Center for Alcohol and Addiction Studies, Brown University and Department of Psychology, University of California, Los Angeles, Los Angeles, CA 90095-1563, USA.
J Abnorm Psychol. 2010 Feb;119(1):115-25. doi: 10.1037/a0017550.
Polymorphisms of the mu-opioid receptor (OPRM1) and dopamine D4 receptor (DRD4) genes are associated with subjective responses to alcohol and urge to drink under laboratory conditions. This study examined these associations in the natural environment using ecological momentary assessment. Participants were non-treatment-seeking heavy drinkers (n = 112, 52% female, 61% alcohol dependent) who enrolled in a study of naltrexone effects on craving and drinking in the natural environment. Data were culled from 5 consecutive days of drinking reports prior to medication randomization. Analyses revealed that, after drinking, carriers of the Asp40 allele of the OPRM1 gene reported higher overall levels of vigor and lower levels negative mood, as compared to homozygotes for the Asn40 variant. Carriers of the long allele (i.e., >or=7 tandem repeats) of the DRD4 endorsed greater urge to drink than homozygotes for the short allele. Effects of OPRM1 and DRD4 variable-number-of-tandem-repeats genotypes appear to be alcohol dose-dependent. Specifically, carriers of the DRD4-L allele reported slight decreases in urge to drink at higher levels of estimated blood alcohol concentration (eBAC), and Asp40 carriers reported decreases in vigor and increases in negative mood as eBAC rose, as compared to carriers of the major allele for each gene. Self-reported vigor and urge to drink were positively associated with alcohol consumption within the same drinking episode. This study extends findings on subjective intoxication, urge to drink, and their genetic bases from controlled laboratory to naturalistic settings.
阿片μ型受体（OPRM1）和多巴胺 D4 受体（DRD4）基因的多态性与实验室条件下对酒精的主观反应和饮酒欲望有关。本研究使用生态瞬时评估法在自然环境中研究了这些关联。参与者是非治疗性的重度饮酒者（n=112，52%为女性，61%为酒精依赖者），他们参加了一项关于纳曲酮对自然环境中饮酒欲望和饮酒的影响的研究。数据来自药物随机分组前连续 5 天的饮酒报告。分析显示，与 Asn40 纯合子相比，在饮酒后，OPRM1 基因 Asp40 等位基因的携带者报告了更高的整体活力水平和更低的负面情绪水平。DRD4 长等位基因（即 >或=7 个串联重复）的携带者比短等位基因的纯合子更有饮酒欲望。OPRM1 和 DRD4 可变数串联重复基因型的作用似乎与酒精剂量有关。具体来说，与每个基因的主要等位基因携带者相比，DRD4-L 等位基因的携带者在更高的估计血液酒精浓度（eBAC）水平下报告饮酒欲望略有下降，而 Asp40 携带者报告活力下降和负面情绪增加随着 eBAC 的升高。自我报告的活力和饮酒欲望与同一饮酒事件中的饮酒量呈正相关。本研究将主观醉酒、饮酒欲望及其遗传基础的研究从受控实验室扩展到自然环境。
