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Gene Review

DRD3  -  dopamine receptor D3

Homo sapiens

Synonyms: D(3) dopamine receptor, D3DR, Dopamine D3 receptor, ETM1, FET1
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Disease relevance of DRD3

  • The association between the dopamine D3 receptor (DRD3) ser9gly genetic polymorphism and tardive dyskinesia (TD), a serious adverse motor disorder after long-term antipsychotic treatment, has been studied extensively in recent years [1].
  • RESULTS: No association was detected using the TDT between DRD3, DRD4, and migraine without aura either in the overall sample or in the subgroup [2].
  • BACKGROUND: The Dopamine D3 receptor (DRD3) gene is thought to be involved in essential hypertension (EH) because dopamine inhibits renin secretion via this receptor and because disruption of the DRD3 gene increases blood pressure in mice [3].
  • The gain-of-function produced by the Gly-9 variant may explain why drugs active against tremor in Parkinson's disease (PD) are usually not effective in the treatment of ET and suggests that DRD3 partial agonists or antagonists should be considered as novel therapeutic options for patients with ET [4].
  • Linkage with the Ser9Gly DRD3 polymorphism in essential tremor families [5].

Psychiatry related information on DRD3


High impact information on DRD3


Chemical compound and disease context of DRD3

  • RESULTS: A higher, but not significant, frequency of DRD3 ser/gly heterozygotes was observed in the tardive dyskinesia group (0.52 versus 0.33, chi2=5, degrees of freedom=2, P=0.08) [14].
  • The DRD3 variant was associated with some scales related to novelty seeking: the Swedish universities Scales of Personality (SSP) Adventure Seeking and the revised NEO personality inventory (NEO-PI-R) Fantasy (O1) and Order (C2) scales [15].
  • Patients were assessed for TD severity using the Abnormal Involuntary Movement Scale (AIMS) and were subsequently genotyped for the MscI polymorphism that identifies a serine to glycine substitution in DRD3 [16].
  • In contrast to nicotine replacement therapy, varenicline and bupropion (which are currently used for the treatment of smokers), DRD3 antagonists do not seem to produce nicotine-like effects in experimental animals and, therefore, may not substitute for nicotine or alleviate nicotine withdrawal symptoms in human smokers [17].

Biological context of DRD3


Anatomical context of DRD3


Associations of DRD3 with chemical compounds

  • In addition, BDNF promotes and maintains dopamine D3 receptor (DRD3) expression [26].
  • We conclude that PDYN gene polymorphism alone does not alter the risk for schizophrenia but, by an epistatic interaction with the Gly allele of DRD3 gene, may contribute to the susceptibility to this disorder [27].
  • CONCLUSIONS: Genetic variations of the DRD2, DRD3, and DRD4 do not influence the occurrence of L -dopa-induced adverse effects [28].
  • The results of research of other genes (DRD2, DRD3, MAO, ADR2A, GABA A3, GABA B3) are not clear yet [29].
  • These data suggest that the DRD3 Ser9Gly polymorphism or, alternatively, another genetic variation that is in linkage disequilibrium, may influence response to risperidone in negative symptoms and social functioning [30].

Other interactions of DRD3

  • The recently cloned D4 dopamine receptor gene (DRD4) shows considerable homology to the D2 and D3 dopamine receptors (DRD2 and DRD3); pharmacologically, its affinity for the atypical antipsychotic clozapine is much higher than that of these other dopamine receptors [31].
  • Furthermore, neither the DRD3 nor the BDNF genotypes and alleles were demonstrated to be associated with TD occurrence [1].
  • The dopamine D3 receptor gene (DRD3) represents a promising candidate to examine in ADHD [23].
  • RESULTS: Results of chi-square statistical analyses indicated that the allele distribution for migraine cases compared to controls was not significantly different for any of the three tested gene markers (chi2 = 0.1, P =.74 for DRD1; chi2 = 1.8, P =.18 for DRD3; and chi2 = 20.3, P =.08 for DRD5) [32].
  • However, assessment of the combined influence of the two polymorphisms demonstrated a significant effect (chi2=8.09, degrees of freedom=3, P=0.04), whereby the combination of the MnSOD -9val and DRD3 9ser alleles was associated with tardive dyskinesia [14].

