baptista T, Lacruz A, Acosta A, Colasante C, de Quijada M, de Mendoza S, Mendoza J M, Hernández L
Laboratory of Behavioral Physiology, School of Medicine, University of Los Andes, Mérida, Venezuela.
Appetite. 2000 Feb;34(1):77-86. doi: 10.1006/appe.1999.0284.
Few pharmacological tools are currently available to counteract the excessive body weight gain often observed during prolonged administration of antipsychotic drugs. Most antipsychotic drugs block dopamine receptors, and both the brain dopaminergic and opioid systems appear to be involved in initiation and maintenance of feeding behavior, respectively. We evaluated whether the opioid antagonist naltrexone (NAL, 0.5-16 mg/kg/ip for 21 days) (a) affects body weight and food intake in gonadally-intact and drug-free female rats, (b) prevents obesity, hyperphagia, hyperprolactinemia and vaginal cycle disruption induced by long-term administration of the antipsychotic drug sulpiride (SUL, 20 mg/kg/ip for 21 days), or (c) reverses the acute hyperphagia induced by SUL (15 microg bilaterally), when directly applied in the perifornical lateral hypothalamus (PFLH). In drug-free rats, only NAL doses above 4 mg/kg, significantly decreased weight gain and food intake. Even though NAL (1 and 8 mg/kg) significantly attenuated SUL-induced hyperphagia and hyperprolactinemia, it did not reverse at any dose the weight gain and permanent diestrous induced by SUL. In addition, local NAL did not prevent the hyperphagia and polidypsia observed after acute intrahypothalamic SUL. Unexpectedly, the cumulative and 24 h food intake in SUL-treated rats was significantly increased by NAL. Collectively, these results do not support a role for endogenous opiates in the neural and endocrine mechanisms involved in weight gain during prolonged antipsychotic drug administration in rats.
目前几乎没有可用的药理学工具来对抗在长期服用抗精神病药物期间经常观察到的体重过度增加。大多数抗精神病药物会阻断多巴胺受体，并且大脑多巴胺能系统和阿片系统似乎分别参与进食行为的启动和维持。我们评估了阿片拮抗剂纳曲酮（NAL，0.5 - 16毫克/千克腹腔注射，持续21天）是否（a）影响性腺完整且未用药的雌性大鼠的体重和食物摄入量，（b）预防由长期服用抗精神病药物舒必利（SUL，20毫克/千克腹腔注射，持续21天）引起的肥胖、食欲亢进、高催乳素血症和阴道周期紊乱，或者（c）当直接应用于穹窿周外侧下丘脑（PFLH）时，是否能逆转由SUL（双侧15微克）引起的急性食欲亢进。在未用药的大鼠中，只有高于4毫克/千克的NAL剂量能显著降低体重增加和食物摄入量。尽管NAL（1和8毫克/千克）显著减轻了SUL诱导的食欲亢进和高催乳素血症，但它在任何剂量下都不能逆转SUL诱导的体重增加和永久性静止期。此外，局部应用NAL并不能预防下丘脑内急性注射SUL后观察到的食欲亢进和多饮。出乎意料的是，NAL显著增加了SUL处理大鼠的累积食物摄入量和24小时食物摄入量。总体而言，这些结果不支持内源性阿片类物质在大鼠长期服用抗精神病药物期间体重增加所涉及的神经和内分泌机制中起作用。
