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Gene Review

Drd1  -  dopamine receptor D1

Mus musculus

Synonyms: C030036C15Rik, D(1A) dopamine receptor, D1 receptor, Dopamine D1 receptor, Drd-1, ...
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Disease relevance of Drd1a

  • The primary effect of exposure to METH is elevation of the level of extracellular DA; therefore, we assessed the role of the DA D1 receptor (D1R) and neurokinin-1 receptor (NK-1R) on the expression of toxicity [1].
  • Considering the significance of the D1 dopamine receptor as a therapeutic target for Parkinson's disease, this D1 receptor over-expressing model provides an important experimental system to probe the basis for altered behavioral responses following stimulation of transgenetically up-regulated receptors [2].
  • The D1 agonist SKF83959 was identified as a specific agonist for the heteromer that activated G(q)/11 by functioning as a full agonist for the D1 receptor and a high-affinity partial agonist for a pertussis toxin-resistant D2 receptor within the complex [3].
  • The neuroleptic responsive and NNR mice have differed for at least eight generations by an order of magnitude in their sensitivity (ED50s) to catalepsy induced by neuroleptics with a high D2/D1 receptor activity profile [4].
  • The selective D-2 receptor agonists, quinpirole and LY 163502, and the mixed D-1/D-2 agonist, apomorphine, induced a dose-dependent hypothermia, whereas the selective D-1 receptor agonists, SK&F 81297, SK&F 38393 and SK&F 75670, induced hyperthermia [5].

Psychiatry related information on Drd1a


High impact information on Drd1a


Chemical compound and disease context of Drd1a


Biological context of Drd1a


Anatomical context of Drd1a


Associations of Drd1a with chemical compounds

  • 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 [28].
  • Compared to wild types, preference and consumption of ethanol were decreased in D1A2A receptor knockout mice, the reduction in ethanol consumption greater even than that seen in D1 receptor-deficient mice [29].
  • Surprisingly, D1R-deficient mice retain cocaine-conditioned place preference [22].
  • Pretreatment with the D1R antagonist SCH-23390 (0.25 mg/kg) 30 min before the first and fourth injections of METH conferred partial protection on DAT sites of the CPu [1].
  • Acute cocaine administration increases substance P levels, suggesting that striatal expression of this neuropeptide can be modulated by D1R-independent processes [22].

Physical interactions of Drd1a


Enzymatic interactions of Drd1a

  • However, the absence of normal DA tone generated significant alterations in DA D1-receptor signalling as indicated by increased mutant striatal levels of phosphorylated DARPP-32 and by an altered motor response to amphetamine [31].

Regulatory relationships of Drd1a


Other interactions of Drd1a


Analytical, diagnostic and therapeutic context of Drd1a

  • To investigate the contribution of the dopamine D1 receptor to this modulation, we have used gene targeting technology to generate D1 receptor mutant mice [11].
  • On PND, 60 male offsprings received an intraperitoneal injection of the D1 receptor agonist 2,3,4,5-tetra-hydro-7,8-diol-1-phenyl-(1H)-3-benzazepine (SKF 38393) (0, 3, and 10 mg/kg), and spontaneous behavior was assessed in an automated activity chamber for 40 min [36].
  • The importance of rebinding to receptors in influencing the kinetics of in vivo binding of PET and SPECT radiotracers was evaluated by examining the binding of a high-affinity D1 receptor radiotracer, [3H]SCH 23390, in tissue homogenates, living brain slices, and in vivo [37].
  • To examine this possibility, we have started to combine the use of D1 receptor mutant mice with cDNA microarrays to identify gene expression changes mediated through the D1 receptors induced by repeated cocaine administration [38].