Analytical, diagnostic and therapeutic context of DRD3

  • The purpose of the present European multicenter study (13 centers) was to test the potential role in BPAD and UPAD of two candidate dopaminergic markers, DRD2 and DRD3, using a case-control association design [33].
  • CONCLUSIONS: Whereas the present Swedish case-control analysis did not yield any evidence for association with the diagnosis, the present meta-analysis suggests that the DRD3 gene confer susceptibility to schizophrenia [34].
  • Interestingly, after treatment of patients with antipsychotics, DRD3 mRNA levels increased to similar levels as those of healthy controls [24].
  • In a meta-analysis of all case-control studies comprising 8761 subjects the association between DRD3 Ser9Gly homozygosity and schizophrenia ( =4.96, degree of freedom=1, p <0.05, odds ratio=1.10, 95% confidence interval=1.01-1.20) persisted [34].
  • Polymerase chain reaction (PCR) was used to amplify the Ser9Gly polymorphic site in the DRD3 gene, and restriction fragment length polymorphism (RFLP) analysis of the PCR product was used to score the A and G alleles [3].


  1. Association analysis of the dopamine D3 receptor gene ser9gly and brain-derived neurotrophic factor gene val66met polymorphisms with antipsychotic-induced persistent tardive dyskinesia and clinical expression in Chinese schizophrenic patients. Liou, Y.J., Liao, D.L., Chen, J.Y., Wang, Y.C., Lin, C.C., Bai, Y.M., Yu, S.C., Lin, M.W., Lai, I.C. Neuromolecular Med. (2004) [Pubmed]
  2. Association between dopamine receptor genes and migraine without aura in a Sardinian sample. Del Zompo, M., Cherchi, A., Palmas, M.A., Ponti, M., Bocchetta, A., Gessa, G.L., Piccardi, M.P. Neurology (1998) [Pubmed]
  3. Ser9Gly polymorphism in the dopamine D3 receptor gene is not associated with essential hypertension in the Japanese. Soma, M., Nakayama, K., Rahmutula, D., Uwabo, J., Sato, M., Kunimoto, M., Aoi, N., Kosuge, K., Kanmatsuse, K. Med. Sci. Monit. (2002) [Pubmed]
  4. A functional variant of the dopamine D3 receptor is associated with risk and age-at-onset of essential tremor. Jeanneteau, F., Funalot, B., Jankovic, J., Deng, H., Lagarde, J.P., Lucotte, G., Sokoloff, P. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  5. Linkage with the Ser9Gly DRD3 polymorphism in essential tremor families. Lucotte, G., Lagarde, J.P., Funalot, B., Sokoloff, P. Clin. Genet. (2006) [Pubmed]
  6. Genetic variation analysis in parkinson disease patients with and without hallucinations: case-control study. Goetz, C.G., Burke, P.F., Leurgans, S., Berry-Kravis, E., Blasucci, L.M., Raman, R., Zhou, L. Arch. Neurol. (2001) [Pubmed]
  7. Dopamine receptor D2 and D3 gene variants are not associated with the antidepressant effect of total sleep deprivation in bipolar depression. Benedetti, F., Serretti, A., Colombo, C., Lilli, R., Lorenzi, C., Smeraldi, E. Psychiatry research. (2003) [Pubmed]
  8. Characterisation, mutation detection, and association analysis of alternative promoters and 5' UTRs of the human dopamine D3 receptor gene in schizophrenia. Anney, R.J., Rees, M.I., Bryan, E., Spurlock, G., Williams, N., Norton, N., Williams, H., Cardno, A., Zammit, S., Jones, S., Jones, G., Hoogendoorn, B., Smith, K., Hamshere, M.L., Coleman, S., Guy, C., O'Donovan, M.C., Owen, M.J., Buckland, P.R. Mol. Psychiatry (2002) [Pubmed]
