Pharmacological Inhibition of Dopaminergic and Other Neurotransmitter Receptors Using Antisense Oligodeoxynucleotides

  • G. Davidkova
  • B. Weiss
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 131)


In recent years a great number of studies have been carried out that apply antisense oligonucleotide technology to investigate neurobiological systems (for recent reviews, see Weiss et al. 1996, 1997a,b; Zon 1995). The antisense approach has been particularly useful in characterizing the pharmacological properties and biological functions of receptors for neurotransmitters. This is due to the rapid discovery of the molecular structure of new subtypes of neurotransmitter receptors, the pharmacological and biological properties of which remain largely unknown. Antisense compounds, by hybridizing specifically to the nucleic acids encoding the different receptor subtypes, have provided a highly selective means to reduce the expression, and thereby the levels, of individual receptors, an effect that is not attainable with traditional pharmacological antagonists. In addition to providing a highly selective means to study various neurobiological events, antisense compounds have the potential to be used as therapeutic agents in the management of neuropsychiatric and neurodegenerative disorders. An antisense strategy to reduce the function of neuroreceptors might have a further distinct advantage over traditional pharmacological antagonists in that antisense agents, unlike the conventional pharmacological antagonists, might not induce the upregulation of the very receptors they are intended to inhibit (Burt et al. 1977; Hyttel 1986; Rogue et al. 1991).


Dopamine Receptor Neurotransmitter Receptor Antisense Oligodeoxynucleotides Dopamine Receptor Subtype Challenge Injection 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Agrawal S (ed) (1996) Antisense therapeutics. Humana, Totowa, NJGoogle Scholar
  2. Agrawal S, Temsamani J, Galbraith W, Tang J (1995) Pharmacokinetics of antisense oligonucleotides. Clin Pharmacokinet 28:7–16PubMedGoogle Scholar
  3. Bourson A, Borroni E, Austin HR, Monsma FJ Jr, Sleight AJ (1995) Determination of the role of the 5-HT, receptor in the rat brain: a study using antisense oligodeoxynucleotides. J Pharmacol Exp Ther 274:173–180PubMedGoogle Scholar
  4. Bouthenet M-L, Souil E, Martres M-P, Sokoloff P, Giros B, Schwartz J-C (1991) Localization of dopamine D3 receptor mRNA in the rat brain using in situ hybridization histochemistry: comparison with dopamine DZ receptor mRNA. Brain Res 564:203–219PubMedGoogle Scholar
  5. Brussaard AB, Baker RE (1995) Antisense oligodeoxynucleotide-induced block of individual GABA A receptor a subunits in cultured visual cortex slices reduces amplitude of inhibitory postsynaptic currents. Neurosci Lett 191:111–115PubMedGoogle Scholar
  6. Bunzow JR, Van Tol HHM, Grandy DK, Albert P, Salon J, Macdonald C, Machida CA, Neve KA, Civelli O (1988) Cloning and expression of a rat Dz dopamine receptor cDNA. Nature 336:783–787PubMedGoogle Scholar
  7. Burt DR, Kamatchi GL (1991) GABA (A) receptor subtypes: from pharmacology to molecular biology. FASEB J 5:2916–2923PubMedGoogle Scholar
  8. Burt DR, Creese I, Snyder SH (1977) Antischizophrenic drugs: chronic treatment elevates dopamine receptor binding in brain. Science 196:326–328PubMedGoogle Scholar