  1. Antagonists of the neurokinin-1 or dopamine D1 receptors confer protection from methamphetamine on dopamine terminals of the mouse striatum. Angulo, J.A., Angulo, N., Yu, J. Ann. N. Y. Acad. Sci. (2004) [Pubmed]
  2. Locomotor behavior of dopamine D1 receptor transgenic/D2 receptor deficient hybrid mice. Dracheva, S., Haroutunian, V. Brain Res. (2001) [Pubmed]
  3. D1-D2 dopamine receptor heterooligomers with unique pharmacology are coupled to rapid activation of Gq/11 in the striatum. Rashid, A.J., So, C.H., Kong, M.M., Furtak, T., El-Ghundi, M., Cheng, R., O'dowd, B.F., George, S.R. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  4. D1 and D2 dopamine receptor distribution in the neuroleptic nonresponsive and neuroleptic responsive lines of mice, a quantitative receptor autoradiographic study. Qian, Y., Hitzemann, B., Hitzemann, R. J. Pharmacol. Exp. Ther. (1992) [Pubmed]
  5. The effects of dopamine D-1 and D-2 receptor agonists on body temperature in male mice. Sánchez, C. Eur. J. Pharmacol. (1989) [Pubmed]
  6. Dopamine D1 receptors involved in locomotor activity and accumbens neural responses to prediction of reward associated with place. Tran, A.H., Tamura, R., Uwano, T., Kobayashi, T., Katsuki, M., Ono, T. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  7. Behavioral responses to cocaine and amphetamine administration in mice lacking the dopamine D1 receptor. Xu, M., Guo, Y., Vorhees, C.V., Zhang, J. Brain Res. (2000) [Pubmed]
  8. ABT-431: the diacetyl prodrug of A-86929, a potent and selective dopamine D1 receptor agonist: in vitro characterization and effects in animal models of Parkinson's disease. Shiosaki, K., Jenner, P., Asin, K.E., Britton, D.R., Lin, C.W., Michaelides, M., Smith, L., Bianchi, B., Didomenico, S., Hodges, L., Hong, Y., Mahan, L., Mikusa, J., Miller, T., Nikkel, A., Stashko, M., Witte, D., Williams, M. J. Pharmacol. Exp. Ther. (1996) [Pubmed]
  9. Social reactivity and D1 dopamine receptors: studies in mice selectively bred for high and low levels of aggression. Lewis, M.H., Gariépy, J.L., Gendreau, P., Nichols, D.E., Mailman, R.B. Neuropsychopharmacology (1994) [Pubmed]
  10. Loss of locomotor sensitisation in response to morphine in D1 receptor deficient mice. Becker, A., Grecksch, G., Kraus, J., Peters, B., Schroeder, H., Schulz, S., Höllt, V. Naunyn Schmiedebergs Arch. Pharmacol. (2001) [Pubmed]
  11. Dopamine D1 receptor mutant mice are deficient in striatal expression of dynorphin and in dopamine-mediated behavioral responses. Xu, M., Moratalla, R., Gold, L.H., Hiroi, N., Koob, G.F., Graybiel, A.M., Tonegawa, S. Cell (1994) [Pubmed]
  12. Elimination of cocaine-induced hyperactivity and dopamine-mediated neurophysiological effects in dopamine D1 receptor mutant mice. Xu, M., Hu, X.T., Cooper, D.C., Moratalla, R., Graybiel, A.M., White, F.J., Tonegawa, S. Cell (1994) [Pubmed]
  13. New evidence for neurotransmitter influences on brain development. Levitt, P., Harvey, J.A., Friedman, E., Simansky, K., Murphy, E.H. Trends Neurosci. (1997) [Pubmed]
  14. Role of the D1A dopamine receptor in the pathogenesis of genetic hypertension. Albrecht, F.E., Drago, J., Felder, R.A., Printz, M.P., Eisner, G.M., Robillard, J.E., Sibley, D.R., Westphal, H.J., Jose, P.A. J. Clin. Invest. (1996) [Pubmed]
  15. Dopamine and acetylcholine cell density in the neuroleptic responsive (NR) and neuroleptic nonresponsive (NNR) lines of mice. Hitzemann, R., Qian, Y., Hitzemann, B. J. Pharmacol. Exp. Ther. (1993) [Pubmed]
  16. Evaluation of selective actions of dopamine D-1 and D-2 receptor agonists and antagonists on opioid antinociception. Rooney, K.F., Sewell, R.D. Eur. J. Pharmacol. (1989) [Pubmed]
  17. Potency and efficacy of dopamine agonists in mouse strains differing in dopamine cell and receptor number. Shannon, H.E., Bemis, K.G., Peters, S.C. Pharmacol. Biochem. Behav. (1991) [Pubmed]
  18. Stimulation of D1 dopamine receptors reveals direct effects of the preferential dopamine autoreceptor agonist B-HT 920 on postsynaptic dopamine receptors. Andén, N.E., Grabowska-Andén, M. Acta Physiol. Scand. (1988) [Pubmed]
