2004). Results revealed that individuals with at least one copy of the G allele showed greater subjective response to the effects of alcohol measured by subjective intoxication, sedation and stimulation, and changes in mood states, as compared to participants who were homozygous for the A allele. These findings have been recently replicated in an independent sample (Ray & Hutchison, 2007) and this candidate gene has been of interest as a potential mediator of the effects of naltrexone for the treatment of alcoholism (Anton et al., 2008; Oslin et al., 2003). Similar findings were reported in animal models with male rhesus macaques. Here the equivalent OPRM1 polymorphism was associated with increased alcohol response, consumption, and preference (Barr et al., 2007). More broadly, these results provide an example of how endophenotypes may be used to advance our understanding of the pathophysiology of alcoholism. Specifically, subjective responses to alcohol are informative regarding the underlying neuropharmacological effects of alcohol – in suggesting that endogenous opioids may be involved in the rewarding subjective effects of alcohol – which in turn may be used to elucidate candidate genes subserving those effects.
