Skip to main content
PMC home page
CNS Drug Reviews logoLink to CNS Drug Reviews
. 2006 Jun 7;9(2):141–158. doi: 10.1111/j.1527-3458.2003.tb00246.x

BP 897, a Selective Dopamine D3 Receptor Ligand with Therapeutic Potential for the Treatment of Cocaine‐Addiction

F J Garcia‐Ladona 1,✉, B F Cox 2
PMCID: PMC6741652  PMID: 12847556

ABSTRACT

BP 897 is a potent (K i= 0.92 nM) dopamine D3 receptor compound developed for the treatment of cocaine abuse and craving. BP 897 has a high selectivity for the dopamine D3 versus D2 receptors (70‐fold) and a moderate affinity for 5‐HT1A receptors, (K i= 84 nM), adrenergic‐α1 (K i= 60 nM) and ‐α2 adrenoceptors (K i= 83 nM). BP 897 displays significant intrinsic activity at the human dopamine D3 receptor by decreasing forskolin‐stimulated cAMP levels and by stimulating mitogenesis of dopamine D3‐expressing NG108–15 cells. Although these findings suggest that BP 897 is a partial agonist, recent studies in Chinese Hamster Ovary (CHO) cells with expressed dopamine D3 receptors demonstrated that BP 897 is devoid of any intrinsic activity but potently inhibits dopamine agonist effects (pIC50= 9.43 and 9.51) in agonist‐induced acidification rate or increase of GTPγS binding, respectively. In addition, BP 897 inhibits in vivo (EC50= 1.1 mg/kg, i.v.) agonist‐induced decrease of firing rate of dopaminergic neurons in the substantia nigra.

It has been clearly shown that BP 897, 1 mg/kg, i.p., reduces cocaine‐seeking behavior in rats, without producing reinforcement on its own. In rhesus monkeys, BP 897 is not self‐administered (up to 30 μg/kg, i.v.) but reduces cocaine self‐administration. The potential usefulness of BP 897 in the treatment of drug‐seeking behavior is further supported by its effects in drug conditioning models. Although BP 897 reduces L‐DOPA‐induced dyskinesia in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated monkeys, it provokes a return of parkinsonian symptoms. At high doses BP 897 has been reported to produce catalepsy in rats. Pharmacokinetic and toxicological data have not yet been published. These interesting preclinical findings with BP 897 provide additional validation for dopamine D3 receptor as a therapeutic target for the treatment of cocaine abuse and its associated central nervous system (CNS) disorders. BP 897 recently entered phase II clinical studies.

Keywords: BP 897, Cocaine, Craving, D3 receptors, Drug abuse, Withdrawal

Full Text

The Full Text of this article is available as a PDF (134.3 KB).

References

  • 1. Accili D, Fishburn CS, Drago J, et al. A targeted mutation of the D3 dopamine receptor gene is associated with hyperactivity in mice. Proc Natl Acad Sci USA 1996;93:1945–1949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2. Acri JB, Carter SR, Alling K, et al. Assessment of cocaine‐like discriminative stimulus effects of dopamine D3 receptor ligands. Eur J Pharmacol 1995;281:R7–R9. [DOI] [PubMed] [Google Scholar]
  • 3. Audinot V, Newman‐Tancredi A, Gobert A, et al. 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 1998;287:187–197. [PubMed] [Google Scholar]
  • 4. Aujla H, Sokoloff P, Beninger RJ. A dopamine D3 receptor partial agonist blocks the expression of conditioned activity. Neuroreport 2002;13:173–176. [DOI] [PubMed] [Google Scholar]
  • 5. Aulakh CS, Wozniak KM, Haas M, Hill JL, Zohar J, Murphy DL. Food intake, neuroendocrine and temperature effects of 8‐OHDPAT in the rat. Eur J Pharmacol 1988;146:253–259. [DOI] [PubMed] [Google Scholar]
