Skip to main content
SpringerLink
Log in

Human dopamine receptor subtypes—in vitro binding analysis using3H-SCH 23390 and3H-raclopride

  • Original Papers
  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary

Affinities and regional densities of the D1- and D2-dopamine receptor subtypes were studied in the human post-mortem brain in vitro using the two selective radioligands3H-SCH23390 and3H-raclopride.3H-Raclopride binding was confined to the caudate nucleus, the putamen and the substantia nigra, while3H-SCH23390 bound to cortical regions as well. The binding of3H-SCH 23390 was reduced by a low concentration of ketanserin, indicating binding to 5-HT2 receptors in addition to the D1dopamine receptors. The endogenous neurotransmitter dopamine interacted potently both with the D1-dopamine receptor and the D2-dopamine receptor, displaying two affinity states for each subtype. The distribution of the dopamine receptor subtypes obtained in the present in vitro investigation is in agreement with data obtained with11C-SCH 23390 and11C-raclopride in positron emission tomographic studies in human volunteers.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Amalric M, Koob GF, Creese I, Swerdlow NR (1986) “Selective” D-1 and D-2 receptor antagonists fail to differentially alter supersensitive locomotor behaviour in the rat. Life Sci 39: 1985–1993

    Google Scholar 

  • Andén NE, Carlsson A, Dahlström A, Fuxe K, Hillarp Nå, Larsson K (1964) Demonstration and mapping out of nigro-neostriatal dopamine neurons. Life Sci 4: 523–530

    Google Scholar 

  • Andersen PH, Nielsen EB (1986) The dopamine D1 receptor: biochemical and behavioural aspects. In: Breese GR, Creese I (eds) Neurobiology of central D1-dopamine receptors. Plenum Press, London, pp 73–91

    Google Scholar 

  • Aquilonius S-M, EckernÄs S-å, Gillberg P-G (1983) Large section cryomicrotomy in human neuroanatomy and neurochemistry. In: Cuello AC (ed) Brain microdissection techniques. Wiley, Chichester (IBRO handbooks series, Methods in the neurosciences, vol 2, pp 155–170

    Google Scholar 

  • Barnett A (1986) Review on dopamine receptors. Drugs Fut 11: 49–56

    Google Scholar 

  • Bannon MJ, Roth H (1983) Pharmacology of mesocortical dopamine neurons. Pharmacol Rev 35: 53–65

    Google Scholar 

  • Billard W, Ruperto V, Crosby G, Iorio LC, Barnett A (1984) Characterization of the binding of3H-SCH23390, a selective D-1 receptor antagonist ligand, in rat striatum. Life Sci 35: 1885–1893

    Google Scholar 

  • Bischoff S, Bittiger H, Krauss J (1980) In vivo (3H)spiperone binding to the rat hippocampal formation: involvement of dopamine receptors. Eur J Pharmacol 68: 305–315

    Google Scholar 

  • Bischoff S, Bittiger H, Delini-Stula A, Ortmann R (1982) Septohippocampal system: target for substituted benzamides. Eur J Pharmacol 79: 225–232

    Google Scholar 

  • Bischoff S, Heinrich M, Sonntag JM, Krauss J (1986) The D-1 dopamine receptor antagonist SCH23390 also interacts potently with brain serotonin (5-HT2) receptors. Eur J Pharmacol 129: 367–370

    Google Scholar 

  • Björklund A, Lindvall O (1984) Dopamine-containing systems in the CNS. In: Björklund O, Hökfelt T (eds) Handbook of chemical neuroanatomy, vol 2, classical transmitters in the CNS, part 1. Elsevier, Amsterdam, pp 55–122

    Google Scholar 

  • Boyson SJ, McGonigle P, Molinoff PB (1986) Quantitative autoradiographic localization of the D1 and D2 subtypes of dopamine receptors in rat brain. J Neurosci 6: 3177–3188

    Google Scholar 

  • Bruinink A, Bischoff S (1986) Detection of dopamine receptors in homogenates of rat hippocampus and other brain areas. Brain Res 386: 78–83

    Google Scholar 

  • Creese I, Burt DR, Snyder SH (1976) Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science 192: 481–483

    Google Scholar 

  • Creese I, Sibley DR, Hamblin MW, Leff SE (1983) The classification of dopamine receptors: relationship to radioligand binding. Ann Rev Neurosci 6: 43–71

    Google Scholar 

  • Creese I, Sibley DR, Leff SE (1984) Agonist interactions with dopamine receptors: relationship to radioligand binding. Fed Proc 43: 2779–2784

    Google Scholar 

  • Dawson TM, Gehlert DR, Yamamura HI, Barnett A, Wamsley JK (1985) D-1 dopamine receptors in the rat brain: autoradiographic localization using (3H)-SCH23390. Eur J Pharmacol 108: 323–325

    Google Scholar 

  • Dawson TM, Gehlert RD, Wamsley JK (1986) Quantitative autoradiographic localization of central dopamine D-1 and D-2 receptors. In: Breese GR, Creese I (eds) Neurobiology of central D1dopamine receptors. Plenum Press, London pp 93–118

    Google Scholar 

  • Fallon JH, Moore RY (1978) Catecholamine innervation of the basal forebrain. IV. Topography of the dopamine projection to the basal forebrain and neostriatum. J Comp Neurol 180: 545–580

    Google Scholar 

  • Farde L, Ehrin E, Eriksson L, Greitz T, Hall H, Hedström CG, Litton JE, Sedvall G (1985) Substituted benzamides as ligands for visualization of dopamine receptor binding in the human brain by positron emission tomography. Proc Natl Acad Sci USA 82: 3863–3867

    Google Scholar 

  • Farde L, Hall H, Ehrin E, Sedvall G (1986) Quantitative analysis of D2 dopamine receptor binding in the living human brain by PET. Science 231: 258–261

