Skip to main content
SpringerLink
Log in

The Role of Dopamine D3 Receptors in Antipsychotic Activity and Cognitive Functions

  • Chapter
  • First Online:
Novel Antischizophrenia Treatments

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 213))

Abstract

Dopamine D3 receptors have a pre- and postsynaptic localization in brain stem nuclei, limbic parts of the striatum, and cortex. Their widespread influence on dopamine release, on dopaminergic function, and on several other neurotransmitters makes them attractive targets for therapeutic intervention. The signaling pathways of D3 receptors are distinct from those of other members of the D2-like receptor family. There is increasing evidence that D3 receptors can form heteromers with dopamine D1, D2, and probably other G-protein-coupled receptors. The functional consequences remain to be characterized in more detail but might open new interesting pharmacological insight and opportunities. In terms of behavioral function, D3 receptors are involved in cognitive, social, and motor functions, as well as in filtering and sensitization processes. Although the role of D3 receptor blockade for alleviating positive symptoms is still unsettled, selective D3 receptor antagonism has therapeutic features for schizophrenia and beyond as demonstrated by several animal models: improved cognitive function, emotional processing, executive function, flexibility, and social behavior. D3 receptor antagonism seems to contribute to atypicality of clinically used antipsychotics by reducing extrapyramidal motor symptoms; has no direct influence on prolactin release; and does not cause anhedonia, weight gain, or metabolic dysfunctions. Unfortunately, clinical data with new, selective D3 antagonists are still incomplete; their cognitive effects have only been communicated in part. In vitro, virtually all clinically used antipsychotics are not D2-selective but also have affinity for D3 receptors. The exact D3 receptor occupancies achieved in patients, particularly in cortical areas, are largely unknown, mainly because only nonselective or agonist PET tracers are currently available. It is unlikely that a degree of D3 receptor antagonism optimal for antipsychotic and cognitive function can be achieved with existing antipsychotics. Therefore, selective D3 antagonism represents a promising mechanism still to be fully exploited for the treatment of schizophrenia, cognitive deficits in schizophrenia, and comorbid conditions such as substance abuse.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 349.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 449.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 449.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abbas AI, Hedlund PB, Huang XP, Tran TB, Meltzer HY, Roth BL (2009) Amisulpride is a potent 5-HT7 antagonist: relevance for antidepressant actions in vivo. Psychopharmacology (Berl) 205:119–128

    Article  CAS  Google Scholar 

  • Accili D, Fishburn CS, Drago J, Steiner H, Lachowicz JE, Park BH, Gauda EB, Lee EJ, Cool MH, Sibley DR, Gerfen CR, Westphal H, Fuchs S (1996) A targeted mutation of the D3 dopamine receptor gene is associated with hyperactivity in mice. Proc Natl Acad Sci U S A 93:1945–1949

    Article  PubMed  CAS  Google Scholar 

  • Ahlenius S, Salmi P (1994) Behavioral and biochemical effects of the dopamine D3 receptor-selective ligand, 7-OH-DPAT, in the normal and the reserpine-treated rat. Eur J Pharmacol 260:177–181

    Article  PubMed  CAS  Google Scholar 

  • Ahlgren-Beckendorf JA, Levant B (2004) Signaling mechanisms of the D3 dopamine receptor. J Recept Signal Transduct Res 24:117–130

    Article  PubMed  CAS  Google Scholar 

  • Amenta F, Barili P, Bronzetti E, Felici L, Mignini F, Ricci A (2000) Localization of dopamine receptor subtypes in systemic arteries. Clin Exp Hypertens 22:277–288

    Article  PubMed  CAS  Google Scholar 

  • Aretha CW, Galloway MP (1996) Dopamine autoreceptor reserve in vitro: possible role of dopamine D3 receptors. Eur J Pharmacol 305:119–122

    Article  PubMed  CAS  Google Scholar 

  • Arranz MJ, Rivera M, Munro JC (2011) Pharmacogenetics of response to antipsychotics in patients with schizophrenia. CNS Drugs 25:933–969

    Article  PubMed  CAS  Google Scholar 

  • Ashby CR, Minabe Y, Stemp G, Hagan JJ, Middlemiss DN (2000) Acute and chronic administration of the selective D3 receptor antagonist SB-277011-A alters activity of midbrain dopamine neurons in rats: an in vivo electrophysiological study. J Pharmacol Exp Ther 294:1166–1174

    PubMed  CAS  Google Scholar 

  • Ashby FG, Turner BO, Horvitz JC (2010) Cortical and basal ganglia contributions to habit learning and automaticity. Trends Cogn Sci 14:208–215

    Article  PubMed  Google Scholar 

  • Audinot V, Newman-Tancredi A, Gobert A, Rivet JM, Brocco M, Lejeune F, Gluck L, Desposte I, Bervoets K, Dekeyne A, Millan MJ (1998) A comparative in vitro and in vivo pharmacological characterization of the novel dopamine D3 receptor antagonists (+)-S 14297, nafadotride, GR 103,691 and U 99194. J Pharmacol Exp Ther 287:187–197

    PubMed  CAS  Google Scholar 

  • Bakker PR, van Harten PN, van Os J (2006) Antipsychotic-induced tardive dyskinesia and the Ser9Gly polymorphism in the DRD3 gene: a meta analysis. Schizophr Res 83:185–192

    Article  PubMed  Google Scholar 

  • Ballard ME, Basso AM, Gallagher KB, Browman KE, Fox GB, Drescher KU, Gross G, Decker MW, Rueter LE, Zhang M (2007) The drug-induced helplessness test: an animal assay for assessing behavioral despair in response to neuroleptic treatment. Psychopharmacology (Berl) 190:1–11

    Article  CAS  Google Scholar 

  • Banasikowski TJ, Bespalov A, Drescher K, Behl B, Unger L, Haupt A, Schoemaker H, Sullivan JP, Gross G, Beninger RJ (2010) Double dissociation of the effects of haloperidol and the dopamine D3 receptor antagonist ABT-127 on acquisition vs. expression of cocaine-conditioned activity in rats. J Pharmacol Exp Ther 335:506–515

    Article  PubMed  CAS  Google Scholar 

  • Barik S, de Beaurepaire R (2005) Dopamine D3 modulation of locomotor activity and sleep in the nucleus accumbens and in lobules 9 and 10 of the cerebellum in the rat. Prog Neuropsychopharmacol Biol Psychiatry 29:718–726

    Article  PubMed  CAS  Google Scholar 

  • Beaulieu JM, Gainetdinov RR (2011) The physiology, signaling, and pharmacology of dopamine receptors. Pharmacol Rev 63:182–217

    Article  PubMed  CAS  Google Scholar 

  • Beaulieu JM, Sotnikova TD, Marion S, Lefkowitz RJ, Gainetdinov RR, Caron MG (2005) An Akt/beta-arrestin 2/PP2A signaling complex mediates dopaminergic neurotransmission and behavior. Cell 122:261–273

    Article  PubMed  CAS  Google Scholar 

  • Beaulieu JM, Tirotta E, Sotnikova TD, Masri B, Salahpour A, Gainetdinov RR, Borrelli E, Caron MG (2007) Regulation of Akt signaling by D2 and D3 dopamine receptors in vivo. J Neurosci 27:881–885

    Article  PubMed  CAS  Google Scholar 

  • Beninger RJ, Banasikowski TJ (2008) Dopaminergic mechanism of reward-related incentive learning: focus on the dopamine D3 receptor. Neurotox Res 14:57–70

    Article  PubMed  CAS  Google Scholar 

  • Ben-Jonathan N, Hnasko R (2001) Dopamine as a prolactin (PRL) inhibitor. Endocr Rev 22:724–763

    Article  PubMed  CAS  Google Scholar 

  • Bennett JP Jr, Piercey MF (1999) Pramipexole—a new dopamine agonist for the treatment of Parkinson’s disease. J Neurol Sci 163:25–31

    Article  PubMed  CAS  Google Scholar 

  • Beom S, Cheong D, Torres G, Caron MG, Kim KM (2004) Comparative studies of molecular mechanisms of dopamine D2 and D3 receptors for the activation of extracellular signal-regulated kinase. J Biol Chem 279:28304–28314

    Article  PubMed  CAS  Google Scholar 

  • Bespalov A, Jongen-Rêlo AL, van Gaalen M, Harich S, Schoemaker H, Gross G (2007) Habituation deficits induced by metabotropic glutamate receptors 2/3 receptor blockade in mice: reversal by antipsychotic drugs. J Pharmacol Exp Ther 320:944–950

    Article  PubMed  CAS  Google Scholar 

  • Bettinetti L, Schlotter K, Hubner H, Gmeiner P (2002) Interactive SAR studies: rational discovery of super-potent and highly selective dopamine D3 receptor antagonists and partial agonists. J Med Chem 45:4594–4597

    Article  PubMed  CAS  Google Scholar 

  • Bhathena A, Wang Y, Kraft JB, Idler KB, Abel SJ, Holley-Shanks RB, Robieson WZ, Spear BB, Redden L, Katz D (2011) Association between dopamine D3 receptor genotype and response to dopamine D3 receptor antagonist in schizophrenic subjects. Clin Pharmacol Ther 89(Supplement 1):S76

    Google Scholar 

  • Bodei S, Arrighi N, Spano P, Sigala S (2009) Should we be cautious on the use of commercially available antibodies to dopamine receptors? Naunyn-Schmiedeberg’s Arch Pharmacol 379:413–415

    Article  PubMed  CAS  Google Scholar 

  • Bordet R, Ridray S, Carboni S, Diaz J, Sokoloff P, Schwartz JC (1997) Induction of dopamine D3 receptor expression as a mechanism of behavioral sensitization to levodopa. Proc Natl Acad Sci U S A 94:3363–3367

    Article  PubMed  CAS  Google Scholar 

  • Bordet R, Ridray S, Schwartz JC, Sokoloff P (2000) Involvement of the direct striatonigral pathway in levodopa-induced sensitization in 6-hydroxydopamine-lesioned rats. Eur J Neurosci 12:2117–2123

    Article  PubMed  CAS  Google Scholar 

  • Boulay D, Depoortere R, Perrault G, Borrelli E, Sanger DJ (1999) Dopamine D2 receptor knock-out mice are insensitive to the hypolocomotor and hypothermic effects of dopamine D2/D3 receptor agonists. Neuropharmacology 38:1389–1396

    Article  PubMed  CAS  Google Scholar 

  • Boulay D, Depoortere R, Oblin A, Sanger DJ, Schoemaker H, Perrault G (2000) Haloperidol-induced catalepsy is absent in dopamine D(2), but maintained in dopamine D(3) receptor knock-out mice. Eur J Pharmacol 391:63–73

    Article  PubMed  CAS  Google Scholar 

  • Bouthenet ML, Souil E, Martres MP, Sokoloff P, Giros B, Schwartz JC (1991) Localization of dopamine D3 receptor mRNA in the rat brain using in situ hybridization histochemistry: comparison with dopamine D2 receptor mRNA. Brain Res 564:203–219

