Advertisement

Dopamine Receptor Signaling and Current and Future Antipsychotic Drugs

  • Kevin N. Boyd
  • Richard B. MailmanEmail author
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 212)

Abstract

All currently efficacious antipsychotic drugs have as part of their mechanism the ability to attenuate some or all of the signaling through the dopamine D2 receptor. More recently, the dopamine D1 receptor has been hypothesized to be a promising target for the treatment of negative and/or cognitive aspects of schizophrenia that are not improved by current antipsychotics. Although cAMP has been presumed to be the primary messenger for signaling through the dopamine receptors, the last decade has unveiled a complexity that has provided exciting avenues for the future discovery of antipsychotic drugs (APDs). We review the signaling mechanisms of currently approved APDs at dopamine D2 receptors, and note that aripiprazole is a compound that is clearly differentiated from other approved drugs. Although aripiprazole has been postulated to cause dopamine stabilization due to its partial D2 agonist properties, a body of literature suggests that an alternative mechanism, functional selectivity, is of primary importance. Finally, we review the signaling at dopamine D1 receptors, and the idea that drugs that activate D1 receptors may have use as APDs for improving negative and cognitive symptoms. We address the current state of drug discovery in the D1 area and its relationship to novel signaling mechanisms. Our conclusion is that although the first APD targeting dopamine receptors was discovered more than a half-century ago, recent research advances offer the possibility that novel and/or improved drugs will emerge in the next decade.

Keywords

Dopamine Schizophrenia Antipsychotic drug Functional selectivity Drug discovery 

Notes

Acknowledgments

This work was supported, in part, by Public Health Service research grants MH082441, MH40537, NS39036, ES007126, and GM007040.

References

  1. Agnati LF, Ferre S, Genedani S, Leo G, Guidolin D, Filaferro M, Carriba P, Casado V, Lluis C, Franco R, Woods AS, Fuxe K (2006) Allosteric modulation of dopamine D2 receptors by homocysteine. J Proteome Res 5:3077–3083PubMedGoogle Scholar
  2. Albin RL, Young AB, Penney JB (1989) The functional anatomy of basal ganglia disorders. Trends Neurosci 12:366–375PubMedGoogle Scholar
  3. Alimohamad H, Rajakumar N, Seah YH, Rushlow W (2005) Antipsychotics alter the protein expression levels of beta-catenin and GSK-3 in the rat medial prefrontal cortex and striatum. Biol Psychiatry 57:533–542PubMedGoogle Scholar
  4. Andrisani OM (1999) CREB-mediated transcriptional control. Crit Rev Eukaryot Gene Expr 9:19–32PubMedGoogle Scholar
  5. Arnsten AF, Cai JX, Murphy BL, Goldman-Rakic PS (1994) Dopamine D1 receptor mechanisms in the cognitive performance of young adult and aged monkeys. Psychopharmacology 116:143–151PubMedGoogle Scholar
  6. Bateup HS, Svenningsson P, Kuroiwa M, Gong S, Nishi A, Heintz N, Greengard P (2008) Cell type-specific regulation of DARPP-32 phosphorylation by psychostimulant and antipsychotic drugs. Nat Neurosci 11:932–939PubMedGoogle Scholar
  7. Beaulieu JM, Caron MG (2005) Beta-arrestin goes nuclear. Cell 123:755–757PubMedGoogle Scholar
  8. Beaulieu JM, Gainetdinov RR (2011) The physiology, signaling, and pharmacology of dopamine receptors. Pharmacol Rev 63:182–217PubMedGoogle Scholar
  9. Beaulieu JM, Gainetdinov RR, Caron MG (2007a) The Akt-GSK-3 signaling cascade in the actions of dopamine. Trends Pharmacol Sci 28:166–172PubMedGoogle Scholar
  10. Beaulieu JM, Marion S, Rodriguiz RM, Medvedev IO, Sotnikova TD, Ghisi V, Wetsel WC, Lefkowitz RJ, Gainetdinov RR, Caron MG (2008) A beta-arrestin 2 signaling complex mediates lithium action on behavior. Cell 132:125–136PubMedGoogle Scholar
  11. 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 122:261–273PubMedGoogle Scholar
  12. Beaulieu JM, Sotnikova TD, Yao WD, Kockeritz L, Woodgett JR, Gainetdinov RR, Caron MG (2004) Lithium antagonizes dopamine-dependent behaviors mediated by an AKT/glycogen synthase kinase 3 signaling cascade. Proc Natl Acad Sci USA 101:5099–5104PubMedGoogle Scholar
  13. Beaulieu JM, Tirotta E, Sotnikova TD, Masri B, Salahpour A, Gainetdinov RR, Borrelli E, Caron MG (2007b) Regulation of Akt signaling by D2 and D3 dopamine receptors in vivo. J Neurosci 27:881–885PubMedGoogle Scholar
  14. Block GA, Martin KJ, de Francisco AL, Turner SA, Avram MM, Suranyi MG, Hercz G, Cunningham J, Abu Alfa AK, Messa P, Coyne DW, Locatelli F, Cohen RM, Evenepoel P, Moe SM, Fournier A, Braun J, McCary LC, Zani VJ, Olson KA, Drueke TB, Goodman WG (2004) Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. N Engl J Med 350:1516–1525PubMedGoogle Scholar
  15. Bokoch GM, Katada T, Northup JK, Hewlett EL, Gilman AG (1983) Identification of the predominant substrate for ADP-ribosylation by islet activating protein. J Biol Chem 258:2072–2075PubMedGoogle Scholar
  16. 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 564:203–219PubMedGoogle Scholar
  17. Boyer JL, Graber SG, Waldo GL, Harden TK, Garrison JC (1994) Selective activation of phospholipase C by recombinant G-protein alpha- and beta gamma-subunits. J Biol Chem 269:2814–2819PubMedGoogle Scholar
  18. Brami-Cherrier K, Valjent E, Garcia M, Pages C, Hipskind RA, Caboche J (2002) Dopamine induces a PI3-kinase-independent activation of Akt in striatal neurons: a new route to cAMP response element-binding protein phosphorylation. J Neurosci 22:8911–8921PubMedGoogle Scholar
  19. Brewster WK, Nichols DE, Riggs RM, Mottola DM, Lovenberg TW, Lewis MH, Mailman RB (1990) trans-10,11-dihydroxy-5,6,6a,7,8,12b-hexahydrobenzo[a]phenanthridine: a highly potent selective dopamine D1 full agonist. J Med Chem 33:1756–1764PubMedGoogle Scholar
  20. Burris KD, Molski TF, Xu C, Ryan E, Tottori K, Kikuchi T, Yocca FD, Molinoff PB (2002) Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human dopamine D2 receptors. J Pharmacol Exp Ther 302:381–389PubMedGoogle Scholar
  21. Cai JX, Arnsten AF (1997) Dose-dependent effects of the dopamine D1 receptor agonists A77636 or SKF81297 on spatial working memory in aged monkeys. J Pharmacol Exp Ther 283:183–189PubMedGoogle Scholar
  22. Carlsson A (1964) Evidence for a role of dopamine in extrapyramidal functions. Acta Neuroveg (Wien) 26:484–493Google Scholar
