NO ASSOCIATION BETWEEN D3 DOPAMINE-RECEPTOR (DRD3) ALLELES AND COCAINE DEPENDENCE

Cocaine is thought to act in the brain primarily by blocking dopamine re-uptake. The dopamine D3 receptor (genetic locus DRD3) is localized to brain regions that have been implicated in the reinforcing effects of a number of substances of abuse, including cocaine. The DRD3 coding region contains a polymorphism identifiable as a polymerase chain rea ction restriction fragment length polymorphism (PCR-RFLP). This polymo rphism leads to an amino acid substitution at position 9 in the extrac ellular N-terminus of the D3 dopamine receptor. We examined alleles of the DRD3 gene in cocaine dependence using a genetic association strat egy in samples of 62 white and 62 black cocaine-dependent individuals. Comparisons were made with local (Connecticut) control subjects for b oth groups, and with a larger sample of literature controls (for the w hite subjects) and a contrast group of schizophrenic patients (for the black subjects). No association was found between cocaine dependence and DRD3 alleles in either group (Bonferroni corrected). There was a s ignificant difference in allele frequency between whites and blacks. T hese results are consistent with no role for genetic variation of the D3 dopamine receptor in susceptibility to cocaine dependence.