Role of mu and delta opioid receptors in alcohol drinking behaviour.
Role of mu and delta opioid receptors in alcohol drinking behaviour.
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mu 和 delta 阿片受体在饮酒行为中的作用。
DOI：
10.2174/1874473710801020239
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
M. Morales
中科院分区：
文献类型：
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作者：
M. Méndez;M. Morales
多巴胺能中脑边缘系统在酒精（乙醇）和其他滥用药物引起的强化机制中起着关键作用。大量证据表明，乙醇强化机制涉及，至少部分地，乙醇诱导的内源性阿片系统的激活。乙醇可以在不同水平上改变阿片能传递，包括阿片肽的生物合成、释放和降解，以及内源性配体与阿片受体的结合。一些研究表明，μ和δ阿片受体在乙醇强化和依赖中起着重要作用。这些研究暗示脑啡肽和β-内啡肽是乙醇在大脑中作用的生理介质。本文综述了阿片受体的药理学特性、在脑内的分布及其内源性配体的主要功能。此后，我们提出的证据支持参与μ和δ阿片受体的乙醇强化机制和高酒精饮酒行为。阿片受体激动剂和拮抗剂的使用，以及乙醇偏好选择的啮齿动物和基因敲除小鼠，有助于了解μ和δ受体在这些过程中的作用。本文还综述了不同实验模型中乙醇对阿片受体选择性配体结合的影响。阿片受体在人类酒精中毒中的相关性通过μ受体多态性与酒精依赖的关联进一步得到证明。这些研究结果的临床意义进行了讨论，在一些酒精中毒患者中观察到的阿片受体拮抗剂，如纳洛酮治疗的差异反应。
The dopaminergic mesolimbic system plays a key role in the mechanisms of reinforcement elicited by alcohol (ethanol) and other drugs of abuse. Numerous lines of evidence indicate that ethanol reinforcement mechanisms involve, at least partially, the ethanol-induced activation of the endogenous opioid system. Ethanol may alter opioidergic transmission at different levels, including the biosynthesis, release, and degradation of opioid peptides, as well as binding of endogenous ligands to opioid receptors. Several studies suggest that mu and delta opioid receptors play a major role in ethanol reinforcement and dependence. These studies implicate enkephalins and beta-endorphin as physiological mediators of ethanol's actions in the brain. In this review we describe the pharmacological characteristics of opioid receptors and their distribution in brain, as well as the major functions of their endogenous ligands. Thereafter, we present evidence supporting the participation of mu and delta opioid receptors in ethanol reinforcement mechanisms and high alcohol drinking behaviour. The use of opioid receptor agonists and antagonists, as well as ethanol-preferring selected rodents and knockout mice, has contributed to understand the role of mu and delta receptors in these processes. The effects of ethanol on binding of selective ligands to opioid receptors in different experimental models are also reviewed. The relevance of opioid receptors in human alcoholism is further evidenced by the association of mu receptor polymorphisms with ethanol dependence. The clinical implication of these findings is discussed regarding the differential responses observed in some alcoholic patients to treatment with opioid receptor antagonists such as naltrexone.