  9. Cao L, Zheng Z-C, Zhao Y-C, Jiang Z-H, Liu Z-G, Chen S-D, Zhou C-F, Liu X-Y (1995) Gene therapy of Parkinson disease model rat by direct injection of plasmid DNA-lipofectin complex. Human Gene Ther 6:1497–1501Google Scholar
  10. Carlsson A, Piercey M (1995) Dopamine receptor subtypes in neurological and psychiatric diseases. Clin Neuropharmacol 18 [Suppl 1] (entire issue)Google Scholar
  11. Carlsson M, Carlsson A (1990) Interactions between glutamatergic and monoaminergic systems within the basal ganglia-implications for schizophrenia and Parkinson’s disease. Trends Neurosci 13:272–276PubMedGoogle Scholar
  12. Casey DE (1991) Neuroleptic drug-induced extrapyramidal syndromes and tardive dyskinesia. Schizophr Res 4:109–120PubMedGoogle Scholar
  13. Chen JF, Weiss B (1991) Ontogenetic expression of DZ dopamine receptor mRNA in rat corpus striatum. Dev Brain Res 63:95–104Google Scholar
  14. Chen JF, Aloyo VJ, Weiss B (1993) Continuous treatment with the D2 dopamine receptor agonist quinpirole decreases DZ dopamine receptors, DZ dopamine receptor messenger RNA and proenkephalin messenger RNA, and increases mu opioid receptors in mouse striatum. Neuroscience 54:669–680PubMedGoogle Scholar
  15. Chen JF, Aloyo VJ, Qin Z-H, Weiss B (1994) Irreversible blockade of Dz dopamine receptors by fluphenazine-N-mustard increases Dz dopamine receptor mRNA and proenkephalin mRNA and decreases D, dopamine receptor mRNA and mu and delta opioid receptors in rat striatum. Neurochem Int 25:355–366PubMedGoogle Scholar
  16. Chiang M-Y, Chan H, Zounes MA, Freier S, Lima W, Bennett CF (1991) Antisense oligonucleotides inhibit intercellular adhesion molecule 1 expression by two distinct mechanisms. J Biol Chem 266:18162–18171PubMedGoogle Scholar
  17. Creese I, Burt DR, Snyder SH (1976) Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science 192:481–483PubMedGoogle Scholar
  18. Creese I, Burt DR, Snyder SH (1977) Dopamine receptor binding enhancement accompanies lesion-induced behavioral supersensitivity. Science 197:596–598PubMedGoogle Scholar
  19. Crooke ST (1992) Therapeutic applications of oligonucleotides. Annu Rev Pharmacol Toxicol 32:329–376PubMedGoogle Scholar
  20. Crooke ST (ed) (1995) Therapeutic applications of oligonucleotides. Landes, Austin, TXGoogle Scholar
  21. Davidkova G, Zhang S-P, Zhou L-W, Nichols RA, Weiss B (1997) Use of antisense RNA expression vectors in neurobiology. In: Weiss B (ed) Antisense oligodeoxynucleotides and antisense RNA: novel pharmacological and therapeutic agents. CRC Press, Boca Raton, FL, pp 213–241Google Scholar
  22. Davidson A, Mengod G, Matus-Leibovitch N, Oron Y (1991) Native Xenopus oocytes express two types of muscarinic receptors. FEBS Lett 284:252–256PubMedGoogle Scholar
  23. Dawson VL, Dawson TM, Wamsley JK (1990) Muscarinic and dopaminergic receptor subtypes on striatal cholinergic interneurons. Brain Res Bull 25:903–912PubMedGoogle Scholar
  24. Deneris ES, Connolly J, Rogers SW, Duvoisin R (1991) Pharmacological and functional diversity of neuronal nicotinic acetylcholine receptors. Trends Pharmacol Sci 29:34–38Google Scholar
  25. Ebadi M, Hama Y (1988) Dopamine, GABA, cholecystokinin and opioids in neuroleptic-induced tardive dyskinesia. Neurosci Biobehav Rev 12:179–187PubMedGoogle Scholar
  26. Faunt JE, Crooker AD (1987) The effects of selective dopamine receptor agonists and antagonists on body temperature in rats. Eur J Pharmacol 133:243–247PubMedGoogle Scholar
  27. Feigner P, Tsai Y, Sukhu L, Wheeler C, Manthorpe M, Marshall J, Cheng S (1995) Improved cationic lipid formulations for in vivo gene therapy. Ann N Y Acad Sci U S A 772:126–138Google Scholar
