Petry N M
Department of Psychology, Harvard University, USA.
Exp Clin Psychopharmacol. 1997 Aug;5(3):183-94.
These experiments examined the role of the benzodiazepine (BZ)-GABA receptor complex in modulating ethanol consumption in rats. Lever presses were reinforced with concurrently available, isocaloric solutions: 10% ethanol-10% sucrose and 24% sucrose. Both reinforcers were available on independent, variable-interval 5-s schedules of reinforcement. In baseline sessions, rats earned approximately 110 sucrose reinforcers and 131 ethanol-sucrose reinforcers, equivalent to about 2 g ethanol per kilogram of body weight. Before experimental sessions, rats received injections of Ro 15-4513, Ro 15-1788, and Ro 15-4513 in combination with Ro 15-4513, chlordiazepoxide, picrotoxin, baclofen, and muscimol. Responding for the ethanol solution was significantly and selectively reduced by the BZ inverse agonist Ro 15-4513, and this effect was blocked by administration of the BZ antagonist Ro 15-1788. Conversely, responding for the ethanol solution increased following a low dose of the BZ agonist chlordiazepoxide. A low dose of baclofen significantly decreased responding for sucrose and increased consumption of ethanol. Picrotoxin and muscimol selectively reduced responding for the ethanol solution. These results are discussed in terms of the relationship between the BZ-GABA receptor complex and ethanol consumption.
这些实验研究了苯二氮䓬(BZ)-γ-氨基丁酸(GABA)受体复合物在调节大鼠乙醇摄入量中的作用。杠杆按压行为通过同时提供的等热量溶液得到强化:10%乙醇-10%蔗糖溶液和24%蔗糖溶液。两种强化物均按照独立的、可变间隔5秒的强化程序提供。在基线期,大鼠获得约110次蔗糖强化和131次乙醇-蔗糖强化,相当于每千克体重约2克乙醇。在实验期之前,大鼠接受了Ro 15-4513、Ro 15-1788以及Ro 15-4513与Ro 15-4513联合、氯氮卓、匹鲁卡品、巴氯芬和蝇蕈醇的注射。BZ反向激动剂Ro 15-4513显著且选择性地降低了对乙醇溶液的反应,并且这种效应被BZ拮抗剂Ro 15-1788的给药所阻断。相反,低剂量的BZ激动剂氯氮卓给药后,对乙醇溶液的反应增加。低剂量的巴氯芬显著降低了对蔗糖的反应并增加了乙醇的摄入量。匹鲁卡品和蝇蕈醇选择性地降低了对乙醇溶液的反应。根据BZ-GABA受体复合物与乙醇摄入之间的关系对这些结果进行了讨论。