    Article  PubMed  CAS  Google Scholar 

  • Bowery BJ, Razzaque Z, Emms F, Patel S, Freedman S, Bristow L, Kulagowski J, Seabrook GR (1996) Antagonism of the effects of (+)-PD 128907 on midbrain dopamine neurones in rat brain slices by a selective D2 receptor antagonist L-741,626. Br J Pharmacol 119:1491–1497

    Article  PubMed  CAS  Google Scholar 

  • Bristow LJ, Cook GP, Gay JC, Kulagowski JJ, Landon L, Murray F, Saywell KL, Young L, Hutson PH (1996) The behavioural and neurochemical profile of the putative dopamine D3 receptor agonist, (+)-PD 128907, in the rat. Neuropharmacology 35:285–294

    Article  PubMed  CAS  Google Scholar 

  • Bromberg-Martin ES, Matsumoto M, Hikosaka O (2010) Dopamine in motivational control: rewarding, aversive, and alerting. Neuron 68:815–834

    Article  PubMed  CAS  Google Scholar 

  • Bushe C, Shaw M (2007) Prevalence of hyperprolactinaemia in a naturalistic cohort of schizophrenia and bipolar outpatients during treatment with typical and atypical antipsychotics. J Psychopharmacol 21:768–773

    Article  PubMed  CAS  Google Scholar 

  • Carlsson J, Coleman RG, Setola V, Irwin JJ, Fan H, Schlessinger A, Sali A, Roth BL, Shoichet BK (2011) Ligand discovery from a dopamine D3 receptor homology model and crystal structure. Nat Chem Biol 7:769–778

    Article  PubMed  CAS  Google Scholar 

  • Carpenter WT, Koenig JI (2008) The evolution of drug development in schizophrenia: past issues and future opportunities. Neuropsychopharmacology 33:2061–2079

    Article  PubMed  CAS  Google Scholar 

  • Carter CS, Barch CDM (2007) Cognitive neuroscience-based approaches to measuring and improving treatment on cognition in schizophrenia: the CNTRICS initiative. Schizophr Bull 33:1131–1137

    Article  PubMed  Google Scholar 

  • Chen PC, Lao CL, Chen JC (2009) The D(3) dopamine receptor inhibits dopamine release in PC-12/hD3 cells by autoreceptor signaling via PP-2B, CK1, and Cdk-5. J Neurochem 110:1180–1190

    Article  PubMed  CAS  Google Scholar 

  • Chien EY, Liu W, Zhao Q, Katritch V, Han GW, Hanson MA, Shi L, Newman AH, Javitch JA, Cherezov V, Stevens RC (2010) Structure of the human dopamine D3 receptor in complex with a D2/D3 selective antagonist. Science 330:1091–1095

    Article  PubMed  CAS  Google Scholar 

  • Chio CL, Lajiness ME, Huff RM (1994) Activation of heterologously expressed D3 dopamine receptors: comparison with D2 dopamine receptors. Mol Pharmacol 45:51–60

    PubMed  CAS  Google Scholar 

  • Cho DI, Zheng M, Kim KM (2010) Current perspectives on the selective regulation of dopamine D2 and D3 receptors. Arch Pharm Res 33:1521–1538

    Article  PubMed  CAS  Google Scholar 

  • Choi JK, Mandeville JB, Chen YI, Grundt P, Sarkar SK, Newman AH, Jenkins BG (2010) Imaging brain regional and cortical laminar effects of selective D3 agonists and antagonists. Psychopharmacology (Berl) 212:59–72

    Article  CAS  Google Scholar 

  • Chourbaji S, Brandwein C, Vogt MA, Dormann C, Mueller R, Drescher KU, Gross G, Gass P (2008) Dopamine receptor 3 (D3) knockout mice show regular emotional behaviour. Pharmacol Res 58:302–307

    Article  PubMed  CAS  Google Scholar 

  • Collip D, Myin-Germeys I, van Os J (2008) Does the concept of “sensitization” provide a plausible mechanism for the putative link between the environment and schizophrenia? Schizophr Bull 34:220–225

    Article  PubMed  Google Scholar 

  • Collo G, Bono F, Cavalleri L, Plebani L, Merlo PE, Millan MJ, Spano PF, Missale C (2012) Pre-synaptic dopamine D(3) receptor mediates cocaine-induced structural plasticity in mesencephalic dopaminergic neurons via ERK and Akt pathways. J Neurochem 120:765–778

    Article  PubMed  CAS  Google Scholar 

  • Cools R, Brouwer WH, de Jong R, Slooff C (2000) Flexibility, inhibition, and planning: frontal dysfunctioning in schizophrenia. Brain Cogn 43:108–112

    PubMed  CAS  Google Scholar 

  • Crider A (1997) Perseveration in schizophrenia. Schizophr Bull 23:63–74

    Article  PubMed  CAS  Google Scholar 

  • Crocq M, Mant R, Asherson P, Williams J, Hode Y, Mayerova A, Collier D, Lannfelt L, Sokoloff P, Schwartz JC (1992) Association between schizophrenia and homozygosity at the dopamine D3 receptor gene. J Med Genet 29:858–860

    Article  PubMed  CAS  Google Scholar 

  • Daly SA, Waddington JL (1993) Behavioural effects of the putative D3 dopamine receptor agonist 7-OH-DPAT in relation to other “D-2-like” agonists. Neuropharmacology 32:509–510

    Article  PubMed  CAS  Google Scholar 

  • Davila V, Yan Z, Craciun LC, Logothetis D, Sulzer D (2003) D3 dopamine autoreceptors do not activate G-protein-gated inwardly rectifying potassium channel currents in substantia nigra dopamine neurons. J Neurosci 23:5693–5697

    PubMed  CAS  Google Scholar 

  • Davis KL, Kahn RS, Ko G, Davidson M (1991) Dopamine in schizophrenia: a review and reconceptualization. Am J Psychiatry 148:1474–1486

    PubMed  CAS  Google Scholar 

  • Depoortere R, Perrault G, Sanger DJ (1996) Behavioural effects in the rat of the putative dopamine D3 receptor agonist 7-OH-DPAT: comparison with quinpirole and apomorphine. Psychopharmacology (Berl) 124:231–240

    Article  CAS  Google Scholar 

  • DeWire SM, Ahn S, Lefkowitz RJ, Shenoy SK (2007) Beta-arrestins and cell signaling. Annu Rev Physiol 69:483–510

    Article  PubMed  CAS  Google Scholar 

  • Diaz J, Levesque D, Lammers CH, Griffon N, Martres MP, Schwartz JC, Sokoloff P (1995) Phenotypical characterization of neurons expressing the dopamine D3 receptor in the rat brain. Neuroscience 65:731–745

    Article  PubMed  CAS  Google Scholar 

  • Diaz J, Pilon C, Le FB, Gros C, Triller A, Schwartz JC, Sokoloff P (2000) Dopamine D3 receptors expressed by all mesencephalic dopamine neurons. J Neurosci 20:8677–8684

    Google Scholar 

  • Drescher KU, Garcia-Ladona FJ, Teschendorf HJ, Traut M, Unger L, Wicke K, Weddige FK, Freeman AS, Gross G (2002) In vivo effects of the selective dopamine D3 receptor antagonist A-437203. Soc Neurosci, Abstr 894.6. Online

    Google Scholar 

  • Drescher KU, Behl B, Freeman AS, Hamilton ME, Wicke KM, Unger LV, Haupt A, Gross G, Schoemaker H, Sullivan JP (2005) ABT-127, a new selective dopamine D3 receptor antagonist: Neurochemical and electrophysiological studies in vivo. Soc Neurosci, Abstr 913.19. Online

    Google Scholar 

  • Durham RA, Eaton MJ, Moore KE, Lookingland KJ (1997) Effects of selective activation of dopamine D2 and D3 receptors on prolactin secretion and the activity of tuberoinfundibular dopamine neurons. Eur J Pharmacol 335:37–42

    Article  PubMed  CAS  Google Scholar 

  • Elmhurst JL, Xie Z, O’Dowd BF, George SR (2000) The splice variant D3nf reduces ligand binding to the D3 dopamine receptor: evidence for heterooligomerization. Brain Res Mol Brain Res 80:63–74

    Article  PubMed  CAS  Google Scholar 

  • Englisch S, Enning F, Grosshans M, Marquardt L, Waltereit R, Zink M (2010) Quetiapine combined with amisulpride in schizophrenic patients with insufficient responses to quetiapine monotherapy. Clin Neuropharmacol 33:227–229

    Article  PubMed  CAS  Google Scholar 

  • Everett PB, Senogles SE (2004) D3 dopamine receptor activates phospholipase D through a pertussis toxin-insensitive pathway. Neurosci Lett 371:34–39

    Article  PubMed  CAS  Google Scholar 

  • Everett PB, Senogles SE (2010) D3 dopamine receptor signals to activation of phospholipase D through a complex with Rho. J Neurochem 112:963–971

    Article  PubMed  CAS  Google Scholar 

  • Feuerstein TJ (2008) Presynaptic receptors for dopamine, histamine, and serotonin. In: Südhof TC, Starke K (eds.), Pharmacology of Neurotransmitter Release. Handbook of Experimental Pharamacology. Springer, Heidelberg 184:289–338

    Google Scholar 

  • Fiorentini C, Busi C, Gorruso E, Gotti C, Spano P, Missale C (2008) Reciprocal regulation of dopamine D1 and D3 receptor function and trafficking by heterodimerization. Mol Pharmacol 74:59–69

    Article  PubMed  CAS  Google Scholar 

  • Fiorentini C, Busi C, Spano P, Missale C (2010) Dimerization of dopamine D1 and D3 receptors in the regulation of striatal function. Curr Opin Pharmacol 10:87–92

    Article  PubMed  CAS  Google Scholar 

  • Fujisawa S, Buzsáki G (2011) A 4 Hz oscillation adaptively synchronizes prefrontal, VTA, and hippocampal activities. Neuron 72:153–165

    Article  PubMed  CAS  Google Scholar 

  • Gallezot JD, Beaver JD, Gunn RN, Nabulsi N, Weinzimmer D, Singhal T, Slifstein M, Fowles K, Ding YS, Huang Y, Laruelle M, Carson RE, Rabiner EA (2012) Affinity and selectivity of [11C]-(+)-PHNO for the D3 and D2receptors in the rhesus monkey brain in vivo. Synapse 66(6):489–500

    Article  PubMed  CAS  Google Scholar 

  • Gendreau PL, Petitto JM, Schnauss R, Frantz KJ, Van HC, Gariepy JL, Lewis MH (1997) Effects of the putative dopamine D3 receptor antagonist PNU 99194A on motor behavior and emotional reactivity in C57BL/6 J mice. Eur J Pharmacol 337:147–155

    Article  PubMed  CAS  Google Scholar 

  • Gendreau PL, Petitto JM, Petrova A, Gariepy J, Lewis MH (2000) D3 and D2 dopamine receptor agonists differentially modulate isolation-induced social-emotional reactivity in mice. Behav Brain Res 114:107–117

