dopamine d3 receptors


Summary: A subtype of dopamine D2 receptors that are highly expressed in the LIMBIC SYSTEM of the brain.

Top Publications

  1. Searle G, Beaver J, Comley R, Bani M, Tziortzi A, Slifstein M, et al. Imaging dopamine D3 receptors in the human brain with positron emission tomography, [11C]PHNO, and a selective D3 receptor antagonist. Biol Psychiatry. 2010;68:392-9 pubmed publisher
    ..This study elucidated the pharmacologic nature of the [(11)C]-(+)-PHNO signal in healthy subjects and provided the first quantification of D(3) receptor availability with PET in the living human brain. ..
  2. Baladi M, Newman A, France C. Dopamine D3 receptors mediate the discriminative stimulus effects of quinpirole in free-feeding rats. J Pharmacol Exp Ther. 2010;332:308-15 pubmed publisher
  3. Liu X, Mao L, Zhang G, Papasian C, Fibuch E, Lan H, et al. Activity-dependent modulation of limbic dopamine D3 receptors by CaMKII. Neuron. 2009;61:425-38 pubmed publisher
    ..Our data identify CaMKIIalpha as a recruitable regulator of dopamine receptor function. By binding and phosphorylating limbic D3Rs, CaMKIIalpha modulates dopamine signaling and psychomotor function in an activity-dependent manner. ..
  4. Gasso P, Mas S, Bernardo M, Alvarez S, Parellada E, Lafuente A. A common variant in DRD3 gene is associated with risperidone-induced extrapyramidal symptoms. Pharmacogenomics J. 2009;9:404-10 pubmed publisher
    ..AP-induced EPS remains a serious public health problem. Our finding of a common SNP (rs167771) in the DRD3 gene provides a strong new candidate gene for risperidone-induced EPS...
  5. Czermak C, Wallner S, Kresse A, Schauer S, Aigner R, Hoefler G, et al. Baseline plasma epinephrine levels predict Wisconsin Card Sorting Test scores in healthy volunteers. Psychoneuroendocrinology. 2009;34:625-8 pubmed publisher
    ..45, p<0.001). Further studies should be undertaken to explore possible neurophysiological links between plasma epinephrine levels and the neurobiology underlying cognitive performance. ..
  6. Harrison S, Nobrega J. A functional role for the dopamine D3 receptor in the induction and expression of behavioural sensitization to ethanol in mice. Psychopharmacology (Berl). 2009;207:47-56 pubmed publisher
    We previously reported that mice lacking dopamine D3 receptors (D3R) were resistant to behavioural sensitization to ethanol (EtOH)...
  7. Ujike H, Katsu T, Okahisa Y, Takaki M, Kodama M, Inada T, et al. Genetic variants of D2 but not D3 or D4 dopamine receptor gene are associated with rapid onset and poor prognosis of methamphetamine psychosis. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33:625-9 pubmed publisher
    ..00037, OR=3.62, 95% CI 2.48-5.28). These findings revealed that genetic variants of DRD2, but not DRD3 or DRD4, confer individual risks for rapid onset, prolonged duration, and spontaneous relapse of methamphetamine psychosis...
  8. Paus S, Gadow F, Knapp M, Klein C, Klockgether T, Wullner U. Motor complications in patients form the German Competence Network on Parkinson's disease and the DRD3 Ser9Gly polymorphism. Mov Disord. 2009;24:1080-4 pubmed publisher
    ..Additional studies incorporating grading of motor complications, and combinations of risk genotypes, are warranted. ..
  9. Davis C, Patte K, Levitan R, Carter J, Kaplan A, Zai C, et al. A psycho-genetic study of associations between the symptoms of binge eating disorder and those of attention deficit (hyperactivity) disorder. J Psychiatr Res. 2009;43:687-96 pubmed publisher

More Information


  1. Chien E, Liu W, Zhao Q, KATRITCH V, Han G, Hanson M, et al. Structure of the human dopamine D3 receptor in complex with a D2/D3 selective antagonist. Science. 2010;330:1091-5 pubmed publisher
    ..This difference provides direction to the design of D3R-selective agents for treating drug abuse and other neuropsychiatric indications. ..