  23. Carlsson A, Lindqvist M (1963) Effect of chlorpromazine and haloperidol on formation of 3-methoxytyramine and normetanephrine in mouse brain. Acta Pharmacol Toxicol (Copenh) 20:140–144Google Scholar
  24. Carlsson A, Lindqvist M, Magnusson T (1957) 3,4-Dihydroxyphenylalanine and 5-hydroxytryptophan as reserpine antagonists. Nature 180(4596):1200PubMedGoogle Scholar
  25. Cass WA, Zahniser NR (1991) Potassium channel blockers inhibit D2 dopamine, but not A1 adenosine, receptor-mediated inhibition of striatal dopamine release. J Neurochem 57:147–152PubMedGoogle Scholar
  26. Castner SA, Williams GV, Goldman-Rakic PS (2000) Reversal of antipsychotic-induced working memory deficits by short-term dopamine D1 receptor stimulation. Science 287:2020–2022PubMedGoogle Scholar
  27. Chen J, Rusnak M, Luedtke RR, Sidhu A (2004) D1 dopamine receptor mediates dopamine-induced cytotoxicity via the ERK signal cascade. J Biol Chem 279:39317–39330PubMedGoogle Scholar
  28. Chio CL, Drong RF, Riley DT, Gill GS, Slightom JL, Huff RM (1994) D4 dopamine receptor-mediated signaling events determined in transfected Chinese hamster ovary cells. J Biol Chem 269:11813–11819PubMedGoogle Scholar
  29. Choi EY, Jeong D, Park KW, Baik JH (1999) G protein-mediated mitogen-activated protein kinase activation by two dopamine D2 receptors. Biochem Biophys Res Commun 256:33–40PubMedGoogle Scholar
  30. Clement-Cormier YC, Kebabian JW, Petzold GL, Greengard P (1974) Dopamine-sensitive adenylate cyclase in mammalian brain: a possible site of action of antipsychotic drugs. Proc Natl Acad Sci USA 71:1113–1117PubMedGoogle Scholar
  31. Conn PJ, Christopoulos A, Lindsley CW (2009) Allosteric modulators of GPCRs: a novel approach for the treatment of CNS disorders. Nat Rev Drug Discov 8:41–54PubMedGoogle Scholar
  32. Corsini GU, Pitzalis GF, Bernardi F, Bocchetta A, Del ZM (1981) The use of dopamine agonists in the treatment of schizophrenia. Neuropharmacology 20:1309–1313PubMedGoogle Scholar
  33. Creese I, Burt DR, Snyder SH (1976) Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science 192:481–483PubMedGoogle Scholar
  34. Dai R, Ali MK, Lezcano N, Bergson C (2008) A crucial role for cAMP and protein kinase A in D1 dopamine receptor regulated intracellular calcium transients. Neurosignals 16:112–123PubMedGoogle Scholar
  35. Darney KJ Jr, Lewis MH, Brewster WK, Nichols DE, Mailman RB (1991) Behavioral effects in the rat of dihydrexidine, a high-potency, full-efficacy D1 dopamine receptor agonist. Neuropsychopharmacology 5:187–195PubMedGoogle Scholar
  36. 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 23:5693–5697PubMedGoogle Scholar
  37. De Camilli P, Macconi D, Spada A (1979) Dopamine inhibits adenylate cyclase in human prolactin-secreting pituitary adenomas. Nature 278:252–254PubMedGoogle Scholar
  38. De Lean A, Stadel JM, Lefkowitz RJ (1980) A ternary complex model explains the agonist-specific binding properties of the adenylate cyclase-coupled beta-adrenergic receptor. J Biol Chem 255:7108–7117PubMedGoogle Scholar
  39. Delay J, Deniker P, Harl JM (1952) Therapeutic method derived from hiberno-therapy in excitation and agitation states. Ann Med Psychol (Paris) 110:267–273Google Scholar
  40. DeLong MR (1990) Primate models of movement disorders of basal ganglia origin. Trends Neurosci 13:281–285PubMedGoogle Scholar
  41. Den Boer JA, van Megen HJ, Fleischhacker WW, Louwerens JW, Slaap BR, Westenberg HG, Burrows GD, Srivastava ON (1995) Differential effects of the D1-DA receptor antagonist SCH39166 on positive and negative symptoms of schizophrenia. Psychopharmacology (Berl) 121:317–322Google Scholar
  42. DiMarzo V, Piomelli D (1992) Participation of prostaglandin E2 in dopamine D2 receptor-dependent potentiation of arachidonic acid release. J Neurochem 59:379–382Google Scholar
  43. Dunlap K, Luebke JI, Turner TJ (1995) Exocytotic Ca2+ channels in mammalian central neurons. Trends Neurosci 18:89–98PubMedGoogle Scholar
  44. Eden RJ, Costall B, Domeney AM, Gerrard PA, Harvey CA, Kelly ME, Naylor RJ, Owen DA, Wright A (1991) Preclinical pharmacology of ropinirole (SK&F 101468-A) a novel dopamine D2 agonist. Pharmacol Biochem Behav 38:147–154PubMedGoogle Scholar
  45. Ehringer H, Hornykiewicz O (1960) Verteilung von Noradrenalin und Dopamin (3-Hydroxytyramine) in Gehirn des Menschen und ihr Verhalten bei Erkrankungen des extrapyramidalen Systems. Klin Wochenschr 38:1236–1239PubMedGoogle Scholar
  46. Feenstra MG, Sumners C, Goedemoed JH, de Vries JB, Rollema H, Horn AS (1983) A comparison of the potencies of various dopamine receptor agonists in models for pre- and postsynaptic receptor activity. Naunyn Schmiedebergs Arch Pharmacol 324:108–115PubMedGoogle Scholar
  47. Fienberg AA, Hiroi N, Mermelstein PG, Song W, Snyder GL, Nishi A, Cheramy A, O’Callaghan JP, Miller DB, Cole DG, Corbett R, Haile CN, Cooper DC, Onn SP, Grace AA, Ouimet CC, White FJ, Hyman SE, Surmeier DJ, Girault J, Nestler EJ, Greengard P (1998) DARPP-32: regulator of the efficacy of dopaminergic neurotransmission. Science 281:838–842PubMedGoogle Scholar
  48. Friedman E, Jin LQ, Cai GP, Hollon TR, Drago J, Sibley DR, Wang HY (1997) D1-like dopaminergic activation of phosphoinositide hydrolysis is independent of D1A dopamine receptors: evidence from D1A knockout mice. Mol Pharmacol 51:6–11PubMedGoogle Scholar
  49. Friedman JH, Berman RM, Goetz CG, Factor SA, Ondo WG, Wojcieszek J, Carson WH, Marcus RN (2006) Open-label flexible-dose pilot study to evaluate the safety and tolerability of aripiprazole in patients with psychosis associated with Parkinson’s disease. Mov Disord 21:2078–2081PubMedGoogle Scholar
  50. Garau L, Govoni S, Stefanini E, Trabucchi M, Spano PF (1978) Dopamine receptors: pharmacological and anatomical evidences indicate that two distinct dopamine receptor populations are present in rat striatum. Life Sci 23:1745–1750PubMedGoogle Scholar
  51. Gay EA, Urban JD, Nichols DE, Oxford GS, Mailman RB (2004) Functional selectivity of D2 receptor ligands in a Chinese hamster ovary hD2L cell line: evidence for induction of ligand-specific receptor states. Mol Pharmacol 66:97–105PubMedGoogle Scholar
  52. George MS, Molnar CE, Grenesko EL, Anderson B, Mu Q, Johnson K, Nahas Z, Knable M, Fernandes P, Juncos J, Huang X, Nichols DE, Mailman RB (2007) A single 20 mg dose of dihydrexidine (DAR-0100), a full dopamine D(1) agonist, is safe and tolerated in patients with schizophrenia. Schizophr Res 93:42–50PubMedGoogle Scholar
