Smolka M, Sander T, Schmidt L G, Samochowiec J, Rommelspacher H, Gscheidel N, Wendel B, Hoehe M R
Department of Psychiatry, Freie Universität Berlin, Germany.
Psychoneuroendocrinology. 1999 Aug;24(6):629-38. doi: 10.1016/s0306-4530(99)00017-7.
The endogenous opioid system plays an important role in the reinforcing properties of alcohol by an interconnected activation of the mesolimbic dopamine system. The Asn40Asp substitution polymorphism of the human mu-opioid-receptor (OPRM) influences binding of opioids and signal transduction and may, thereby, contribute to the development of alcoholism. The present study tested whether the Asn40Asp substitution polymorphism of the OPRM gene is associated with a variation in central dopaminergic sensitivity during alcohol withdrawal in alcoholics.
Sensitivity of central dopamine receptors was assessed by apomorphine-induced growth hormone (GH) secretion in 97 alcohol-dependent patients before and 1 week after alcohol cessation, and in a subgroup of 19 alcoholics after 3 months of abstinence. GH response was defined as area under the hormone/time curve. Comparisons of the GH response were conducted between alcoholics carrying the Asn40Asp genotype versus those with the Asn40Asn genotype using U-test statistics.
Marginal differences in apomorphine-induced GH response were found between both genotype groups before detoxification (P = 0.799 (n = 97)/P = 0.459 (n = 19)) and after 3 months of abstinence (P = 0.331 (n = 19)). In contrast, the GH response measured seven days after alcohol withdrawal was significantly increased in alcoholics with the Asn40Asp genotype compared with those carrying the Asn40Asn genotype (P = 0.013 (n = 97)/P = 0.026 (n = 19)).
Our results suggest that genetic variation of the mu-opioid receptor modulates the central dopaminergic sensitivity during acute alcohol withdrawal.
内源性阿片系统通过中脑边缘多巴胺系统的相互连接激活，在酒精的强化特性中发挥重要作用。人类μ-阿片受体（OPRM）的Asn40Asp替代多态性影响阿片类药物的结合和信号转导，因此可能有助于酒精中毒的发展。本研究测试了OPRM基因的Asn40Asp替代多态性是否与酒精依赖者戒酒期间中枢多巴胺能敏感性的变化有关。
通过阿扑吗啡诱导的生长激素（GH）分泌，在97名酒精依赖患者戒酒前和戒酒后1周，以及在19名酒精依赖者戒断3个月后的亚组中，评估中枢多巴胺受体的敏感性。GH反应定义为激素/时间曲线下的面积。使用U检验统计量，对携带Asn40Asp基因型的酒精依赖者与携带Asn40Asn基因型的酒精依赖者之间的GH反应进行比较。
在解毒前（P = 0.799（n = 97）/P = 0.459（n = 19））和戒断3个月后（P = 0.331（n = 19）），两个基因型组之间在阿扑吗啡诱导的GH反应上存在微小差异。相比之下，与携带Asn40Asn基因型的酒精依赖者相比，携带Asn40Asp基因型的酒精依赖者在戒酒7天后测得的GH反应显著增加（P = 0.013（n = 97）/P = 0.026（n = 19））。
我们的结果表明，μ-阿片受体的基因变异在急性酒精戒断期间调节中枢多巴胺能敏感性。
