内源性阿片系统和酒精成瘾。
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内源性阿片系统和酒精成瘾。
精神药理学(Berl)。1997年1月,129 (2):99 - 111。
- PubMed ID
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9040115 (在PubMed]
- 文摘
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酒精产生大量的药理作用通过其与各种神经递质和神经调质。在后者中,内源性阿片类物质发挥关键作用的奖励(上瘾)乙醇的性质。三种类型的阿片受体(μ,δ和κ)代表各自的目标主要阿片肽(分别为β-内啡肽,肽和dynorphins)。μ的奖励(加强)属性——和delta-receptor配体激活的中脑边缘多巴胺系统提升的中脑腹侧被盖(VTA)吻侧结构;其中,伏隔核(NAC)在药物成瘾是特别重要的。相比之下,烦躁不安kappa-receptors激活的结果。这些对立效应的影响神经系统的表现,分别在南汽的多巴胺释放增加和减少。了多方面的证据表明酒精干扰内源性阿片与多巴胺传输机制密切相关的边缘通路。认为多巴胺缩合的产物和所醛(tetrahydroisoquinolines)发挥作用还存在争议。然而,信息的直接(急性和慢性)影响酒精对阿片受体的绑定属性,以及调制阿片肽的合成和分泌(如β-内啡肽释放建议增加)。 In view of the reinforcing properties of alcohol, it is relevant to consider behavioural studies involving alcohol self-administration in rodents and primates. Low doses of morphine have been found to increase, and higher doses of the opiate to decrease, alcohol consumption. Conversely, opioid antagonists such as naloxone and naltrexone (which bind to non-selectively opioid receptors) have been shown to decrease alcohol consumption under various experimental conditions. Similar results have been reported when selective mu- or delta-receptor antagonists are administered. Results obtained in genetic models of high preference for alcohol also support the view that alcohol intake depends on the activity of the endogenous opioid reward system and that alcohol consumption may serve to compensate for inherent deficits in this system. One hypothetical model proposes that reward results from activation of mu-opioid receptors in the VTA and/or delta-receptor in the NAC; both these nuclei are targets of endogenous beta-endorphin. It is suggested that alcohol interferes with this reward pathway either directly or indirectly. The available experimental data accord well with those obtained from clinical studies which opioid antagonists have been used to prevent relapse in alcoholics. Conceptual considerations concerning communalities between various forms of addictions are also discussed in this review.