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Gene Review

Drd2  -  dopamine receptor D2

Mus musculus

Synonyms: D(2) dopamine receptor, D2 receptor, D2R, Dopamine D2 receptor, Drd-2
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Disease relevance of Drd2


Psychiatry related information on Drd2

  • Our results indicate that genetic differences in quinpirole sensitivity and tolerance are associated with QTLs near Drd2, and that baseline locomotor activity is associated with a suggestive QTL in proximity to the dopamine transporter gene Dat1 [4].
  • Defining the age-related critical periods and understanding the role of the two D2R isoforms in aging may facilitate the development of new strategies for delaying or ameliorating age-related motor and learning impairments [5].
  • The dopamine D2 receptor (D2) is implicated in drug addiction, learning and memory [6].
  • The hot plate response latencies were not significantly different between the dopamine D2 receptor knockout and wild-type animals, although the stimulus temperature-dependent decrease in the response latency was steeper in the wild-type group [7].
  • These findings suggest that signaling mediated by the dopamine D2 receptor is important for regulating associative and reversal learning and may have implications for the treatment of human attention disorders [8].

High impact information on Drd2

  • Importantly, overexpression of RAP30 in cultured primary striatal cells protects neurons from mutant htt-induced cellular toxicity and alleviates the transcriptional inhibition of the dopamine D2 receptor gene by mutant htt [9].
  • In this issue of Cell, the laboratories of Marc Caron and Li-Huei Tsai identify two very different molecules--beta-arrestin 2 and Par-4, respectively--that unexpectedly are involved in dopamine signaling via the D2 receptor [10].
  • Calmodulin can effectively compete with Par-4 binding in a Ca2+-dependent manner, providing a route for Ca2+-mediated downregulation of D2DR efficacy [11].
  • By a mechanism of alternative splicing, the D2 receptor gene encodes two molecularly distinct isoforms, D2S and D2L, previously thought to have the same function [12].
  • We conclude that the D2 receptor plays a crucial role in the motivational component of drug addiction [13].

Chemical compound and disease context of Drd2


Biological context of Drd2

  • The current study addresses this issue by measuring D2 dopamine (DA) receptor binding, the expression of Drd2, the number of midbrain DA neurons in the BXD recombinant inbred (RI) series and then compares these strain means with those previously reported for a variety of ethanol and other drug-related phenotypes [18].
  • The lack of development of up-regulation of Drd1 and Drd2 genes after repeated treatment with amphetamine probably explains the reduced place conditioning in CCK(2) receptor deficient mice [19].
  • We definitively mapped a QTL on Chromosome (Chr) 9 linked to the D(2) dopamine receptor gene, Drd2, for hypothermic sensitivity to quinpirole, and identify a suggestive QTL in the same chromosomal region for tolerance to quinpirole after repeated treatments [4].
  • Incubation of striatal slices from wild-type mice with quinpirole, a dopamine D2 receptor agonist, decreased the state of phosphorylation of TH at Ser-40 and its enzymatic activity [20].
  • D1R mutants do not become locomotor activated with cocaine or show upregulated immediate early gene (IEG) expression, but D2 receptor-dependent IEG changes are intact [21].

Anatomical context of Drd2

  • The expression of Tyhy gene was elevated in the mesolimbic structures and Drd2 gene was down-regulated in the mesencephalon of saline-treated homozygous mice in comparison with respective wild-type group [19].
  • Drd2 expression in forebrain samples from the RI and parental strains ranged 1.5- to h2-fold and was moderate-0.47 [18].
  • These results show that A2AR and D2R have antagonistic and independent activities in controlling neuronal and motor functions in the basal ganglia [2].
  • D1 and D2 receptor antagonist injections in the prefrontal cortex selectively impair spatial learning in mice [22].
  • Neurons exhibiting dopamine D2 receptor immunoreactivity in the substantia nigra of the mutant weaver mouse [23].

Associations of Drd2 with chemical compounds

  • We used Drd2(-/-) and Prlr(-/-) mutant mice to bypass this feedback and investigate possible dopamine-independent effects of PRL on lactotroph function [1].
  • Overall, the data suggest ethanol preference and CPP are associated with the expression of Drd2 or closely linked genetic loci [18].
  • Adenosine A2A (A2AR) and dopamine D2 (D2R) receptors are colocalized in striatal medium spiny neurons [2].
  • In addition, the level of expression of enkephalin and substance P, which were altered in D2R-/-, were also reestablished to normal levels after A2AR antagonist treatment [2].
  • CD1 mice were bilaterally microinjected in the PFC with either the D1 receptor antagonist, SCH23390 (SCH 6.25; 12.5; 50 ng), or the D2 receptor antagonist, sulpiride (SULP 12.5; 50; 100 ng) and placed into an open field containing five different objects [22].