  28. Feigner PL, Gadek TR, Holm M, Roman R, Chan HW, Wenz M, Northrop JP, Ringold GM, Danielson M (1987) Lipofection: a novel highly efficient lipid mediated DNA transfection procedure. Proc Natl Acad Sci U S A 84:7413–7417Google Scholar
  29. Filtz T, Guan W, Artymyshyn RP, Pacheco M, Ford C, Molinoff P (1994) Mechanisms of up-regulation of D2L dopamine receptors by agonists and antagonists in transfected HEK-293 cells. J Pharmacol Exp Ther 271:1574–1582PubMedGoogle Scholar
  30. Filtz TM, Artymyshyn RP, Guan W, Molinoff PB (1993) Paradoxical regulation of dopamine receptors in transfected 293 cells. Mol Pharmacol 44:371–379PubMedGoogle Scholar
  31. Garver DL, Bissette G, Yao JK, Nemeroff CB (1991) CSF neurotensin concentrations in psychosis: relationship to symptoms and drug response. Am J Psychiatr 148:485–488Google Scholar
  32. Gingrich J, Caron M (1993) Recent advances in the molecular biology of dopamine receptors. Annu Rev Neurosci 16:299–231PubMedGoogle Scholar
  33. Gura T (1995) Antisense has growing pains. Science 270:575–577PubMedGoogle Scholar
  34. Hadjiconstantinou M, Neff NH, Zhou L-W, Weiss B (1996) D2 dopamine receptor antisense increases the activity and mRNA of tyrosine hydroxylase and aromatic L-amino acid decarboxylase in mouse brain. Neurosci Lett 217:105–108PubMedGoogle Scholar
  35. Helene C, Toulme J (1990) Specific regulation of gene expression by antisense, sense and antigene nucleic acids. Biochim Biophys Acta 1049:99–125PubMedGoogle Scholar
  36. Holopainen I, Wojcik WJ (1993) A specific antisense oligodeoxynucleotide to mRNAs encoding receptors with seven transmembrane spanning regions decreases muscarinic m2 and gamma-aminobutyric acid$ receptors in rat cerebellar granule cells. J Pharmacol Exp Ther 264:423–430PubMedGoogle Scholar
  37. Humphrey PPA, Hartig P, Hoyer D (1993) A proposed new nomenclature for 5-HT receptors. Trends Pharmacol Sci 14:233–236PubMedGoogle Scholar
  38. Hyttel J (1986) Effect of prolonged treatment with neuroleptics on dopamine D, and D2 receptor density in corpus striatum of mice. Acta Pharmacol Toxico1 59:387–391Google Scholar
  39. Jeste DV, Caligiuri MP (1993) Tardive dyskinesia. Schizophr Bull 19:303–315PubMedGoogle Scholar
  40. Johansson MH, Westlind-Danielson A (1994) Forskolin-induced up-regulation and functional supersensitivity of dopamine D2 long receptors expressed by Ltk-cells.Eur J Pharmacol 269:149–155PubMedGoogle Scholar
  41. Kane JM (1995) Current problems with the pharmacotherapy of schizophrenia. Clin Neuropharmacol 18:S154–S161Google Scholar
  42. Karle J, Nielsen M (1995) Modest reduction of benzodiazepine binding in rat brain in vivo induced by antisense oligonucleotide to GABAA receptor gamma2 subunit subtype. Eur J Pharmacol Mol Pharmacol 291:439–441Google Scholar
  43. Karle J, Witt MR, Nielsen M (1995) Antisense oligonucleotide to GABAA receptor gamma2 subunit induces loss of neurones in rat hippocampus. Neurosci Lett 202:97–100PubMedGoogle Scholar
  44. Kebabian JW, Calne DB (1979) Multiple receptors for dopamine. Nature 277:93–96 Koob GF, Maldonado R, Stinus L (1992) Neural substrates of opiate withdrawal. Trends Neurosci 15:186–191Google Scholar
  45. Kuhar MJ, Ritz MC, Boja JW (1991) The dopamine hypothesis of the reinforcing properties of cocaine. Trends Neurosci 14:299–302PubMedGoogle Scholar
