Since 1990, association studies have amassed strong evidence implicating the D₂ dopamine receptor (DRD2) gene in alcoholism. Specifically, the TaqI A minor (A1) allele of the DRD2 gene has been associated with alcoholism. The DRD2 gene has also been found to be involved in other substance use disorders including cocaine, nicotine and opioid dependence, and obesity. Beyond association studies, pharmacologic studies have shown reduced brain D₂ dopamine receptor numbers in A1⁺ allele carriers (A1A1 and A1A2 genotypes) compared to A1^- allele carriers (A2A2 genotype). Through a number of other approaches, different phenotypes have also been identified in subjects with the A1⁺ and A1^- alleles. These include metabolic, neurophysiological, neuropsychological, personality, stress and treatment studies. It is hypothesized that in an effort to compensate for deficiencies in the dopaminergic system, substance abusers may seek to stimulate the mesocorticolimbic circuits 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 increases brain dopamine levels.