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J R Soc Med. 1996 July; 89(7): 396–400.
PMCID: PMC1295855

The D2 dopamine receptor gene as a determinant of reward deficiency syndrome.


The dopaminergic system, and in particular the dopamine D2 receptor, has been profoundly implicated in reward mechanisms in the brain. Dysfunction of the D2 dopamine receptors leads to aberrant substance seeking behaviour (alcohol, drug, tobacco, and food) and other related behaviours (pathological gambling, Tourette's syndrome, and attention deficit hyperactivity disorder). We propose that variants of the D2 dopamine receptor gene are important common genetic determinants of the 'reward deficiency syndrome'.

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  • Blum K, Noble EP, Sheridan PJ, Montgomery A, Ritchie T, Jagadeeswaran P, Nogami H, Briggs AH, Cohn JB. Allelic association of human dopamine D2 receptor gene in alcoholism. JAMA. 1990 Apr 18;263(15):2055–2060. [PubMed]
  • Bolos AM, Dean M, Lucas-Derse S, Ramsburg M, Brown GL, Goldman D. Population and pedigree studies reveal a lack of association between the dopamine D2 receptor gene and alcoholism. JAMA. 1990 Dec 26;264(24):3156–3160. [PubMed]
  • Gelernter J, O'Malley S, Risch N, Kranzler HR, Krystal J, Merikangas K, Kennedy JL, Kidd KK. No association between an allele at the D2 dopamine receptor gene (DRD2) and alcoholism. JAMA. 1991 Oct 2;266(13):1801–1807. [PubMed]
  • Turner E, Ewing J, Shilling P, Smith TL, Irwin M, Schuckit M, Kelsoe JR. Lack of association between an RFLP near the D2 dopamine receptor gene and severe alcoholism. Biol Psychiatry. 1992 Feb 1;31(3):285–290. [PubMed]
  • Cook BL, Wang ZW, Crowe RR, Hauser R, Freimer M. Alcoholism and the D2 receptor gene. Alcohol Clin Exp Res. 1992 Aug;16(4):806–809. [PubMed]
  • Goldman D, Dean M, Brown GL, Bolos AM, Tokola R, Virkkunen M, Linnoila M. D2 dopamine receptor genotype and cerebrospinal fluid homovanillic acid, 5-hydroxyindoleacetic acid and 3-methoxy-4-hydroxyphenylglycol in alcoholics in Finland and the United States. Acta Psychiatr Scand. 1992 Nov;86(5):351–357. [PubMed]
  • Goldman D, Brown GL, Albaugh B, Robin R, Goodson S, Trunzo M, Akhtar L, Lucas-Derse S, Long J, Linnoila M, et al. DRD2 dopamine receptor genotype, linkage disequilibrium, and alcoholism in American Indians and other populations. Alcohol Clin Exp Res. 1993 Apr;17(2):199–204. [PubMed]
  • Suarez BK, Parsian A, Hampe CL, Todd RD, Reich T, Cloninger CR. Linkage disequilibria at the D2 dopamine receptor locus (DRD2) in alcoholics and controls. Genomics. 1994 Jan 1;19(1):12–20. [PubMed]
  • Blum K, Sheridan PJ, Wood RC, Braverman ER, Chen TJ, Comings DE. Dopamine D2 receptor gene variants: association and linkage studies in impulsive-addictive-compulsive behaviour. Pharmacogenetics. 1995 Jun;5(3):121–141. [PubMed]
  • Nakajima S. Subtypes of dopamine receptors involved in the mechanism of reinforcement. Neurosci Biobehav Rev. 1989 Summer-Fall;13(2-3):123–128. [PubMed]
  • Di Chiara G, Imperato A. Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5274–5278. [PubMed]
  • Grandy DK, Litt M, Allen L, Bunzow JR, Marchionni M, Makam H, Reed L, Magenis RE, Civelli O. The human dopamine D2 receptor gene is located on chromosome 11 at q22-q23 and identifies a TaqI RFLP. Am J Hum Genet. 1989 Nov;45(5):778–785. [PubMed]
  • Hauge XY, Grandy DK, Eubanks JH, Evans GA, Civelli O, Litt M. Detection and characterization of additional DNA polymorphisms in the dopamine D2 receptor gene. Genomics. 1991 Jul;10(3):527–530. [PubMed]