  • 6. Beardsley PM. Is there a role for dopamine D3 R agents in drug abuse Behav Pharmacol Soc Eur Behav Pharmacol Soc 1999;[Abstract]. [Google Scholar]
  • 7. Beardsley PM, Sokoloff P, Balster RL, Schwartz JC. The D3 R partial agonist, BP 897, attenuates the discriminative stimulus effects of cocaine and D‐amphetamine and is not self‐administered. Behav Pharmacol 2001;12:1–11. [DOI] [PubMed] [Google Scholar]
  • 8. Boulay D, Depoortere R, Rostene W, Perrault G, Sanger DJ. Dopamine D3 receptor agonists produce similar decreases in body temperature and locomotor activity in D3 knock‐out and wild‐type mice. Neuropharmacology 1999;38:555–565. [DOI] [PubMed] [Google Scholar]
  • 9. Boulay D, Depoortere R, Perrault G, Borrelli E, Sanger DJ. Dopamine D2 receptor knock‐out mice are insensitive to the hypolocomotor and hypothermic effects of dopamine D2/D3 receptor agonists. Neuropharmacology 1999;38:1389–1396. [DOI] [PubMed] [Google Scholar]
  • 10. Bowery B, Rothwell LA, Seabrook GR. Comparison between the pharmacology of dopamine receptors mediating the inhibition of cell firing in rat brain slices through the substantia nigra pars compacta and ventral tegmental area. Br J Pharmacol 1994;112:873–880. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11. Bowery BJ, Razzaque Z, Emms F, et al. 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 1996;119:1491–1497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12. Bressand K, Louvel J, Sokoloff P. Role of D3 dopamine receptor in cocaine‐cue conditioning: An in vivo electrophysiological study. Dopamine 2002;P2.4:126 [Abstract]. [Google Scholar]
  • 13. Caine SB, Koob GF. Modulation of cocaine self‐administration in the rat through D3 dopamine receptors. Science 1993;260:1814–1816. [DOI] [PubMed] [Google Scholar]
  • 14. Caine SB, Koob GF, Parsons LH, Everitt BJ, Schwartz JC, Sokoloff P. D3 receptor test in vitro predicts decreased cocaine self‐administration in rats. Neuroreport 1997;8:2373–2377. [DOI] [PubMed] [Google Scholar]
  • 15. Coldwell MC, Boyfield I, Brown AM, Stemp G, Middlemiss DN. Pharmacological characterization of extracellular acidification rate responses in human D2 (long), D3 and D4.4 receptors expressed in Chinese hamster ovary cells. Br J Pharmacol 1999;127:1135–1144. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16. Deutch A, Lee MC, Iadarola M. Regionally specific effects of atypical antipsychotic drugs on striatal Fos expression: The nucleus accumbens shell as a locus of antipsychotic action. Mol Cell Neurosci 1992;3:332–341. [DOI] [PubMed] [Google Scholar]
  • 17. Eriksson E, Svensson K, Clark D. The putative dopamine autoreceptor agonist B‐HT 920 decreases nigral dopamine cell firing rate and prolactin release in rat. Life Sci 1985;36:1819–1827. [DOI] [PubMed] [Google Scholar]
  • 18. Fischman MW, Johanson CE. Cocaine In: Schuster Ch. R., Kuhar MJ, Eds. Pharmacological aspects of drug dependence. Vol. 118 Heidelberg : Springer‐Verlag, 1996:159–195. [Google Scholar]
  • 19. Frantz K, Babcock D, Van Hartesveldt C. The locomotor effects of a putative dopamine D3 receptor agonist in developing rats. Eur J Pharmacol 1996;302:1–6. [DOI] [PubMed] [Google Scholar]
  • 20. Gawing FH. Neuroleptic reduction of cocaine‐induced paranoia but not euphoria. Psychopharmacology (Berl) 1986;90:142–143. [DOI] [PubMed] [Google Scholar]
  • 21. Gawing FH. Cocaine addiction: Psychology and neurophysiology. Science 1991;251:1580–1586. [DOI] [PubMed] [Google Scholar]
