Substance abuse vulnerability and D2 receptor genes

Dopamine systems are key to the actions of several substances. Interindividual differences in genes encoding proteins involved in dopaminergic neurotransmission could plausibly explain some of the genetic bases for inter-individual differences in vulnerability to substance abuse. The restriction fragment length polymorphism (RFLP) markers Taq/ A1 and B1 at the dopamine D₂ receptor (DRD2) gene locus in Caucasians are associated with substance abuse behaviors. In most, but not all, studies of alcoholics and polysubstance abusers, these Taq/ A1 and B1 gene markers are present more often in substance abusers than in control individuals. No study has identified substance abusers or controls by sampling randomly from the general population; allelic association findings could thus conceivably be confounded by RFLP differences based on ethnicity or other factors. However, meta-analyses of the data from controlled studies available to date are consistent with the proposal that DRD2 gene variants contribute to inter-individual differences in vulnerability to alcoholism and polysubstance abuse.