  • Sarkar G, Sommer SS. Haplotyping by double PCR amplification of specific alleles. Biotechniques. 1991 Apr;10(4):436–440. [PubMed]
  • Parsian A, Fisher L, O'Malley KL, Todd RD. A new TaqI RFLP within intron 2 of human dopamine D2 receptor gene (DRD2). Nucleic Acids Res. 1991 Dec 25;19(24):6977–6977. [PMC free article] [PubMed]
  • Blum K, Noble EP, Sheridan PJ, Finley O, Montgomery A, Ritchie T, Ozkaragoz T, Fitch RJ, Sadlack F, Sheffield D, et al. Association of the A1 allele of the D2 dopamine receptor gene with severe alcoholism. Alcohol. 1991 Sep-Oct;8(5):409–416. [PubMed]
  • Blum K, Noble EP, Sheridan PJ, Montgomery A, Ritchie T, Ozkaragoz T, Fitch RJ, Wood R, Finley O, Sadlack F. Genetic predisposition in alcoholism: association of the D2 dopamine receptor TaqI B1 RFLP with severe alcoholics. Alcohol. 1993 Jan-Feb;10(1):59–67. [PubMed]
  • Parsian A, Todd RD, Devor EJ, O'Malley KL, Suarez BK, Reich T, Cloninger CR. Alcoholism and alleles of the human D2 dopamine receptor locus. Studies of association and linkage. Arch Gen Psychiatry. 1991 Jul;48(7):655–663. [PubMed]
  • Amadéo S, Abbar M, Fourcade ML, Waksman G, Leroux MG, Madec A, Selin M, Champiat JC, Brethome A, Leclaire Y, et al. D2 dopamine receptor gene and alcoholism. J Psychiatr Res. 1993 Apr-Jun;27(2):173–179. [PubMed]
  • Arinami T, Itokawa M, Komiyama T, Mitsushio H, Mori H, Mifune H, Hamaguchi H, Toru M. Association between severity of alcoholism and the A1 allele of the dopamine D2 receptor gene TaqI A RFLP in Japanese. Biol Psychiatry. 1993 Jan 15;33(2):108–114. [PubMed]
  • Noble EP, Syndulko K, Fitch RJ, Ritchie T, Bohlman MC, Guth P, Sheridan PJ, Montgomery A, Heinzmann C, Sparkes RS, et al. D2 dopamine receptor TaqI A alleles in medically ill alcoholic and nonalcoholic patients. Alcohol Alcohol. 1994 Nov;29(6):729–744. [PubMed]
  • Smith SS, O'Hara BF, Persico AM, Gorelick DA, Newlin DB, Vlahov D, Solomon L, Pickens R, Uhl GR. Genetic vulnerability to drug abuse. The D2 dopamine receptor Taq I B1 restriction fragment length polymorphism appears more frequently in polysubstance abusers. Arch Gen Psychiatry. 1992 Sep;49(9):723–727. [PubMed]
  • Noble EP, Blum K, Khalsa ME, Ritchie T, Montgomery A, Wood RC, Fitch RJ, Ozkaragoz T, Sheridan PJ, Anglin MD, et al. Allelic association of the D2 dopamine receptor gene with cocaine dependence. Drug Alcohol Depend. 1993 Oct;33(3):271–285. [PubMed]
  • O'Hara BF, Smith SS, Bird G, Persico AM, Suarez BK, Cutting GR, Uhl GR. Dopamine D2 receptor RFLPs, haplotypes and their association with substance use in black and Caucasian research volunteers. Hum Hered. 1993 Jul-Aug;43(4):209–218. [PubMed]
  • Noble EP, Blum K, Ritchie T, Montgomery A, Sheridan PJ. Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism. Arch Gen Psychiatry. 1991 Jul;48(7):648–654. [PubMed]
  • McBride WJ, Chernet E, Dyr W, Lumeng L, Li TK. Densities of dopamine D2 receptors are reduced in CNS regions of alcohol-preferring P rats. Alcohol. 1993 Sep-Oct;10(5):387–390. [PubMed]
  • Stefanini E, Frau M, Garau MG, Garau B, Fadda F, Gessa GL. Alcohol-preferring rats have fewer dopamine D2 receptors in the limbic system. Alcohol Alcohol. 1992 Mar;27(2):127–130. [PubMed]
  • Boehme RE, Ciaranello RD. Dopamine receptor binding in inbred mice: strain differences in mesolimbic and nigrostriatal dopamine binding sites. Proc Natl Acad Sci U S A. 1981 May;78(5):3255–3259. [PubMed]
