Addiction and its reward process through polymorphisms of the D2dopamine receptor gene: a review
- 1 March 2000
- journal article
- review article
- Published by Cambridge University Press (CUP) in European Psychiatry
- Vol. 15 (2) , 79-89
- https://doi.org/10.1016/s0924-9338(00)00208-x
Abstract
Since 1990, association studies have amassed strong evidence implicating the D(2) 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 D(2) 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.Keywords
This publication has 68 references indexed in Scilit:
- Association and linkage studies of the TAQI A1 allele at the dopamine D2 receptor gene in samples of female and male alcoholicsAmerican Journal of Medical Genetics, 1995
- Prolonged P300 latency in a neuropsychiatric population with the D2 Dopamine receptor A1 allelePharmacogenetics, 1994
- D2 dopamine receptor gene and cigarette smoking: A reward gene?Medical Hypotheses, 1994
- Linkage Disequilibria at the D2 Dopamine Receptor Locus (DRD2) in Alcoholics and ControlsGenomics, 1994
- Alcoholism and the D2 dopamine receptor genePublished by American Medical Association (AMA) ,1993
- The Dopamine D2 Receptor (DRD2) as a Major Gene in Obesity and HeightBiochemical Medicine and Metabolic Biology, 1993
- Neuropsychological Deficits Are Correlated with Frontal Hypometabolism in Positron Emission Tomography Studies of Older Alcoholic PatientsAlcohol, Clinical and Experimental Research, 1993
- D2 dopamine receptor genotype and cerebrospinal fluid homovanillic acid, 5‐hydroxyindoleacetic acid and 3‐methoxy‐4‐hydroxyphenylglycol in alcoholics in Finland and the United StatesActa Psychiatrica Scandinavica, 1992
- PET determination of regional cerebral glucose metabolism in alcohol‐dependent men and healthy controls using 11C‐glucoseActa Psychiatrica Scandinavica, 1988
- Neurogenetic Adaptive Mechanisms in AlcoholismScience, 1987