  9. DRD2, DRD3 and 5HT2A receptor genes polymorphisms in obsessive-compulsive disorder. Nicolini, H., Cruz, C., Camarena, B., Orozco, B., Kennedy, J.L., King, N., Weissbecker, K., de la Fuente, J.R., Sidenberg, D. Mol. Psychiatry (1996) [Pubmed]
  10. Psychotic symptoms in Alzheimer's disease are not influenced by polymorphic variation at the dopamine receptor DRD3 gene. Craig, D., Hart, D.J., Carson, R., McIlroy, S.P., Passmore, A.P. Neurosci. Lett. (2004) [Pubmed]
  11. Non-nicotinic therapies for smoking cessation. Siu, E.C., Tyndale, R.F. Annu. Rev. Pharmacol. Toxicol. (2007) [Pubmed]
  12. Pharmacogenomics in schizophrenia: the quest for individualized therapy. Basile, V.S., Masellis, M., Potkin, S.G., Kennedy, J.L. Hum. Mol. Genet. (2002) [Pubmed]
  13. Dopamine selectively induces migration and homing of naive CD8+ T cells via dopamine receptor D3. Watanabe, Y., Nakayama, T., Nagakubo, D., Hieshima, K., Jin, Z., Katou, F., Hashimoto, K., Yoshie, O. J. Immunol. (2006) [Pubmed]
  14. Interaction between polymorphisms of the dopamine D3 receptor and manganese superoxide dismutase genes in susceptibility to tardive dyskinesia. Zhang, Z.J., Zhang, X.B., Hou, G., Yao, H., Reynolds, G.P. Psychiatr. Genet. (2003) [Pubmed]
  15. Association study between dopamine D3 receptor gene variant and personality traits. Jönsson, E.G., Burgert, E., Crocq, M.A., Gustavsson, J.P., Forslund, K., Mattila-Evenden, M., Rylander, G., Flyckt, L.K., Bjerkenstedt, L., Wiesel, F.A., Asberg, M., Bergman, H. Am. J. Med. Genet. B Neuropsychiatr. Genet. (2003) [Pubmed]
  16. Association of the MscI polymorphism of the dopamine D3 receptor gene with tardive dyskinesia in schizophrenia. Basile, V.S., Masellis, M., Badri, F., Paterson, A.D., Meltzer, H.Y., Lieberman, J.A., Potkin, S.G., Macciardi, F., Kennedy, J.L. Neuropsychopharmacology (1999) [Pubmed]
  17. Dopamine D3 receptor ligands for the treatment of tobacco dependence. Le Foll, B., Goldberg, S.R., Sokoloff, P. Expert opinion on investigational drugs (2007) [Pubmed]
  18. Dopamine-related genes and their relationships to monoamine metabolites in CSF. Jönsson, E., Sedvall, G., Brené, S., Gustavsson, J.P., Geijer, T., Terenius, L., Crocq, M.A., Lannfelt, L., Tylec, A., Sokoloff, P., Schwartz, J.C., Wiesel, F.A. Biol. Psychiatry (1996) [Pubmed]
  19. Dopamine receptor genetic variation, psychosis, and aggression in Alzheimer disease. Sweet, R.A., Nimgaonkar, V.L., Kamboh, M.I., Lopez, O.L., Zhang, F., DeKosky, S.T. Arch. Neurol. (1998) [Pubmed]
  20. Dopamine receptor D3 mRNA expression in human lymphocytes is negatively correlated with the personality trait of persistence. Czermak, C., Lehofer, M., Renger, H., Wagner, E.M., Lemonis, L., Rohrhofer, A., Schauenstein, K., Liebmann, P.M. J. Neuroimmunol. (2004) [Pubmed]
  21. No association between polymorphisms in the human dopamine D3 and D4 receptors genes and alcoholism. Parsian, A., Chakraverty, S., Fisher, L., Cloninger, C.R. Am. J. Med. Genet. (1997) [Pubmed]