  46. Landgraf R, Gerstberger R, Montkowski A, Probst JC, Wotjak C, Holsboer F, Engelmann M (1995) V1 vasopressin receptor antisense oligodeoxynucleotide into septum reduces vasopressin binding, social discrimination abilities, and anxiety-related behavior in rats. J Neurosci 15:4250–4258PubMedGoogle Scholar
  47. Leonetti J, Degols G, Clarenc J, Mechti N, Lebleu B (1993) Cell delivery and mechanisms of action of antisense oligodeoxynucleotides. Prog Nucleic Acids Res Mol Biol 44:143–154Google Scholar
  48. Leonetti JP, Mechti N, Degols G, Gagnor C, Lebleu B (1991) Intracellular distribution of microinjected antisense oligonucleotides. Proc Natl Acad Sci U S A 88:2702–2706PubMedGoogle Scholar
  49. Levitt P (1984) A monoclonal antibody to limbic system neurons. Science 223:229–301Google Scholar
  50. Lewis JG, Lin K-Y, Kothavale A, Flanagan WM, Matteuci MD, DePrince R, Mook R Jr, Hendren W, Wagner RW (1996) A serum-resistant cytofectin for cellular delivery of antisense oligonucleotides and plasmid DNA. Proc Natl Acad Sci U S A 93:3176–3181PubMedGoogle Scholar
  51. Lewohl J, Crane DI, Dodd PR (1996) Alcohol, alcoholic brain damage, and GABA A receptor isoform gene expression. Neurochem Int 29:677–684PubMedGoogle Scholar
  52. Listerud M, Brussaard A, Devay P, Colman D, Role L (1991) Functional contribution of neuronal AChR subunits revealed by antisense oligodeoxynucleotides. Science 254:1518–1521PubMedGoogle Scholar
  53. Loke SL, Stein CA, Zhang XH, Mori K, Nakanishi M, Subasinghe C, Cohen JS (1989) Characterization of oligonucleotide transport into living cells. Proc Natl Acad Sci U S A 86:3474–3478PubMedGoogle Scholar
  54. Lowenberg TW, Baron BM, De Lecea L, Miller JD, Prosser RA, Rea MA, Foye PE, Racke M, Slone A, Siegel BW, Danielson PE, Sutcliffe JG, Erlander MG (1993) A novel adenyl cyclase-activating serotonin receptor (5-HT,) implicated in the regulation of mammalian circadian rhythms. Neuron 11:449–458Google Scholar
  55. Macdonald RL, Olsen RW (1994) GABA (A) receptor channels. Annu Rev Neurosci 17:569–602PubMedGoogle Scholar
  56. Mack KJ, Todd R, O’Malley K (1991) The mouse dopamine D2 receptor gene: sequence homology with the rat and human genes and expression of alternative transcripts. J Neurochem 57:795–801PubMedGoogle Scholar
  57. Mandel RJ, Hartgraves SL, Severson JA, Woodward JJ, Wilcox RE, Randall PK (1993) A quantitative estimate of the role of striatal D-2 receptor proliferation in dopaminergic behavioral supersensitivity: the contribution of mesolimbic dopamine to the magnitude of 6-OHDA lesion-induced agonist sensitivity in the rat. Behav Brain Res 59:53–64PubMedGoogle Scholar
  58. Mansour A, Meador-Woodruff JH, Bunzow JR, Civelli O, Akil H, Watson SJ (1990) Localization of dopamine D2 receptor mRNA and Dt and D, receptor binding in the rat brain and pituitary: an in situ hybridization-receptor autoradiographïc analysis. J Neurosci 10:2587–2600PubMedGoogle Scholar
  59. Matthes H, Boschert U, Amlaiky N, Grailhe R, Plassat J-L, Muscatelli F, Mattei M-G, Hen R (1993) Mouse 5-hydroxytryptamine 513 receptors define a new family of serotonin receptors: cloning, functional expression and chromosomal localization. Mol Pharmacol 43:313–319PubMedGoogle Scholar
  60. Matus-Leibovitch N, Mengod G, Oron Y (1992) Kinetics of the functional loss of different muscarinic receptor isoforms in Xenopus oocytes. Biochem J 285:753–758PubMedGoogle Scholar
  61. McMillen BA (1983) CNS stimulants: two distinct mechanisms of action for amphetamine-like drugs. Trends Pharmacol Sci 4:429–432Google Scholar
