INFLUENCE OF THE DOPAMINE D2 RECEPTOR (DRD2) GENOTYPE ON NEUROADAPTIVE EFFECTS OF ALCOHOL AND THE CLINICAL OUTCOME OF ALCOHOLISM

The present study was performed to test the hypotheses that allelic va riants at the human dopamine D2 receptor gene locus (DRD2) confer susc eptibility to alcoholism or are associated with clinical subtypes of a lcoholism, We investigated an A --> G substitution polymorphism in the 3'-untranslated region of exon 8 (E8) of DRD2 with allele frequencies of f(G) = 0.295 - 0.329. No significant association of the DRD2 genot ype or allele frequencies with alcoholism was found in an association study including 283 alcoholics and 146 non-alcoholic controls, However , the frequent homozygous E8 A/A genotype with f(AA) = 0.47 - 0.48 was associated with increased anxiety and depression scores in alcoholics during the follow up after clinical detoxification treatment. In addi tion, E8 A/A was associated with increased suicide attempts and showed a tendency towards more severe withdrawal symptoms, early relapse and reduced responsiveness to the dopaminergic agonist apomorphine, Regre ssion analysis revealed the DRD2 E8 genotype as the only significant f actor determining withdrawal severity in female alcoholics, The findin gs suggest an influence of the DRD2 genotype on the neuropharmacologic al effects of chronic alcohol exposure and the clinical course of alco holism.