    Article  PubMed  CAS  Google Scholar 

  • Geneste H, Amberg W, Backfisch G, Beyerbach A, Braje WM, Delzer J, Haupt A, Hutchins CW, King LL, Sauer DR, Unger L, Wernet W (2006) Synthesis and SAR of highly potent and selective dopamine D3 receptor antagonists: variations on the 1H-pyrimidin-2-one theme. Bioorg Med Chem Lett 16:1934–1937

    Article  PubMed  CAS  Google Scholar 

  • Geyer MA (2006) The family of sensorimotor gating disorders: comorbidities or diagnostic overlaps? Neurotox Res 10:211–220

    Article  PubMed  CAS  Google Scholar 

  • Geyer MA, Krebs-Thomson K, Braff DL, Swerdlow NR (2001) Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review. Psychopharmacology (Berl) 156:117–154

    Article  CAS  Google Scholar 

  • Girgis RR, Xu X, Miyake N, Easwaramoorthy B, Gunn RN, Rabiner EA, Abi-Dargham A, Slifstein M (2011) In vivo binding of antipsychotics to D3 and D2 receptors: a PET study in baboons with [(11)C]-(+)-PHNO. Neuropsychopharmacology 36:887–895

    Article  PubMed  CAS  Google Scholar 

  • Glickstein SB, Hof PR, Schmauss C (2002) Mice lacking dopamine D2 and D3 receptors have spatial working memory deficits. J Neurosci 22:5619–5629

    PubMed  CAS  Google Scholar 

  • Glickstein SB, Desteno DA, Hof PR, Schmauss C (2005) Mice lacking dopamine D2 and D3 receptors exhibit differential activation of prefrontal cortical neurons during tasks requiring attention. Cereb Cortex 15:1016–1024

    Article  PubMed  Google Scholar 

  • Gobert A, Rivet JM, Audinot V, Cistarelli L, Spedding M, Vian J, Peglion JL, Millan MJ (1995) Functional correlates of dopamine D3 receptor activation in the rat in vivo and their modulation by the selective antagonist, (+)-S 14297: II. Both D2 and “silent” D3 autoreceptors control synthesis and release in mesolimbic, mesocortical and nigrostriatal pathways. J Pharmacol Exp Ther 275:899–913

    PubMed  CAS  Google Scholar 

  • Gobert A, Lejeune F, Rivet JM, Cistarelli L, Millan MJ (1996) Dopamine D3 (auto) receptors inhibit dopamine release in the frontal cortex of freely moving rats in vivo. J Neurochem 66:2209–2212

    Article  PubMed  CAS  Google Scholar 

  • Grace AA, Bunney BS, Moore H, Todd CL (1997) Dopamine-cell depolarization block as a model for the therapeutic actions of antipsychotic drugs. Trends Neurosci 20:31–37

    Article  PubMed  CAS  Google Scholar 

  • Graff-Guerrero A, Willeit M, Ginovart N, Mamo D, Mizrahi R, Rusjan P, Vitcu I, Seeman P, Wilson A, Kapur S (2008) Brain region binding of the D2/3 agonist [11C]-(+)-PHNO and the D2/3 antagonist [11 C]raclopride in healthy humans. Hum Brain Mapp 29:400–410

    Article  PubMed  Google Scholar 

  • Graff-Guerrero A, Mamo D, Shammi CM, Mizrahi R, Marcon H, Barsoum P, Rusjan P, Houle S, Wilson AA, Kapur S (2009a) 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 66:606–615

    Article  PubMed  CAS  Google Scholar 

  • Graff-Guerrero A, Mizrahi R, Agid O, Marcon H, Barsoum P, Rusjan P, Wilson AA, Zipursky R, Kapur S (2009b) The dopamine D2 receptors in high-affinity state and D3 receptors in schizophrenia: a clinical [11C]-(+)-PHNO PET study. Neuropsychopharmacology 34: 1078–1086

    Article  PubMed  CAS  Google Scholar 

  • Graff-Guerrero A, Redden L, Abi-Saab W, Katz DA, Houle S, Barsoum P, Bhathena A, Palaparthy R, Saltarelli MD, Kapur S (2010) Blockade of [11 C](+)-PHNO binding in human subjects by the dopamine D3 receptor antagonist ABT-925. Int J Neuropsychopharmacol 13:273–287

    Article  PubMed  CAS  Google Scholar 

  • Griffon N, Pilon C, Sautel F, Schwartz JC, Sokoloff P (1997) Two intracellular signaling pathways for the dopamine D3 receptor: opposite and synergistic interactions with cyclic AMP. J Neurochem 68:1–9

    Article  PubMed  CAS  Google Scholar 

  • Gross G, Bialojan S, Drescher K, Freeman AS, Garcia-Ladona FJ, Höger T, Lansky A, Needham P, Teschendorf HJ, Traut M, Sokoloff P, Unger L, Wicke K (1997) Evaluation of D3 receptor antagonists. Eur Neuropsychopharmacol 7(Suppl 2):S120

    Article  Google Scholar 

  • Gross G, Bialojan S, Drescher K, Freeman AS, Garcia-Ladona FJ, Höger T, Needham P, Teschendorf HJ, Treiber HJ, Traut M, Sokoloff P, Starck D, Unger L, Wicke K (1998) Pharmacological characterisation of novel D3 receptor antagonists. Naunyn-Schmiedeberg’s Arch Pharmacol 358:R375

    Google Scholar 

  • Gross G, Drescher KU, Haupt A, Teschendorf HJ, Jongen-Rêlo AL, Wicke KM, Zhang M, Browman KE, Ballard ME, Rueter LE, Decker MW, Schoemaker H, Sullivan JP (2005) ABT-127, a new selective dopamine D3 receptor antagonist: behavioral pharmacology studies. Soc Neurosci, Abstr 913.20. Online

    Google Scholar 

  • Gross G, Drescher K, Bespalov A (2008) Dopamine D3 vs D2 receptor antagonism: from transgenic models to therapeutic options. Eur Neuropsychopharmacol 18:S186–S.27.03

    Article  Google Scholar 

  • Gross ML, Koch A, Mühlbauer B, Adamczak M, Ziebart H, Drescher K, Gross G, Berger I, Amann KU, Ritz E (2006) Renoprotective effect of a dopamine D3 receptor antagonist in experimental type II diabetes. Lab Invest 86:262–274

    Article  PubMed  CAS  Google Scholar 

  • Gründer G (2010) Cariprazine, an orally active D2/D3 receptor antagonist, for the potential treatment of schizophrenia, bipolar mania and depression. Curr Opin Investig Drugs 11:823–832

    PubMed  Google Scholar 

  • Gründer G, Benkert O (2002) Prolactin secretion is not a core dimension of “atypicality”. Psychopharmacology (Berl) 162:93

    Article  CAS  Google Scholar 

  • Gründer G, Wetzel H, Schlosser R, Anghelescu I, Hillert A, Lange K, Hiemke C, Benkert O (1999) Neuroendocrine response to antipsychotics: effects of drug type and gender. Biol Psychiatry 45:89–97

    Article  PubMed  Google Scholar 

  • Gründer G, Landvogt C, Vernaleken I, Buchholz HG, Ondracek J, Siessmeier T, Hartter S, Schreckenberger M, Stoeter P, Hiemke C, Rosch F, Wong DF, Bartenstein P (2006) The striatal and extrastriatal D2/D3 receptor-binding profile of clozapine in patients with schizophrenia. Neuropsychopharmacology 31:1027–1035

    Article  PubMed  CAS  Google Scholar 

  • Guillin O, Diaz J, Carroll P, Griffon N, Schwartz JC, Sokoloff P (2001) BDNF controls dopamine D3 receptor expression and triggers behavioural sensitization. Nature 411:86–89

    Article  PubMed  CAS  Google Scholar 

  • Gurevich EV, Joyce JN (1999) Distribution of dopamine D3 receptor expressing neurons in the human forebrain: comparison with D2 receptor expressing neurons. Neuropsychopharmacology 20:60–80

    Article  PubMed  CAS  Google Scholar 

  • Gyertyan I, Saghy K (2007) The selective dopamine D3 receptor antagonists, SB 277011-A and S 33084 block haloperidol-induced catalepsy in rats. Eur J Pharmacol 572:171–174

    Article  PubMed  CAS  Google Scholar 

  • Gyertyan I, Saghy K, Laszy J, Elekes O, Kedves R, Gemesi LI, Pasztor G, Zajer-Balazs M, Kapas M, Agai CE, Domany G, Kiss B, Szombathelyi Z (2008) Subnanomolar dopamine D3 receptor antagonism coupled to moderate D2 affinity results in favourable antipsychotic-like activity in rodent models: II. behavioural characterisation of RG-15. Naunyn-Schmiedeberg’s Arch Pharmacol 378:529–539

    Article  PubMed  CAS  Google Scholar 

  • Hall HÇ, Halldin C, Dijkstra D, Wikström HÇ, Wise LD, Pugsley TA, Sokoloff P, Pauli S, Farde L, Sedvall GÇ (1996) Autoradiographic localisation of D3-dopamine receptors in the human brain using the selective D3-dopamine receptor agonist (+)-[3 H]PD 128907. Psychopharmacology (Berl) 128:240–247

    Article  CAS  Google Scholar 

  • Harrison SJ, Nobrega JN (2009) A functional role for the dopamine D3 receptor in the induction and expression of behavioural sensitization to ethanol in mice. Psychopharmacology (Berl) 207:47–56

    Article  CAS  Google Scholar 

  • Hedlund PB (2009) The 5-HT7 receptor and disorders of the nervous system: an overview. Psychopharmacology (Berl) 206:345–354

    Article  CAS  Google Scholar 

  • Heidbreder CA, Gardner EL, Xi ZX, Thanos PK, Mugnaini M, Hagan JJ, Ashby CR Jr (2005) The role of central dopamine D3 receptors in drug addiction: a review of pharmacological evidence. Brain Res Brain Res Rev 49:77–105

    Article  PubMed  CAS  Google Scholar 

  • Hellstrand M, Danielsen EA, Steen VM, Ekman A, Eriksson E, Nilsson CL (2004) The ser9gly SNP in the dopamine D3 receptor causes a shift from cAMP related to PGE2 related signal transduction mechanisms in transfected CHO cells. J Med Genet 41:867–871

    Article  PubMed  CAS  Google Scholar 

  • Humphries MD, Prescott TJ (2010) The ventral basal ganglia, a selection mechanism at the crossroads of space, strategy, and reward. Prog Neurobiol 90:385–417

    Article  PubMed  Google Scholar 

  • Hunter RG, Jones D, Vicentic A, Hue G, Rye D, Kuhar MJ (2006) Regulation of CART mRNA in the rat nucleus accumbens via D3 dopamine receptors. Neuropharmacology 50:858–864

    Article  PubMed  CAS  Google Scholar 

  • Jackisch R, Zumstein A, Hertting G, Starke K (1980) Interneurones are probably not involved in the presynaptic dopaminergic control of dopamine release in rabbit caudate nucleus. Naunyn-Schmiedeberg’s Arch Pharmacol 314:129–133