  2. Kiss B, Horvath A, Némethy Z, Schmidt E, Laszlovszky I, Bugovics G, et al. Cariprazine (RGH-188), a dopamine D(3) receptor-preferring, D(3)/D(2) dopamine receptor antagonist-partial agonist antipsychotic candidate: in vitro and neurochemical profile. J Pharmacol Exp Ther. 2010;333:328-40 pubmed publisher
  3. Besson M, Belin D, McNamara R, Theobald D, Castel A, Beckett V, et al. Dissociable control of impulsivity in rats by dopamine d2/3 receptors in the core and shell subregions of the nucleus accumbens. Neuropsychopharmacology. 2010;35:560-9 pubmed publisher
    ..Such divergent roles may have relevance for the etiology and treatment of clinical disorders of behavioral control, including attention-deficit hyperactivity disorder and drug addiction. ..
  4. Lucht M, Samochowiec A, Samochowiec J, Jasiewicz A, Grabe H, Geissler I, et al. Influence of DRD2 and ANKK1 genotypes on apomorphine-induced growth hormone (GH) response in alcohol-dependent patients. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34:45-9 pubmed publisher
    ..Small sample size in our study limits the generalizability of our results. ..
  5. Depoortere R, Bardin L, Rodrigues M, Abrial E, Aliaga M, Newman Tancredi A. Penile erection and yawning induced by dopamine D2-like receptor agonists in rats: influence of strain and contribution of dopamine D2, but not D3 and D4 receptors. Behav Pharmacol. 2009;20:303-11 pubmed publisher
    ..5 mg/kg). The present data do not support a major implication of either DA D3 or D4 receptors in the control of PE and YA in rats, but indicate a preponderant role of DA D2 receptors. ..
  6. Brown D, Mishra M, Zhang S, Biswas S, Parrington I, Antonio T, et al. Investigation of various N-heterocyclic substituted piperazine versions of 5/7-{[2-(4-aryl-piperazin-1-yl)-ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-ol: effect on affinity and selectivity for dopamine D3 receptor. Bioorg Med Chem. 2009;17:3923-33 pubmed publisher
    ..In the functional GTPgammaS binding study, one of the lead molecules, (-)-15, exhibited potent agonist activity at both D2 and D3 receptors with preferential affinity at D3. ..
  7. Kumar R, Riddle L, Griffin S, Chu W, Vangveravong S, Neisewander J, et al. Evaluation of D2 and D3 dopamine receptor selective compounds on L-dopa-dependent abnormal involuntary movements in rats. Neuropharmacology. 2009;56:956-69 pubmed publisher
  8. Chen S, Shen Y, Chen C. Effects of the DRD3 Ser9Gly polymorphism on aripiprazole efficacy in schizophrenic patients as modified by clinical factors. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33:470-4 pubmed publisher
    ..This study suggests that DRD3 Ser9Gly polymorphism may not contribute significantly to inter-individual differences in therapeutic efficacy of aripiprazole, but some clinical factors may predict treatment efficacy. ..
  9. Egerton A, Rees E, Bose S, Lappin J, Stokes P, Turkheimer F, et al. Truth, lies or self-deception? Striatal D(2/3) receptor availability predicts individual differences in social conformity. Neuroimage. 2010;53:777-81 pubmed publisher
    ..54 p=0.06) but not SDE (r=0.23, ns). Whilst these associations are modest, results suggest that striatal D(2/3) receptor availability may be particularly associated with social conformity, rather than self-deception. ..
  10. Boileau I, Guttman M, Rusjan P, Adams J, Houle S, Tong J, et al. Decreased binding of the D3 dopamine receptor-preferring ligand [11C]-(+)-PHNO in drug-naive Parkinson's disease. Brain. 2009;132:1366-75 pubmed publisher
  11. Viaro R, Marti M, Morari M. Dual motor response to l-dopa and nociceptin/orphanin FQ receptor antagonists in 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) treated mice: Paradoxical inhibition is relieved by D(2)/D(3) receptor blockade. Exp Neurol. 2010;223:473-84 pubmed publisher
    ..Finally, it confirms that NOP receptor antagonists may be proven effective in reversing parkinsonism when administered alone or in combination with dopamine agonists. ..