  • 22. Giros B, Jaber M, Jones SR, Wightman RM, Caron MG. Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. Nature 1996;379:606–612. [DOI] [PubMed] [Google Scholar]
  • 23. Gmeiner P, Hübner H, Bettinetti L, Schlotter K. Highly selective dopamine D3 receptor partial agonists: Molecular design and pharmacological investigations. Dopamine 2002;P1.24:74 [Abstract]. [Google Scholar]
  • 24. Graybiel AM, Moratalla R, Robertson HA. Amphetamine and cocaine induce drug‐specific activation of the c‐fos gene in striosome‐matrix compartments and limbic subdivisions of the striatum. Proc Natl Acad Sci USA 1990;87:6912–6916. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25. Gross G, Bialojan S, Drescher K, et al. Evaluation of D3 receptor antagonists. Eur Neuropsychopharmacol 1997;7:S120. [Google Scholar]
  • 26. Haney M, Collins ED, Ward AS, Foltin RW, Fischman MW. Effect of a selective dopamine D1 agonist (ABT‐431) on smoked cocaine self‐administration in humans. Psychopharmacologia 1999;143:102–110. [DOI] [PubMed] [Google Scholar]
  • 27. Herrling S, Woods JH. Chlorpromazine effects on cocaine‐reinforced responding in rhesus monkeys: Reciprocal modification of rate‐altering effects of drugs. J Pharmacol Exp Ther 1980;214:354–361. [PubMed] [Google Scholar]
  • 28. Huang Y, Martinez D, Simpson N, Guo N, Montoya J, Laruelle M. Synthesis and evaluation of [C‐11] BP 897 as a potential PET radioligand for Da D3 receptor. Soc Neurosci 2000;[Abstract]. [Google Scholar]
  • 29. Hubner CB, Koob GF. Bromocriptine produces decreases in cocaine self‐administration in the rat. Neuropharmacology 1990;3:101–108. [PubMed] [Google Scholar]
  • 30. Jaffe JH. Drug addiction and drug abuse In: Goodman Gilman A, Rall TW, Nies AS, et al., Eds. The pharmacological basis of therapeutics. New York : McGraw‐Hill Inc., 1992:522–573. [Google Scholar]
  • 31. Joyce JN. Dopamine D3 receptors, from anatomy to neuropsychiatry. Neuro Sci News 1999;2:11–21. [Google Scholar]
  • 32. Joyce JN. Dopamine D3 receptor as a therapeutic target for antipsychotic and antiparkinsonian drugs. Pharmacol Ther 2001;90:231–259. [DOI] [PubMed] [Google Scholar]
  • 33. Jung MY, Schmauss C. Decreased c‐fos responses to dopamine D1 receptor agonist stimulation in mice deficient for D3 receptors. J Biol Chem 1999;274:29406–29412. [DOI] [PubMed] [Google Scholar]
  • 34. Kelland MD, Freeman AS, Chiodo LA. (+/‐)‐3,4‐Methylenedioxymethamphetamine‐induced changes in the basal activity and pharmacological responsiveness of nigrostriatal dopamine neurons. Eur J Pharmacol 1989;169:11–21. [DOI] [PubMed] [Google Scholar]
  • 35. Koeltzow TE, Xu M, Cooper DC, et al. Alterations in dopamine release but not dopamine autoreceptor function in dopamine D3 receptor mutant mice. J Neurosci 1998;18:2231–2238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36. Koob GF. Drugs of abuse: Anatomy, pharmacology and function of reward pathways. TIPS 1992;13:177–184. [DOI] [PubMed] [Google Scholar]
  • 37. Kreiss DS, Bergstrom DA, Gonzalez AM, Huang KX, Sibley DR, Walters JR. Dopamine receptor agonist potencies for inhibition of cell firing correlate with dopamine D3 receptor binding affinities. Eur J Pharmacol 1995;277:209–214. [DOI] [PubMed] [Google Scholar]
  • 38. Kuhar MJ, Pilotte NS. Neurochemical changes in cocaine withdrawal. TIPS 1996;17:260–264. [DOI] [PubMed] [Google Scholar]
  • 39. Landwehrmeyer B, Mengod G, Palacios JM. Dopamine D3 receptor mRNA and binding sites in human brain. Brain Res Mol Brain Res 1993;18:187–192. [DOI] [PubMed] [Google Scholar]