    Article  PubMed  CAS  Google Scholar 

  • Jeanneteau F, Funalot B, Jankovic J, Deng H, Lagarde JP, Lucotte G, Sokoloff P (2006) A functional variant of the dopamine D3 receptor is associated with risk and age-at-onset of essential tremor. Proc Natl Acad Sci U S A 103:10753–10758

    Google Scholar 

  • Jongen-Rêlo AL, Drescher KU, Teschendorf HJ, Rueter LE, Unger LV, Gross G, Schoemaker H (2004a) Effects of dopamine D3 receptor antagonists and antipsychotic drugs on the disruption of huddling behavior by dopamine agonists. Soc Neurosci, Abstr 350.1. Online

    Google Scholar 

  • Jongen-Rêlo AL, Schuetz E, Drescher K, Rueter L, Browman K, Kohlhaas KL, Gross G, Schoemaker H (2004b) Pharmacological characterization of the behavioral sensitization to quinpirole in rats. Behav Pharmacol 15(5-6):A17–A18

    Article  Google Scholar 

  • Joyce JN (2001) Dopamine D3 receptor as a therapeutic target for antipsychotic and antiparkinsonian drugs. Pharmacol Ther 90:231–259

    Article  PubMed  CAS  Google Scholar 

  • Kagaya T, Yonaga M, Furuya Y, Hashimoto T, Kuroki J, Nishizawa Y (1996) Dopamine D3 agonists disrupt social behavior in rats. Brain Res 721:229–232

    Article  PubMed  CAS  Google Scholar 

  • Kapur S, Mamo D (2003) Half a century of antipsychotics and still a central role for dopamine D2 receptors. Prog Neuropsychopharmacol Biol Psychiatry 27:1081–1090

    Article  PubMed  CAS  Google Scholar 

  • Kapur S, Zipursky R, Jones C, Remington G, Houle S (2000) Relationship between dopamine D2 occupancy, clinical response, and side effects: a double-blind PET study of first-episode schizophrenia. Am J Psychiatry 157:514–520

    Article  PubMed  CAS  Google Scholar 

  • Karasinska JM, George SR, Cheng R, O’Dowd BF (2005) Deletion of dopamine D1 and D3 receptors differentially affects spontaneous behaviour and cocaine-induced locomotor activity, reward and CREB phosphorylation. Eur J Neurosci 22:1741–1750

    Article  PubMed  Google Scholar 

  • Karpa KD, Lin R, Kabbani N, Levenson R (2000) The dopamine D3 receptor interacts with itself and the truncated D3 splice variant d3nf: D3-D3nf interaction causes mislocalization of D3 receptors. Mol Pharmacol 58:677–683

    PubMed  CAS  Google Scholar 

  • Kessler RM, Ansari MS, Riccardi P, Li R, Jayathilake K, Dawant B, Meltzer HY (2005) Occupancy of striatal and extrastriatal dopamine D2/D3 receptors by olanzapine and haloperidol. Neuropsychopharmacology 30:2283–2289

    Article  PubMed  CAS  Google Scholar 

  • Kim KM, Valenzano KJ, Robinson SR, Yao WD, Barak LS, Caron MG (2001) Differential regulation of the dopamine D2 and D3 receptors by G protein-coupled receptor kinases and beta-arrestins. J Biol Chem 276:37409–37414

    Article  PubMed  CAS  Google Scholar 

  • Kiss B, Laszlovszky I, Horvath A, Nemethy Z, Schmidt E, Bugovics G, Fazekas K, Gyertyan I, Gai-Csongor E, Domany G, Szombathelyi Z (2008) Subnanomolar dopamine D3 receptor antagonism coupled to moderate D2 affinity results in favourable antipsychotic-like activity in rodent models: I. neurochemical characterisation of RG-15. Naunyn-Schmiedeberg’s Arch Pharmacol 378:515–528

    Article  PubMed  CAS  Google Scholar 

  • Kiss B, Horvath A, Nemethy Z, Schmidt E, Laszlovszky I, Bugovics G, Fazekas K, Hornok K, Orosz S, Gyertyan I, Gai-Csongor E, Domany G, Tihanyi K, Adham N, Szombathelyi Z (2010) Cariprazine (RGH-188), a dopamine D3 receptor-preferring, D3/D2 dopamine receptor antagonist-partial agonist antipsychotic candidate: in vitro and neurochemical profile. J Pharmacol Exp Ther 333:328–340

    Article  PubMed  CAS  Google Scholar 

  • Koeltzow TE, Xu M, Cooper DC, Hu XT, Tonegawa S, Wolf ME, White FJ (1998) Alterations in dopamine release but not dopamine autoreceptor function in dopamine D3 receptor mutant mice. J Neurosci 18:2231–2238

    PubMed  CAS  Google Scholar 

  • Kolasiewicz W, Maj J, Ossowska K (2008) The involvement of cerebellar dopamine D3 receptors in locomotor activity of rats. J Neural Transm 115:677–681

    Article  PubMed  CAS  Google Scholar 

  • Komossa K, Rummel-Kluge C, Hunger H, Schmid F, Schwarz S, Silveira da Mota Neto JI, Kissling W, Leucht S (2010) Amisulpride versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev, Issue 1. Art. No.: CD006624

    Google Scholar 

  • Kreiss DS, Bergstrom DA, Gonzalez AM, Huang KX, Sibley DR, Walters JR (1995) Dopamine receptor agonist potencies for inhibition of cell firing correlate with dopamine D3 receptor binding affinities. Eur J Pharmacol 277:209–214

    Article  PubMed  CAS  Google Scholar 

  • Kufareva I, Rueda M, Katritch V, Stevens RC, Abagyan R (2011) Status of GPCR modeling and docking as reflected by community-wide GPCR Dock 2010 assessment. Structure 19:1108–1126

    Article  PubMed  CAS  Google Scholar 

  • Kuroki T, Meltzer HY, Ichikawa J (1999) Effects of antipsychotic drugs on extracellular dopamine levels in rat medial prefrontal cortex and nucleus accumbens. J Pharmacol Exp Ther 288:774–781

    PubMed  CAS  Google Scholar 

  • Kuzhikandathil EV, Oxford GS (1999) Activation of human D3 dopamine receptor inhibits P/Q-type calcium channels and secretory activity in AtT-20 cells. J Neurosci 19:1698–1707

    PubMed  CAS  Google Scholar 

  • Kuzhikandathil EV, Oxford GS (2000) Dominant-negative mutants identify a role for GIRK channels in D3 dopamine receptor-mediated regulation of spontaneous secretory activity. J Gen Physiol 115:697–706

    Article  PubMed  CAS  Google Scholar 

  • Kuzhikandathil EV, Yu W, Oxford GS (1998) Human dopamine D3 and D2L receptors couple to inward rectifier potassium channels in mammalian cell lines. Mol Cell Neurosci 12:390–402

    Article  PubMed  CAS  Google Scholar 

  • Lacroix LP, Hows ME, Shah AJ, Hagan JJ, Heidbreder CA (2003) Selective antagonism at dopamine D3 receptors enhances monoaminergic and cholinergic neurotransmission in the rat anterior cingulate cortex. Neuropsychopharmacology 28:839–849

    PubMed  CAS  Google Scholar 

  • Lacroix LP, Ceolin L, Zocchi A, Varnier G, Garzotti M, Curcuruto O, Heidbreder CA (2006) Selective dopamine D3 receptor antagonists enhance cortical acetylcholine levels measured with high-performance liquid chromatography/tandem mass spectrometry without anti-cholinesterases. J Neurosci Methods 157:25–31

    Article  PubMed  CAS  Google Scholar 

  • Lan H, Teeter MM, Gurevich VV, Neve KA (2009) An intracellular loop 2 amino acid residue determines differential binding of arrestin to the dopamine D2 and D3 receptors. Mol Pharmacol 75:19–26

    Article  PubMed  CAS  Google Scholar 

  • Landwehrmeyer B, Mengod G, Palacios JM (1993) Dopamine D3 receptor mRNA and binding sites in human brain. Brain Res Mol Brain Res 18:187–192

    Article  PubMed  CAS  Google Scholar 

  • Lane JR, Powney B, Wise A, Rees S, Milligan G (2008) G protein coupling and ligand selectivity of the D2L and D3 dopamine receptors. J Pharmacol Exp Ther 325:319–330

    Article  PubMed  CAS  Google Scholar 

  • Laszy J, Laszlovszky I, Gyertyan I (2005) Dopamine D3 receptor antagonists improve the learning performance in memory-impaired rats. Psychopharmacology (Berl) 179:567–575

    Article  CAS  Google Scholar 

  • Le Foll B, Diaz J, Sokoloff P (2003) Increased dopamine D3 receptor expression accompanying behavioral sensitization to nicotine in rats. Synapse 47:176–183

    Article  PubMed  CAS  Google Scholar 

  • Le Moine C, Bloch B (1996) Expression of the D3 dopamine receptor in peptidergic neurons of the nucleus accumbens: comparison with the D1 and D2 dopamine receptors. Neuroscience 73:131–143

    Article  PubMed  Google Scholar 

  • Legangneux E, McEwen J, Wesnes KA, Bergougnan L, Miget N, Canal M, L’Heritier C, Pinquier JL, Rosenzweig P (2000) The acute effects of amisulpride (50 mg and 200 mg) and haloperidol (2 mg) on cognitive function in healthy elderly volunteers. J Psychopharmacol 14:164–171

    Article  PubMed  CAS  Google Scholar 

  • Leucht S (2004) Amisulpride a selective dopamine antagonist and atypical antipsychotic: results of a meta-analysis of randomized controlled trials. Int J Neuropsychopharmacol 7(Suppl 1):S15–S20

    Article  PubMed  CAS  Google Scholar 

  • Leucht S, Pitschel-Walz G, Engel RR, Kissling W (2002) Amisulpride, an unusual “atypical” antipsychotic: a meta-analysis of randomized controlled trials. Am J Psychiatry 159:180–190

    Article  PubMed  Google Scholar 

  • Leucht S, Wagenpfeil S, Hamann J, Kissling W (2004) Amisulpride is an “atypical” antipsychotic associated with low weight gain. Psychopharmacology (Berl) 173:112–115

    Article  CAS  Google Scholar 

  • Levant B (1995) Differential sensitivity of [3 H]7-OH-DPAT-labeled binding sites in rat brain to inactivation by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline. Brain Res 698:146–154

    Article  PubMed  CAS  Google Scholar 

  • Levant B (1998) Differential distribution of D3 dopamine receptors in the brains of several mammalian species. Brain Res 800:269–274

    Article  PubMed  CAS  Google Scholar 

  • Levesque D, Diaz J, Pilon C, Martres MP, Giros B, Souil E, Schott D, Morgat JL, Schwartz JC, Sokoloff P (1992) Identification, characterization, and localization of the dopamine D3 receptor in rat brain using 7-[3 H]hydroxy-N, N-di-n-propyl-2-aminotetralin. Proc Natl Acad Sci U S A 89:8155–8159

    Article  PubMed  CAS  Google Scholar 

  • Liu K, Bergson C, Levenson R, Schmauss C (1994) On the origin of mRNA encoding the truncated dopamine D3-type receptor D3nf and detection of D3nf-like immunoreactivity in human brain. J Biol Chem 269:29220–29226

