The endogenous opioid system plays an integral role in the pathophysiology of alcohol misuse (Dackis and O’Brien, 2005). Alcohol consumption increases opioidergic activity, which inhibits gamma aminobutyric acid (GABA) neurotransmission and results in acute dopamine release from mesocorticolimbic neurons (Kreek, 1996).This acute dopamine release is critically involved in the rewarding and reinforcing effects of alcohol and other addictive substances (Weiss and Porrino, 2002). Given the essential role of the endogenous opioid system in the pharmacological effects of alcohol, OPRM1 has received considerable attention as a candidate gene for alcoholism risk (for a review, see Ray et al., 2012). Although association findings between this SNP and alcohol dependence are mixed (for meta-analysis, see Arias et al., 2006), significant limitations of existing work, such as sample selection biases, clinical heterogeneity across studies, and insufficient specificity in the diagnostic phenotype of alcohol dependence, may account for disparate findings (Ray et al., 2012).
