Ethanol-reinforced behaviour in the rat: effects of naltrexone
Ethanol-reinforced behaviour in the rat: effects of naltrexone
复制标题
DOI：
10.1016/s0014-2999(99)00245-9
复制
发表时间：
1999-06-25
影响因子：
5
通讯作者：
Koros, E
中科院分区：
文献类型：
--
作者：
Bienkowski, P;Kostowski, W;Koros, E
据多次报道，内源性阿片类途径在乙醇饮用行为中发挥着重要作用。与这些发现一致，一种非选择性阿片受体拮抗剂纳曲酮似乎可以降低戒毒酗酒者的复发率。本研究的目的是评估纳曲酮对（i）自我给药乙醇的影响； (ii) 对乙醇的反应消失； (iii) 由乙醇相关刺激的非偶然出现引起的乙醇寻求的恢复。训练雄性 Wister 大鼠在操作过程中压杠杆获取 8% 乙醇，其中在蔗糖存在下引入乙醇。通过在单独的对照实验中研究纳曲酮对水增强行为的影响来评估纳曲酮作用的选择性。急性注射纳曲酮（1 或 3 mg/kg）不会改变乙醇的自我给药。重复纳曲酮治疗（3 mg/kg，在连续三次自我给药之前）逐渐减少乙醇摄入量。在消退过程中，急性施用 3 mg/kg 纳曲酮抑制了先前用乙醇增强的反应。类似地，纳曲酮 (1-3 mg/kg) 有效且剂量依赖性地抑制由充满 8% 乙醇的液体勺的非偶然输送产生的乙醇寻找的恢复。在对照实验中，较低剂量的纳曲酮（1-3 mg/kg）对水的强化或非强化（消光）杠杆按压没有产生任何影响。这些结果表明：（i）纳曲酮亚慢性治疗导致乙醇自我给药逐渐减少； (ii) 单剂量的纳曲酮可能会增加灭绝并减弱提示诱导的乙醇强化行为的恢复。 (C) 1999 Elsevier Science B.V. 保留所有权利。
It has been repeatedly reported that endogenous opioid pathways play an important role in ethanol drinking behaviour. In line with these findings, a non-selective opioid receptor antagonist, naltrexone, seems to reduce relapse rates in detoxified alcoholics. The aim of the present study was to evaluate the effects of naltrexone on (i) ethanol self-administration; (ii) extinction of responding for ethanol; (iii) reinstatement of ethanol-seeking induced by non-contingent presentations of ethanol-associated stimuli. Male Wister rats were trained to lever-press for 8% ethanol in an operant procedure where ethanol was introduced in the presence of sucrose. The selectivity of naltrexone's actions was assessed by studying its effects on water-reinforced behaviour in separate control experiments. Acute injections of naltrexone (1 or 3 mg/kg) did not alter ethanol self-administration. Repeated treatment with naltrexone (3 mg/kg, before three consecutive self-administration sessions) progressively reduced ethanol intake. In the extinction procedure, acute administration of 3 mg/kg naltrexone suppressed responding previously reinforced with ethanol. Similarly, naltrexone (1-3 mg/kg) potently and dose-dependently inhibited reinstatement of ethanol-seeking produced by non-contingent deliveries of the liquid dipper filled with 8% ethanol. In the control experiments, lower doses of naltrexone (1-3 mg/kg) did not exert any effect on either reinforced or non-reinforced (extinction) lever-pressing for water. These results indicate that: (i) subchronic treatment with naltrexone leads to progressive reduction of ethanol self-administration; (ii) single doses of naltrexone may increase extinction and attenuate cue-induced reinstatement of ethanol-reinforced behaviour. (C) 1999 Elsevier Science B.V. All rights reserved.