  53. Gerfen CR (2000a) Dopamine-mediated gene regulation in models of Parkinson’s disease. Ann Neurol 47:S42–S50PubMedGoogle Scholar
  54. Gerfen CR (2000b) Molecular effects of dopamine on striatal-projection pathways. Trends Neurosci 23:S64–S70PubMedGoogle Scholar
  55. Gerfen CR, Engber TM, Mahan LC, Susel Z, Chase TN, Monsma FJJ, Sibley DR (1990) D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. Science 250:1429–1432PubMedGoogle Scholar
  56. Ghahremani MH, Forget C, Albert PR (2000) Distinct roles for Galphai2 and Gbetagamma in signaling to DNA synthesis and Galpha(i)3 in cellular transformation by dopamine D2S receptor activation in BALB/c 3T3 cells. Mol Cell Biol 20:1497–1506PubMedGoogle Scholar
  57. Giardina WJ, Williams M (2001) Adrogolide HCl (ABT-431; DAS-431), a prodrug of the dopamine D (1) receptor agonist, A-86929: preclinical pharmacology and clinical data. CNS Drug Rev 7:305–316PubMedGoogle Scholar
  58. Giros B, Sokoloff P, Martres MP, Riou JF, Emorine LJ, Schwartz JC (1989) Alternative splicing directs the expression of two D2 dopamine receptor isoforms. Nature 342:923–926PubMedGoogle Scholar
  59. Goldman-Rakic PS, Castner SA, Svensson TH, Siever LJ, Williams GV (2004) Targeting the dopamine D1 receptor in schizophrenia: insights for cognitive dysfunction. Psychopharmacology (Berl) 174:3–16Google Scholar
  60. Graybiel AM (1990) Neurotransmitters and neuromodulators in the basal ganglia. Trends Neurosci 13:244–254PubMedGoogle Scholar
  61. Greengard P, Allen PB, Nairn AC (1999) Beyond the dopamine receptor: the DARPP-32/protein phosphatase-1 cascade. Neuron 23:435–447PubMedGoogle Scholar
  62. Greif GJ, Lin YJ, Liu JC, Freedman JE (1995) Dopamine-modulated potassium channels on rat striatal neurons: specific activation and cellular expression. J Neurosci 15:4533–4544PubMedGoogle Scholar
  63. Han JS, McMahan RW, Holland P, Gallagher M (1997) The role of an amygdalo-nigrostriatal pathway in associative learning. J Neurosci 17:3913–3919PubMedGoogle Scholar
  64. Haney M, Collins ED, Ward AS, Foltin RW, Fischman MW (1999) Effect of a selective dopamine D1 agonist (ABT-431) on smoked cocaine self-administration in humans. Psychopharmacology (Berl) 143:102–110Google Scholar
  65. Hasbi A, O’Dowd BF, George SR (2011) Dopamine D1-D2 receptor heteromer signaling pathway in the brain: emerging physiological relevance. Mol Brain 4:26, PMC3138392PubMedGoogle Scholar
  66. Heijtz RD, Kolb B, Forssberg H (2007) Motor inhibitory role of dopamine D1 receptors: implications for ADHD. Physiol Behav 92:155–160PubMedGoogle Scholar
  67. Hepler JR, Kozasa T, Smrcka AV, Simon MI, Rhee SG, Sternweis PC, Gilman AG (1993) Purification from Sf9 cells and characterization of recombinant Gq alpha and G11 alpha. Activation of purified phospholipase C isozymes by G alpha subunits. J Biol Chem 268:14367–14375PubMedGoogle Scholar
  68. Hersi AI, Rowe W, Gaudreau P, Quirion R (1995) Dopamine D1 receptor ligands modulate cognitive performance and hippocampal acetylcholine release in memory-impaired aged rats. Neuroscience 69:1067–1074PubMedGoogle Scholar
  69. Hotte M, Thuault S, Lachaise F, Dineley KT, Hemmings HC, Nairn AC, Jay TM (2006) D1 receptor modulation of memory retrieval performance is associated with changes in pCREB and pDARPP-32 in rat prefrontal cortex. Behav Brain Res 171:127–133PubMedGoogle Scholar
  70. Huang X, Lawler CP, Lewis MM, Nichols DE, Mailman RB (2001) D1 dopamine receptors. Int Rev Neurobiol 48:65–139PubMedGoogle Scholar
  71. Huber D, Lober S, Hubner H, Gmeiner P (2012) Bivalent molecular probes for dopamine D(2)-like receptors. Bioorg Med Chem 20:455–466PubMedGoogle Scholar
  72. Huff RM (1996) Signal transduction pathways modulated by the D2 subfamily of dopamine receptors. Cell Signal 8:453–459PubMedGoogle Scholar
  73. Huff RM (1997) Signaling pathways modulated by dopamine receptors. In: Neve KA, Neve RL (eds) The dopamine receptors. Humana Press, Totowa, NJ, pp 167–192Google Scholar
  74. Huff RM, Chio CL, Lajiness ME, Goodman LV (1998) Signal transduction pathways modulated by D2-like dopamine receptors. Adv Pharmacol 42:454–457PubMedGoogle Scholar
  75. Hussain T, Lokhandwala MF (1998) Renal dopamine receptor function in hypertension. Hypertension 32:187–197PubMedGoogle Scholar
  76. Hyman SE, Cole RL, Konradi C, Kosofsky BE (1995) Dopamine regulation of transcription factor-target interactions in rat striatum. Chem Senses 20:257–260PubMedGoogle Scholar
  77. Iversen LL (1975) Dopamine receptors in the brain. Science 188:1084–1089PubMedGoogle Scholar
  78. Iwamoto T, Okumura S, Iwatsubo K, Kawabe J, Ohtsu K, Sakai I, Hashimoto Y, Izumitani A, Sango K, Ajiki K, Toya Y, Umemura S, Goshima Y, Arai N, Vatner SF, Ishikawa Y (2003) Motor dysfunction in type 5 adenylyl cyclase-null mice. J Biol Chem 278:16936–16940PubMedGoogle Scholar
  79. Jakubik J, Bacakova L, Lisa V, el Fakahany EE, Tucek S (1996) Activation of muscarinic acetylcholine receptors via their allosteric binding sites. Proc Natl Acad Sci USA 93:8705–8709, PMC38737PubMedGoogle Scholar
  80. Jiang M, Spicher K, Boulay G, Wang Y, Birnbaumer L (2001) Most central nervous system D2 dopamine receptors are coupled to their effectors by Go. Proc Natl Acad Sci USA 98:3577–3582, PMC30695PubMedGoogle Scholar
  81. Jin LQ, Wang HY, Friedman E (2001) Stimulated D1 dopamine receptors couple to multiple Galpha proteins in different brain regions. J Neurochem 78:981–990PubMedGoogle Scholar
  82. Jönsson EG, Ivo R, Forslund K, Mattila-Evenden M, Rylander G, Cichon S, Propping P, Nöthen MM, Asberg M, Sedvall GC (2001) No association between a promoter dopamine D(4) receptor gene variant and schizophrenia. Am J Med Genet 105:525–528PubMedGoogle Scholar
  83. Jönsson EG, Ivo R, Gustavsson JP, Geijer T, Forslund K, Mattila-Evenden M, Rylander G, Cichon S, Propping P, Bergman H, Sberg M, Nöthen MM (2002) No association between dopamine D4 receptor gene variants and novelty seeking. Mol Psychiatry 7:18–20PubMedGoogle Scholar
  84. Kang J, Shi Y, Xiang B, Qu B, Su W, Zhu M, Zhang M, Bao G, Wang F, Zhang X, Yang R, Fan F, Chen X, Pei G, Ma L (2005) A nuclear function of beta-arrestin1 in GPCR signaling: regulation of histone acetylation and gene transcription. Cell 123:833–847PubMedGoogle Scholar
  85. Kanterman RY, Mahan LC, Briley EM, Monsma FJ Jr, Sibley DR, Axelrod J, Felder CC (1991) Transfected D2 dopamine receptors mediate the potentiation of arachidonic acid release in Chinese hamster ovary cells. Mol Pharmacol 39:364–369PubMedGoogle Scholar
