The mechanisms behind relapse to ethanol intake in recovering alcoholics are still unclear. The negative reinforcing effects contributing to ethanol addiction, including relapse, are considered to be partly driven by the κ-opioidergic system. As the κ-opioidergic system interacts with the mesolimbic reward pathway, the aim of the study was to clarify the role of nucleus accumbens shell κ-opioidergic mechanisms in relapse to ethanol intake by using the alcohol deprivation effect (ADE) paradigm. The ADE is defined as a transient increase in voluntary ethanol intake after a forced period of abstinence. Male Long-Evans rats were trained to voluntarily consume 10% (v/v) ethanol solution. Ethanol access and deprivation cycles were initiated after stable ethanol intake baselines had been reached and bilateral guide cannulas had been implanted above the nucleus accumbens shell. One cycle consisted of 10 days of 90 min access to ethanol followed by 6 days of ethanol deprivation. The ADE was measured in the beginning of a new cycle. Rats received JDTic, a selective κ-antagonist, either subcutaneously (10 mg/kg) or intra-accumbally (15 µg/site) or, as a reference substance, systemic naltrexone (0.3 mg/kg) before ethanol re-access, and the effects on the ADE were evaluated. Systemic and intra-accumbal JDTic significantly attenuated the ADE on the first day of ethanol re-access, as did systemic naltrexone. Additionally, naltrexone decreased ethanol intake levels. These results suggest that nucleus accumbens shell κ-opioidergic mechanisms may have a role in mediating relapse to ethanol intake. Additionally, κ-antagonism could be a valuable adjunct in ethanol relapse prevention.

中文翻译：

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选择性κ-阿片受体拮抗剂JDTic减弱大鼠酒精剥夺效应

酒精摄入量恢复后复发的机制仍不清楚。导致乙醇成瘾的负面增强效应，包括复发，被认为部分由 κ-阿片能系统驱动。由于 κ-阿片能系统与中脑边缘奖赏通路相互作用，该研究的目的是通过使用酒精剥夺效应 (ADE) 范式阐明伏隔核壳 κ-阿片能机制在乙醇摄入复发中的作用。ADE 被定义为强制禁欲期后自愿乙醇摄入量的短暂增加。雄性 Long-Evans 大鼠被训练自愿消耗 10% (v/v) 乙醇溶液。在达到稳定的乙醇摄入基线并在伏隔核壳上方植入双侧引导套管后，开始乙醇进入和剥夺循环。一个循环包括 10 天 90 分钟的乙醇获取，然后是 6 天的乙醇剥夺。在新周期开始时测量 ADE。大鼠接受 JDTic，一种选择性 κ-拮抗剂，皮下注射 (10 mg/kg) 或皮下注射 (15 µg/部位) 或作为参考物质，全身纳曲酮 (0.3 mg/kg) 在乙醇重新进入之前，和评估对 ADE 的影响。全身性和蓄积内 JDTic 在重新获得乙醇的第一天显着减弱了 ADE，全身性纳曲酮也是如此。此外，纳曲酮降低了乙醇摄入水平。这些结果表明伏隔核壳 κ-阿片能机制可能在介导乙醇摄入复发中起作用。此外，κ-拮抗作用可能是预防乙醇复发的重要辅助手段。