  • 40. Landwehrmeyer B, Mengod G, Palacios JM. Differential visualization of dopamine D2 and D3 receptor sites in rat brain. A comparative study using in situ hybridization histochemistry and ligand binding autoradiography. Eur J Neurosci 1993;5:145–153. [DOI] [PubMed] [Google Scholar]
  • 41. Laurier LG, Corrigall WA, George SR. Dopamine receptor density, sensitivity and mRNA levels are altered following self‐administration of cocaine in the rat. Brain Res 1994;634:31–40. [DOI] [PubMed] [Google Scholar]
  • 42. Le Foll B, Frances H, Ferry S, Diaz J, Schwartz JC, Sokoloff P. The dopamine D3 receptor modulates reactivity to cocaine, morphine, and nicotine‐associated cues: Role of the somatosensory cortex. Dopamine 2002;P2.10:132 [Abstract]. [Google Scholar]
  • 43. Le Foll B, Schwartz JC, Sokoloff P. Dopamine D3 receptor agents as potential new medications for drug addiction. Eur Psychiatry 2000;15:140–146. [DOI] [PubMed] [Google Scholar]
  • 44. Lejeune F, Millan MJ. Activation of dopamine D3 autoreceptors inhibits firing of ventral tegmental dopaminergic neurones in vivo. Eur J Pharmacol 1995;275:R7–R9. [DOI] [PubMed] [Google Scholar]
  • 45. Levant B, Grigoriadis DE, DeSouza EB. [3H]quinpirole binding to putative D2 and D3 dopamine receptors in rat brain and pituitary gland: A quantitative autoradiographic study. J Pharmacol Exp Ther 1993;264:991–1001. [PubMed] [Google Scholar]
  • 46. Levant B, Vansell NR. In vivo occupancy of D2 dopamine receptors by nafadotride. Neuropsychopharmacology 1997;17:67–71. [DOI] [PubMed] [Google Scholar]
  • 47. Levant B, Ling ZD, Carvey PM. Dopamine D3 receptors. Relevance for the drug treatment of Parkinson's disease. CNS Drugs 1999;12:391–402. [Google Scholar]
  • 48. Levesque D, Diaz J, Pilon C, et al. Identification, characterization, and localization of the dopamine D3 receptor in rat brain using 7–[3H]hydroxy‐N, N‐di‐n‐propyl‐2‐aminotetralin. Proc Natl Acad Sci USA 1992;89:8155–8159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49. Lin JY, Yen SH, Shieh KR, Liang SL, Pan JT. Dopamine and 7‐OH‐DPAT may act on D3 receptors to inhibit tuberoinfundibular dopaminergic neurons. Brain Res Bull 2000;52:567–572. [DOI] [PubMed] [Google Scholar]
  • 50. MacGibbon GA, Lawlor PA, Bravo R, Dragunow M. Clozapine and haloperidol produce a differential pattern of immediate early gene expression in rat caudate‐putamen, nucleus accumbens, lateral septum and islands of Calleja. Brain Res Mol Brain Res 1994;23:21–32. [DOI] [PubMed] [Google Scholar]
  • 51. Malmberg A, Mikaels A, Mohell N. Agonist and inverse agonist activity at the dopamine D3 receptor measured by guanosine 5′‐gamma‐thio‐triphosphate‐35S‐binding. J Pharmacol Exp Ther 1998;285:119–126. [PubMed] [Google Scholar]
  • 52. Mash DC. Are neuroadaptations in D3 dopamine receptors linked to the development of cocaine dependence Mol Psychiatry 1997;2:7–8. [PubMed] [Google Scholar]
  • 53. Meador‐Woodruff JH, Little KY, Damask SP, Mansour A, Watson SJ. Effects of cocaine on dopamine receptor gene expression: A study in the postmortem human brain. Biol Psychiatry 1993;34:348–355. [DOI] [PubMed] [Google Scholar]
  • 54. Mello NK, Negus SS. Preclinical evaluation of pharmacotherapies for treatment of cocaine and opioid abuse using drug self‐administration procedures. Neuropsychopharmacology 1996;14:375–424. [DOI] [PubMed] [Google Scholar]
