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Associations of OPRM1 A118G and alcohol sensitivity with intravenous alcohol self-administration in young adults

机译：年轻人中OPRM1 A118G和酒精敏感性与静脉内酒精自我管理的相关性

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Human laboratory and animal models implicate variation in the -opioid receptor gene (OPRM1) as relevant for alcohol-related reward. OPRM1 is associated with alcohol self-administration in non-human primate studies, but the relevance of this finding to human models is unclear. This study used computer-assisted self-infusion of ethanol (CASE) to examine associations among OPRM1 A118G genotype, subjective responses to alcohol and intravenous alcohol self-administration in young heavy drinkers (n=40, mean age=19.95 years, SD=0.82). Participants completed a 2-hour CASE session comprising a priming phase followed by ad libitum self-administration in a free-access paradigm. Participants achieved a mean peak breath alcohol concentration (BrAC) of 81.18mg% (SD=24.96). Those with the OPRM1 118G variant (GA or GG genotypes) achieved significantly higher peak BrAC (M=94.90mg%, SD=16.56) than those with the AA genotype (M=74.46mg%, SD=25.36), reflecting a significantly greater number of alcohol requests among GA/GG participants. Eighty percent of GA/GG participants surpassed a threshold defining a laboratory analog of heavy alcohol exposure (80mg%) compared with 46 percent of AA participants. Results indicated significant associations between subjective measures of alcohol sensitivity and CASE outcomes, although the pattern of findings differed across self-report measures. Subjective responses did not differ by OPRM1 status. These results offer further support for the feasibility of the CASE paradigm and provide initial evidence for an association of OPRM1 with alcohol self-administration in a human laboratory context.
机译：人类实验室和动物模型暗示阿片受体基因（OPRM1）的变异与酒精相关的奖励有关。在非人类灵长类动物研究中，OPRM1与酒精自我管理相关，但尚不清楚这一发现与人类模型的相关性。这项研究使用计算机辅助的乙醇自我灌输（CASE）来研究年轻重度饮酒者（n = 40，平均年龄= 19.95岁，SD = 0.82）中OPRM1 A118G基因型，对酒精的主观反应和静脉内酒精自我管理之间的关联。 ）。参与者完成了一个2小时的CASE会话，包括启动阶段，然后以自由访问的方式随意进行自我管理。参与者的平均呼吸酒精峰值浓度（BrAC）为81.18mg％（SD = 24.96）。具有OPRM1 118G变体（GA或GG基因型）的受试者的BrAC峰值（M = 94.90mg％，SD = 16.56）显着高于具有AA基因型（M = 74.46mg％，SD = 25.36）的受试者，反映出更大的BrAC峰。 GA / GG参与者中的酒精要求数。 80％的GA / GG参与者超过了定义重度酒精暴露的实验室类似物（80mg％）的阈值，而AA参与者的这一比例为46％。结果表明，酒精敏感性和CASE结果的主观测量之间存在显着关联，尽管发现的模式在自我报告测量中有所不同。主观反应没有因OPRM1状态而异。这些结果为CASE范式的可行性提供了进一步的支持，并为在人类实验室环境中OPRM1与酒精自我管理的关联提供了初步证据。

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