Gianoulakis C, de Waele J P
Douglas Hospital Research Centre, Montreal, Quebec, Canada.
Metab Brain Dis. 1994 Jun;9(2):105-31. doi: 10.1007/BF01999765.
At the present time alcoholism is recognized as a metabolic disease exhibiting the clinical features of craving for alcohol, loss of control over drinking, tolerance and physical dependence on alcohol, while both epidemiological and experimental studies have demonstrated that genetic factors may be important in determining whether an individual has a high or low vulnerability to develop alcoholism. Evidence also indicates that alcoholism is not characterized by a single gene single allele inheritance. Instead it seems that multiple genes and environmental factors interact to increase or decrease an individual's vulnerability to become an alcoholic. Current research is aimed at investigating whether certain behavioral, physiological and biochemical markers are highly associated with the incidence of alcoholism. Among the biochemical markers currently under investigation is the endogenous opioid system and its implication in mediating the reinforcing effects of ethanol. It is the objective of this manuscript to review current research on: (a) the interactions of ethanol with the endogenous opioid system at the molecular level; (b) the existence of genetically determined differences in the response of the endogenous opioid system to ethanol between subjects at high and low risk for excessive ethanol consumption, as well as between lines of animals showing preference or aversion for ethanol solutions; (c) the decrease of alcohol consumption following pretreatment with opioid antagonists; and (d) the possible use of specific opioid receptor antagonists together with behavioral therapy to modify drinking behavior, to control craving and to prevent relapse.
目前，酒精中毒被公认为是一种代谢性疾病，具有对酒精的渴望、饮酒失控、耐受性以及对酒精的身体依赖性等临床特征，而流行病学和实验研究均表明，遗传因素在决定个体患酒精中毒的易感性高低方面可能起着重要作用。证据还表明，酒精中毒并非由单一基因单等位基因遗传所决定。相反，似乎是多个基因和环境因素相互作用，增加或降低个体成为酗酒者的易感性。当前的研究旨在调查某些行为、生理和生化标志物是否与酒精中毒的发生率高度相关。目前正在研究的生化标志物之一是内源性阿片系统及其在介导乙醇强化作用中的意义。本手稿的目的是综述当前关于以下方面的研究：(a)乙醇与内源性阿片系统在分子水平上的相互作用；(b)在过量饮酒高风险和低风险个体之间，以及在对乙醇溶液表现出偏好或厌恶的动物品系之间，内源性阿片系统对乙醇反应的遗传决定差异的存在情况；(c)用阿片类拮抗剂预处理后酒精摄入量的减少；以及(d)特定阿片受体拮抗剂与行为疗法联合使用以改变饮酒行为、控制渴望和预防复发的可能性。