  86. Karle J, Clemmesen L, Hansen L, Andersen M, Andersen J, Fensbo C, Sloth-Nielsen M, Skrumsager BK, Lublin H, Gerlach J (1995) NNC 01–0687, a selective dopamine D1 receptor antagonist, in the treatment of schizophrenia. Psychopharmacology (Berl) 121:328–329Google Scholar
  87. Karlsson P, Smith L, Farde L, Harnryd C, Sedvall G, Wiesel FA (1995) Lack of apparent antipsychotic effect of the D1-dopamine receptor antagonist SCH39166 in acutely ill schizophrenic patients. Psychopharmacology (Berl) 121:309–316Google Scholar
  88. Kebabian JW, Calne DB (1979) Multiple receptors for dopamine. Nature 277:93–96PubMedGoogle Scholar
  89. Kebabian JW, Petzold GL, Greengard P (1972) Dopamine-sensitive adenylate cyclase in caudate nucleus of rat brain, and its similarity to the “dopamine receptor”. Proc Natl Acad Sci USA 69:2145–2149PubMedGoogle Scholar
  90. Kenakin T (1990) Drugs and receptors. An overview of the current state of knowledge. Drugs 40:666–687PubMedGoogle Scholar
  91. Kenakin TP (1997) Pharmacologic analysis of drug-receptor interaction. Lippincott-Raven Publishers, Philadelphia, PA. ISBN ISSN/ISBN 0397518153 (hc)Google Scholar
  92. Kikuchi T, Tottori K, Uwahodo Y, Hirose T, Miwa T, Oshiro Y, Morita S (1995) 7-(4-[4-(2,3-Dichlorophenyl)-1-piperazinyl]butyloxy)-3,4-dihydro-2(1H)-quinolinone (OPC-14597), a new putative antipsychotic drug with both presynaptic dopamine autoreceptor agonistic activity and postsynaptic D2 receptor antagonistic activity. J Pharmacol Exp Ther 274:329–336PubMedGoogle Scholar
  93. Kilts CD, Anderson CM, Ely TD, Mailman RB (1988) The biochemistry and pharmacology of mesoamygdaloid dopamine neurons. Ann N Y Acad Sci 537:173–187PubMedGoogle Scholar
  94. Kilts JD, Connery HS, Arrington EG, Lewis MM, Lawler CP, Oxford GS, O’Malley KL, Todd RD, Blake BL, Nichols DE, Mailman RB (2002) Functional selectivity of dopamine receptor agonists. II. Actions of dihydrexidine in D2L receptor-transfected MN9D cells and pituitary lactotrophs. J Pharmacol Exp Ther 301:1179–1189PubMedGoogle Scholar
  95. Kim SJ, Kim MY, Lee EJ, Ahn YS, Baik JH (2004) Distinct regulation of internalization and mitogen-activated protein kinase activation by two isoforms of the dopamine D2 receptor. Mol Endocrinol 18:640–652PubMedGoogle Scholar
  96. Kimura K, White BH, Sidhu A (1995) Coupling of human D-1 dopamine receptors to different guanine nucleotide binding proteins. Evidence that D-1 dopamine receptors can couple to both Gs and G(o). J Biol Chem 270:14672–14678PubMedGoogle Scholar
  97. Kisilevsky AE, Mulligan SJ, Altier C, Iftinca MC, Varela D, Tai C, Chen L, Hameed S, Hamid J, Macvicar BA, Zamponi GW (2008) D1 receptors physically interact with N-type calcium channels to regulate channel distribution and dendritic calcium entry. Neuron 58:557–570PubMedGoogle Scholar
  98. Koga E, Momiyama T (2000) Presynaptic dopamine D2-like receptors inhibit excitatory transmission onto rat ventral tegmental dopaminergic neurones. J Physiol 523(Pt 1):163–173PubMedGoogle Scholar
  99. Kotler M, Manor I, Sever Y, Eisenberg J, Cohen H, Ebstein RP, Tyano S (2000) Failure to replicate an excess of the long dopamine D4 exon III repeat polymorphism in ADHD in a family-based study. Am J Med Genet 96:278–281PubMedGoogle Scholar
  100. Kotowski SJ, Hopf FW, Seif T, Bonci A, von Zastrow M (2011) Endocytosis promotes rapid dopaminergic signaling. Neuron 71:278–290PubMedGoogle Scholar
  101. Kozasa T, Hepler JR, Smrcka AV, Simon MI, Rhee SG, Sternweis PC, Gilman AG (1993) Purification and characterization of recombinant G16 alpha from Sf9 cells: activation of purified phospholipase C isozymes by G-protein alpha subunits. Proc Natl Acad Sci USA 90:9176–9180PubMedGoogle Scholar
  102. Kurose H, Katada T, Amano T, Ui M (1983) Specific uncoupling by islet-activating protein, pertussis toxin, of negative signal transduction via alpha-adrenergic, cholinergic, and opiate receptors in neuroblastoma x glioma hybrid cells. J Biol Chem 258:4870–4875PubMedGoogle Scholar
  103. 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 19:1698–1707PubMedGoogle Scholar
  104. L’hirondel M, Cheramy A, Godeheu G, Artaud F, Saiardi A, Borrelli E, Glowinski J (1998) Lack of autoreceptor-mediated inhibitory control of dopamine release in striatal synaptosomes of D2 receptor-deficient mice. Brain Res 792:253–262PubMedGoogle Scholar
  105. L’hirondel M, Cheramy A, Godeheu G, Glowinski J (1995) Effects of arachidonic acid on dopamine synthesis, spontaneous release, and uptake in striatal synaptosomes from the rat. J Neurochem 64:1406–1409PubMedGoogle Scholar
  106. Lacey MG, Mercuri NB, North RA (1987) Dopamine acts on D2 receptors to increase potassium conductance in neurones of the rat substantia nigra zona compacta. J Physiol (Lond) 392:397–416Google Scholar
  107. LaHoste GJ, Henry BL, Marshall JF (2000) Dopamine D1 receptors synergize with D2, but not D3 or D4, receptors in the striatum without the involvement of action potentials. J Neurosci 20:6666–6671PubMedGoogle Scholar
  108. Lahti AC, Weiler MA, Corey PK, Lahti RA, Carlsson A, Tamminga CA (1998) Antipsychotic properties of the partial dopamine agonist (−)-3-(3-hydroxyphenyl)-N-n-propylpiperidine(preclamol) in schizophrenia. Biol Psychiatry 43:2–11PubMedGoogle Scholar
  109. Lawler CP, Prioleau C, Lewis MM, Mak C, Jiang D, Schetz JA, Gonzalez AM, Sibley DR, Mailman RB (1999) Interactions of the novel antipsychotic aripiprazole (OPC-14597) with dopamine and serotonin receptor subtypes. Neuropsychopharmacology 20:612–627PubMedGoogle Scholar
  110. Lawler CP, Watts VJ, Booth RG, Southerland SB, Mailman RB (1994) Discrete functional selectivity of drugs: OPC-14597 a selective antagonist for post-synaptic dopamine D2 receptors. Soc Neurosci Abstr 20:525Google Scholar
  111. Le Moine C, Bloch B (1995) D1 and D2 dopamine receptor gene expression in the rat striatum: sensitive cRNA probes demonstrate prominent segregation of D1 and D2 mRNAs in distinct neuronal populations of the dorsal and ventral striatum. J Comp Neurol 355:418–426PubMedGoogle Scholar
  112. Lee CH, Park D, Wu D, Rhee SG, Simon MI (1992) Members of the Gq alpha subunit gene family activate phospholipase C beta isozymes. J Biol Chem 267:16044–16047PubMedGoogle Scholar