    PubMed  CAS  Google Scholar 

  • Liu XY, Mao LM, Zhang GC, Papasian CJ, Fibuch EE, Lan HX, Zhou HF, Xu M, Wang JQ (2009) Activity-dependent modulation of limbic dopamine D3 receptors by CaMKII. Neuron 61:425–438

    Google Scholar 

  • Loiseau F, Millan MJ (2009) Blockade of dopamine D3 receptors in frontal cortex, but not in sub-cortical structures, enhances social recognition in rats: similar actions of D1 receptor agonists, but not of D2 antagonists. Eur Neuropsychopharmacol 19:23–33

    Article  PubMed  CAS  Google Scholar 

  • Ludewig K, Geyer MA, Vollenweider FX (2003) Deficits in prepulse inhibition and habituation in never-medicated, first-episode schizophrenia. Biol Psychiatry 54:121–128

    Article  PubMed  Google Scholar 

  • Luippold G, Pech B, Schneider S, Drescher K, Muller R, Gross G, Mühlbauer B (2006) Absence of amino acid-induced glomerular hyperfiltration in dopamine D3 receptor knockout mice. Naunyn-Schmiedeberg’s Arch Pharmacol 372:284–290

    Article  PubMed  CAS  Google Scholar 

  • Lundstrom K, Turpin MP (1996) Proposed schizophrenia-related gene polymorphism: expression of the Ser9Gly mutant human dopamine D3 receptor with the Semliki Forest virus system. Biochem Biophys Res Commun 225:1068–1072

    Article  PubMed  CAS  Google Scholar 

  • Ma G, He Z, Fang W, Tang W, Huang K, Li Z, He G, Xu Y, Feng G, Zheng T, Zhou J, He L, Shi Y (2008) The Ser9Gly polymorphism of the dopamine D3 receptor gene and risk of schizophrenia: an association study and a large meta-analysis. Schizophr Res 101:26–35

    Article  PubMed  Google Scholar 

  • Maggio R, Millan MJ (2010) Dopamine D2-D3 receptor heteromers: pharmacological properties and therapeutic significance. Curr Opin Pharmacol 10:100–107

    Article  PubMed  CAS  Google Scholar 

  • Maggio R, Scarselli M, Novi F, Millan MJ, Corsini GU (2003) Potent activation of dopamine D3/D2 heterodimers by the antiparkinsonian agents, S32504, pramipexole and ropinirole. J Neurochem 87:631–641

    Article  PubMed  CAS  Google Scholar 

  • Mannoury la Cour C, Salles MJ, Pasteau V, Millan MJ (2011) Signaling pathways leading to phosphorylation of Akt and GSK-3beta by activation of cloned human and rat cerebral D2 and D3 receptors. Mol Pharmacol 79:91–105

    Article  PubMed  CAS  Google Scholar 

  • Marcellino D, Ferre S, Casado V, Cortes A, Le FB, Mazzola C, Drago F, Saur O, Stark H, Soriano A, Barnes C, Goldberg SR, Lluis C, Fuxe K, Franco R (2008) Identification of dopamine D1-D3 receptor heteromers. Indications for a role of synergistic D1–D3 receptor interactions in the striatum. J Biol Chem 283:26016–26025

    Article  PubMed  CAS  Google Scholar 

  • Mattingly BA, Fields SE, Langfels MS, Rowlett JK, Robinet PM, Bardo MT (1996) Repeated 7-OH-DPAT treatments: behavioral sensitization, dopamine synthesis and subsequent sensitivity to apomorphine and cocaine. Psychopharmacology (Berl) 125:33–42

    Article  CAS  Google Scholar 

  • Mattingly BA, Rice LL, Langfels M, Fields SE (2000) Repeated treatments with 7-OH-DPAT: context-independent behavioral sensitization and conditioned hyperactivity. Pharmacol Biochem Behav 65:241–246

    Article  PubMed  CAS  Google Scholar 

  • Mayer A, Limberger N, Starke K (1988) Transmitter release patterns of noradrenergic, dopaminergic and cholinergic axons in rabbit brain slices during short pulse trains, and the operation of presynaptic autoreceptors. Naunyn-Schmiedeberg’s Arch Pharmacol 338:632–643

    Article  PubMed  CAS  Google Scholar 

  • Mccormick PN, Kapur S, Reckless G, Wilson AA (2009) Ex vivo [11 C]—(1)-PHNO binding is unchanged in animal models displaying increased high-affinity states of the D 2 receptor in vitro. Synapse 1009:998–1009

    Article  CAS  Google Scholar 

  • McCormick PN, Kapur S, Graff-Guerrero A, Raymond R, Nobrega JN, Wilson AA (2010) The antipsychotics olanzapine, risperidone, clozapine, and haloperidol are D2-selective ex vivo but not in vitro. Neuropsychopharmacology 35:1826–1835

    PubMed  CAS  Google Scholar 

  • McElroy JF (1994) Discriminative stimulus properties of 7-OH-DPAT, a dopamine D3-selective receptor ligand. Pharmacol Biochem Behav 48:531–533

    Article  PubMed  CAS  Google Scholar 

  • Meltzer HY (2012) Serotonergic Mechanisms as Targets for Existing and Novel Antipsychotics. In: Gross G, Geyer M (eds) Current Antipsychotics; Handbook of Experimental Pharamacology, vol. 212. Springer, Heidelberg

    Google Scholar 

  • Micale V, Cristino L, Tamburella A, Petrosino S, Leggio GM, Di MV, Drago F (2010) Enhanced cognitive performance of dopamine D3 receptor “knock-out” mice in the step-through passive-avoidance test: assessing the role of the endocannabinoid/endovanilloid systems. Pharmacol Res 61:531–536

    Article  PubMed  CAS  Google Scholar 

  • Millan MJ (2005) Dopamine D3 receptors as a novel target for improving the treatment of schizophrenia. Med Sci (Paris) 21:434–442

    Article  Google Scholar 

  • Millan MJ, Brocco M (2008) Cognitive impairment in schizophrenia: a review of developmental and genetic models, and pro-cognitive profile of the optimised D(3) > D(2) antagonist, S33138. Therapie 63:187–229

    Article  PubMed  Google Scholar 

  • Millan MJ, Peglion JL, Vian J, Rivet JM, Brocco M, Gobert A, Newman-Tancredi A, Dacquet C, Bervoets K, Girardon S (1995) Functional correlates of dopamine D3 receptor activation in the rat in vivo and their modulation by the selective antagonist, (+)-S 14297: 1. Activation of postsynaptic D3 receptors mediates hypothermia, whereas blockade of D2 receptors elicits prolactin secretion and catalepsy. J Pharmacol Exp Ther 275:885–898

    PubMed  CAS  Google Scholar 

  • Millan MJ, Gressier H, Brocco M (1997) The dopamine D3 receptor antagonist, (+)-S 14297, blocks the cataleptic properties of haloperidol in rats. Eur J Pharmacol 321:R7–R9

    Article  PubMed  CAS  Google Scholar 

  • Millan MJ, Dekeyne A, Rivet JM, Dubuffet T, Lavielle G, Brocco M (2000a) S33084, a novel, potent, selective, and competitive antagonist at dopamine D(3)-receptors: II. Functional and behavioral profile compared with GR218,231 and L741,626. J Pharmacol Exp Ther 293:1063–1073

    PubMed  CAS  Google Scholar 

  • Millan MJ, Gobert A, Newman-Tancredi A, Lejeune F, Cussac D, Rivet JM, Audinot V, Dubuffet T, Lavielle G (2000b) S33084, a novel, potent, selective, and competitive antagonist at dopamine D3-receptors: I. Receptorial, electrophysiological and neurochemical profile compared with GR218,231 and L741,626. J Pharmacol Exp Ther 293:1048–1062

    PubMed  CAS  Google Scholar 

  • Millan MJ, Brocco M, Papp M, Serres F, La Rochelle CD, Sharp T, Peglion JL, Dekeyne A (2004a) S32504, a novel naphtoxazine agonist at dopamine D3/D2 receptors: III. Actions in models of potential antidepressive and anxiolytic activity in comparison with ropinirole. J Pharmacol Exp Ther 309:936–950

    Article  PubMed  CAS  Google Scholar 

  • Millan MJ, Seguin L, Gobert A, Cussac D, Brocco M (2004b) The role of dopamine D3 compared with D2 receptors in the control of locomotor activity: a combined behavioural and neurochemical analysis with novel, selective antagonists in rats. Psychopharmacology (Berl) 174:341–357

    Article  CAS  Google Scholar 

  • Millan MJ, Cara BD, Dekeyne A, Panayi F, Groote LD, Cistarelli L, Billiras R, Gobert A (2007) Selective blockade of dopamine D3 versus D2 receptors enhances frontocortical cholinergic transmission and social memory in rats: a parallel neurochemical and behavioural analysis. J Neurochem 100:1047–61

    Article  PubMed  CAS  Google Scholar 

  • Millan MJ, Loiseau F, Dekeyne A, Gobert A, Flik G, Cremers TI, Rivet JM, Sicard D, Billiras R, Brocco M (2008a) S33138 (N-[4-[2-[(3aS,9bR)-8-cyano-1,3a,4,9b-tetrahydro[1] benzopyrano[3,4-c]pyrrol-2(3 H)-yl)-ethyl]phenyl-acetamide), a preferential dopamine D3 versus D2 receptor antagonist and potential antipsychotic agent: III. Actions in models of therapeutic activity and induction of side effects. J Pharmacol Exp Ther 324:1212–1226

    Article  PubMed  CAS  Google Scholar 

  • Millan MJ, Svenningsson P, Ashby CR Jr, Hill M, Egeland M, Dekeyne A, Brocco M, Di CB, Lejeune F, Thomasson N, Munoz C, Mocaer E, Crossman A, Cistarelli L, Girardon S, Iob L, Veiga S, Gobert A (2008b) S33138 [N-[4-[2-[(3aS,9bR)-8-cyano-1,3a,4,9b-tetrahydro[1]-benzopyrano[3,4-c]pyrr ol-2(3 H)-yl)-ethyl]phenylacetamide], a preferential dopamine D3 versus D2 receptor antagonist and potential antipsychotic agent. II. A neurochemical, electrophysiological and behavioral characterization in vivo. J Pharmacol Exp Ther 324:600–611

    Article  PubMed  CAS  Google Scholar 

  • Millan MJ, Buccafusco JJ, Loiseau F, Watson DJG, Decamp E, Fone KCF, Thomasson-perret N, Hill M, Mocaer E, Schneider JS (2010) The dopamine D3 receptor antagonist, S33138, counters cognitive impairment in a range of rodent and primate procedures. Int J Neuropsychopharmacol 13:1035–51

    Article  PubMed  CAS  Google Scholar 

  • Millan MJ, Agid Y, Brune M, Bullmore ET, Carter CS, Clayton NS, Connor R, Davis S, Deakin B, Derubeis RJ, Dubois B, Geyer MA, Goodwin GM, Gorwood P, Jay TM, Joels M, Mansuy IM, Meyer-Lindenberg A, Murphy D, Rolls E, Saletu B, Spedding M, Sweeney J, Whittington M, Young LJ (2012) Cognitive dysfunction in psychiatric disorders: characteristics, causes and the quest for improved therapy. Nat Rev Drug Discov 11:141–168

