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Gene Review

Drd4  -  dopamine receptor D4

Mus musculus

Synonyms: AW125663, D(2C) dopamine receptor, D(4) dopamine receptor, D4R, Dopamine D4 receptor, ...
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Disease relevance of Drd4


Psychiatry related information on Drd4


High impact information on Drd4

  • Biochemical analyses revealed that dopamine synthesis and its conversion to DOPAC were elevated in the dorsal striatum from D4R-/- mice [5].
  • Although less active in open field tests, D4R-/- mice outperformed wild-type mice on the rotarod and displayed locomotor supersensitivity to ethanol, cocaine, and methamphetamine [5].
  • The modulation by D4 ligands of the dark level of light-sensitive cAMP in photoreceptors demonstrates the physiological coupling of the D4 receptor subtype [6].
  • Of the known Ptx-sensitive G-protein alpha subunits, MN9D-expressed Galphai2, GalphaoA, and GalphaoB; however, none of these coupled to the D4 receptor [7].
  • Although striatal dopamine contents and tyrosine hydroxylase-positive midbrain neurons were reduced to the same extent in both genotypes, Drd4(-/-) mice lesioned with 6-OHDA did not develop hyperactivity [3].

Chemical compound and disease context of Drd4


Biological context of Drd4


Anatomical context of Drd4


Associations of Drd4 with chemical compounds


Other interactions of Drd4

  • Immunohistochemical study and RT-PCR analysis revealed the expression of the D2 receptor in the basal epidermis and the D4 receptor in the uppermost layer of the epidermis [18].
  • The receptor's entire coding region was contained within a 6 kb EcoRI genomic fragment, indicating that the murine D4 receptor gene is significantly smaller than the corresponding D2 and D3 receptor genes, the coding regions of which each stretch over 30 kb [10].
  • To investigate whether other dopamine receptor subtypes regulate NF-kappaB, we established NG108-15 cells stably expressing D3R, D4R and D5R (NGD3R, NGD4R and NGD5R) [16].
  • A dopamine D2/D4 receptor agonist, quinpirole, reduced cAMP levels in dark-adapted normal retinas in vitro, but not in rds/rds retinas [19].
  • In vitro, L-745,870 (0.1-1 microM) exhibited D4 receptor antagonist activity, reversing dopamine (1 microM) mediated 1) inhibition of adenylate cyclase in hD4HEK and hD4CHO cells; 2) stimulation of [35S] GTPgammaS binding and 3) stimulation of extracellular acidification rate, but did not exhibit any significant intrinsic activity in these assays [20].