  113. Lee SP, So CH, Rashid AJ, Varghese G, Cheng R, Lanca AJ, O’Dowd BF, George SR (2004) Dopamine D1 and D2 receptor Co-activation generates a novel phospholipase C-mediated calcium signal. J Biol Chem 279:35671–35678PubMedGoogle Scholar
  114. Leff P, Scaramellini C, Law C, McKechnie K (1997) A three-state receptor model of agonist action. Trends Pharmacol Sci 18(10):355–362PubMedGoogle Scholar
  115. Leonard SK, Anderson CM, Lachowicz JE, Schulz DW, Kilts CD, Mailman RB (2003a) Amygdaloid D1 receptors are not linked to stimulation of adenylate cyclase. Synapse 50:320–333PubMedGoogle Scholar
  116. Leonard SK, Petitto JM, Anderson CM, Mooney DH, Lachowicz JE, Schulz DW, Kilts CD, Mailman RB (2003b) D1 dopamine receptors in the amygdala exhibit unique properties. Ann N Y Acad Sci 985:536–539Google Scholar
  117. Levey AI, Hersch SM, Rye DB, Sunahara RK, Niznik HB, Kitt CA, Price DL, Maggio R, Brann MR, Ciliax BJ (1993) Localization of D1 and D2 dopamine receptors in brain with subtype-specific antibodies. Proc Natl Acad Sci USA 90:8861–8865PubMedGoogle Scholar
  118. Li X, Rosborough KM, Friedman AB, Zhu W, Roth KA (2007) Regulation of mouse brain glycogen synthase kinase-3 by atypical antipsychotics. Int J Neuropsychopharmacol 10:7–19PubMedGoogle Scholar
  119. Lidow MS, Goldman-Rakic PS, Gallager DW, Rakic P (1991) Distribution of dopaminergic receptors in the primate cerebral cortex: quantitative autoradiographic analysis using [3H]raclopride, [3H]spiperone and [3H]SCH23390. Neuroscience 40:657–671PubMedGoogle Scholar
  120. Lieberman JA (2004) Dopamine partial agonists: a new class of antipsychotic. CNS Drugs 18:251–267PubMedGoogle Scholar
  121. Lin CW, Miller TR, Witte DG, Bianchi BR, Stashko M, Manelli AM, Frail DE (1995) Characterization of cloned human dopamine D1 receptor-mediated calcium release in 293 cells. Mol Pharmacol 47:131–139PubMedGoogle Scholar
  122. Liu L, Shen RY, Kapatos G, Chiodo LA (1994) Dopamine neuron membrane physiology: characterization of the transient outward current (IA) and demonstration of a common signal transduction pathway for IA and IK. Synapse 17:230–240PubMedGoogle Scholar
  123. Lledo PM, Homburger V, Bockaert J, Vincent JD (1992) Differential G protein-mediated coupling of D2 dopamine receptors to K+ and Ca2+ currents in rat anterior pituitary cells. Neuron 8:455–463PubMedGoogle Scholar
  124. Lovenberg TW, Brewster WK, Mottola DM, Lee RC, Riggs RM, Nichols DE, Lewis MH, Mailman RB (1989) Dihydrexidine, a novel selective high potency full dopamine D-1 receptor agonist. Eur J Pharmacol 166:111–113PubMedGoogle Scholar
  125. Luo Y, Kokkonen GC, Wang X, Neve KA, Roth GS (1998) D2 dopamine receptors stimulate mitogenesis through pertussis toxin-sensitive G proteins and Ras-involved ERK and SAP/JNK pathways in rat C6-D2L glioma cells. J Neurochem 71:980–990PubMedGoogle Scholar
  126. Mailman R, Huang X, Nichols DE (2001) Parkinson’s disease and D1 dopamine receptors. Curr Opin Invest Drugs 2:1582–1591Google Scholar
  127. Mailman RB (2007) GPCR functional selectivity has therapeutic impact. Trends Pharmacol Sci 28:390–396PubMedGoogle Scholar
  128. Mailman RB, Gay EA (2004) Novel mechanisms of drug action: functional selectivity at D2 dopamine receptors (a lesson for drug discovery). Med Chem Res 13:115–126Google Scholar
  129. Mailman RB, Huang X (2007) Dopamine receptor pharmacology. In: Koller WC, Melamed E (eds) Parkinson’s disease and related disorders, part 1. Elsevier, Edinburgh, pp 77–105Google Scholar
  130. Mailman RB, Nichols DE, Lewis MM, Blake BL, Lawler CP (1998) Functional effects of novel dopamine ligands: dihydrexidine and Parkinson’s disease as a first step. In: Jenner P, Demirdemar R (eds) Dopamine receptor subtypes: from basic science to clinical application. IOS Stockton Press, Amsterdam, pp 64–83. ISBN ISSN/ISBN 90-5199-291-2Google Scholar
  131. Mailman RB, Nichols DE, Tropsha A (1997) Molecular drug design and dopamine receptors. In: Neve KA, Neve RL (eds) The dopamine receptors. Humana Press, Totowa, NJ, pp 105–133Google Scholar
  132. Mailman RB, Schulz DW, Kilts CD, Lewis MH, Rollema H, Wyrick S (1986a) Multiple forms of the D1 dopamine receptor: its linkage to adenylate cyclase and psychopharmacological effects. Psychopharmacol Bull 22:593–598PubMedGoogle Scholar
  133. Mailman RB, Schulz DW, Kilts CD, Lewis MH, Rollema H, Wyrick S (1986b) The multiplicity of the D1 dopamine receptor. Adv Exp Med Biol 204:53–72PubMedGoogle Scholar
  134. Mailman RB, Schulz DW, Lewis MH, Staples L, Rollema H, DeHaven DL (1984) SCH-23390: a selective D1 dopamine antagonist with potent D2 behavioral actions. Eur J Pharmacol 101:159–160PubMedGoogle Scholar
  135. Mannoury la Cour C, Vidal S, Pasteau V, Cussac D, Millan MJ (2007) Dopamine D1 receptor coupling to Gs/olf and Gq in rat striatum and cortex: a scintillation proximity assay (SPA)/antibody-capture characterization of benzazepine agonists. Neuropharmacology 52:1003–1014PubMedGoogle Scholar
  136. Martin-Iverson MT, Yamada N (1992) Synergistic behavioural effects of dopamine D1 and D2 receptor agonists are determined by circadian rhythms. Eur J Pharmacol 215:119–125PubMedGoogle Scholar
  137. Meller E, Bohmaker K, Namba Y, Friedhoff AJ, Goldstein M (1987) Relationship between receptor occupancy and response at striatal dopamine autoreceptors. Mol Pharmacol 31:592–598PubMedGoogle Scholar
  138. Memo M, Missale C, Carruba MO, Spano PF (1986) D2 dopamine receptors associated with inhibition of dopamine release from rat neostriatum are independent of cyclic AMP. Neurosci Lett 71:192–196PubMedGoogle Scholar
  139. Mercuri NB, Saiardi A, Bonci A, Picetti R, Calabresi P, Bernardi G, Borrelli E (1997) Loss of autoreceptor function in dopaminergic neurons from dopamine D2 receptor deficient mice. Neuroscience 79:323–327PubMedGoogle Scholar
  140. Mercurio F, Zhu H, Murray BW, Shevchenko A, Bennett BL, Li J, Young DB, Barbosa M, Mann M, Manning A, Rao A (1997) IKK-1 and IKK-2: cytokine-activated IkappaB kinases essential for NF-kappaB activation. Science 278:860–866PubMedGoogle Scholar
  141. Michaelides MR, Hong Y, DiDomenico SJ, Asin KE, Britton DR, Lin CW, Williams M, Shiosaki K (1995) (5aR,11bS)-4,5,5a,6,7,11b-hexahydro-2-propyl-3-thia-5-azacyclopent-1- ena[c]-phenanthrene-9,10-diol (A-86929): a potent and selective dopamine D1 agonist that maintains behavioral efficacy following repeated administration and characterization of its diacetyl prodrug (ABT-431). J Med Chem 38:3445–3447PubMedGoogle Scholar