  12. Ghosh B, Antonio T, Reith M, Dutta A. Discovery of 4-(4-(2-((5-Hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)(propyl)amino)ethyl)piperazin-1-yl)quinolin-8-ol and its analogues as highly potent dopamine D2/D3 agonists and as iron chelator: in vivo activity indicates potential application in s. J Med Chem. 2010;53:2114-25 pubmed publisher
    ..This reports initial development of unique lead molecules that might find potential use in symptomatic and neuroprotective treatment of PD. ..
  13. Keeling B, Vilariño Güell C, Ross O, Wszolek Z, Uitti R, Farrer M. DRD3 Ser9Gly and HS1BP3 Ala265Gly are not associated with Parkinson disease. Neurosci Lett. 2009;461:74-5 pubmed publisher
    ..Statistical analysis failed to identify significant differences in the frequency of these variants between the case and control groups; therefore our results do not support a role for these DRD3 and HS1BP3 variants in PD. ..
  14. Ghosh B, Antonio T, Gopishetty B, Reith M, DUTTA A. Further delineation of hydrophobic binding sites in dopamine D(2)/D(3) receptors for N-4 substituents on the piperazine ring of the hybrid template 5/7-{[2-(4-aryl-piperazin-1-yl)-ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-ol. Bioorg Med Chem. 2010;18:5661-74 pubmed publisher
    ..5). ..
  15. van Munster B, Yazdanpanah M, Tanck M, de Rooij S, van de Giessen E, Sijbrands E, et al. Genetic polymorphisms in the DRD2, DRD3, and SLC6A3 gene in elderly patients with delirium. Am J Med Genet B Neuropsychiatr Genet. 2010;153B:38-45 pubmed publisher
    ..Although validation of these results is needed our results support a role for the dopamine transporter and dopamine receptor 2 in the pathogenesis of delirium. ..
  16. Miyamoto M, Miyamoto T, Iwanami M, Suzuki K, Hirata K. [Pathophysiology of restless legs syndrome]. Brain Nerve. 2009;61:523-32 pubmed
    ..In conclusion, disturbances in the central dopaminergic system, disturbances in iron metabolism, and genetics seem to be the primary factors in the pathophysiology of RLS. ..
  17. Bergen A, Conti D, Van Den Berg D, Lee W, Liu J, Li D, et al. Dopamine genes and nicotine dependence in treatment-seeking and community smokers. Neuropsychopharmacology. 2009;34:2252-64 pubmed publisher
    ..A community cohort of N=175 multiplex ever-smoking pedigrees (N=423 ever smokers) provided nominal evidence for association with the FTND at these top ranked SNPs, uncorrected for multiple comparisons. ..
  18. Everett P, Senogles S. D3 dopamine receptor signals to activation of phospholipase D through a complex with Rho. J Neurochem. 2010;112:963-71 pubmed publisher
    ..The data suggest that D3 receptor/RhoA association and activation is necessary for D3 receptor-mediated PLD activation. ..
  19. Kubikova L, Wada K, Jarvis E. Dopamine receptors in a songbird brain. J Comp Neurol. 2010;518:741-69 pubmed publisher
    ..Our findings are consistent with hypotheses that dopamine receptors may be involved in song development and social context-dependent behaviors...
  20. Stice E, Yokum S, Bohon C, Marti N, Smolen A. Reward circuitry responsivity to food predicts future increases in body mass: moderating effects of DRD2 and DRD4. Neuroimage. 2010;50:1618-25 pubmed publisher
  21. Silvano E, Millan M, Mannoury La Cour C, Han Y, Duan L, Griffin S, et al. The tetrahydroisoquinoline derivative SB269,652 is an allosteric antagonist at dopamine D3 and D2 receptors. Mol Pharmacol. 2010;78:925-34 pubmed publisher
    ..Finally, Schild analysis using G?(i3) assays, and studies of radioligand association and dissociation kinetics, supported allosteric actions of SB269,652 at D(3) and D(2) receptors. ..