  • 55. Merchant KM, Figur LM, Evans DL. Induction of c‐fos mRNA in rat medial prefrontal cortex by antipsychotic drugs: Role of dopamine D2 and D3 receptors. Cerebral Cortex 1991;6:561–570. [DOI] [PubMed] [Google Scholar]
  • 56. Millan MJ, Peglion JL, Vian J, et al. 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 1995;275:885–898. [PubMed] [Google Scholar]
  • 57. Millan MJ, Gobert A, Newman‐Tancredi A, et al. 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 2000;293:1048–1062. [PubMed] [Google Scholar]
  • 58. Murray AM, Ryoo HL, Gurevich E, Joyce JN. Localization of dopamine D3 receptors to mesolimbic and D2 receptors to mesostriatal regions of human forebrain. Proc Natl Acad Sci USA 1994;91:11271–11275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 59. Nader MA, Green KL, Luedtke RR, Mach RH. The effects of benzamide analogues on cocaine self‐administration in rhesus monkeys. Psychopharmacologia 1999;147:143–152. [DOI] [PubMed] [Google Scholar]
  • 60. Newman‐Tancredi A, Conte C, Chaput C, Verriele L, Millan MJ. Agonist and inverse agonist efficacy at human recombinant serotonin 5‐HT1A receptors as a function of receptor: G‐protein stoichiometry. Neuropharmacology 1997;36:451–459. [DOI] [PubMed] [Google Scholar]
  • 61. Newman‐Tancredi A, Cussac D, Audinot V, Pasteau V, Gavaudan S, Millan MJ. G‐protein activation by human dopamine D3 receptors in high‐expressing Chinese hamster ovary cells: A guanosine‐5′‐O‐(3‐[35S]thio)‐triphosphate binding and antibody study. Mol Pharmacol 1999;55:564–574. [PubMed] [Google Scholar]
  • 62. Ng JP, Hubert GW, Justice JB Jr. Increased stimulated release and uptake of dopamine in nucleus accumbens after repeated cocaine administration as measured by in vivo voltammetry. J Neurochem 1991;56:1485–1492. [DOI] [PubMed] [Google Scholar]
  • 63. O'Brien CP. Drug addiction and drug abuse In: Hardman JG, Limbird LE, Eds. The pharmacological basis of therapeutics. 10th Edition McGraw‐Hill, 2001:621–642. [Google Scholar]
  • 64. Perachon S, Betancur C, Pilon C, Rostene W, Schwartz JC, Sokoloff P. Role of dopamine D3 receptors in thermoregulation: A reappraisal. Neuroreport 2000;11:221–225. [DOI] [PubMed] [Google Scholar]
  • 65. Piercey MF, Hoffmann WE, Smith MW, Hyslop DK. Inhibition of dopamine neuron firing by pramipexole, a dopamine D3 receptor‐preferring agonist: Comparison to other dopamine receptor agonists. Eur J Pharmacol 1996;312:35–44. [DOI] [PubMed] [Google Scholar]
  • 66. Pilla M, Perachon S, Sautel F, et al. Selective inhibition of cocaine‐seeking behaviour by a partial dopamine D3 receptor agonist. Nature 1999;400:371–375. [DOI] [PubMed] [Google Scholar]
  • 67. Pilla M, Hutcheson DM, Adib‐Samil P, Potton E, Everitt BJ. Seeking responses for cocaine, heroin and natural reinforcers are differentially modulated by dopamine D3 receptors. Soc Neurosci 2001;27:647.16. [Google Scholar]
  • 68. Pouletty P. Drug addictions: Towards socially accepted and medically treatable diseases. Nat Rev Drug Discovery 2002;1:731–736. [DOI] [PubMed] [Google Scholar]
  • 69. Pulvirenti L, Koob GF. Lisuride reduces intravenous cocaine self‐administration in rats. Pharmacol Biochem Behav 1994;47:819–822. [DOI] [PubMed] [Google Scholar]
  • 70. Pulvirenti L, Koob GF. Dopamine receptor agonists, partial agonists and psycho stimulant addiction. TIPS 1994;15:374–379. [DOI] [PubMed] [Google Scholar]
  • 71. Richtand NM, Woods SC, Berger SP, Strakowski SM. D3 dopamine receptor, behavioral sensitization, and psychosis. Neurosci Biobehav Rev 2001;25:427–443. [DOI] [PubMed] [Google Scholar]