  142. Mill J, Curran S, Kent L, Richards S, Gould A, Virdee V, Huckett L, Sharp J, Batten C, Fernando S, Simanoff E, Thompson M, Zhao J, Sham P, Taylor E, Asherson P (2001) Attention deficit hyperactivity disorder (ADHD) and the dopamine D4 receptor gene: evidence of association but no linkage in a UK sample. Mol Psychiatry 6:440–444PubMedGoogle Scholar
  143. Minowa MT, Lee SH, Mouradian MM (1996) Autoregulation of the human D1A dopamine receptor gene by cAMP. DNA Cell Biol 15:759–767PubMedGoogle Scholar
  144. Mitchell R, McCulloch D, Lutz E, Johnson M, MacKenzie C, Fennell M, Fink G, Zhou W, Sealfon SC (1998) Rhodopsin-family receptors associate with small G proteins to activate phospholipase D. Nature 392:411–414PubMedGoogle Scholar
  145. Miyamoto S, Duncan GE, Mailman RB, Jeffrey A. Lieberman (2000) Developing novel antipsychotic drugs: strategies and goals. Current Opinions in Central & Peripheral Nervous System Investigational Drugs. 2: 25–39Google Scholar
  146. Montague DM, Striplin CD, Overcash JS, Drago F, Lawler CP, Mailman RB (2001) Quantification of D1B (D5) receptors in dopamine D1A receptor-deficient mice. Synapse 39:319–322PubMedGoogle Scholar
  147. Mottola DM, Brewster WK, Cook LL, Nichols DE, Mailman RB (1992) Dihydrexidine, a novel full efficacy D1 dopamine receptor agonist. J Pharmacol Exp Ther 262:383–393PubMedGoogle Scholar
  148. Mottola DM, Cook LL, Jones SR, Booth RG, Nichols DE, Mailman RB (1991) Dihydrexidine, a selective dopamine receptor agonist that may discriminate postsynaptic D2 receptors. Soc Neurosci Abstr 17:818Google Scholar
  149. Mottola DM, Kilts JD, Lewis MM, Connery HS, Walker QD, Jones SR, Booth RG, Hyslop DK, Piercey M, Wightman RM, Lawler CP, Nichols DE, Mailman RB (2002) Functional selectivity of dopamine receptor agonists. I. Selective activation of postsynaptic dopamine D2 receptors linked to adenylate cyclase. J Pharmacol Exp Ther 301:1166–1178PubMedGoogle Scholar
  150. Mu Q, Johnson K, Morgan PS, Grenesko EL, Molnar CE, Anderson B, Nahas Z, Kozel FA, Kose S, Knable M, Fernandes P, Nichols DE, Mailman RB, George MS (2007) A single 20 mg dose of the full D(1) dopamine agonist dihydrexidine (DAR-0100) increases prefrontal perfusion in schizophrenia. Schizophr Res 94:332–341PubMedGoogle Scholar
  151. Nagai T, Takuma K, Kamei H, Ito Y, Nakamichi N, Ibi D, Nakanishi Y, Murai M, Mizoguchi H, Nabeshima T, Yamada K (2007) Dopamine D1 receptors regulate protein synthesis-dependent long-term recognition memory via extracellular signal-regulated kinase 1/2 in the prefrontal cortex. Learn Mem 14:117–125PubMedGoogle Scholar
  152. Neve KA, Seamans JK, Trantham-Davidson H (2004) Dopamine receptor signaling. J Recept Signal Transduct Res 24:165–205PubMedGoogle Scholar
  153. O’Hara CM, Uhland-Smith A, O’Malley KL, Todd RD (1996) Inhibition of dopamine synthesis by dopamine D2 and D3 but not D4 receptors. J Pharmacol Exp Ther 277:186–192PubMedGoogle Scholar
  154. O’Malley KL, Harmon S, Tang L, Todd RD (1992) The rat dopamine D4 receptor: sequence, gene structure, and demonstration of expression in the cardiovascular system. New Biol 4:137–146PubMedGoogle Scholar
  155. Oak JN, Lavine N, van Tol HH (2001) Dopamine D4 and D2L receptor stimulation of the mitogen-activated protein kinase pathway is dependent on trans-activation of the platelet-derived growth factor receptor. Mol Pharmacol 60:92–103PubMedGoogle Scholar
  156. Oak JN, Oldenhof J, van Tol HH (2000) The dopamine D4 receptor: one decade of research. Eur J Pharmacol 405:303–327PubMedGoogle Scholar
  157. Okada Y, Miyamoto T, Toda K (2003) Dopamine modulates a voltage-gated calcium channel in rat olfactory receptor neurons. Brain Res 968:248–255PubMedGoogle Scholar
  158. Okumu FW, Lee RY, Blanchard JD, Queirolo A, Woods CM, Lloyd PM, Okikawa J, Gonda I, Farr SJ, Rubsamen R, Adjei AL, Bertz RJ (2002) Evaluation of the AERx pulmonary delivery system for systemic delivery of a poorly soluble selective D-1 agonist, ABT-431. Pharm Res 19:1009–1012PubMedGoogle Scholar
  159. Oxford GS, Wagoner PK (1989) The inactivating K+ current in GH3 pituitary cells and its modification by chemical reagents. J Physiol (Lond) 410:587–612Google Scholar
  160. Panchalingam S, Undie AS (2000) Optimized binding of [35S]GTPgammaS to Gq-like proteins stimulated with dopamine D1-like receptor agonists. Neurochem Res 25:759–767PubMedGoogle Scholar
  161. Piomelli D, Greengard P (1990) Lipoxygenase metabolites of arachidonic acid in neuronal transmembrane signalling. Trends Pharmacol Sci 11:367–373PubMedGoogle Scholar
  162. Piomelli D, Pilon C, Giros B, Sokoloff P, Martres MP, Schwartz JC (1991) Dopamine activation of the arachidonic acid cascade as a basis for D1/D2 receptor synergism. Nature 353:164–167PubMedGoogle Scholar
  163. Rascol O, Blin O, Thalamas C, Descombes S, Soubrouillard C, Azulay P, Fabre N, Viallet F, Lafnitzegger K, Wright S, Carter JH, Nutt JG (1999) ABT-431, a D1 receptor agonist prodrug, has efficacy in Parkinson’s disease. Ann Neurol 45:736–741PubMedGoogle Scholar
  164. Rascol O, Nutt JG, Blin O, Goetz CG, Trugman JM, Soubrouillard C, Carter JH, Currie LJ, Fabre N, Thalamas C, Giardina WJ, Wright S (2001) Induction by dopamine D1 receptor agonist ABT-431 of dyskinesia similar to levodopa in patients with Parkinson’s disease. Arch Neurol 58:249–254PubMedGoogle Scholar
  165. Rashid AJ, O’Dowd BF, Verma V, George SR (2007a) Neuronal Gq/11-coupled dopamine receptors: an uncharted role for dopamine. Trends Pharmacol Sci 28:551–555PubMedGoogle Scholar
  166. Rashid AJ, So CH, Kong MM, Furtak T, El-Ghundi M, Cheng R, O’Dowd BF, George SR (2007b) D1-D2 dopamine receptor heterooligomers with unique pharmacology are coupled to rapid activation of Gq/11 in the striatum. Proc Natl Acad Sci USA 104:654–659PubMedGoogle Scholar
  167. Robertson GS, Vincent SR, Fibiger HC (1992) D1 and D2 dopamine receptors differentially regulate c-fos expression in striatonigral and striatopallidal neurons. Neuroscience 49:285–296PubMedGoogle Scholar
  168. Roth BL, Sheffler DJ, Kroeze WK (2004) Magic shotguns versus magic bullets: selectively non-selective drugs for mood disorders and schizophrenia. Nat Rev Drug Discov 3:353–359PubMedGoogle Scholar
  169. Runnels LW, Scarlata SF (1999) Determination of the affinities between heterotrimeric G protein subunits and their phospholipase C-beta effectors. Biochemistry 38:1488–1496PubMedGoogle Scholar
