Maccioni Paola, Pes Daniela, Fantini Noemi, Carai Mauro A M, Gessa Gian Luigi, Colombo Giancarlo
Bernard B. Brodie Department of Neuroscience, University of Cagliari, Viale Diaz 182, I-09126 Cagliari, Italy.
Alcohol. 2008 Mar;42(2):107-13. doi: 10.1016/j.alcohol.2008.01.001.
gamma-Hydroxybutyric acid (GHB) reduces alcohol drinking, promotes abstinence from alcohol, suppresses craving for alcohol, and ameliorates alcohol withdrawal syndrome in alcoholics. At preclinical level, GHB suppresses alcohol withdrawal signs and alcohol intake in rats. The present study was designed to investigate whether GHB administration was capable of affecting alcohol's motivational properties (the possible animal correlate of human craving for alcohol) in selectively bred Sardinian alcohol-preferring rats. To this aim, rats were initially trained to lever press for alcohol (15%, vol/vol) under a procedure of operant, oral alcohol self-administration (fixed ratio 4 in 30-min daily sessions). Once responding for alcohol had stabilized, rats were divided into two groups and allocated to two independent experiments. Experiment 1 assessed the effect of GHB (0, 25, 50, and 100mg/kg, i.p.) on breakpoint for alcohol, defined as the lowest response requirement not achieved by each rat when exposed to a single-session progressive ratio schedule of reinforcement. Experiment 2 assessed the effect of GHB (0, 25, 50, and 100mg/kg, i.p.) on single-session extinction responding for alcohol (alcohol was absent and unreinforced responding was recorded). Breakpoint and extinction responding for alcohol are reliable indexes of alcohol's motivational strength. In Experiment 1, all doses of GHB reduced--by approximately 20% in comparison to saline-treated rats--breakpoint for alcohol. In Experiment 2, administration of 25, 50, and 100mg/kg GHB reduced--by approximately 25%, 40%, and 50%, respectively, in comparison to saline-treated rats--extinction responding for alcohol. Conversely, no dose of GHB altered breakpoint and extinction responding for sucrose (3%, wt/vol) in two independent subsets of Sardinian alcohol-preferring rats. Together, these data suggest that GHB administration specifically suppressed alcohol's motivational properties in Sardinian alcohol-preferring rats. These results are consistent with the anticraving properties of GHB observed in clinical studies.
γ-羟基丁酸（GHB）可减少酒精摄入，促使戒酒，抑制对酒精的渴望，并改善酗酒者的酒精戒断综合征。在临床前水平，GHB可抑制大鼠的酒精戒断症状和酒精摄入量。本研究旨在调查给予GHB是否能够影响选择性培育的撒丁岛嗜酒大鼠中酒精的动机特性（人类对酒精渴望的可能动物关联因素）。为此，首先对大鼠进行训练，使其在操作性口服酒精自我给药程序（每日30分钟的固定比率4）下按压杠杆获取酒精（15%，体积/体积）。一旦对酒精的反应稳定下来，将大鼠分为两组并分配到两个独立实验中。实验1评估了GHB（0、25、50和100mg/kg，腹腔注射）对酒精断点的影响，酒精断点定义为每只大鼠在暴露于单节段渐进比率强化程序时未达到的最低反应要求。实验2评估了GHB（0、25、50和100mg/kg，腹腔注射）对酒精单节段消退反应的影响（无酒精且记录未强化反应）。酒精的断点和消退反应是酒精动机强度的可靠指标。在实验1中，与生理盐水处理的大鼠相比，所有剂量的GHB均使酒精断点降低了约20%。在实验2中，与生理盐水处理的大鼠相比，给予25、50和100mg/kg的GHB分别使酒精消退反应降低了约25%、40%和50%。相反，在撒丁岛嗜酒大鼠的两个独立亚组中，没有剂量的GHB改变对蔗糖（3%，重量/体积）的断点和消退反应。总之，这些数据表明给予GHB可特异性抑制撒丁岛嗜酒大鼠中酒精的动机特性。这些结果与临床研究中观察到的GHB的抗渴望特性一致。