Physical interactions of Drd2


Regulatory relationships of Drd2


Other interactions of Drd2


Analytical, diagnostic and therapeutic context of Drd2


  1. Lack of prolactin receptor signaling in mice results in lactotroph proliferation and prolactinomas by dopamine-dependent and -independent mechanisms. Schuff, K.G., Hentges, S.T., Kelly, M.A., Binart, N., Kelly, P.A., Iuvone, P.M., Asa, S.L., Low, M.J. J. Clin. Invest. (2002) [Pubmed]
  2. Rescue of locomotor impairment in dopamine D2 receptor-deficient mice by an adenosine A2A receptor antagonist. Aoyama, S., Kase, H., Borrelli, E. J. Neurosci. (2000) [Pubmed]
  3. Dopaminergic D2 receptor knockout mouse: an animal model of prolactinoma. Cristina, C., García-Tornadú, I., Díaz-Torga, G., Rubinstein, M., Low, M.J., Becú-Villalobos, D. Frontiers of hormone research. (2006) [Pubmed]
  4. Mapping quantitative trait loci that regulate sensitivity and tolerance to quinpirole, a dopamine mimetic selective for D(2)/D(3) receptors. Buck, K., Lischka, T., Dorow, J., Crabbe, J. Am. J. Med. Genet. (2000) [Pubmed]
  5. Effects of age and dopamine D2L receptor-deficiency on motor and learning functions. Fetsko, L.A., Xu, R., Wang, Y. Neurobiol. Aging (2005) [Pubmed]
  6. Dopamine D2L receptor knockout mice display deficits in positive and negative reinforcing properties of morphine and in avoidance learning. Smith, J.W., Fetsko, L.A., Xu, R., Wang, Y. Neuroscience (2002) [Pubmed]
  7. Influence of the dopamine D2 receptor knockout on pain-related behavior in the mouse. Mansikka, H., Erbs, E., Borrelli, E., Pertovaara, A. Brain Res. (2005) [Pubmed]
  8. Dopamine D2 receptors mediate two-odor discrimination and reversal learning in C57BL/6 mice. Kruzich, P.J., Grandy, D.K. BMC neuroscience [electronic resource]. (2004) [Pubmed]
  9. In vitro analysis of huntingtin-mediated transcriptional repression reveals multiple transcription factor targets. Zhai, W., Jeong, H., Cui, L., Krainc, D., Tjian, R. Cell (2005) [Pubmed]
  10. Decoding dopamine signaling. Bibb, J.A. Cell (2005) [Pubmed]
  11. Par-4 links dopamine signaling and depression. Park, S.K., Nguyen, M.D., Fischer, A., Luke, M.P., Affar, e.l. .B., Dieffenbach, P.B., Tseng, H.C., Shi, Y., Tsai, L.H. Cell (2005) [Pubmed]
  12. Distinct functions of the two isoforms of dopamine D2 receptors. Usiello, A., Baik, J.H., Rougé-Pont, F., Picetti, R., Dierich, A., LeMeur, M., Piazza, P.V., Borrelli, E. Nature (2000) [Pubmed]
  13. Absence of opiate rewarding effects in mice lacking dopamine D2 receptors. Maldonado, R., Saiardi, A., Valverde, O., Samad, T.A., Roques, B.P., Borrelli, E. Nature (1997) [Pubmed]
  14. Altered GABAergic neurotransmission in mice lacking dopamine D2 receptors. An, J.J., Bae, M.H., Cho, S.R., Lee, S.H., Choi, S.H., Lee, B.H., Shin, H.S., Kim, Y.N., Park, K.W., Borrelli, E., Baik, J.H. Mol. Cell. Neurosci. (2004) [Pubmed]
  15. Ovarian dependence for pituitary tumorigenesis in D2 dopamine receptor-deficient mice. Hentges, S.T., Low, M.J. Endocrinology (2002) [Pubmed]
  16. Cocaine-induced locomotor activity and cocaine discrimination in dopamine D2 receptor mutant mice. Chausmer, A.L., Elmer, G.I., Rubinstein, M., Low, M.J., Grandy, D.K., Katz, J.L. Psychopharmacology (Berl.) (2002) [Pubmed]
  17. Effects of a Drd2 deletion mutation on ethanol-induced locomotor stimulation and sensitization suggest a role for epistasis. Palmer, A.A., Low, M.J., Grandy, D.K., Phillips, T.J. Behav. Genet. (2003) [Pubmed]
  18. Dopamine D2 receptor binding, Drd2 expression and the number of dopamine neurons in the BXD recombinant inbred series: genetic relationships to alcohol and other drug associated phenotypes. Hitzemann, R., Hitzemann, B., Rivera, S., Gatley, J., Thanos, P., Shou, L.L., Williams, R.W. Alcohol. Clin. Exp. Res. (2003) [Pubmed]