  170. Ryman-Rasmussen JP, Griffith A, Oloff S, Vaidehi N, Brown JT, Goddard WA III, Mailman RB (2007) Functional selectivity of dopamine D(1) receptor agonists in regulating the fate of internalized receptors. Neuropharmacology 52:562–575PubMedGoogle Scholar
  171. Ryman-Rasmussen JP, Nichols DE, Mailman RB (2005) Differential activation of adenylate cyclase and receptor internalization by novel dopamine D1 receptor agonists. Mol Pharmacol 68:1039–1048PubMedGoogle Scholar
  172. Sahu A, Tyeryar KR, Vongtau HO, Sibley DR, Undieh AS (2009) D5 dopamine receptors are required for dopaminergic activation of phospholipase C. Mol Pharmacol 75:447–453, PMC2684903PubMedGoogle Scholar
  173. Sands WA, Palmer TM (2008) Regulating gene transcription in response to cyclic AMP elevation. Cell Signal 20:460–466PubMedGoogle Scholar
  174. Schmidt LA, Fox NA, Perez-Edgar K, Hu S, Hamer DH (2001) Association of DRD4 with attention problems in normal childhood development. Psychiatr Genet 11:25–29PubMedGoogle Scholar
  175. Schneider JS, Sun ZQ, Roeltgen DP (1994) Effects of dihydrexidine, a full dopamine D-1 receptor agonist, on delayed response performance in chronic low dose MPTP-treated monkeys. Brain Res 663:140–144PubMedGoogle Scholar
  176. Seabrook GR, Knowles M, Brown N, Myers J, Sinclair H, Patel S, Freedman SB, Mcallister G (1994a) Pharmacology of high-threshold calcium currents in GH4C1 pituitary cells and their regulation by activation of human D2 and D4 dopamine receptors. Br J Pharmacol 112:728–734PubMedGoogle Scholar
  177. Seabrook GR, Mcallister G, Knowles MR, Myers J, Sinclair H, Patel S, Freedman SB, Kemp JA (1994b) Depression of high-threshold calcium currents by activation of human D2 (short) dopamine receptors expressed in differentiated NG108-15 cells. Br J Pharmacol 111:1061–1066PubMedGoogle Scholar
  178. Seeman P, Chau-Wong M, Tedesco J, Wong K (1975) Brain receptors for antipsychotic drugs and dopamine: direct binding assays. Proc Natl Acad Sci USA 72:4376–4380PubMedGoogle Scholar
  179. Seeman P, Lee T (1975) Antipsychotic drugs: direct correlation between clinical potency and presynaptic action on dopamine neurons. Science 188:1217–1219PubMedGoogle Scholar
  180. Self DW, Karanian DA, Spencer JJ (2000) Effects of the novel D1 dopamine receptor agonist ABT-431 on cocaine self-administration and reinstatement. Ann N Y Acad Sci 909:133–144PubMedGoogle Scholar
  181. Senogles SE (2000) The D2s dopamine receptor stimulates phospholipase D activity: a novel signaling pathway for dopamine. Mol Pharmacol 58:455–462PubMedGoogle Scholar
  182. Sesack SR, Aoki C, Pickel VM (1994) Ultrastructural localization of D2 receptor-like immunoreactivity in midbrain dopamine neurons and their striatal targets. J Neurosci 14:88–106PubMedGoogle Scholar
  183. Shapiro DA, Renock S, Arrington E, Sibley DR, Chiodo LA, Roth BL, Mailman RB (2003) Aripiprazole, a novel atypical antipsychotic drug with a unique and robust pharmacology. Neuropsychopharmacology 28:1400–1411PubMedGoogle Scholar
  184. Shiosaki K, Jenner P, Asin KE, Britton DR, Lin CW, Michaelides M, Smith L, Bianchi B, Didomenico S, Hodges L, Hong Y, Mahan L, Mikusa J, Miller T, Nikkel A, Stashko M, Witte D, Williams M (1996) ABT-431: the diacetyl prodrug of A-86929, a potent and selective dopamine D1 receptor agonist: in vitro characterization and effects in animal models of Parkinson’s disease. J Pharmacol Exp Ther 276:150–160PubMedGoogle Scholar
  185. Shohamy D, Adcock RA (2010) Dopamine and adaptive memory. Trends Cogn Sci 14:464–472PubMedGoogle Scholar
  186. Slifstein M, Suckow RF, Javitch JA, Cooper T, Lieberman J, Abi-Dargham A (2011) Characterization of in vivo pharmacokinetic properties of the dopamine D1 receptor agonist DAR-0100A in nonhuman primates using PET with [11C]-NNC112 and [11C]-raclopride. J Cereb Blood Flow Metab 31:293–304, PMC3049493PubMedGoogle Scholar
  187. Smith HP, Nichols DE, Mailman RB, Lawler CP (1997) Locomotor inhibition, yawning and vacuous chewing induced by a novel dopamine D2 post-synaptic receptor agonist. Eur J Pharmacol 323:27–36PubMedGoogle Scholar
  188. Smith RC, Tamminga C, Davis JM (1977) Effect of apomorphine on schizophrenic symptoms. J Neural Transm 40:171–176PubMedGoogle Scholar
  189. Snyder GL, Fienberg AA, Huganir RL, Greengard P (1998) A dopamine/D1 receptor/protein kinase A/dopamine- and cAMP-regulated phosphoprotein (Mr 32 kDa)/protein phosphatase-1 pathway regulates dephosphorylation of the NMDA receptor. J Neurosci 18:10297–10303PubMedGoogle Scholar
  190. Sokoloff P, Andrieux M, Besancon R, Pilon C, Martres MP, Giros B, Schwartz JC (1992) Pharmacology of human dopamine D3 receptor expressed in a mammalian cell line: comparison with D2 receptor. Eur J Pharmacol 225:331–337PubMedGoogle Scholar
  191. 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 347:146–151PubMedGoogle Scholar
  192. Stahl SM (2001) Dopamine system stabilizers, aripiprazole, and the next generation of antipsychotics, part 1, “Goldilocks” actions at dopamine receptors. J Clin Psychiatry 62:841–842PubMedGoogle Scholar
  193. Starr MS (1995) Glutamate/dopamine D1/D2 balance in the basal ganglia and its relevance to Parkinson’s disease. Synapse 19:264–293PubMedGoogle Scholar
  194. Steele TD, Hodges DB Jr, Levesque TR, Locke KW (1997) D1 agonist dihydrexidine releases acetylcholine and improves cognitive performance in rats. Pharmacol Biochem Behav 58:477–483PubMedGoogle Scholar
  195. Stephenson RP (1956) A modification of receptor theory. Br J Pharmacol 11:379–393Google Scholar
  196. Stoof JC, Kebabian JW (1981) Opposing roles for D-1 and D-2 dopamine receptors in efflux of cyclic AMP from rat neostriatum. Nature 294:366–368PubMedGoogle Scholar
  197. Surmeier DJ, Bargas J, Hemmings HC Jr, Nairn AC, Greengard P (1995) Modulation of calcium currents by a D1 dopaminergic protein kinase/phosphatase cascade in rat neostriatal neurons. Neuron 14:385–397PubMedGoogle Scholar
  198. 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 89:10178–10182PubMedGoogle Scholar
  199. Surmeier DJ, Kitai ST (1993) D1 and D2 dopamine receptor modulation of sodium and potassium currents in rat neostriatal neurons. Prog Brain Res 99:309–324PubMedGoogle Scholar
  200. Surmeier DJ, Song WJ, Yan Z (1996) Coordinated expression of dopamine receptors in neostriatal medium spiny neurons. J Neurosci 16:6579–6591PubMedGoogle Scholar