    Article  PubMed  CAS  Google Scholar 

  • Missale C, Fiorentini C, Collo G, Spano P (2010) The neurobiology of dopamine receptors: evolution from the dual concept to heterodimer complexes. J Recept Signal Transduct Res 30:347–354

    Article  PubMed  CAS  Google Scholar 

  • Mizrahi R, Agid O, Borlido C, Suridjan I, Rusjan P, Houle S, Remington G, Wilson AA, Kapur S (2011) Effects of antipsychotics on D3 receptors: A clinical PET study in first episode antipsychotic naive patients with schizophrenia using [11C]-(+)-PHNO. Schizophr Res 131:63–8

    Article  PubMed  Google Scholar 

  • Mortimer AM (2009) Update on the management of symptoms in schizophrenia: focus on amisulpride. Neuropsychiatr Dis Treat 5:267–277

    Article  PubMed  CAS  Google Scholar 

  • Mortimer AM, Joyce E, Balasubramaniam K, Choudhary PC, Saleem PT (2007) Treatment with amisulpride and olanzapine improve neuropsychological function in schizophrenia. Hum Psychopharmacol 22:445–454

    Article  PubMed  CAS  Google Scholar 

  • Munro J, Matthiasson P, Osborne S, Travis M, Purcell S, Cobb AM, Launer M, Beer MD, Kerwin R (2004) Amisulpride augmentation of clozapine: an open non-randomized study in patients with schizophrenia partially responsive to clozapine. Acta Psychiatr Scand 110:292–298

    Article  PubMed  CAS  Google Scholar 

  • Natesan S, Reckless GE, Barlow KB, Nobrega JN, Kapur S (2008) Amisulpride the ‘atypical’ atypical antipsychotic—comparison to haloperidol, risperidone and clozapine. Schizophr Res 105:224–235

    Article  PubMed  Google Scholar 

  • Newman-Tancredi A, Cussac D, Audinot V, Pasteau V, Gavaudan S, Millan MJ (1999) G protein activation by human dopamine D3 receptors in high-expressing Chinese hamster ovary cells: A guanosine-5′-O-(3-[35 S]thio)-triphosphate binding and antibody study. Mol Pharmacol 55:564–574

    PubMed  CAS  Google Scholar 

  • Nimchinsky EA, Hof PR, Janssen WG, Morrison JH, Schmauss C (1997) Expression of dopamine D3 receptor dimers and tetramers in brain and in transfected cells. J Biol Chem 272: 29229–29237

    Article  PubMed  CAS  Google Scholar 

  • Nissbrandt H, Ekman A, Eriksson E, Heilig M (1995) Dopamine D3 receptor antisense influences dopamine synthesis in rat brain. Neuroreport 6:573–576

    Article  PubMed  CAS  Google Scholar 

  • Nitsche MA, Monte-Silva K, Kuo MF, Paulus W (2010) Dopaminergic impact on cortical excitability in humans. Rev Neurosci 21:289–298

    PubMed  CAS  Google Scholar 

  • Nobrega JN, Seeman P (1994) Dopamine D2 receptors mapped in rat brain with [3H](+)PHNO. Synapse 17:167–172

    Article  PubMed  CAS  Google Scholar 

  • Novi F, Millan MJ, Corsini GU, Maggio R (2007) Partial agonist actions of aripiprazole and the candidate antipsychotics S33592, bifeprunox, N-desmethylclozapine and preclamol at dopamine D2L receptors are modified by co-transfection of D3 receptors: potential role of heterodimer formation. J Neurochem 102:1410–1424

    Article  PubMed  CAS  Google Scholar 

  • Nuechterlein KH, Barch DM, Gold JM, Goldberg TE, Green MF, Heaton RK (2004) Identification of separable cognitive factors in schizophrenia. Schizophr Res 72:29–39

    Article  PubMed  Google Scholar 

  • Nuss P, Tessier C (2010) Antipsychotic medication, functional outcome and quality of life in schizophrenia: focus on amisulpride. Curr Med Res Opin 26:787–801

    Article  PubMed  CAS  Google Scholar 

  • Obiol-Pardo C, Lopez L, Pastor M, Selent J (2011) Progress in the structural prediction of G protein-coupled receptors: D3 receptor in complex with eticlopride. Proteins 79:1695–1703

    Article  PubMed  CAS  Google Scholar 

  • Peng RY, Mansbach RS, Braff DL, Geyer MA (1990) A D2 dopamine receptor agonist disrupts sensorimotor gating in rats. Implications for dopaminergic abnormalities in schizophrenia. Neuropsychopharmacology 3:211–218

    PubMed  CAS  Google Scholar 

  • Piercey MF, Hoffmann WE, Smith MW, Hyslop DK (1996) Inhibition of dopamine neuron firing by pramipexole, a dopamine D3 receptor-preferring agonist: comparison to other dopamine receptor agonists. Eur J Pharmacol 312:35–44

    Article  PubMed  CAS  Google Scholar 

  • Pierre JM (2005) Extrapyramidal symptoms with atypical antipsychotics. Incidence, prevention and management. Drug Saf 28:191–208

    Article  PubMed  CAS  Google Scholar 

  • Pilon C, Levesque D, Dimitriadou V, Griffon N, Martres MP, Schwartz JC, Sokoloff P (1994) Functional coupling of the human dopamine D3 receptor in a transfected NG 108-15 neuroblastoma-glioma hybrid cell line. Eur J Pharmacol 268:129–139

    Article  PubMed  CAS  Google Scholar 

  • Potkin S, Keattor D, Mukherjee J, Preda A, Highum D, Gage A, Xie J, Ghahramani P, Laszlovszky I (2009) Dopamine D3 and D2 receptor occupancy of cariprazine in schizophrenic patients. Eur Neuropsychopharmacol 19(Suppl 3):S316

    Article  Google Scholar 

  • Pou C, Mannoury la Cour C, Stoddart LA, Millan MJ, Milligan G (2012) Functional homomers and heteromers of dopamine D2L and D3 receptors co-exist at the cell surface. J Biol Chem 287(12):8864–78

    Article  PubMed  CAS  Google Scholar 

  • Pritchard LM, Logue AD, Hayes S, Welge JA, Xu M, Zhang J, Berger SP, Richtand NM (2003) 7-OH-DPAT and PD 128907 selectively activate the D3 dopamine receptor in a novel environment. Neuropsychopharmacology 28:100–107

    Article  PubMed  CAS  Google Scholar 

  • Pritchard LM, Logue AD, Taylor BC, Ahlbrand R, Welge JA, Tang Y, Sharp FR, Richtand NM (2006) Relative expression of D3 dopamine receptor and alternative splice variant D3nf mRNA in high and low responders to novelty. Brain Res Bull 70:296–303

    Article  PubMed  CAS  Google Scholar 

  • Pritchard LM, Newman AH, McNamara RK, Logue AD, Taylor B, Welge JA, Xu M, Zhang J, Richtand NM (2007) The dopamine D3 receptor antagonist NGB 2904 increases spontaneous and amphetamine-stimulated locomotion. Pharmacol Biochem Behav 86:718–726

    Article  PubMed  CAS  Google Scholar 

  • Pugsley TA, Davis MD, Akunne HC, MacKenzie RG, Shih YH, Damsma G, Wikstrom H, Whetzel SZ, Georgic LM, Cooke LW (1995) Neurochemical and functional characterization of the preferentially selective dopamine D3 agonist PD 128907. J Pharmacol Exp Ther 275:1355–1366

    PubMed  CAS  Google Scholar 

  • Quik M, Police S, He L, Di Monte DA, Langston JW (2000) Expression of D(3) receptor messenger RNA and binding sites in monkey striatum and substantia nigra after nigrostriatal degeneration: effect of levodopa treatment. Neuroscience 98:263–273

    Article  PubMed  CAS  Google Scholar 

  • Reavill C, Taylor SG, Wood MD, Ashmeade T, Austin NE, Avenell KY, Boyfield I, Branch CL, Cilia J, Coldwell MC, Hadley MS, Hunter AJ, Jeffrey P, Jewitt F, Johnson CN, Jones DN, Medhurst AD, Middlemiss DN, Nash DJ, Riley GJ, Routledge C, Stemp G, Thewlis KM, Trail B, Vong AK, Hagan JJ (2000) Pharmacological actions of a novel, high-affinity, and selective human dopamine D3 receptor antagonist, SB-277011-A. J Pharmacol Exp Ther 294:1154–1165

    PubMed  CAS  Google Scholar 

  • Redden L, Rendenbach-Mueller B, Abi-Saab WM, Katz DA, Goenjian A, Robieson WZ, Wang Y, Goss SL, Greco N, Saltarelli MD (2011) A double-blind, randomized, placebo-controlled study of the dopamine D3 receptor antagonist ABT-925 in patients with acute schizophrenia. J Clin Psychopharmacol 31:221–225

    Article  PubMed  CAS  Google Scholar 

  • Richtand NM (2006) Behavioral sensitization, alternative splicing, and D3 dopamine receptor-mediated inhibitory function. Neuropsychopharmacology 31:2368–2375

    Article  PubMed  CAS  Google Scholar 

  • Richtand NM, Logue AD, Welge JA, Perdiue J, Tubbs LJ, Spitzer RH, Sethuraman G, Geracioti TD (2000) The dopamine D3 receptor antagonist nafadotride inhibits development of locomotor sensitization to amphetamine. Brain Res 867:239–242

    Article  PubMed  CAS  Google Scholar 

  • Richtand NM, Woods SC, Berger SP, Strakowski SM (2001) D3 dopamine receptor, behavioral sensitization, and psychosis. Neurosci Biobehav Rev 25:427–443

    Article  PubMed  CAS  Google Scholar 

  • Richtand NM, Welge JA, Levant B, Logue AD, Hayes S, Pritchard LM, Geracioti TD, Coolen LM, Berger SP (2003) Altered behavioral response to dopamine D3 receptor agonists 7-OH-DPAT and PD 128907 following repetitive amphetamine administration. Neuropsychopharmacology 28:1422–1432

    Article  PubMed  CAS  Google Scholar 

  • Richtand NM, Liu Y, Ahlbrand R, Sullivan JR, Newman AH, McNamara RK (2010) Dopaminergic regulation of dopamine D3 and D3nf receptor mRNA expression. Synapse 64:634–643

    Article  PubMed  CAS  Google Scholar 

  • Ridley RM (1994) The psychology of perseverative and stereotyped behaviour. Prog Neurobiol 44:221–231

    CAS  Google Scholar 

  • Ridray S, Griffon N, Mignon V, Souil E, Carboni S, Diaz J, Schwartz JC, Sokoloff P (1998) Coexpression of dopamine D1 and D3 receptors in islands of Calleja and shell of nucleus accumbens of the rat: opposite and synergistic functional interactions. Eur J Neurosci 10:1676–1686