  22. Gjedde A, Kumakura Y, Cumming P, Linnet J, Møller A. Inverted-U-shaped correlation between dopamine receptor availability in striatum and sensation seeking. Proc Natl Acad Sci U S A. 2010;107:3870-5 pubmed publisher
  23. Yakushev I, Dupont E, Buchholz H, Tillmanns J, Debus F, Cumming P, et al. In vivo imaging of dopamine receptors in a model of temporal lobe epilepsy. Epilepsia. 2010;51:415-22 pubmed publisher
  24. Clément P, Pozzato C, Heidbreder C, Alexandre L, Giuliano F, Melotto S. Delay of ejaculation induced by SB-277011, a selective dopamine D3 receptor antagonist, in the rat. J Sex Med. 2009;6:980-988 pubmed publisher
  25. la Fougere C, Popperl G, Levin J, Wängler B, Böning G, Uebleis C, et al. The value of the dopamine D2/3 receptor ligand 18F-desmethoxyfallypride for the differentiation of idiopathic and nonidiopathic parkinsonian syndromes. J Nucl Med. 2010;51:581-7 pubmed publisher
    ..The PET procedure for this differential diagnosis was superior to the reported experience with (123)I-iodobenzamide SPECT. ..
  26. Micale V, Cristino L, Tamburella A, Petrosino S, Leggio G, Drago F, et al. Altered responses of dopamine D3 receptor null mice to excitotoxic or anxiogenic stimuli: Possible involvement of the endocannabinoid and endovanilloid systems. Neurobiol Dis. 2009;36:70-80 pubmed publisher
  27. Harrison S, Nobrega J. Differential susceptibility to ethanol and amphetamine sensitization in dopamine D3 receptor-deficient mice. Psychopharmacology (Berl). 2009;204:49-59 pubmed publisher
    b>Dopamine D3 receptors (D3Rs) have been implicated in behavioral sensitization to various drugs of abuse, but their role in ethanol (EtOH) sensitization has not been directly examined...
  28. Villar V, Jones J, Armando I, Palmes Saloma C, Yu P, Pascua A, et al. G protein-coupled receptor kinase 4 (GRK4) regulates the phosphorylation and function of the dopamine D3 receptor. J Biol Chem. 2009;284:21425-34 pubmed publisher
    ..These data demonstrate that GRK4, specifically the GRK4-gamma and GRK4-alpha isoforms, phosphorylates the D(3) receptor and is crucial for its signaling in human proximal tubule cells. ..
  29. Lopez L, Selent J, Ortega R, Masaguer C, Dominguez E, Areias F, et al. Synthesis, 3D-QSAR, and structural modeling of benzolactam derivatives with binding affinity for the D(2) and D(3) receptors. ChemMedChem. 2010;5:1300-17 pubmed publisher
    ..The implications of these results for the design of more potent and selective benzolactam derivatives are presented and discussed. ..
  30. Minuzzi L, Cumming P. Agonist binding fraction of dopamine D2/3 receptors in rat brain: a quantitative autoradiographic study. Neurochem Int. 2010;56:747-52 pubmed publisher
    ..Thus [(3)H]NPA and [(3)H]raclopride binding sites have nearly identical abundances in rat dorsal striatum, but are distinct in the ventral striatum, and with respect to their displacement by LSD. ..
  31. Laymon C, Mason N, Frankle W, Carney J, Lopresti B, Litschge M, et al. Human biodistribution and dosimetry of the D2/3 agonist 11C-N-propylnorapomorphine (11C-NPA) determined from PET. J Nucl Med. 2009;50:814-7 pubmed publisher
    ..81 x 10(-2) mSv.MBq(-1). On the basis of averaged dosimetry results, an administration of less than 1,780 MBq (<48 mCi) of (11)C-NPA yields an organ dose of under 50 mSv (5 rem) to all organs. ..
  32. Maggio R, Millan M. Dopamine D2-D3 receptor heteromers: pharmacological properties and therapeutic significance. Curr Opin Pharmacol. 2010;10:100-7 pubmed publisher
    ..A hypothetical relationship of the above observations to the pathophysiology and possibly treatment of neuropsychiatric diseases is discussed. ..
