Hodge C W, Chappelle A M, Samson H H
Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157-1083, USA.
Alcohol Clin Exp Res. 1995 Dec;19(6):1486-93. doi: 10.1111/j.1530-0277.1995.tb01012.x.
Long-Evans rats (n = 12) were trained to lever-press on a fixed-ratio 4 schedule of reinforcement with ethanol (10% v/v) presented as the reinforcer. After implantation of bilateral stainless-steel guide cannulae aimed at the nucleus accumbens, site-specific microinjections of muscimol (1-30 ng) and bicuculline (1-10 ng) were tested for effects on ethanol-reinforced responding. Baseline response patterns were characterized by initial high rates that terminated abruptly after approximately 20 min. Muscimol administration in the nucleus accumbens decreased the total number of ethanol-reinforced responses and obtained reinforcers. Bicuculline also decreased ethanol-reinforced responses and reinforcers at the highest dose tested. When a dose of bicuculline (1 ng) that was ineffective by itself was coadministered with an effective dose of muscimol (10 ng), the muscimol-induced decreases in responding were blocked. Analysis of response patterns showed that muscimol decreased ethanol self-administration by terminating responding, normally lasting 20 min, after approximately 10 min with no changes in local response rate. Bicuculline decreased total responding by producing parallel, but nonsignificant, changes in time course and response rate. These data suggest that GABAergic transmission in the nucleus accumbens is involved in the termination, but not the onset or maintenance of ethanol self-administration. The specificity of this effect gives emphasis to the importance of measuring behavioral parameters, as well as products of behavior (such as intake volume) in the study of ethanol self-administration.
选用12只雄性Long-Evans大鼠,训练它们在固定比率为4的强化程序下进行杠杆按压,以10%(体积/体积)乙醇作为强化物。在双侧植入靶向伏隔核的不锈钢引导套管后,对伏隔核进行位点特异性微量注射蝇蕈醇(1 - 30纳克)和荷包牡丹碱(1 - 10纳克),检测其对乙醇强化反应的影响。基线反应模式的特征是初始反应率较高,约20分钟后突然终止。向伏隔核注射蝇蕈醇会减少乙醇强化反应的总数和获得的强化物数量。在测试的最高剂量下,荷包牡丹碱也会减少乙醇强化反应和强化物数量。当单独无效的剂量荷包牡丹碱(1纳克)与有效剂量的蝇蕈醇(10纳克)共同给药时,蝇蕈醇诱导的反应减少被阻断。反应模式分析表明,蝇蕈醇通过在大约10分钟后终止通常持续20分钟的反应来减少乙醇自我给药,局部反应率无变化。荷包牡丹碱通过在时间进程和反应率上产生平行但不显著的变化来减少总反应。这些数据表明,伏隔核中的γ-氨基丁酸能传递参与了乙醇自我给药的终止,但不参与其开始或维持。这种效应的特异性强调了在乙醇自我给药研究中测量行为参数以及行为产物(如摄入量)的重要性。