  62. Meguro H, Mori H, Araki H, Kushiya E, Kutsuwada T, Yamazaki M (1992) Functional characterization of a heteromeric NMDA receptor channel expressed from cloned cDNAs. Nature 357:70–74PubMedGoogle Scholar
  63. Meltzer HY (1994) An overview of the mechanism of action of clozapine. J Clin Psychiatr Suppl B55:47–52Google Scholar
  64. Mizobe T, Maghsoudi K, Sitwala K, Tianzhi G, Ou J, Maze M (1996) Antisense technology reveals the alpha 2A adrenoreceptor to be the subtype mediating the hypnotic response to the highly selective agonist, dexmedetomidine, in the locus coeruleus of the rat. J Clin Invest 98:1076–1080PubMedGoogle Scholar
  65. Monsma FJ, Shen Y, Ward RP, Hamblin MW, Sibley DR (1993) Cloning and expression of a novel serotonin receptor with high affinity for tricyclic psychotropic drugs. Mol Pharmacol 43:320–327PubMedGoogle Scholar
  66. Monyer H, Sprengel R, Schoepfer R, Herb A, Higuchi M, Lomeli H, Burnashev N, Sakman B, Seeburg P (1992) Heterotrimeric NMDA receptors: molecular and functional distribution of subtypes. Science 256:1217–1221PubMedGoogle Scholar
  67. Muller S, Sullivan P, Clegg D, Feinstein S (1990) Efficient transfection and expression of heterologous genes in PC12 cells. DNA Cell Biol 9:221–229PubMedGoogle Scholar
  68. Neckers L, Whitesell L (1993) Antisense technology: biological utility and practical considerations. Am J Physiol 265:L1–L12PubMedGoogle Scholar
  69. Nevo I, Hamon M (1995) Neurotransmitter and neuromodulatory mechanisms involved in alcohol abuse and alcoholism. Neurochem Int 26:305–336PubMedGoogle Scholar
  70. Nissbrandt H, Ekman A, Eriksson E, Heilig M (1995) Dopamine D3 receptor antisense influences dopamine synthesis in rat brain. Neuroreport 6:573–576PubMedGoogle Scholar
  71. Nordstrom A-L, Farde L, Wiesel F-A, Forslund K, Pauli S, Halldin C, Uppfeldt G (1993) Central D2-dopamine receptor occupancy in relation to antipsychotic drug effects: a double-blind PET study of schizophrenic patients. Biol Psychiat 33:227–235PubMedGoogle Scholar
  72. Olsen RW, Tobin AJ (1990) Molecular biology of GABA (A) receptors. FASEB J 4:1469–1480PubMedGoogle Scholar
  73. Olsen RW, Bureau MH, Endo S, Smith GB, Brecha N, Sternini C, Tobin AJ (1992) GABA (A) receptor subtypes identified by molecular biology, protein chemistry and binding. Mol Neuropharmacol 2:129–133Google Scholar
  74. O’Malley KL, Mack KJ, Gandelman KY, Todd RD (1990) Organization and expression of the rat D2A receptor gene: identification of alternative transcripts and a variant donor splice site. Biochemistry 29:1367–1371PubMedGoogle Scholar
  75. Ono T, Fujino Y, Tsuchiya T, Tsuda M (1990) Plasmid DNAs directly injected into mouse brain with lipofectin can be incorporated and expressed by brain cells. Neurosci Lett 117:259–263PubMedGoogle Scholar
  76. Qin Z-H, Zhou L-W, Weiss B (1994) D2 dopamine receptor messenger RNA is altered to a greater extent by blockade of glutamate receptors than by blockade of dopamine receptors. Neuroscience 60:97–114PubMedGoogle Scholar
  77. Qin Z-H, Zhou L-W, Zhang S-P, Wang Y, Weiss B (1995) D2 dopamine receptor antisense oligodeoxynucleotide inhibits the synthesis of a functional pool of D2 dopamine receptors. Mol Pharmacol 48:730–737PubMedGoogle Scholar
  78. Reynolds GP (1996) Dopamine receptors and schizophrenia. Biochem Soc Transact 24:202–205Google Scholar