    Article  PubMed  CAS  Google Scholar 

  • Rivet JM, Audinot V, Gobert A, Peglion JL, Millan MJ (1994) Modulation of mesolimbic dopamine release by the selective dopamine D3 receptor antagonist, (+)-S 14297. Eur J Pharmacol 265:175–177

    Article  PubMed  CAS  Google Scholar 

  • Robinson SW, Caron MG (1997) Selective inhibition of adenylyl cyclase type V by the dopamine D3 receptor. Mol Pharmacol 52:508–514

    PubMed  CAS  Google Scholar 

  • Rodriguez-Arias M, Felip CM, Broseta I, Minarro J (1999) The dopamine D3 antagonist U-99194A maleate increases social behaviors of isolation-induced aggressive male mice. Psychopharmacology (Berl) 144:90–94

    Article  CAS  Google Scholar 

  • Sawaguchi T (2000) The role of D1-dopamine receptors in working memory-guided movements mediated by frontal cortical areas. Parkinsonism Relat Disord 7:9–19

    Article  PubMed  Google Scholar 

  • Scatton B, Claustre Y, Cudennec A, Oblin A, Perrault G, Sanger DJ, Schoemaker H (1997) Amisulpride: from animal pharmacology to therapeutic action. Int Clin Psychopharmacol 12(Suppl 2):S29–S36

    Article  PubMed  Google Scholar 

  • Schlosser R, Gründer G, Anghelescu I, Hillert A, Ewald-Gründer S, Hiemke C, Benkert O (2002) Long-term effects of the substituted benzamide derivative amisulpride on baseline and stimulated prolactin levels. Neuropsychobiology 46:33–40

    Article  PubMed  CAS  Google Scholar 

  • Schmauss C (1996) Enhanced cleavage of an atypical intron of dopamine D3-receptor pre-mRNA in chronic schizophrenia. J Neurosci 16:7902–7909

    PubMed  CAS  Google Scholar 

  • Schmidt WJ, Beninger RJ (2006) Behavioural sensitization in addiction, schizophrenia, Parkinson’s disease and dyskinesia. Neurotox Res 10:161–166

    Article  PubMed  CAS  Google Scholar 

  • Schoemaker H, Claustre Y, Fage D, Rouquier L, Chergui K, Curet O, Oblin A, Gonon F, Carter C, Benavides J, Scatton B (1997) Neurochemical characteristics of amisulpride, an atypical dopamine D2/D3 receptor antagonist with both presynaptic and limbic selectivity. J Pharmacol Exp Ther 280:83–97

    PubMed  CAS  Google Scholar 

  • Schotte A, Janssen PF, Gommeren W, Luyten WH, Leysen JE (1992) Autoradiographic evidence for the occlusion of rat brain dopamine D3 receptors in vivo. Eur J Pharmacol 218:373–375

    Article  PubMed  CAS  Google Scholar 

  • Schotte A, Janssen PF, Bonaventure P, Leysen JE (1996) Endogenous dopamine limits the binding of antipsychotic drugs to D3 receptors in the rat brain: a quantitative autoradiographic study. Histochem J 28:791–799

    Article  PubMed  CAS  Google Scholar 

  • Schuetz E, Jongen-Rêlo AL, Drescher KU, Gross G, Schoemaker H (2004) The effect of the dopamine D3 receptor antagonist A-437203 on the development and expression of locomotor sensitization to quinpirole in rats. Soc Neurosci, Abstr 350.1. Online

    Google Scholar 

  • Schultz W (2007) Behavioral dopamine signals. Trends Neurosci 30:203–210

    Article  PubMed  CAS  Google Scholar 

  • Schwartz JC, Diaz J, Bordet R, Griffon N, Perachon S, Pilon C, Ridray S, Sokoloff P (1998a) Functional implications of multiple dopamine receptor subtypes: the D1/D3 receptor coexistence. Brain Res Brain Res Rev 26:236–242

    Article  PubMed  CAS  Google Scholar 

  • Schwartz JC, Ridray S, Bordet R, Diaz J, Sokoloff P (1998b) D1/D3 receptor relationships in brain coexpression, coactivation, and coregulation. Adv Pharmacol 42:408–411

    Article  PubMed  CAS  Google Scholar 

  • Searle G, Beaver JD, Comley RA, Bani M, Tziortzi A, Slifstein M, Mugnaini M, Griffante C, Wilson AA, Merlo-Pich E, Houle S, Gunn R, Rabiner EA, Laruelle M (2010) Imaging dopamine D3 receptors in the human brain with positron emission tomography, [11 C]PHNO, and a selective D3 receptor antagonist. Biol Psychiatry 68:392–399

    Article  PubMed  CAS  Google Scholar 

  • Seeman P (2002) Atypical antipsychotics: mechanism of action. Can J Psychiatry 47:27–38

    PubMed  Google Scholar 

  • Seeman P (2006) Targeting the dopamine D2 receptor in schizophrenia. Expert Opin Ther Targets 10:515–531

    Article  PubMed  CAS  Google Scholar 

  • Seeman P, Ulpian C, Larsen RD, Anderson PS (1993) Dopamine receptors labelled by PHNO. Synapse 14:254–62

    Article  PubMed  CAS  Google Scholar 

  • Seeman P, Wilson A, Gmeiner P, Kapur S (2006) Dopamine D2 and D3 receptors in human putamen, caudate nucleus, and globus pallidus. Synapse 60:205–211

    Article  PubMed  CAS  Google Scholar 

  • Shafer RA, Levant B (1998) The D3 dopamine receptor in cellular and organismal function. Psychopharmacology (Berl) 135:1–16

    Article  CAS  Google Scholar 

  • Shahid M, Walker GB, Zorn SH, Wong EH (2009) Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol 23:65–73

    Article  PubMed  CAS  Google Scholar 

  • SIRS (2012) The 3rd Schizophrenia International Research Society Conference, 14–18 April 2012, Florence, Italy: Summaries of oral sessions. Schizophrenia Res (in press)

    Google Scholar 

  • Smith AG, Neill JC, Costall B (1999) The dopamine D3/D2 receptor agonist 7-OH-DPAT induces cognitive impairment in the marmoset. Pharmacol Biochem Behav 63:201–211

    Article  PubMed  CAS  Google Scholar 

  • Sokoloff P, Leriche L (2007) Drugs acting on D3 receptors in neuropsychiatric disorders: facts and prospects. Implication for schizophrenia and its treatment in the regulation of BDNF-dependence on D3 receptor expression. Encephale 33:870–872

    Article  PubMed  CAS  Google Scholar 

  • Sokoloff P, Giros B, Martres MP, Bouthenet ML, Schwartz JC (1990) Molecular cloning and characterization of a novel dopamine receptor D3 as a target for neuroleptics. Nature 347:146–151

    Article  PubMed  CAS  Google Scholar 

  • Sokoloff P, Martres MP, Giros B, Bouthenet ML, Schwartz JC (1992) The third dopamine receptor D3 as a novel target for antipsychotics. Biochem Pharmacol 43:659–666

    Article  PubMed  CAS  Google Scholar 

  • Stanwood GD, Artymyshyn RP, Kung MP, Kung HF, Lucki I, McGonigle P (2000) Quantitative autoradiographic mapping of rat brain dopamine D3 binding with [(125)I]7-OH-PIPAT: evidence for the presence of D3 receptors on dopaminergic and nondopaminergic cell bodies and terminals. J Pharmacol Exp Ther 295:1223–1231

    PubMed  CAS  Google Scholar 

  • Starke K, Spath L, Lang JD, Adelung C (1983) Further functional in vitro comparison of pre- and postsynaptic dopamine receptors in the rabbit caudate nucleus. Naunyn-Schmiedeberg’s Arch Pharmacol 323:298–306

    Article  PubMed  CAS  Google Scholar 

  • Stemp G, Ashmeade T, Branch CL, Hadley MS, Hunter AJ, Johnson CN, Nash DJ, Thewlis KM, Vong AK, Austin NE, Jeffrey P, Avenell KY, Boyfield I, Hagan JJ, Middlemiss DN, Reavill C, Riley GJ, Routledge C, Wood M (2000) Design and synthesis of trans-N-[4-[2-(6-cyano-1,2,3, 4-tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-4-quinolinecarboxamide (SB-277011): A potent and selective dopamine D3 receptor antagonist with high oral bioavailability and CNS penetration in the rat. J Med Chem 43:1878–1885

    Article  PubMed  CAS  Google Scholar 

  • Surmeier DJ, Eberwine J, Wilson CJ, Cao Y, Stefani A, Kitai ST (1992) Dopamine receptor subtypes colocalize in rat striatonigral neurons. Proc Natl Acad Sci USA 89:10178–10182

    Article  PubMed  CAS  Google Scholar 

  • Surmeier DJ, Yan Z, Song WJ (1998) Coordinated expression of dopamine receptors in neostriatal medium spiny neurons. Adv Pharmacol 42:1020–1023

    Article  PubMed  Google Scholar 

  • Suzuki M, Hurd YL, Sokoloff P, Schwartz JC, Sedvall G (1998) D3 dopamine receptor mRNA is widely expressed in the human brain. Brain Res 779:58–74

    Article  PubMed  CAS  Google Scholar 

  • Tadori Y, Forbes RA, McQuade RD, Kikuchi T (2011) Functional potencies of dopamine agonists and antagonists at human dopamine D2 and D3 receptors. Eur J Pharmacol 666:43–52

    Article  PubMed  CAS  Google Scholar 

  • Tenback DE, van Harten PN, van Os J (2009) Non-therapeutic risk factors for onset of tardive dyskinesia in schizophrenia: a meta-analysis. Movement Disorders 24:2309–2315

    Article  PubMed  Google Scholar 

  • Thomasson-Perret N, Penelaud PF, Theron D, Gouttefangeas S, Mocaer E (2008) Markers of D2 and D3 receptor activity in vivo: PET scan and prolactin. Therapie 63:237–242

    Article  PubMed  Google Scholar 

  • Torvinen M, Marcellino D, Canals M, Agnati LF, Lluis C, Franco R, Fuxe K (2005) Adenosine A 2A Receptor and Dopamine D 3 Receptor Interactions: Evidence of Functional A 2A/D 3 Heteromeric Complexes. Mol Pharmacol 67:400–407

    Article  PubMed  CAS  Google Scholar 

  • Turrone P, Kapur S, Seeman MV, Flint AJ (2002) Elevation of prolactin levels by atypical antipsychotics. Am J Psychiatry 159:133–135

    Article  PubMed  Google Scholar 

  • Tyson PJ, Laws KR, Flowers KA, Tyson A, Mortimer AM (2006) Cognitive function and social abilities in patients with schizophrenia: relationship with atypical antipsychotics. Psychiatry Clin Neurosci 60:473–479

    Article  PubMed  CAS  Google Scholar 

  • Ukai M, Tanaka T, Kameyama T (1997) Effects of the dopamine D3 receptor agonist, R(+)-7-hydroxy-N, N-di-n-propyl-2-aminotetralin, on memory processes in mice. Eur J Pharmacol 324:147–151