  19. B-HT 920 is a full agonist at both pre- and postsynaptic D-2 dopamine receptors. Andén, N.E., Grabowska-Andén, M. J. Neural Transm. Gen. Sect. (1990) [Pubmed]
  20. Regulation of dopamine D-receptor activation in vivo by protein phosphatase 2B (calcineurin). Adlersberg, M., Hsiung, S.C., Glickstein, S.B., Liu, K.P., Tamir, H., Schmauss, C. J. Neurochem. (2004) [Pubmed]
  21. 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]
  22. 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]
  23. D1 dopamine receptor regulation of the levels of the cell-cycle-controlling proteins, cyclin D, P27 and Raf-1, in cerebral cortical precursor cells is mediated through cAMP-independent pathways. Zhang, L., Bai, J., Undie, A.S., Bergson, C., Lidow, M.S. Cereb. Cortex (2005) [Pubmed]
  24. Reversal of supersensitive striatal dopamine D1 receptor signaling and extracellular signal-regulated kinase activity in dopamine-deficient mice. Kim, D.S., Palmiter, R.D., Cummins, A., Gerfen, C.R. Neuroscience (2006) [Pubmed]
  25. C57BL/6J mice exhibit reduced dopamine D3 receptor-mediated locomotor-inhibitory function relative to DBA/2J mice. McNamara, R.K., Levant, B., Taylor, B., Ahlbrand, R., Liu, Y., Sullivan, J.R., Stanford, K., Richtand, N.M. Neuroscience (2006) [Pubmed]
  26. Receptor subtypes involved in the presynaptic and postsynaptic actions of dopamine on striatal interneurons. Centonze, D., Grande, C., Usiello, A., Gubellini, P., Erbs, E., Martin, A.B., Pisani, A., Tognazzi, N., Bernardi, G., Moratalla, R., Borrelli, E., Calabresi, P. J. Neurosci. (2003) [Pubmed]
  27. D1-like dopaminergic activation of phosphoinositide hydrolysis is independent of D1A dopamine receptors: evidence from D1A knockout mice. Friedman, E., Jin, L.Q., Cai, G.P., Hollon, T.R., Drago, J., Sibley, D.R., Wang, H.Y. Mol. Pharmacol. (1997) [Pubmed]
  28. 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]
  29. Receptor crosstalk: characterization of mice deficient in dopamine D1 and adenosine A2A receptors. Short, J.L., Ledent, C., Drago, J., Lawrence, A.J. Neuropsychopharmacology (2006) [Pubmed]
  30. Hyperdopaminergia and altered locomotor activity in GABAB1-deficient mice. Vacher, C.M., Gassmann, M., Desrayaud, S., Challet, E., Bradaia, A., Hoyer, D., Waldmeier, P., Kaupmann, K., Pévet, P., Bettler, B. J. Neurochem. (2006) [Pubmed]
  31. Altered dopaminergic innervation and amphetamine response in adult Otx2 conditional mutant mice. Borgkvist, A., Puelles, E., Carta, M., Acampora, D., Ang, S.L., Wurst, W., Goiny, M., Fisone, G., Simeone, A., Usiello, A. Mol. Cell. Neurosci. (2006) [Pubmed]
  32. A dopamine/D1 receptor/protein kinase A/dopamine- and cAMP-regulated phosphoprotein (Mr 32 kDa)/protein phosphatase-1 pathway regulates dephosphorylation of the NMDA receptor. Snyder, G.L., Fienberg, A.A., Huganir, R.L., Greengard, P. J. Neurosci. (1998) [Pubmed]
  33. Generation and pharmacological analysis of M2 and M4 muscarinic receptor knockout mice. Gomeza, J., Zhang, L., Kostenis, E., Felder, C.C., Bymaster, F.P., Brodkin, J., Shannon, H., Xia, B., Duttaroy, A., Deng, C.X., Wess, J. Life Sci. (2001) [Pubmed]
  34. TS+OCD-like neuropotentiated mice are supersensitive to seizure induction. Campbell, K.M., Veldman, M.B., McGrath, M.J., Burton, F.H. Neuroreport (2000) [Pubmed]
  35. Hyperactivity and dopamine D1 receptor activation in mice lacking girk2 channels. Blednov, Y.A., Stoffel, M., Cooper, R., Wallace, D., Mane, N., Harris, R.A. Psychopharmacology (Berl.) (2002) [Pubmed]
  36. Neurobehavioral effects of prenatal exposure to AZT: a preliminary investigation with the D1 receptor agonist SKF 38393 in mice. Venerosi, A., Valanzano, A., Puopolo, M., Calamandrei, G. Neurotoxicology and teratology. (2005) [Pubmed]
  37. Evaluation of the importance of rebinding to receptors in slowing the approach to equilibrium of high-affinity PET and SPECT radiotracers. Gifford, A.N., Gatley, S.J., Volkow, N.D. Synapse (1998) [Pubmed]
  38. Identification of chronic cocaine-induced gene expression through dopamine d1 receptors by using cDNA microarrays. Zhang, J., Zhang, D., Xu, M. Ann. N. Y. Acad. Sci. (2002) [Pubmed]
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