  79. Rogue P, Hanauer A, Zwiller J, Malviya AN, Vincendon G (1991) Up-regulation of dopamine D2 receptor mRNA in rat striatum by chronic neuroleptic treatment. Eur J Pharmacol 207:165–168PubMedGoogle Scholar
  80. Seeman P (1987) Dopamine receptors and the dopamine hypothesis of schizophrenia. Synapse 1:133–152PubMedGoogle Scholar
  81. Seeman P (1988) Tardive dyskinesia, dopamine receptors, and neuroleptic damage to cell membranes. J Clin Psychopharmacol 8:3S–9SPubMedGoogle Scholar
  82. Seeman P (1993) Schizophrenia as a brain disease. Arch Neurol 50:1093–1095PubMedGoogle Scholar
  83. Seeman P, Corbett R, Van Tol HHM (1997) Atypical neuroleptics have low affinity for dopamine D, receptors or are selective for D4 receptors. Neuropsychopharmacol 16:93–115Google Scholar
  84. Sibley D, Monsma F, Shen Y (1993) Molecular neurobiology of D, and D, dopamine receptors. In: Waddington JL (ed) D,:D, dopamine receptor interactions. Academic, San Diego, pp 1–17Google Scholar
  85. Silvia CP, King GR, Lee TH, Xue Z-Y, Caron MG, Ellinwood EH (1994) Intranigral administration of D2 dopamine receptor antisense oligodeoxynucleotides establishes a role for nigrostriatal D2 autoreceptors in the motor actions of cocaine. Mol Pharmacol 46:51–57PubMedGoogle Scholar
  86. Smith GB, Olsen RW (1995) Functional domains of GABA (A) receptors. Trends Pharmacol Sci 16:162–167PubMedGoogle Scholar
  87. Sokoloff P, Schwartz J-C (1995) Novel dopamine receptors half a decade later. Trends Pharmacol Sci 16:270–275PubMedGoogle Scholar
  88. Sokoloff P, Giros B, Martres MP, Bouthenet ML, Schwartz JC (1990) Molecular cloning and characterization of a novel dopamine receptor (D,) as a target for neuroleptics. Nature 347:146–151PubMedGoogle Scholar
  89. Sommer W, Bjelke B, Ganten D, Fuxe K (1993) Antisense oligonucleotide to c-fos induces ipsilateral rotational behaviour to d-amphetamine. Neuroreport 5:277–280PubMedGoogle Scholar
  90. Starr S, Kozell L, Neve K (1995) Drug-induced up-regulation of dopamine D2 receptors on cultured cells. J Neurochem 65:569–577PubMedGoogle Scholar
  91. Stein CA, Cheng Y-C (1993) Antisense oligonucleotides as therapeutic agents-Is the bullet really magical. Science 261:1004–1012PubMedGoogle Scholar
  92. Sun F-Y, Faden AI (1995) Pretreatment with antisense oligodeoxynucleotides directed against the NMDA-R1 receptor enhances survival and behavioral recovery following traumatic brain injury in rats. Brain Res 693:163–168PubMedGoogle Scholar
  93. Sunahara RK, Niznik HB, Weiner DM, Storman TM, Brann MR, Kennerdy JL, Gelernter JE, Rozmahel R, Yang Y, Israel Y, Seeman P, O’Dowd BF (1990) Human dopamine D, receptor encoded by an intronless gene on chromosome 5. Nature 347:80–83PubMedGoogle Scholar
  94. Szklarczyk A, Kaczmarek L (1995) Antisense oligodeoxyribonucleotides: stability and distribution after intracerebral injection into rat brain. J Neurosci Methods 60:181–187PubMedGoogle Scholar
  95. Thierry AR, Rahman A, Dritschilo A (1992) Liposomal delivery as a new approach to transport antisense oligodeoxynucleotides. In: Erickson RP, Izant JG (eds) Gene regulation: biology of antisense RNA and DNA. Raven, New York, pp 147–159Google Scholar
  96. Tiberi M, Jarvie KR, Silvia C, Falardeau P, Gingrich JA, Godinot N, Bertrand L, YangFeng TL, Fremeau RT Jr, Caron MG (1991) Cloning, molecular characterization, and chromosomal assignment of a gene encoding a second D, dopamine receptor subtype: differential expression pattern in rat brain compared with the DIA receptor. Proc Natl Acad Sci U S A 88:7491–7495PubMedGoogle Scholar