    Article  PubMed  CAS  Google Scholar 

  • Unger L, Wernet W, Sokoloff P, Wicke K, Gross G (2002) In vitro characterization of the selective dopamine D3 receptor antagonist A-437203. Soc Neurosci, Abstr 894.5. Online

    Google Scholar 

  • Unger L, Wernet W, Müller R, Jongen-Rêlo AL, Garcia-Ladona FJ, Moreland RB, Drescher KU, Haupt A, Hahn A, Schoemaker H, Sullivan JP (2005) ABT-127, a new selective dopamine D3 receptor antagonist: binding and functional properties in vitro. Abstr Soc Neurosci 913.18. Online

    Google Scholar 

  • Valerio A, Belloni M, Gorno ML, Tinti C, Memo M, Spano P (1994) Dopamine D2, D3, and D4 receptor mRNA levels in rat brain and pituitary during aging. Neurobiol Aging 15:713–719

    Article  PubMed  CAS  Google Scholar 

  • van Os J, Fahy T, Jones P, Harvey I, Toone B, Murray R (1997) Tardive dyskinesia: who is at risk? Acta Psychiatr Scand 96:206–16

    Article  PubMed  Google Scholar 

  • Vanhauwe JF, Fraeyman N, Francken BJ, Luyten WH, Leysen JE (1999) Comparison of the ligand binding and signaling properties of human dopamine D2 and D3 receptors in Chinese hamster ovary cells. J Pharmacol Exp Ther 290:908–916

    PubMed  CAS  Google Scholar 

  • Varga LI, Ko-Agugua N, Colasante J, Hertweck L, Houser T, Smith J, Watty AA, Nagar S, Raffa RB (2009) Critical review of ropinirole and pramipexole—putative dopamine D3-receptor selective agonists—for the treatment of RLS. J Clin Pharm Ther 34:493–505

    Article  PubMed  CAS  Google Scholar 

  • Vernaleken I, Siessmeier T, Buchholz HG, Hartter S, Hiemke C, Stoeter P, Rosch F, Bartenstein P, Gründer G (2004) High striatal occupancy of D2-like dopamine receptors by amisulpride in the brain of patients with schizophrenia. Int J Neuropsychopharmacol 7:421–430

    Article  PubMed  CAS  Google Scholar 

  • Vezina P, Leyton M (2009) Conditioned cues and the expression of stimulant sensitization in animals and humans. Neuropharmacology 56(Suppl 1):160–168

    Article  PubMed  CAS  Google Scholar 

  • Voorn P, Vanderschuren LJ, Groenewegen HJ, Robbins TW, Pennartz CM (2004) Putting a spin on the dorsal-ventral divide of the striatum. Trends Neurosci 27:468–474

    Article  PubMed  CAS  Google Scholar 

  • Wagner M, Quednow BB, Westheide J, Schlaepfer TE, Maier W, Kuhn KU (2005) Cognitive improvement in schizophrenic patients does not require a serotonergic mechanism: randomized controlled trial of olanzapine vs amisulpride. Neuropsychopharmacology 30:381–390

    Article  PubMed  CAS  Google Scholar 

  • Watson DJG, Marsden CA, Millan MJ, Fone KC (2011) Blockade of dopamine D3 but not D2 receptors reverses the novel object discrimination impairment produced by post-weaning social isolation: implications for schizophrenia and its treatment. Int J Neuropsychopharmacol 15:471–484

    Google Scholar 

  • Watson DJ, Loiseau F, Ingallinesi M, Millan MJ, Marsden CA, Fone KC (2012) Selective blockade of dopamine D(3) receptors enhances while D(2) receptor antagonism impairs social novelty discrimination and novel object recognition in rats: a key role for the prefrontal cortex. Neuropsychopharmacology 37:770–786

    Article  PubMed  CAS  Google Scholar 

  • Wetzel H, Wiesner J, Hiemke C, Benkert O (1994) Acute antagonism of dopamine D2-like receptors by amisulpride: effects on hormone secretion in healthy volunteers. J Psychiatr Res 28:461–473

    Article  PubMed  CAS  Google Scholar 

  • Wicke K, Garcia-Ladona J (2001) The dopamine D3 receptor partial agonist, BP 897, is an antagonist at human dopamine D3 receptors and at rat somatodendritic dopamine D3 receptors. Eur J Pharmacol 424:85–90

    Article  PubMed  CAS  Google Scholar 

  • Willeit M, Ginovart N, Kapur S, Houle S, Hussey D, Seeman P, Wilson AA (2006) High-affinity states of human brain dopamine D2/3 receptors imaged by the agonist [11C]-(+)-PHNO. Biol Psychiatry 59:389–394

    Article  PubMed  CAS  Google Scholar 

  • Winters BD, Saksida LM, Bussey TJ (2008) Object recognition memory: neurobiological mechanisms of encoding, consolidation and retrieval. Neurosci Biobehav Rev 32:1055–1070

    Article  PubMed  Google Scholar 

  • Woodward ND, Zald DH, Ding Z, Riccardi P, Ansari MS, Baldwin RM, Cowan RL, Li R, Kessler RM (2009) Cerebral morphology and dopamine D2/D3 receptor distribution in humans: a combined [18 F]fallypride and voxel-based morphometry study. Neuroimage 46:31–38

    Article  PubMed  Google Scholar 

  • Xing B, Kong H, Meng X, Wei SG, Xu M, Li SB (2010a) Dopamine D1 but not D3 receptor is critical for spatial learning and related signaling in the hippocampus. Neuroscience 169:1511–1519

    Article  PubMed  CAS  Google Scholar 

  • Xing B, Meng X, Wei S, Li S (2010b) Influence of dopamine D3 receptor knockout on age-related decline of spatial memory. Neurosci Lett 481:149–153

    Article  PubMed  CAS  Google Scholar 

  • Xu M, Koeltzow TE, Santiago GT, Moratalla R, Cooper DC, Hu XT, White NM, Graybiel AM, White FJ, Tonegawa S (1997) Dopamine D3 receptor mutant mice exhibit increased behavioral sensitivity to concurrent stimulation of D1 and D2 receptors. Neuron 19:837–848

    Article  PubMed  CAS  Google Scholar 

  • Xu M, Koeltzow TE, Cooper DC, Tonegawa S, White FJ (1999) Dopamine D3 receptor mutant and wild-type mice exhibit identical responses to putative D3 receptor-selective agonists and antagonists. Synapse 31:210–215

    Article  PubMed  CAS  Google Scholar 

  • Young JW, Powell SB, Risbrough V, Marston HM, Geyer MA (2009) Using the MATRICS to guide development of a preclinical cognitive test battery for research in schizophrenia. Pharmacol Ther 122:150–202

    Article  PubMed  CAS  Google Scholar 

  • Yuan J, Chen X, Brodbeck R, Primus R, Braun J, Wasley JW, Thurkauf A (1998) NGB 2904 and NGB 2849: two highly selective dopamine D3 receptor antagonists. Bioorg Med Chem Lett 8:2715–2718

    Article  PubMed  CAS  Google Scholar 

  • Zai CC, Tiwari AK, De Luca V, Muller DJ, Bulgin N, Hwang R, Zai GC, King N, Voineskos AN, Meltzer HY, Lieberman JA, Potkin SG, Remington G, Kennedy JL (2009) Genetic study of BDNF, DRD3, and their interaction in tardive dyskinesia. Eur Neuropsychopharmacol 19:317–328

    Article  PubMed  CAS  Google Scholar 

  • Zapata A, Witkin JM, Shippenberg TS (2001) Selective D3 receptor agonist effects of (+)-PD 128907 on dialysate dopamine at low doses. Neuropharmacology 41:351–359

    Article  PubMed  CAS  Google Scholar 

  • Zapata A, Kivell B, Han Y, Javitch JA, Bolan EA, Kuraguntla D, Jaligam V, Oz M, Jayanthi LD, Samuvel DJ, Ramamoorthy S, Shippenberg TS (2007) Regulation of dopamine transporter function and cell surface expression by D3 dopamine receptors. J Biol Chem 282:35842–35854

    Article  PubMed  CAS  Google Scholar 

  • Zhang L, Lou D, Jiao H, Zhang D, Wang X, Xia Y, Zhang J, Xu M (2004) Cocaine-induced intracellular signaling and gene expression are oppositely regulated by the dopamine D1 and D3 receptors. J Neurosci 24:3344–3354

    Article  PubMed  CAS  Google Scholar 

  • Zhang M, Ballard ME, Kohlhaas KL, Browman KE, Jongen-Relo AL, Unger LV, Fox GB, Gross G, Decker MW, Drescher KU, Rueter LE (2006) Effect of dopamine D3 antagonists on PPI in DBA/2 J mice or PPI deficit induced by neonatal ventral hippocampal lesions in rats. Neuropsychopharmacology 31:1382–1392

    Article  PubMed  CAS  Google Scholar 

  • Zhang M, Ballard ME, Unger LV, Haupt A, Gross G, Decker MW, Drescher KU, Rueter LE (2007) Effects of antipsychotics and selective D3 antagonists on PPI deficits induced by PD 128907 and apomorphine. Behav Brain Res 182:1–11

    Article  PubMed  CAS  Google Scholar 

  • Zhang L, Li J, Liu N, Wang B, Gu J, Zhang M, Zhou Z, Jiang Y, Zhang L, Zhang L (2012) Signaling via dopamine D1 and D3 receptors oppositely regulates cocaine-induced structural remodeling of dendrites and spines. Neurosignals 20:15–34

    Article  PubMed  CAS  Google Scholar 

  • Zink M, Henn FA, Thome J (2004a) Combination of amisulpride and olanzapine in treatment-resistant schizophrenic psychoses. Eur Psychiatry 19:56–58

    Article  PubMed  Google Scholar 

  • Zink M, Knopf U, Henn FA, Thome J (2004b) Combination of clozapine and amisulpride in treatment-resistant schizophrenia–case reports and review of the literature. Pharmacopsychiatry 37:26–31

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Abbott, Neuroscience Research, GPRD, 67061, Ludwigshafen, Germany

    Gerhard Gross & Karla Drescher

  2. Institut für Pharmakologie, Universität Duisburg-Essen, Universitätsklinikum Essen, Hufelandstr. 55, 45122, Essen, Germany

    Gerhard Gross

Authors
  1. Gerhard Gross
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Karla Drescher
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gerhard Gross .

Editor information

Editors and Affiliations

  1. Dept. Psychiatry, University of California San Diego, Gilman Drive 9500, La Jolla, 92093-0804, California, USA

    Mark A. Geyer

  2. Institut für Pharmakologie, Universität, Neuroscience Research, Abbott GmbH & Co. KG, Knollstraße, Ludwigshafen, 67061, Germany

    Gerhard Gross

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Gross, G., Drescher, K. (2012). The Role of Dopamine D3 Receptors in Antipsychotic Activity and Cognitive Functions. In: Geyer, M., Gross, G. (eds) Novel Antischizophrenia Treatments. Handbook of Experimental Pharmacology, vol 213. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-25758-2_7

Download citation

Publish with us

Policies and ethics

Search

Navigation