  33. Mela F, Millan M, Brocco M, Morari M. The selective D(3) receptor antagonist, S33084, improves parkinsonian-like motor dysfunction but does not affect L-DOPA-induced dyskinesia in 6-hydroxydopamine hemi-lesioned rats. Neuropharmacology. 2010;58:528-36 pubmed publisher
    ..However, D(3) receptor antagonism may be associated with antiparkinsonian properties. The clinical relevance of these observations will be of interest to explore further. ..
  34. Gao X, Su L, Zhao A, Luo X, Xia K. [Association of 14 polymorphisms in the five candidate genes and attention deficit hyperactivity disorder]. Zhongguo Dang Dai Er Ke Za Zhi. 2009;11:617-22 pubmed
    ..The specific combination of three sites of SNP in SNAP-25 gene and DRDI gene is found and shows an association with ADHD in 12 polymorphisms of the five candidate genes on glutamatergic/dopaminergic pathway. ..
  35. Tuppurainen H, Kuikka J, Viinamaki H, Husso M, Tiihonen J. Dopamine D2/3 receptor binding potential and occupancy in midbrain and temporal cortex by haloperidol, olanzapine and clozapine. Psychiatry Clin Neurosci. 2009;63:529-37 pubmed publisher
  36. Asai H, Hirano M, Furiya Y, Udaka F, Morikawa M, Kanbayashi T, et al. Cerebrospinal fluid-orexin levels and sleep attacks in four patients with Parkinson's disease. Clin Neurol Neurosurg. 2009;111:341-4 pubmed publisher
    ..Despite the small number of patients studied, our results suggest that orexin transmission is most likely involved in SAs in PD and that abrogation of D3 receptor stimulation may increase orexin and thereby inhibit SAs. ..
  37. Finnema S, Halldin C, Bang Andersen B, Gulyas B, Bundgaard C, Wikström H, et al. Dopamine D(2/3) receptor occupancy of apomorphine in the nonhuman primate brain--a comparative PET study with [11C]raclopride and [11C]MNPA. Synapse. 2009;63:378-89 pubmed publisher
    ..50 mg/kg and 31 ng/ml for [11C]MNPA. The present observations do not support the existence of two affinity states in vivo. It might thus be speculated that all D(2/3) receptors are in the high affinity state at in vivo conditions...
  38. Reeves S, Brown R, Howard R, Grasby P. Increased striatal dopamine (D2/D3) receptor availability and delusions in Alzheimer disease. Neurology. 2009;72:528-34 pubmed publisher
    ..Whether this represents up-regulation of dopamine (D2) or possibly dopamine (D3) receptors and how this relates to responsivity of the striatal dopaminergic system merit further exploration. ..
  39. Yoshikawa T, Yoshida N. The possible involvement of dopamine D3 receptors in the regulation of gastric emptying in rats. Life Sci. 2010;87:638-42 pubmed publisher
    ..The results presented here suggest that peripheral dopamine D(2) receptors and, at least in part, dopamine D(3) and central dopamine D(2)/D(3) receptors play an important role in the regulation of gastric motility in rats. ..
  40. Crunelle C, Miller M, de Bruin K, van den Brink W, Booij J. Varenicline increases striatal dopamine D(2/3) receptor binding in rats. Addict Biol. 2009;14:500-2 pubmed publisher
    ..Varenicline increases dopamine D(2/3) receptor availability in drug-naïve rats. Therefore, varenicline may be an effective treatment for addictions other than smoking. ..
  41. Winner B, Desplats P, Hagl C, Klucken J, Aigner R, Ploetz S, et al. Dopamine receptor activation promotes adult neurogenesis in an acute Parkinson model. Exp Neurol. 2009;219:543-52 pubmed publisher
    ..Analyzing the neurogenic fate decisions mediated by D2/D3 signaling pathways may lead to new avenues to induce neural repair in the adult brain...
