Heyser C J, Schulteis G, Durbin P, Koob G F
Scripps Research Institute, Department of Neuropharmacology, La Jolla, CA 92037, USA.
Neuropsychopharmacology. 1998 Feb;18(2):125-33. doi: 10.1016/S0893-133X(97)00130-9.
Acamprosate (calcium-acetyl homotaurinate) is a relatively new compound developed for the treatment of alcoholism and has been shown to be effective in attenuating relapse in human alcoholics. In the current study, the effects of this drug were further examined using an animal model of oral ethanol self-administration in a limited access paradigm. Male Wistar rats were trained to respond for ethanol (10% w/v) or water in a two-lever free-choice operant condition. Acute administration of acamprosate (400 mg/kg) reduced ethanol consumption and increased responding for water. Chronic administration of lower daily doses of acamprosate (100 and 200 mg/kg) blocked the increased ethanol consumption typically observed in rats after an imposed abstinence period. This effect of acamprosate was selective for ethanol, as responding for water was unaffected at any dose tested. These results with rats suggest a model by which to explore the mechanisms for anti-relapse effects of acamprosate.
阿坎酸(钙乙酰高牛磺酸)是一种为治疗酒精中毒而研发的相对较新的化合物,已被证明在减轻人类酗酒者的复发方面有效。在当前的研究中,使用有限接触范式下的口服乙醇自我给药动物模型进一步研究了这种药物的作用。雄性Wistar大鼠在双杠杆自由选择操作性条件下接受训练,以获取乙醇(10% w/v)或水。急性给予阿坎酸(400 mg/kg)可减少乙醇摄入量,并增加对水的反应。慢性给予较低日剂量的阿坎酸(100和200 mg/kg)可阻止在强制戒酒期后大鼠通常出现的乙醇摄入量增加。阿坎酸的这种作用对乙醇具有选择性,因为在任何测试剂量下对水的反应均未受影响。大鼠的这些结果提示了一种探索阿坎酸抗复发作用机制的模型。