  22. Long forms of the dopamine receptor (DRD4) gene VNTR are more prevalent in substance abusers: no interaction with functional alleles of the catechol-o-methyltransferase (COMT) gene. Vandenbergh, D.J., Rodriguez, L.A., Hivert, E., Schiller, J.H., Villareal, G., Pugh, E.W., Lachman, H., Uhl, G.R. Am. J. Med. Genet. (2000) [Pubmed]
  23. A transmission disequilibrium test of the Ser9/Gly dopamine D3 receptor gene polymorphism in adult attention-deficit hyperactivity disorder. Muglia, P., Jain, U., Kennedy, J.L. Behav. Brain Res. (2002) [Pubmed]
  24. Decreased levels of dopamine D3 receptor mRNA in schizophrenic and bipolar patients. Vogel, M., Pfeifer, S., Schaub, R.T., Grabe, H.J., Barnow, S., Freyberger, H.J., Cascorbi, I. Neuropsychobiology (2004) [Pubmed]
  25. The dopamine D3 receptor and drug dependence: effects on reward or beyond? Le Foll, B., Goldberg, S.R., Sokoloff, P. Neuropharmacology (2005) [Pubmed]
  26. Brain derived neurotrophic factor (BDNF) gene variants association with age at onset and therapeutic response in schizophrenia. Krebs, M.O., Guillin, O., Bourdell, M.C., Schwartz, J.C., Olie, J.P., Poirier, M.F., Sokoloff, P. Mol. Psychiatry (2000) [Pubmed]
  27. Allelic variation in the human prodynorphin gene promoter and schizophrenia. Ventriglia, M., Bocchio Chiavetto, L., Bonvicini, C., Tura, G.B., Bignotti, S., Racagni, G., Gennarelli, M. Neuropsychobiology (2002) [Pubmed]
  28. L -dopa-induced adverse effects in PD and dopamine transporter gene polymorphism. Kaiser, R., Hofer, A., Grapengiesser, A., Gasser, T., Kupsch, A., Roots, I., Brockmöller, J. Neurology (2003) [Pubmed]
  29. Biochemical markers and genetic research of ADHD. Paclt, I., Koudelová, J., Krepelová, A., Uhlíková, P., Gazdíková, M., Bauer, P. Neuro Endocrinol. Lett. (2005) [Pubmed]
  30. Dopamine D3 receptor Ser9Gly polymorphism and risperidone response. Lane, H.Y., Hsu, S.K., Liu, Y.C., Chang, Y.C., Huang, C.H., Chang, W.H. Journal of clinical psychopharmacology. (2005) [Pubmed]
  31. The D4 dopamine receptor (DRD4) maps to distal 11p close to HRAS. Gelernter, J., Kennedy, J.L., van Tol, H.H., Civelli, O., Kidd, K.K. Genomics (1992) [Pubmed]
  32. Dopamine receptor genes and migraine with and without aura: an association study. Shepherd, A.G., Lea, R.A., Hutchins, C., Jordan, K.L., Brimage, P.J., Griffiths, L.R. Headache. (2002) [Pubmed]
  33. Positive association of dopamine D2 receptor polymorphism with bipolar affective disorder in a European Multicenter Association Study of affective disorders. Massat, I., Souery, D., Del-Favero, J., Van Gestel, S., Serretti, A., Macciardi, F., Smeraldi, E., Kaneva, R., Adolfsson, R., Nylander, P.O., Blackwood, D., Muir, W., Papadimitriou, G.N., Dikeos, D., Oruc, L., Segman, R.H., Ivezic, S., Aschauer, H., Ackenheil, M., Fuchshuber, S., Dam, H., Jakovljevic, M., Peltonen, L., Hilger, C., Hentges, F., Staner, L., Milanova, V., Jazin, E., Lerer, B., Van Broeckhoven, C., Mendlewicz, J. Am. J. Med. Genet. (2002) [Pubmed]
  34. Dopamine D3 receptor gene Ser9Gly variant and schizophrenia: association study and meta-analysis. Jönsson, E.G., Flyckt, L., Burgert, E., Crocq, M.A., Forslund, K., Mattila-Evenden, M., Rylander, G., Asberg, M., Nimgaonkar, V.L., Edman, G., Bjerkenstedt, L., Wiesel, F.A., Sedvall, G.C. Psychiatr. Genet. (2003) [Pubmed]
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