  201. Svensson E, Wikstrom MA, Hill RH, Grillner S (2003) Endogenous and exogenous dopamine presynaptically inhibits glutamatergic reticulospinal transmission via an action of D2-receptors on N-type Ca2+ channels. Eur J Neurosci 17:447–454PubMedGoogle Scholar
  202. Swanson JM, Sunohara GA, Kennedy JL, Regino R, Fineberg E, Wigal T, Lerner M, Williams L, LaHoste GJ, Wigal S (1998) Association of the dopamine receptor D4 (DRD4) gene with a refined phenotype of attention deficit hyperactivity disorder (ADHD): a family-based approach. Mol Psychiatry 3:38–41PubMedGoogle Scholar
  203. Tamminga CA (2002) Partial dopamine agonists in the treatment of psychosis. J Neural Transm 109:411–420PubMedGoogle Scholar
  204. Tamminga CA, Carlsson A (2002) Partial dopamine agonists and dopaminergic stabilizers, in the treatment of psychosis. Curr Drug Targets CNS Neurol Disord 1:141–147PubMedGoogle Scholar
  205. Tamminga CA, Cascella NG, Lahti RA, Lindberg M, Carlsson A (1992) Pharmacologic properties of (−)-3PPP (preclamol) in man. J Neural Transm Gen Sect 88:165–175PubMedGoogle Scholar
  206. Tamminga CA, Gotts MD, Thaker GK, Alphs LD, Foster NL (1986) Dopamine agonist treatment of schizophrenia with N-propylnorapomorphine. Arch Gen Psychiatry 43:398–402PubMedGoogle Scholar
  207. Tamminga CA, Schaffer MH, Smith RC, Davis JM (1978) Schizophrenic symptoms improve with apomorphine. Science 200:567–568PubMedGoogle Scholar
  208. Tang L, Todd RD, O’Malley KL (1994) Dopamine D2 and D3 receptors inhibit dopamine release. J Pharmacol Exp Ther 270:475–479PubMedGoogle Scholar
  209. Taylor JR, Lawrence MS, Redmond DE Jr, Elsworth JD, Roth RH, Nichols DE, Mailman RB (1991) Dihydrexidine, a full dopamine D1 agonist, reduces MPTP-induced parkinsonism in monkeys. Eur J Pharmacol 199:389–391PubMedGoogle Scholar
  210. Undie AS, Weinstock J, Sarau HM, Friedman E (1994) Evidence for a distinct D1-like dopamine receptor that couples to activation of phosphoinositide metabolism in brain. J Neurochem 62:2045–2048PubMedGoogle Scholar
  211. Ungerstedt U (1971) Stereotaxic mapping of the monoamine pathways in the rat brain. Acta Physiol Scand Suppl 367:1–48PubMedGoogle Scholar
  212. Urban JD, Clarke WP, von Zastrow M, Nichols DE, Kobilka B, Weinstein H, Javitch JA, Roth BL, Christopoulos A, Sexton PM, Miller KJ, Spedding M, Mailman RB (2007a) Functional selectivity and classical concepts of quantitative pharmacology. J Pharmacol Exp Ther 320:1–13PubMedGoogle Scholar
  213. Urban JD, Vargas GA, von Zastrow M, Mailman RB (2007b) Aripiprazole has functionally selective actions at dopamine D(2) receptor-mediated signaling pathways. Neuropsychopharmacology 32:67–77PubMedGoogle Scholar
  214. Urs NM, Daigle TL, Caron MG (2011) A dopamine D1 receptor-dependent beta-arrestin signaling complex potentially regulates morphine-induced psychomotor activation but not reward in mice. Neuropsychopharmacology 36:551–558, PMC3021093PubMedGoogle Scholar
  215. Valjent E, Bertran-Gonzalez J, Herve D, Fisone G, Girault JA (2009) Looking BAC at striatal signaling: cell-specific analysis in new transgenic mice. Trends Neurosci 32:538–547PubMedGoogle Scholar
  216. van Tol HH, Bunzow JR, Guan HC, Sunahara RK, Seeman P, Niznik HB, Civelli O (1991) Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine. Nature 350:610–614PubMedGoogle Scholar
  217. Vanhauwe JF, Josson K, Luyten WH, Driessen AJ, Leysen JE (2000) G-protein sensitivity of ligand binding to human dopamine D2 and D3 receptors expressed in Escherichia coli: clues for a constrained D(3) receptor structure. J Pharmacol Exp Ther 295:274–283PubMedGoogle Scholar
  218. Vial D, Piomelli D (1995) Dopamine D2 receptors potentiate arachidonate release via activation of cytosolic, arachidonate-specific phospholipase A2. J Neurochem 64:2765–2772PubMedGoogle Scholar
  219. Voyno-Yasenetskaya T, Conklin BR, Gilbert RL, Hooley R, Bourne HR, Barber DL (1994) G alpha 13 stimulates Na-H exchange. J Biol Chem 269:4721–4724PubMedGoogle Scholar
  220. Wang HY, Malbon CC (2011) Probing the physical nature and composition of signalsomes. J Mol Signal 6:1, PMC3027200PubMedGoogle Scholar
  221. Wang HY, Undie AS, Friedman E (1995) Evidence for the coupling of Gq protein to D1-like dopamine sites in rat striatum: possible role in dopamine-mediated inositol phosphate formation. Mol Pharmacol 48:988–994PubMedGoogle Scholar
  222. Wang Q, Jolly JP, Surmeier JD, Mullah BM, Lidow MS, Bergson CM, Robishaw JD (2001) Differential dependence of the D1 and D5 dopamine receptors on the G protein gamma 7 subunit for activation of adenylylcyclase. J Biol Chem 276:39386–39393PubMedGoogle Scholar
  223. Welsh GI, Hall DA, Warnes A, Strange PG, Proud CG (1998) Activation of microtubule-associated protein kinase (Erk) and p70 S6 kinase by D2 dopamine receptors. J Neurochem 70:2139–2146PubMedGoogle Scholar
  224. White FJ, Bednarz LM, Wachtel SR, Hjorth S, Brooderson RJ (1988) Is stimulation of both D1 and D2 receptors necessary for the expression of dopamine-mediated behaviors? Pharmacol Biochem Behav 30:189–193PubMedGoogle Scholar
  225. Yan Z, Song WJ, Surmeier J (1997) D2 dopamine receptors reduce N-type Ca2+ currents in rat neostriatal cholinergic interneurons through a membrane-delimited, protein-kinase-C- insensitive pathway. J Neurophysiol 77:1003–1015PubMedGoogle Scholar
  226. Young CE, Yang CR (2004) Dopamine D1/D5 receptor modulates state-dependent switching of soma-dendritic Ca2+ potentials via differential protein kinase A and C activation in rat prefrontal cortical neurons. J Neurosci 24:8–23PubMedGoogle Scholar
  227. Yu PY, Eisner GM, Yamaguchi I, Mouradian MM, Felder RA, Jose PA (1996) Dopamine D1A receptor regulation of phospholipase C isoform. J Biol Chem 271:19503–19508PubMedGoogle Scholar
  228. Zamponi GW, Snutch TP (1998) Decay of prepulse facilitation of N type calcium channels during G protein inhibition is consistent with binding of a single Gbeta subunit. Proc Natl Acad Sci USA 95:4035–4039PubMedGoogle Scholar
  229. Zhang L, Reith ME (1996) Regulation of the functional activity of the human dopamine transporter by the arachidonic acid pathway. Eur J Pharmacol 315:345–354PubMedGoogle Scholar
  230. Zhuang X, Belluscio L, Hen R (2000) G(olf)alpha mediates dopamine D1 receptor signaling. J Neurosci 20:RC91PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Departments of Pharmacology and NeurologyThe Neuroscience Institute, Pennsylvania State University College of Medicine and Milton S. Hershey Medical CenterHersheyUSA

Personalised recommendations