Article

A Polymorphism of the ??-Opioid Receptor Gene (OPRM1) and Sensitivity to the Effects of Alcohol in Humans

University of Colorado, Boulder, CO 80309-0345, USA.
Alcoholism Clinical and Experimental Research (Impact Factor: 3.21). 01/2005; 28(12):1789-95. DOI: 10.1097/01.ALC.0000148114.34000.B9
Source: PubMed

ABSTRACT

Recent research has implicated the endogenous opioid system in the development of alcohol use disorders. The A118G polymorphism of the OPRM1 gene has been shown to confer functional differences to mu-opioid receptors, such that the G variant binds beta-endorphin three times more strongly than the A variant. The goal of this study was to test whether the A118G polymorphism is associated with sensitivity to the effects of alcohol.
Participants who were either homozygous for the A allele (n = 23) or heterozygous (n = 15) received intravenous doses of alcohol designed to reach three target levels of breath alcohol concentration: 0.02, 0.04, and 0.06. The testing procedure consisted of measures of subjective intoxication, stimulation, sedation, and mood states at baseline and at each of the three target breath alcohol concentrations.
The results suggested that individuals with the G allele reported higher subjective feelings of intoxication, stimulation, sedation, and happiness across trials as compared with participants with the A allele. Furthermore, participants with the G allele were almost three times more likely to report a positive family history of alcohol use disorders than participants with the A allele.
These findings may help to explain previous research suggesting that naltrexone is more effective among individuals with the G allele. A medication that reduces feelings of euphoria after alcohol consumption may be more successful among individuals with a genetic predisposition to greater feelings of euphoria after consuming alcohol.

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    • "The OPRM1 gene encodes for the µ-opioid receptor (MOR, receptor of endogenous opioids including heroin, morphine, and methadone). The OPRM1 polymorphism consists of an adenine to guanine substitution which affects the reinforcing (thus addictive) effect of drugs in various brain regions ( Ray et al., 2011) This polymorphism has been linked to a variety of substance use characteristics including sensitivity to the effects of alcohol (Ray & Hutchison, 2004) and adolescent alcohol misuse (Miranda et al., 2010), heroin addiction (Shi et al., 2002), and nicotine reinforcement ( Ray et al., 2006). OPRM1 has also been associated with neural sensitivity to social rejection (Way, Taylor, & Eisenberger, 2009). "

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    • "In one study, the ability of naltrexone to decrease the " high " induced by alcohol was stronger in subjects that were carriers of the G allele variant (Ray and Hutchison, 2007 ). In another study, evaluating sensitivity of different doses of alcohol administered intravenously in order to control for blood alcohol levels with great precision, it was found that the G carriers had higher subjective feeling of intoxication, stimulation , sedation, and happiness, suggesting enhanced sensitivity to the effects of alcohol (Ray and Hutchison, 2004). Interestingly, a functional analogue of the A118G polymorphism has been found in nonhuman primates. "
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    • "An experimental study focusing on behavioral mechanisms of alcohol reward in a sample of heavy drinkers has shown that compared with A-allele homozygotes, G-allele carriers report greater subjective reinforcement from alcohol in the laboratory (Ray and Hutchison, 2004). Similar results were obtained in a naturalistic study of the effects of alcohol (Ray et al., 2010b). "
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