Colombo G, Agabio R, Carai M A, Lobina C, Pani M, Reali R, Gessa G L
C. N. R. Center for Neuropharmacology, University of Cagliari, Via Porcell 4, I-09124, Cagliari, Italy.
Alcohol. 2000 Apr;20(3):237-45. doi: 10.1016/s0741-8329(99)00087-7.
The present paper reviews the drug discrimination studies, both from the literature and from this laboratory, conducted to investigate the pharmacological profile of the discriminative stimulus effects of gamma-hydroxybutyric acid. Collectively, the results of these studies suggest that: (1) the discriminative stimulus effects of gamma-hydroxybutyric acid are composed of different cues, each one being the effect of gamma-hydroxybutyric acid on a specific receptor system; (2) the proportion of each component cue varies as the training dose of gamma-hydroxybutyric acid is increased; (3) the gamma-aminobutyric acid B-mediated cue is a major ingredient of the mixed stimulus of gamma-hydroxybutyric acid, but it is more prominent at high training doses than at low training doses of gamma-hydroxybutyric acid; and (4) positive modulation of the gamma-aminobutyric acid A receptor is a relevant part of the discriminative stimulus effects of low gamma-hydroxybutyric acid doses. Finally, data indicating symmetrical generalization between the discriminative stimulus effects of a specific range of doses of gamma-hydroxybutyric acid and those of ethanol are discussed in regard to their further support of the hypothesis that gamma-hydroxybutyric acid may exert its antialcohol effects through a substitution mechanism.
本文回顾了文献及本实验室开展的药物辨别研究，这些研究旨在探究γ-羟基丁酸辨别刺激效应的药理学特征。总体而言，这些研究结果表明：（1）γ-羟基丁酸的辨别刺激效应由不同线索组成，每条线索都是γ-羟基丁酸对特定受体系统的作用；（2）随着γ-羟基丁酸训练剂量的增加，各成分线索的比例会发生变化；（3）γ-氨基丁酸B介导的线索是γ-羟基丁酸混合刺激的主要成分，但在γ-羟基丁酸高训练剂量时比低训练剂量时更为突出；（4）γ-氨基丁酸A受体的正向调节是低剂量γ-羟基丁酸辨别刺激效应的一个相关部分。最后，讨论了表明特定剂量范围的γ-羟基丁酸与乙醇辨别刺激效应之间存在对称泛化的数据，这些数据进一步支持了γ-羟基丁酸可能通过替代机制发挥抗酒精作用这一假说。