  97. Uhlmann E, Peyman A (1990) Antisense oligodeoxynucleotides: a new therapeutic principle. Chem Rev 544:579Google Scholar
  98. Valerio A, Alberici A, Tinti C, Spano P, Memo M (1994) Antisense strategy unravels a dopamine receptor distinct from the D2 subtype, uncoupled with adenylyl cyclase, inhibiting prolactin release from rat pituitary cells. J Neurochem 62:1260–1266PubMedGoogle Scholar
  99. Van Tol HHM, Bunzow JR, Guan HC, Sunahara RK, Seeman P, Niznik HB, Civelli O (1991) Cloning of a human dopamine D, receptor gene with high affinity for the antipsychotic clozapine. Nature 350:610–614PubMedGoogle Scholar
  100. Wahlestedt C, Golanov E, Yamamoto S, Yee F, Ericson H, Yoo H, Inturrisi CE, Reis DJ (1993) Antisense oligodeoxynucleotides to NMDA-R1 receptor channel protect cortical neurons from excitotoxicity and reduce focal ischaemic infarctions. Nature 363:260–263PubMedGoogle Scholar
  101. Wang H-Y, Zhou L-W, Friedman E, Weiss B (1993) Differential regulation of release of acetylcholine in the striatum in mice following continuous exposure to selective D1 and D2 dopaminergic agonists. Neuropharmacology 32:85–91PubMedGoogle Scholar
  102. Weiner DM, Levey AI, Sunahara RK, Niznik HB, O’Dowd BF, Seeman P, Brann MR (1991) D, and D2 dopamine receptor mRNA in rat brain. Proc Natl Acad Sci U S A 88:1859–1863PubMedGoogle Scholar
  103. Weiss B (ed) (1997) Antisense oligodeoxynucleotides and antisense RNA: novel pharmacological and therapeutic agents. CRC Press, Boca Raton, FLGoogle Scholar
  104. Weiss B, Zhou L-W, Chen JF, Szele F, Bai G (1990) Distribution and modulation of the D2 dopamine receptor mRNA in mouse brain: molecular and behavioral correlates. Adv Biosci 77:9–25Google Scholar
  105. Weiss B, Chen JF, Zhang S, Zhou L-W (1992) Developmental and age-related changes in the D2 dopamine receptor mRNA subtypes in rat brain. Neurochem Int 20 [Suppl]:49S–58SPubMedGoogle Scholar
  106. Weiss B, Zhou L-W, Zhang S-P, Qin Z-H (1993) Antisense oligodeoxynucleotide inhibits D2 dopamine receptor-mediated behavior and D2 messenger RNA. Neuroscience 55:607–612PubMedGoogle Scholar
  107. Weiss B, Zhou L-W, Zhang S-P (1996) Dopamine antisense oligodeoxynucleotides as potential novel tools for studying drug abuse. In: Raffa RB, Porreca F (eds) Antisense strategies for the study of receptor mechanisms. Landes, Georgetown, TX, pp 71–89Google Scholar
  108. Weiss B, Davidkova G, Zhang S-P (1997a) Antisense strategies in neurobiology. Neurochem Int 31:321–348Google Scholar
  109. Weiss B, Zhang S-P, Zhou L-W (1997b) Antisense strategies in dopamine receptor pharmacology. Life Sci 60:433–455Google Scholar
  110. Weiss B, Davidkova G, Zhou L-W, Zhang S-P, Morabito M (1997c) Expression of D2 dopamine receptor antisense RNA in brain inhibits D2-mediated behaviors. Neurochem Int 31:571–580Google Scholar
  111. Whitesell L, Geselowitz D, Chavany C, Fahmy B, Walbridge S, Alger JR, Neckers LM (1993) Stability, clearance, and disposition of intraventricularly administered oligodeoxynucleotides: implications for therapeutic application within the central nervous system. Proc Natl Acad Sci U S A 90:4665–4669PubMedGoogle Scholar
  112. Wickstom E (ed) (1991) Prospects for antisense nucleic acid therapy of cancer and AIDS. Wiley-Liss, New YorkGoogle Scholar
  113. Winkler JD, Thermos K, Weiss B (1987) Differential effects of fluphenazine-Nmustard on calmodulin activity and on D, and D2 dopaminergic responses. Psychopharmacology 92:285–291PubMedGoogle Scholar