  • 72. Ridray S, Griffon N, Mignon V, et al. 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 1998;10:1676–1686. [DOI] [PubMed] [Google Scholar]
  • 73. Roberts DCS, Vickers G. Atypical neuroleptics increase self‐administration of cocaine: An evaluation of a behavioural screen for antipsychotic activity. Psychopharmacology (Berl) 1984;82:135–139. [DOI] [PubMed] [Google Scholar]
  • 74. Roberts DCS, Loh EA, Vickers G. Self‐administraton of cocaine on a progressive ratio schedule in rats: Dose‐response relationship and effect of haloperidol pretreatment. Psychopharmacology (Berl) 1989;97:535–538. [DOI] [PubMed] [Google Scholar]
  • 75. Robertson GS, Fibiger HC. Neuroleptics increase c‐fos expression in the forebrain: Contrasting effects of haloperidol and clozapine. Neuroscience 1992;46:315–328. [DOI] [PubMed] [Google Scholar]
  • 76. Rocha B. Cocaine self‐administration in dopamine‐transporter knockout mice. Nat Neurosci 1998;1:132–137. [DOI] [PubMed] [Google Scholar]
  • 77. Ruskin DN, Marshall JF. Amphetamine‐ and cocaine‐induced fos in the rat striatum depends on D2 dopamine receptor activation. Synapse 1994;18:233–240. [DOI] [PubMed] [Google Scholar]
  • 78. Scanley BE, Gandelman MS, Laruelle M, et al. [123I]IPCIT and [123I][beta]‐CIT as SPECT tracers for the dopamine transporter: A comparative analysis in nonhuman primates. Nucl Med Biol 2000;27:13–21. [DOI] [PubMed] [Google Scholar]
  • 79. Scarselli M, Novi F, Schallmach E, et al. D2/D3 dopamine receptor heterodimers exhibit unique functional properties. J Biol Chem 2001;276:30308–30314. [DOI] [PubMed] [Google Scholar]
  • 80. Schoemaker H, Pimoule C, Arbilla S, Scatton B, Javoy‐Agid F, Langer SZ. Sodium‐dependent [3H]cocaine binding associated with dopamine uptake sites in the rat striatum and human putamen decrease after dopamine denervation and in Parkinson's disease. Naunyn-Schmiedeberg's Arch Pharmacol 1985;329:227–235. [DOI] [PubMed] [Google Scholar]
  • 81. . SCRIP. Bioproject acquires GlaxoSmithKline research unit. SCRIP World Pharm News 2001;2679:11. [Google Scholar]
  • 82. Seabrook GR, Kemp JA, Freedman SB, Patel S, Sinclair HA, McAllister G. Functional expression of human D3 dopamine receptors in differentiated neuroblastoma gliomaNG108–15 cells. Br J Pharmacol 1994;111:391–393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 83. Segal DM, Moraes CT, Mash DC. Up‐regulation of D3 dopamine receptor mRNA in the nucleus accumbens of human cocaine fatalities. Brain Res Mol Brain Res 1997;45:335–339. [DOI] [PubMed] [Google Scholar]
  • 84. Self DW, Barnhart WJ, Lehman DA, Nestler EJ. Opposite modulation of cocaine‐seeking behavior by D1‐and D2‐like dopamine receptor agonists. Science 1996;271:1586–1589. [DOI] [PubMed] [Google Scholar]
  • 85. Sinnott RS, Mach RH, Nader MA. Dopamine D2/D3 receptors modulate cocaine's reinforcing and discriminative stimulus effects in rhesus monkeys. Drug Alcohol Depend 1999;54:97–110. [DOI] [PubMed] [Google Scholar]
  • 86. Sokoloff P, Giros B, Martres MP, Bouthenet ML, Schwartz JC. Molecular cloning and characterization of a novel dopamine receptor D3 as a target for neuroleptics. Nature 1990;347:146–151. [DOI] [PubMed] [Google Scholar]
  • 87. Sokoloff P, Giros B, Martres MP, et al. Localization and function of the D3 dopamine receptor. Arzneimittelforschung 1992;42:224–230. [PubMed] [Google Scholar]
  • 88. Sokoloff P, Martres MP, Giros B, Bouthenet ML, Schwartz JC. The third dopamine receptor D3 as a novel target for antipsychotics. Biochem Pharmacol 1992;43:659–666. [DOI] [PubMed] [Google Scholar]
