mu-opioid receptor variants and dopaminergic sensitivity in alcohol withdrawal

Object: The endogenous opioid system plays an important role in the reinfor cing properties of alcohol by an interconnected activation of the mesolimbi c dopamine system. The Asn40Asp substitution polymorphism of the human mu-o pioid-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 ge ne is associated with a variation in central dopaminergic sensitivity durin g alcohol withdrawal in alcoholics. Method: Sensitivity of central dopamine receptors was assessed by apomorphine-induced growth hormone (GH) secretio n in 97 alcohol-dependent patients before and 1 week after alcohol cessatio n, and in a subgroup of 19 alcoholics after 3 months of abstinence. GH resp onse was defined as area under the hormone/time curve. Comparisons of the G H response were conducted between alcoholics carrying the Asn40Asp genotype versus those with the Asn40Asn genotype using U-test statistics. Results: 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 significan tly increased in alcoholics with the Asn40Asp genotype compared with those carrying the Asn40Asn genotype (P = 0.013 (n = 97)/P = 0.026 (n = 19)). Con clusion: Our results suggest that genetic variation of the mu-opioid recept or modulates the central opaminergic sensitivity during acute alcohol withd rawal. (C) 1999 Elsevier Science Ltd. All rights reserved.