  114. Yee F, Ericson H, Reis DJ, Wahlestedt C (1994) Cellular uptake of intracerebroventricularly administered biotin-or digoxigenin-labeled antisense oligodeoxynucleotides in the rat. Cell Mol Neurobiol 14:475–486PubMedGoogle Scholar
  115. Yu C, Brussaard AB, Yang X, Listerud M, Role LW (1993) Uptake of antisense oligonucleotides and functional block of acetylcholine receptor subunit gene expression in primary embryonic neurons. Dev Genet 14:296–304PubMedGoogle Scholar
  116. Yu P-Y, Eisner G, Yamaguchi I, Mouradian M, Felder RA, Jose PA (1996) Dopamine D,A receptor regulation of phospholipase C isoform. J Biol Chem 271:19503–19508PubMedGoogle Scholar
  117. Zacco A, Cooper V, Chantler PD, Fisher-Hyland S, Horton H-L, Levitt P (1990) Isolation, biochemical characterization and ultrastructural analysis of the limbic system-associated membrane protein (LAMP), a protein expressed by neurons comprising functional neural circuits. J Neurosci 10:73–90PubMedGoogle Scholar
  118. Zang Z, Florijn W, Creese I (1994) Reduction in muscarinic receptors by antisense oligodeoxynucleotide. Biochem Pharmacol 48:225–228PubMedGoogle Scholar
  119. Zhang LJ, Lachowicz JE, Sibley DR (1994) The D,S and D2L dopamine receptor isoforms are differentially regulated in Chinese hamster ovary cells. Mol Pharmacol 45:878–889PubMedGoogle Scholar
  120. Zhang M, Creese I (1993) Antisense oligodeoxynucleotide reduces brain dopamine D, receptors: behavioral correlates. Neurosci Lett 161:223–226PubMedGoogle Scholar
  121. Zhang S-P, Zhou L-W, Weiss B (1994) Oligodeoxynucleotide antisense to the D, dopamine receptor mRNA inhibits D, dopamine receptor-mediated behaviors in normal mice and in mice lesioned with 6-hydroxydopamine. J Pharmacol Exp Ther 271:1462–1470PubMedGoogle Scholar
  122. Zhang S-P, Zhou L-W, Morabito M, Lin RCS, Weiss B (1996) Uptake and distribution of fluorescein-labeled D2 dopamine receptor antisense oligodeoxynucleotide in mouse brain. J Mol Neurosci 7:13–28PubMedGoogle Scholar
  123. Zhou L-W, Zhang S-P, Connell TA, Weiss B (1993) AF64A lesions of mouse striatum result in ipsilateral rotations to D2 dopamine agonists but contralateral rotations to muscarinic cholinergic agonists. J Pharmacol Exp Ther 264:824–830PubMedGoogle Scholar
  124. Zhou L-W, Zhang S-P, Qin Z-H, Weiss B (1994) In vivo administration of an oligodeoxynucleotide antisense to the D2 dopamine receptor mRNA inhibits D2 dopamine receptor-mediated behavior and the expression of D2 dopamine receptors in mouse striatum. J Pharmacol Exp Ther 268:1015–1023PubMedGoogle Scholar
  125. Zhou L-W, Zhang S-P, Weiss B (1996) Intrastriatal administration of an oligodeoxynucleotide antisense to the D2 dopamine receptor mRNA inhibits D2 dopamine receptor-mediated behavior and D2 dopamine receptors in normal mice and in mice lesioned with 6-hydroxydopamine. Neurochem Int 29:583–595PubMedGoogle Scholar
  126. Zhu WJ, Wang JF, Vicini S, Grayson DR (1996) Alpha 6 and gamma 2 subunit antisense oligodeoxynucleotides alter gamma-aminobutyric acid receptor pharmacology in cerebellar granule neurons. Mol Pharmacol 50:23–33PubMedGoogle Scholar
  127. Zon G (1995) Brief overview of control of genetic expression by antisense oligonucleotides and in vivo applications. Mol Neurobiol 10:219–229PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • G. Davidkova
  • B. Weiss

There are no affiliations available

Personalised recommendations