Gessa G L, Agabio R, Carai M A, Lobina C, Pani M, Reali R, Colombo G
Bernard B. Brodie Department of Neuroscience, University of Cagliari, Cagliari, Italy.
Alcohol. 2000 Apr;20(3):271-6. doi: 10.1016/s0741-8329(99)00091-9.
Treatment with gamma-hydroxybutyric acid has been reported to effectively decrease alcohol craving and consumption as well as alcohol withdrawal symptoms in alcoholics. We describe the results of animal studies demonstrating the ability of gamma-hydroxybutyric acid to reduce (1) the severity of ethanol withdrawal signs in rats rendered physically dependent on ethanol and (2) voluntary ethanol intake in selectively bred Sardinian alcohol-preferring rats. Furthermore, we review experimental data suggesting that gamma-hydroxybutyric acid and ethanol have several pharmacological effects in common. Relevant similarities are: (1) stimulation of firing rate of dopaminergic neurons and dopamine release in specific rat brain areas; (2) development of cross-tolerance to the motor-impairing effects after repeated administration in rats; 3) abuse potential, as indicated by self-administration of pharmacologically relevant doses of gamma-hydroxybutyric acid in rats and mice; (4) induction of anxiolytic effects in rats; and (5) induction of similar discriminative stimulus effects, as evidenced by symmetrical generalization in a drug discrimination study in rats. These lines of evidence are discussed in relation to gamma-hydroxybutyric acid exerting its antialcohol effects by a substitution mechanism.
据报道，用γ-羟基丁酸治疗可有效降低酗酒者对酒精的渴望和饮酒量以及酒精戒断症状。我们描述了动物研究的结果，这些结果证明γ-羟基丁酸能够（1）减轻对乙醇产生身体依赖的大鼠的乙醇戒断症状的严重程度，以及（2）减少选择性培育的撒丁岛嗜酒大鼠的自愿乙醇摄入量。此外，我们回顾了实验数据，这些数据表明γ-羟基丁酸和乙醇有几种共同的药理作用。相关的相似之处有：（1）刺激特定大鼠脑区多巴胺能神经元的放电频率和多巴胺释放；（2）大鼠反复给药后对运动损害作用产生交叉耐受性；（3）滥用可能性，如大鼠和小鼠对药理相关剂量的γ-羟基丁酸进行自我给药所示；（4）在大鼠中诱导抗焦虑作用；（5）诱导相似的辨别刺激作用，如大鼠药物辨别研究中的对称泛化所证明。这些证据线索与γ-羟基丁酸通过替代机制发挥其抗酒精作用有关进行了讨论。