  • 89. Spealman RD, Bergman J, Madras BK, Kamien JB, Melia KF. Role of D1 and D2 dopamine receptors in the behavioral effects of cocaine. Neurochem Int 1992;20 (Suppl): 147S–152S. [DOI] [PubMed] [Google Scholar]
  • 90. Staley JK, Mash DC. Adaptive increase in D3 dopamine receptors in the brain reward circuits of human cocaine fatalities. J Neurosci 1996;16:6100–6106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 91. Steiner H, Gerfen CR. Cocaine‐induced c‐fos messenger RNA is inversely related to dynorphin expression in striatum. J Neurosci 1993;13:5066–5081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 92. Tahar H, Grondin R, Doan VD, et al. Behavioural effects of selective dopamine D3 receptor agonist/antagonist in primate model of Parkinson's disease. Soc Neurosci Abstr 1999;25:640. [Google Scholar]
  • 93. Unterwald EM, Ho A, Rubenfeld JM, Kreek MJ. Time course of the development of behavioral sensitization and dopamine receptor up‐regulation during binge cocaine administration. J Pharmacol Exp Ther 1994;270:1387–1396. [PubMed] [Google Scholar]
  • 94. Vanhauwe JF, Fraeyman N, Francken BJ, Luyten WH, Leysen JE. Comparison of the ligand binding and signaling properties of human dopamine D2 and D3 receptors in Chinese hamster ovary cells. J Pharmacol Exp Ther 1999;290:908–916. [PubMed] [Google Scholar]
  • 95. Vorel SR, Ashby CR Jr, Paul M, et al. Dopamine D3 receptor antagonism inhibits cocaine‐seeking and cocaine‐enhanced brain reward in rats. J Neurosci 2002;22:9595–9603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 96. Wallace DR, Mactutus CF, Booze RM. Repeated intravenous cocaine administration: Locomotor activity and dopamine D2/D3 receptors. Synapse 1996;23:152–163. [DOI] [PubMed] [Google Scholar]
  • 97. Wedd MR, Vanover KE, Woolverton WL. Reinforcing effect of the D1 agonist SKF 81297 in rhesus monkeys. Psychopharmacology (Berl) 1993;113:51–52. [DOI] [PubMed] [Google Scholar]
  • 98. Weiss F, Markou A, Lorang MT, Koob GF. Basal extracellular dopamine levels in the nucleus accumbens are decreased during cocaine withdrawal after unlimited‐access self‐administration. Brain Res 1992;593:314–318. [DOI] [PubMed] [Google Scholar]
  • 99. Werkman TR, Kruse CG, Nievelstein H, Long SK, Wadman WJ. In vitro modulation of the firing rate of dopamine neurons in the rat substantia nigra pars compacta and the ventral tegmental area by antipsychotic drugs. Neuropharmacology 2001;40:927–936. [DOI] [PubMed] [Google Scholar]
  • 100. Wicke K, Garcia‐Ladona J. 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 2001;424:85–90. [DOI] [PubMed] [Google Scholar]
  • 101. Wise RA. Neurobiology of addiction. Curr Opin Neurobiol 2000;6:243–251. [DOI] [PubMed] [Google Scholar]
  • 102. Withers NW, Pulvirenti L, Koob GF, Gillin JC. Cocaine abuse and dependence. J Clin Psychopharmacol 1995;15:63–78. [DOI] [PubMed] [Google Scholar]
  • 103. Wood MD, Boyfield I, Nash DJ, Jewitt FR, Avenell KY, Riley GJ. Evidence for antagonist activity of the dopamine D3 receptor partial agonist, BP 897, at human dopamine D3 receptor. Eur J Pharmacol 2000;407:47–51. [DOI] [PubMed] [Google Scholar]
  • 104. Zapata A, Witkin JM, Shippenberg TS. Selective D3 receptor agonist effects of (+)‐PD 128907 on dialysate dopamine at low doses. Neuropharmacology 2001;41:351–359. [DOI] [PubMed] [Google Scholar]

Articles from CNS Drug Reviews are provided here courtesy of Wiley

RESOURCES