  19. Differences in behavioural effects of amphetamine and dopamine-related gene expression in wild-type and homozygous CCK(2) receptor deficient mice. Rünkorg, K., Värv, S., Matsui, T., Kõks, S., Vasar, E. Neurosci. Lett. (2006) [Pubmed]
  20. Distinct roles of dopamine D2L and D2S receptor isoforms in the regulation of protein phosphorylation at presynaptic and postsynaptic sites. Lindgren, N., Usiello, A., Goiny, M., Haycock, J., Erbs, E., Greengard, P., Hokfelt, T., Borrelli, E., Fisone, G. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  21. Dopamine receptors and dopamine transporter in brain function and addictive behaviors: insights from targeted mouse mutants. Drago, J., Padungchaichot, P., Accili, D., Fuchs, S. Dev. Neurosci. (1998) [Pubmed]
  22. D1 and D2 receptor antagonist injections in the prefrontal cortex selectively impair spatial learning in mice. Rinaldi, A., Mandillo, S., Oliverio, A., Mele, A. Neuropsychopharmacology (2007) [Pubmed]
  23. Neurons exhibiting dopamine D2 receptor immunoreactivity in the substantia nigra of the mutant weaver mouse. Xu, S.G., Prasad, C., Smith, D.E. Neuroscience (1999) [Pubmed]
  24. Amphetamine discrimination: effects of dopamine receptor agonists. Nielsen, E.B., Randrup, K., Andersen, P.H. Eur. J. Pharmacol. (1989) [Pubmed]
  25. Dose-response analysis of locomotor activity and stereotypy in dopamine D3 receptor mutant mice following acute amphetamine. McNamara, R.K., Logue, A., Stanford, K., Xu, M., Zhang, J., Richtand, N.M. Synapse (2006) [Pubmed]
  26. Locomotor behavior of dopamine D1 receptor transgenic/D2 receptor deficient hybrid mice. Dracheva, S., Haroutunian, V. Brain Res. (2001) [Pubmed]
  27. Different effects of five dopamine receptor subtypes on nuclear factor-kappaB activity in NG108-15 cells and mouse brain. Takeuchi, Y., Fukunaga, K. J. Neurochem. (2004) [Pubmed]
  28. A2A receptor and striatal cellular functions: regulation of gene expression, currents, and synaptic transmission. Schiffmann, S.N., Dassesse, D., d'Alcantara, P., Ledent, C., Swillens, S., Zoli, M. Neurology (2003) [Pubmed]
  29. Dopamine control of striatal gene expression during development: relevance to knockout mice for the dopamine transporter. Fauchey, V., Jaber, M., Bloch, B., Le Moine, C. Eur. J. Neurosci. (2000) [Pubmed]
  30. Characterization of the human dopamine D3 receptor expressed in transfected cell lines. MacKenzie, R.G., VanLeeuwen, D., Pugsley, T.A., Shih, Y.H., Demattos, S., Tang, L., Todd, R.D., O'Malley, K.L. Eur. J. Pharmacol. (1994) [Pubmed]
  31. Olfactory discrimination deficits in mice lacking the dopamine transporter or the D2 dopamine receptor. Tillerson, J.L., Caudle, W.M., Parent, J.M., Gong, C., Schallert, T., Miller, G.W. Behav. Brain Res. (2006) [Pubmed]
  32. Selective increase of Nurr1 mRNA expression in mesencephalic dopaminergic neurons of D2 dopamine receptor-deficient mice. Tseng, K.Y., Roubert, C., Do, L., Rubinstein, M., Kelly, M.A., Grandy, D.K., Low, M.J., Gershanik, O.S., Murer, M.G., Giros, B., Raisman-Vozari, R. Brain Res. Mol. Brain Res. (2000) [Pubmed]
  33. GH in the dwarf dopaminergic D2 receptor knockout mouse: somatotrope population, GH release, and responsiveness to GH-releasing factors and somatostatin. Garc??a-Tornad??, I., Rubinstein, M., Gaylinn, B.D., Hill, D., Arany, E., Low, M.J., D??az-Torga, G., Becu-Villalobos, D. J. Endocrinol. (2006) [Pubmed]
  34. Lack of operant ethanol self-administration in dopamine D2 receptor knockout mice. Risinger, F.O., Freeman, P.A., Rubinstein, M., Low, M.J., Grandy, D.K. Psychopharmacology (Berl.) (2000) [Pubmed]
  35. Early expression of D3 dopamine receptors in murine embryonic development. Fishburn, C.S., Bedford, M., Lonai, P., Fuchs, S. FEBS Lett. (1996) [Pubmed]
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