Reward and relapse: complete gene-induced dissociation in an animal model of alcohol dependence.
Reward and relapse: complete gene-induced dissociation in an animal model of alcohol dependence.
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奖励和复发：酒精依赖动物模型中基因诱导的完全解离。
DOI：
10.1111/j.1530-0277.2011.01606.x
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Israel,Yedy
中科院分区：
文献类型：
--
作者：
Quintanilla,MariaE;Tampier,Lutske;Karahanian,Eduardo;Rivera-Meza,Mario;Herrera-Marschitz,Mario;Israel,Yedy
背景在连续自我饮酒的动物模型中，身体依赖性并不构成乙醇摄入的主要因素，有两个因素可能导致酒精自我给药的持续存在：（i）乙醇的奖励效应和（ii）伴随自我给药过程存在的情境调节线索。目前的研究旨在了解这些因素对长期自我施用重度酒精（作为复发的指标）的相对贡献。方法Wistar 衍生的 UChB 高乙醇饮酒大鼠被允许在 24 小时内摄入 10% 乙醇和水。在最初的研究中，在获得乙醇之前，将旨在抑制乙醛产生的抗过氧化氢酶 shRNA 基因编码慢病毒载体注射到动物的腹侧被盖区 (VTA)。在随后的研究中，在动物达到高水平乙醇摄入量60至80天后，将慢病毒载体给予24小时或1小时消耗乙醇的动物。在最终研究中，将奎宁（0.01％）添加到乙醇溶液中，以改变动物长期摄入的酒精的调节味觉/嗅觉线索。结果数据表明，将抗过氧化氢酶载体施用到幼稚动物的VTA中会阻断奖励和酒精自我施用，但在已经习惯于摄入乙醇超过2个月的大鼠中，它在抑制酒精自我施用方面没有活性。当酒精溶液的环境调节线索改变时，抗过氧化氢酶载体对长期自我施用乙醇的动物的乙醇摄入缺乏抑制作用被完全逆转。结论数据强调了调节因素在复发中的重要性，并表明仅消除或减弱它，并结合长期药物治疗以减少乙醇奖励，可能对减少酒精自我施用具有长期效果。
BackgroundIn animal models of continuous alcohol self-administration, in which physical dependence does not constitute the major factor of ethanol intake, 2 factors likely contribute to the perpetuation of alcohol self-administration: (i) the rewarding effects of ethanol and (ii) the contextual conditioning cues that exist along with the process of self-administration. Present studies are aimed at understanding the relative contribution of these factors on the perpetuation of heavy alcohol self-administration, as an indication of relapse.MethodsWistar-derived UChB high ethanol drinker rats were allowed access to 10% ethanol and water on a 24-hour basis. In initial studies, an anticatalase shRNA gene-coding lentiviral vector aimed at inhibiting acetaldehyde generation was administered into the ventral tegmental area (VTA) of the animals prior to ethanol access. In subsequent studies, the lentiviral vector was administered to animals, which had consumed ethanol on a 24-hour basis, or a 1-hour basis, after the animals had reached high levels of ethanol intake for 60 to 80 days. In final studies, quinine (0.01%) was added to the ethanol solution to alter the conditioning taste ⁄ smell cues of alcohol that animals had chronically ingested.ResultsData indicate that the administration of an anticatalase vector into the VTA of naı¨ ve animals blocked reward and alcohol self-administration, while it was, nevertheless, inactive in inhibiting alcohol self-administration in rats that had been conditioned to ingest ethanol for over 2 months. The lack of inhibitory effect of the anticatalase vector on ethanol intake in animals that had chronically self-administered ethanol was fully reversed when the contextual conditioning cues of the alcohol solution were changed.ConclusionsData highlight the importance of conditioning factors in relapse and suggest that only abolishing or blunting it, along with long-lasting pharmacological treatment to reduce ethanol reward, may have protracted effects in reducing alcohol self-administration.