Analytical, diagnostic and therapeutic context of Drd4


  1. Differential expression of dopamine D2 and D4 receptor and tyrosine hydroxylase mRNA in mice prone, or resistant, to chronic high-fat diet-induced obesity. Huang, X.F., Yu, Y., Zavitsanou, K., Han, M., Storlien, L. Brain Res. Mol. Brain Res. (2005) [Pubmed]
  2. 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]
  3. The dopamine D4 receptor is essential for hyperactivity and impaired behavioral inhibition in a mouse model of attention deficit/hyperactivity disorder. Avale, M.E., Falzone, T.L., Gelman, D.M., Low, M.J., Grandy, D.K., Rubinstein, M. Mol. Psychiatry (2004) [Pubmed]
  4. Effects of L-745,870, a dopamine D4 receptor antagonist, on naloxone-induced morphine dependence in mice. Mamiya, T., Matsumura, T., Ukai, M. Ann. N. Y. Acad. Sci. (2004) [Pubmed]
  5. Mice lacking dopamine D4 receptors are supersensitive to ethanol, cocaine, and methamphetamine. Rubinstein, M., Phillips, T.J., Bunzow, J.R., Falzone, T.L., Dziewczapolski, G., Zhang, G., Fang, Y., Larson, J.L., McDougall, J.A., Chester, J.A., Saez, C., Pugsley, T.A., Gershanik, O., Low, M.J., Grandy, D.K. Cell (1997) [Pubmed]
  6. Photoreceptors of mouse retinas possess D4 receptors coupled to adenylate cyclase. Cohen, A.I., Todd, R.D., Harmon, S., O'Malley, K.L. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  7. The rat D4 dopamine receptor couples to cone transducin (Galphat2) to inhibit forskolin-stimulated cAMP accumulation. Yamaguchi, I., Harmon, S.K., Todd, R.D., O'Malley, K.L. J. Biol. Chem. (1997) [Pubmed]
  8. Cocaine-induced locomotor activity and cocaine discrimination in dopamine D4 receptor mutant mice. Katz, J.L., Chausmer, A.L., Elmer, G.I., Rubinstein, M., Low, M.J., Grandy, D.K. Psychopharmacology (Berl.) (2003) [Pubmed]
  9. Behavioral evidence for modulation by sigma ligands of (+)MK-801-induced hyperlocomotion in monoamine-depleted mice. Okuyama, S., Imagawa, Y., Tomisawa, K. Neuropharmacology (1996) [Pubmed]
  10. Molecular cloning and characterisation of the gene encoding the murine D4 dopamine receptor. Fishburn, C.S., Carmon, S., Fuchs, S. FEBS Lett. (1995) [Pubmed]
  11. Genomic structure and tissue distribution of the mouse dopamine D4 receptor. Suzuki, T., Kobayashi, K., Nagatsu, T. Neurosci. Lett. (1995) [Pubmed]
  12. Dopamine D4 receptor-induced postsynaptic inhibition of GABAergic currents in mouse globus pallidus neurons. Shin, R.M., Masuda, M., Miura, M., Sano, H., Shirasawa, T., Song, W.J., Kobayashi, K., Aosaki, T. J. Neurosci. (2003) [Pubmed]
  13. Absence of dopamine D4 receptors results in enhanced reactivity to unconditioned, but not conditioned, fear. Falzone, T.L., Gelman, D.M., Young, J.I., Grandy, D.K., Low, M.J., Rubinstein, M. Eur. J. Neurosci. (2002) [Pubmed]
  14. Enhanced expression of dopamine D(1) and glutamate NMDA receptors in dopamine D(4) receptor knockout mice. Gan, L., Falzone, T.L., Zhang, K., Rubinstein, M., Baldessarini, R.J., Tarazi, F.I. J. Mol. Neurosci. (2004) [Pubmed]
  15. Dysfunctional light-evoked regulation of cAMP in photoreceptors and abnormal retinal adaptation in mice lacking dopamine D4 receptors. Nir, I., Harrison, J.M., Haque, R., Low, M.J., Grandy, D.K., Rubinstein, M., Iuvone, P.M. J. Neurosci. (2002) [Pubmed]
  16. 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]
  17. Angiotensin-II type 1 receptor-mediated hypertension in D4 dopamine receptor-deficient mice. Bek, M.J., Wang, X., Asico, L.D., Jones, J.E., Zheng, S., Li, X., Eisner, G.M., Grandy, D.K., Carey, R.M., Soares-da-Silva, P., Jose, P.A. Hypertension (2006) [Pubmed]
  18. Dopamine D2-like receptor agonists accelerate barrier repair and inhibit the epidermal hyperplasia induced by barrier disruption. Fuziwara, S., Suzuki, A., Inoue, K., Denda, M. J. Invest. Dermatol. (2005) [Pubmed]
  19. Regulation of cAMP by light and dopamine receptors is dysfunctional in photoreceptors of dystrophic retinal degeneration slow(rds) mice. Nir, I., Haque, R., Iuvone, P.M. Exp. Eye Res. (2001) [Pubmed]
  20. Biological profile of L-745,870, a selective antagonist with high affinity for the dopamine D4 receptor. Patel, S., Freedman, S., Chapman, K.L., Emms, F., Fletcher, A.E., Knowles, M., Marwood, R., Mcallister, G., Myers, J., Curtis, N., Kulagowski, J.J., Leeson, P.D., Ridgill, M., Graham, M., Matheson, S., Rathbone, D., Watt, A.P., Bristow, L.J., Rupniak, N.M., Baskin, E., Lynch, J.J., Ragan, C.I. J. Pharmacol. Exp. Ther. (1997) [Pubmed]
  21. Development and characterization of antibodies directed against the mouse D4 dopamine receptor. Mauger, C., Sivan, B., Brockhaus, M., Fuchs, S., Civelli, O., Monsma, F. Eur. J. Neurosci. (1998) [Pubmed]
  22. In vivo evaluation of [(123)I]-3-(4-iodobenzyl)-1,2,3,4-tetrahydro-8-hydroxychromeno[3,4-c]pyridin-5-one: a presumed dopamine D4 receptor ligand for SPECT studies. Staelens, L., Oltenfreiter, R., Blanckaert, P., Kersemans, V., Vandenbulcke, K., Van De Wiele, C., Slegers, G. Nucl. Med. Biol. (2005) [Pubmed]
  23. Dopamine D4 receptor isoform mRNA and protein are expressed in the rat cortical collecting duct. Sun, D., Wilborn, T.W., Schafer, J.A. Am. J. Physiol. (1998) [Pubmed]
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