A polymorphism of the mu-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: 3.31). 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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: While food addiction has no formally-recognized definition, it is typically operationalized according to the diagnostic principles established by the Yale Food Addiction Scale-an inventory based on the symptom criteria for substance dependence in the DSM-IV. Currently, there is little biologically-based research investigating the risk factors for food addiction. What does exist has focused almost exclusively on dopaminergic reward pathways in the brain. While brain opioid signaling has also been strongly implicated in the control of food intake, there is no research examining this neural circuitry in the association with food addiction. The purpose of the study was therefore to test a model predicting that a stronger activation potential of opioid circuitry-as indicated by the functional A118G marker of the mu-opioid receptor gene-would serve as an indirect risk factor for food addiction via a heightened hedonic responsiveness to palatable food. Results confirmed these relationships. In addition, our findings that the food-addiction group had significantly higher levels of hedonic responsiveness to food suggests that this bio-behavioral trait may foster a proneness to overeating, to episodes of binge eating, and ultimately to a compulsive and addictive pattern of food intake.
    Nutrients 10/2014; 6(10):4338-4353. · 3.15 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background It has been proposed that therapeutic responses to naltrexone in alcoholism are moderated by variation at the mu-opioid receptor gene locus (OPRM1). This remains controversial, because human results vary, and no prospectively genotyped studies have been reported. We generated humanized mice carrying the respective human OPRM1 A118G alleles. Here, we used this model system to examine the role of OPRM1 A118G variation for opioid antagonist effects on alcohol responses. Methods Effects of naltrexone on alcohol reward were examined using intracranial self-stimulation. Effects of naltrexone or nalmefene on alcohol intake were examined in continuous access home-cage two-bottle free-choice drinking and operant alcohol self-administration paradigms. Results Alcohol lowered brain stimulation reward (BSR) thresholds in 118GG mice in a manner characteristic of rewarding drugs, and this effect was blocked by naltrexone. BSR thresholds were unchanged by alcohol or naltrexone in 118AA mice. In the home cage, increased alcohol intake emerged in 118GG mice with increasing alcohol concentrations, and was 33% higher at 17% alcohol. At this concentration, naltrexone selectively suppressed alcohol intake in 118GG animals to a level virtually identical to that of 118AA mice. No effect of naltrexone was found in the latter group. Similarly, both naltrexone and nalmefene were more effective in suppressing operant alcohol self-administration in 118GG mice. Conclusions In a model that allows close experimental control, OPRM1 A118G variation robustly moderates effects of opioid antagonism on alcohol reward and consumption. These findings strongly support a personalized medicine approach to alcoholism treatment that takes in account OPRM1 genotype.
    Biological Psychiatry 09/2014; · 9.47 Impact Factor
  • Source
    Proceedings of the National Academy of Sciences 04/2014; 111(16):5968-5973. · 9.81 Impact Factor


1 Download
Available from