Addiction and its reward process through polymorphisms of the D-2 dopaminereceptor gene: a review

Since 1990, association studies have amassed strong evidence implicating th e D-2 dopamine receptor (DRD2) gene in alcoholism. Specifically, the Taql A minor (A1) allele of the DRD2 gene has been associated with alcoholism. Th e DRD2 gene has also been found to be involved in other substance use disor ders including cocaine, nicotine and opioid dependence, and obesity. Beyond association studies, pharmacologic studies have shown reduced brain D-2 do pamine receptor numbers in A1(+) allele carriers (A1A1 and A1A2 genotypes) compared to A1(-) allele carriers (A2A2 genotype). Through a number of othe r approaches, different phenotypes have also been identified in subjects wi th the A1(+) and A1(-) alleles. These include metabolic, neurophysiological , neuropsychological, personality, stress and treatment studies. It is hypo thesized that in an effort to compensate for deficiencies in the dopaminerg ic system, substance abusers may seek to stimulate the mesocorticolimbic ci rcuits of the brain, long thought to be important in behavioral reward and reinforcement. In effect, one form of the DRD2 gene, the A1 allele, renders the dopaminergic system inefficient and rewards substance abuse that incre ases brain dopamine levels. (C) 2000 Editions scientifiques et medicales El sevier SAS.