mu-opioid receptor variants and dopaminergic sensitivity in alcohol withdrawal

The endogenous opioid system plays an important role in the reinforcing properties of alcohol by an interconnected activation of the mesolimbic dopamine system. The Asn40Asp substitution polymorphism of the human mu-opioid-receptor (OPRM) influences binding of opioids and signal transduction and may, thereby, contribute to the development of alcoholism. The present study tested whether the Asn40Asp substitution polymorphism of the OPRM gene is associated with a variation in central dopaminergic sensitivity during alcohol withdrawal in alcoholics.

Sensitivity of central dopamine receptors was assessed by apomorphine-induced growth hormone (GH) secretion in 97 alcohol-dependent patients before and 1 week after alcohol cessation, and in a subgroup of 19 alcoholics after 3 months of abstinence. GH response was defined as area under the hormone/time curve. Comparisons of the GH response were conducted between alcoholics carrying the Asn40Asp genotype versus those with the Asn40Asn genotype using U-test statistics.

Marginal differences in apomorphine-induced GH response were found between both genotype groups before detoxification (P = 0.799 (n = 97)/P = 0.459 (n = 19)) and after 3 months of abstinence (P = 0.331 (n = 19)). In contrast, the GH response measured seven days after alcohol withdrawal was significantly increased in alcoholics with the Asn40Asp genotype compared with those carrying the Asn40Asn genotype (P = 0.013 (n = 97)/P = 0.026 (n = 19)).

Our results suggest that genetic variation of the mu-opioid receptor modulates the central dopaminergic sensitivity during acute alcohol withdrawal.