  42. Wilffert B, Al Hadithy A, Sing V, Matroos G, Hoek H, van Os J, et al. The role of dopamine D3, 5-HT2A and 5-HT2C receptor variants as pharmacogenetic determinants in tardive dyskinesia in African-Caribbean patients under chronic antipsychotic treatment: Curacao extrapyramidal syndromes study IX. J Psychopharmacol. 2009;23:652-9 pubmed publisher
  43. Yarkov A, Der T, Joyce J. Locomotor activity induced by MK-801 is enhanced in dopamine D3 receptor knockout mice but suppression by dopamine D3/D2 antagonists does not occur through the dopamine D3 receptor. Eur J Pharmacol. 2010;627:167-72 pubmed publisher
  44. Graff Guerrero A, Mamo D, Shammi C, Mizrahi R, Marcon H, Barsoum P, et al. The effect of antipsychotics on the high-affinity state of D2 and D3 receptors: a positron emission tomography study With [11C]-(+)-PHNO. Arch Gen Psychiatry. 2009;66:606-15 pubmed publisher
    ..The radiotracer [(11)C]-(+)-PHNO and the data open up new avenues for exploring the potential therapeutic significance of the D(3) receptor in schizophrenia. ..
  45. Kim S, Shin I, Kim J, Youn T, Yang S, Hwang M, et al. The 5-HT2 receptor profiles of antipsychotics in the pathogenesis of obsessive-compulsive symptoms in schizophrenia. Clin Neuropharmacol. 2009;32:224-6 pubmed publisher
    ..In conclusion, this case supports the hypothesis that the antagonist effect on 5-HT(2) receptors may be related to atypical antipsychotic-induced OCS. ..
  46. Lin C, Lee S, Chang Y, Wu J, Wu Y, Wu P, et al. Temperamentsxgenes in bipolar I and bipolar II disorder patients. Psychiatry Res. 2010;177:364-6 pubmed publisher
    ..This study provided evidence that differences existed between BP-I and BPII in gene and temperament interactions. ..
  47. Landvogt C, Buchholz H, Bernedo V, Schreckenberger M, Werhahn K. Alteration of dopamine D2/D3 receptor binding in patients with juvenile myoclonic epilepsy. Epilepsia. 2010;51:1699-706 pubmed publisher
    ..Whether these changes can be regarded as merely functional or whether they relate to the pathophysiology of juvenile myoclonic epilepsy still remains unclear. ..
  48. Guo M, Liu X, Mao L, Wang J. Regulation of dopamine D3 receptors by protein-protein interactions. Neurosci Bull. 2010;26:163-7 pubmed publisher
    Galphai/o protein-coupled dopamine D3 receptors (D3Rs) are preferentially expressed in the limbic system, including the nucleus accumbens...
  49. Lennox K, Sherman M. Efficient experimental design for binary matched pairs data. Stat Med. 2009;28:2952-66 pubmed publisher
    ..We also demonstrate our technique using the transmission/disequilibrium test (TDT) to check for linkage between schizophrenia and a locus related to the D(3) dopamine receptor, and on a hypnosis pain management data set. ..
  50. Martinez D, Orlowska D, Narendran R, Slifstein M, Liu F, Kumar D, et al. Dopamine type 2/3 receptor availability in the striatum and social status in human volunteers. Biol Psychiatry. 2010;67:275-8 pubmed publisher
    ..The results of this study support the hypothesis that social status and social support is correlated with D(2/3) receptor binding. ..
  51. Butini S, Campiani G, Franceschini S, Trotta F, Kumar V, Guarino E, et al. Discovery of bishomo(hetero)arylpiperazines as novel multifunctional ligands targeting dopamine D(3) and serotonin 5-HT(1A) and 5-HT(2A) receptors. J Med Chem. 2010;53:4803-7 pubmed publisher
  52. Kitagawa K, Kitamura Y, Miyazaki T, Miyaoka J, Kawasaki H, Asanuma M, et al. Effects of pramipexole on the duration of immobility during the forced swim test in normal and ACTH-treated rats. Naunyn Schmiedebergs Arch Pharmacol. 2009;380:59-66 pubmed publisher
    ..The immobility-decreasing effect of pramipexole may be mediated by dopamine D2 and D3 receptors. ..
  53. Holmes I, Blunt R, Lorthioir O, Blowers S, Gribble A, Payne A, et al. The identification of a selective dopamine D2 partial agonist, D3 antagonist displaying high levels of brain exposure. Bioorg Med Chem Lett. 2010;20:2013-6 pubmed publisher