Colombo G, Agabio R, Carai M A, Lobina C, Pani M, Reali R, Addolorato G, Gessa G L
CNR Center for Neuropharmacology, Bernard B. Brodie Department of Neuroscience, University of Cagliari, Italy.
Alcohol Clin Exp Res. 2000 Jan;24(1):58-66.
The similarities between the pharmacological effects of the gamma-aminobutyric acid receptor agonist, baclofen, and the alcohol-substituting agent, gamma-hydroxybutyric acid, led us to investigate whether baclofen was capable of reducing (a) ethanol withdrawal syndrome in ethanol-dependent rats and (b) voluntary ethanol intake in ethanol-preferring rats.
In experiment 1, Wistar rats were rendered physically dependent on ethanol by the repeated administration of intoxicating doses of ethanol for 6 consecutive days. Baclofen was acutely administered intraperitoneally at doses of 10, 20, and 40 mg/kg. In experiment 2, baclofen (0, 2.5, 5, and 10 mg/kg, intraperitoneally) was administered once a day for 14 consecutive days to ethanol-preferring sP rats that had continuous access to ethanol (10%, v/v) and water under the two-bottle free choice regimen.
In experiment 1, baclofen dose-dependently decreased the intensity of ethanol withdrawal signs; furthermore, 20 mg/kg of baclofen protected from audiogenic seizures in ethanol-withdrawn rats. In experiment 2, baclofen selectively and dose-dependently reduced voluntary ethanol intake; a compensatory increase in water intake left total fluid intake virtually unchanged.
These results are in close agreement with those of a preliminary clinical study and suggest that baclofen may constitute a novel therapeutic agent for alcoholism.
γ-氨基丁酸受体激动剂巴氯芬与酒精替代剂γ-羟基丁酸在药理作用上的相似性，促使我们研究巴氯芬是否能够减轻（a）乙醇依赖大鼠的乙醇戒断综合征，以及（b）乙醇偏好大鼠的自愿乙醇摄入量。
在实验1中，通过连续6天重复给予中毒剂量的乙醇，使Wistar大鼠对乙醇产生身体依赖。巴氯芬以10、20和40mg/kg的剂量腹腔内急性给药。在实验2中，对在两瓶自由选择方案下可连续获取乙醇（10%，v/v）和水的乙醇偏好sP大鼠，每天腹腔内给予一次巴氯芬（0、2.5、5和10mg/kg），连续给药14天。
在实验1中，巴氯芬剂量依赖性地降低了乙醇戒断症状的强度；此外，20mg/kg的巴氯芬可保护乙醇戒断大鼠免受听源性惊厥。在实验2中，巴氯芬选择性地且剂量依赖性地减少了自愿乙醇摄入量；水摄入量的代偿性增加使总液体摄入量基本保持不变。
这些结果与一项初步临床研究的结果密切一致，并表明巴氯芬可能构成一种治疗酒精中毒的新型治疗药物。