  • Dyr W, McBride WJ, Lumeng L, Li TK, Murphy JM. Effects of D1 and D2 dopamine receptor agents on ethanol consumption in the high-alcohol-drinking (HAD) line of rats. Alcohol. 1993 May-Jun;10(3):207–212. [PubMed]
  • Noble EP. The D2 dopamine receptor gene: a review of association studies in alcoholism. Behav Genet. 1993 Mar;23(2):119–129. [PubMed]
  • Comings DE, Muhleman D, Ahn C, Gysin R, Flanagan SD. The dopamine D2 receptor gene: a genetic risk factor in substance abuse. Drug Alcohol Depend. 1994 Feb;34(3):175–180. [PubMed]
  • Noble EP, Noble RE, Ritchie T, Syndulko K, Bohlman MC, Noble LA, Zhang Y, Sparkes RS, Grandy DK. D2 dopamine receptor gene and obesity. Int J Eat Disord. 1994 Apr;15(3):205–217. [PubMed]
  • Comings DE, Flanagan SD, Dietz G, Muhleman D, Knell E, Gysin R. The dopamine D2 receptor (DRD2) as a major gene in obesity and height. Biochem Med Metab Biol. 1993 Oct;50(2):176–185. [PubMed]
  • Comings DE, Comings BG, Muhleman D, Dietz G, Shahbahrami B, Tast D, Knell E, Kocsis P, Baumgarten R, Kovacs BW, et al. The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders. JAMA. 1991 Oct 2;266(13):1793–1800. [PubMed]
  • Devor EJ. The D2 dopamine receptor and Tourette's syndrome. JAMA. 1992 Feb 5;267(5):651–652. [PubMed]
  • Noble EP, St Jeor ST, Ritchie T, Syndulko K, St Jeor SC, Fitch RJ, Brunner RL, Sparkes RS. D2 dopamine receptor gene and cigarette smoking: a reward gene? Med Hypotheses. 1994 Apr;42(4):257–260. [PubMed]
  • Comings DE, Ferry L, Bradshaw-Robinson S, Burchette R, Chiu C, Muhleman D. The dopamine D2 receptor (DRD2) gene: a genetic risk factor in smoking. Pharmacogenetics. 1996 Feb;6(1):73–79. [PubMed]
  • George SR, Cheng R, Nguyen T, Israel Y, O'Dowd BF. Polymorphisms of the D4 dopamine receptor alleles in chronic alcoholism. Biochem Biophys Res Commun. 1993 Oct 15;196(1):107–114. [PubMed]
  • Uhl G, Blum K, Noble E, Smith S. Substance abuse vulnerability and D2 receptor genes. Trends Neurosci. 1993 Mar;16(3):83–88. [PubMed]
  • Pickens RW, Svikis DS, McGue M, Lykken DT, Heston LL, Clayton PJ. Heterogeneity in the inheritance of alcoholism. A study of male and female twins. Arch Gen Psychiatry. 1991 Jan;48(1):19–28. [PubMed]
  • Pato CN, Macciardi F, Pato MT, Verga M, Kennedy JL. Review of the putative association of dopamine D2 receptor and alcoholism: a meta-analysis. Am J Med Genet. 1993 Jul 15;48(2):78–82. [PubMed]
  • Berman SM, Whipple SC, Fitch RJ, Noble EP. P3 in young boys as a predictor of adolescent substance use. Alcohol. 1993 Jan-Feb;10(1):69–76. [PubMed]
  • Noble EP, Berman SM, Ozkaragoz TZ, Ritchie T. Prolonged P300 latency in children with the D2 dopamine receptor A1 allele. Am J Hum Genet. 1994 Apr;54(4):658–668. [PubMed]
  • Blum K, Braverman ER, Dinardo MJ, Wood RC, Sheridan PJ. Prolonged P300 latency in a neuropsychiatric population with the D2 dopamine receptor A1 allele. Pharmacogenetics. 1994 Dec;4(6):313–322. [PubMed]
  • Crabbe JC, Belknap JK, Buck KJ. Genetic animal models of alcohol and drug abuse. Science. 1994 Jun 17;264(5166):1715–1723. [PubMed]
  • Lilienfeld SO. Reply to Maltzman's "Why alcoholism is a disease". J Psychoactive Drugs. 1995 Jul-Sep;27(3):287–291. [PubMed]
  • Nishimura N, Ogura C, Ohta I. Effects of the dopamine-related drug bromocriptine on event-related potentials and its relation to the law of initial value. Psychiatry Clin Neurosci. 1995 Mar;49(1):79–86. [PubMed]

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