    Google Scholar 

  • Farde L, Halldin C, Stone-Elander S, Sedvall G (1987a) PET analysis of human dopamine receptor subtypes using11C-SCH23390 and11C-raclopride. Psychopharmacology 92: 278–284

    Google Scholar 

  • Farde L, Wiesel F, Hall H, Halldin C, Stone-Elander S, Sedvall G (1987b) PET reveals unchanged D2-dopamine receptors in drugnaive schizophrenics. Arch Gen Psychiatry 44: 671–672

    Google Scholar 

  • Fuxe K, ögren SO, Fredholm B, Agnati L, Hökfelt T, Perez de la Mora M (1976) Possibilities of a differential blockade of central monoamine receptors. In: de Ajuriaguerra J, Tissot R (eds) Rhinencéphale neurotransmitteurs et psychoses. Georg & Cie, Geneva, pp 253–289

    Google Scholar 

  • Gawell L, Hall H, Köhler C (1985) Preparation of tritium labelled benzamide dopamine-D2 ligands at high specific activity. J Labelled Compound Radiopharm 22: 1033–1043

    Google Scholar 

  • Gehlert DR, Wamsley JK (1984) Autoradiographic localization of (3H)-sulpiride binding sites in the rat rain. Eur J Pharmacol 98: 311–312

    Google Scholar 

  • Gehlert DR, Wamsley JK (1985) Dopamine receptors in the rat brain: quantitative autoradiographic localization using (3H)-sulpiride. Neurochem Int 7: 717–723

    Google Scholar 

  • Glowinski J, Tassin JP, Thierry AM (1983) The mesocortico-prefrontal dopaminergic neurons. TINS 6: 415–418

    Google Scholar 

  • Hall H, Thor L (1979) Evaluation of a semiautomatic filtration technique for receptor binding studies. Life Sci 24: 2293–2300

    Google Scholar 

  • Hall H, SÄllemark M, Jerning E (1986) Effects of remoxipride and some related new substituted salicylamides on rat brain receptors. Acta Pharmacol Toxicol 58: 61–70

    Google Scholar 

  • Hall H, Wedel I (1986) Comparisons between the in vitro binding of two substituted benzamides and two butyrophenones to dopamine-D2 receptors in the rat striatum. Acta Pharmacol Toxicol 58: 368–373

    Google Scholar 

  • Hyttel J (1983) SCH23390—the first selective dopamine D1 antagonist. Eur J Pharmacol 91: 153–154

    Google Scholar 

  • Hyttel J, Christensen AV (1984) Do dopamine D-1 receptors contribute to the antipsychotic effects and side effects of neuroleptic drugs? Clin Pharmacol [Suppl] 7: 546–547

    Google Scholar 

  • Kebabian JW, Agui T, van Oene JC, Shigematsu K, Saavedra JM (1986) The D1 dopamine receptor: new perspectives. TIPS 7: 96–99

    Google Scholar 

  • Kebabian JW, Calne DB (1979) Multiple receptors for dopamine. Nature 277: 93–96

    Google Scholar 

  • Köhler C, Hall H, ögren SO, Gawell L (1985) Specific in vitro and in vivo binding of3H-raclopride, a potent substituted drug with high affinity for dopamine D-2 receptors in the rat brain. Biochem Pharmacol 34: 2251–2259

    Google Scholar 

  • Köhler C, RadesÄter A-C (1986) Autoradiographic visualization of dopamine D-2 receptors in the monkey brain using the selective benzamide drug (3H)raclopride. Neurosci Lett 66: 85–90

    Google Scholar 

  • Leff SE, Chen A, Creese I (1984) Sulpiride isomers exhibit reversed stereospecificity for D-1 and D-2 dopamine receptors in the CNS. Neuropharmacology 23: 589–590

    Google Scholar 

  • Leysen JE, Niemegeers CJE, Van Nueten JM, Laduron PM (1982) (3H)Ketanserin (R41468), a selective3H-ligand for serotonin2 receptor binding sites—binding properties, brain distribution, and functional role. Mol Pharmacol 21: 301–314

    Google Scholar 

  • Lindvall O, Björklund A (1974) The organization of the ascending catecholamine neuron systems in the rat brain as revealed by the glyoxylic acid fluorescence method. Acta Physiol Scand [Suppl] 412: 1–48

    Google Scholar 

  • Martres MP, Bouthenet ML, Sales N, Sokoloff P, Schwartz JC (1985) Widespread distribution of brain dopamine receptors evidenced with (125I) iodosulpride, a highly selective ligand. Science 228: 752–755

    Google Scholar 

  • Munson PJ, Rodbard D (1980) Ligand: a versatile computerized approach for characterization of ligand-binding systems. Anal Biochem 107: 220–239

    Google Scholar 

  • Peroutka SJ, Snyder SH (1980) Relationship of neuroleptic drug effects at brain dopamine, serotonin, adrenergic and histamine receptors to clinical potency. Am J Psychiatry 137: 1518–1522

    Google Scholar 

  • Sedvall G, Farde L, Stone-Elander S, Halldin C (1986) Dopamine D1 receptor binding in the living human brain. In: Breese GR, Creese I (eds) Neurobiology of central D1 dopamine receptors. Plenum Press, London, pp 119–124

    Google Scholar 

  • Schultz DW, Wyrick SD, Mailman RB (1985)3H-SCH23390 has the characteristics of a dopamine receptor ligand in the rat central nervous system. Eur J Pharmacol 106: 211–212

    Google Scholar 

  • Seeman P (1980) Brain dopamine receptors. Pharmacol Rev 32: 229–313

    Google Scholar 

  • Seeman P, Lee T, Chau-Wong M, Wong K (1976) Antipsychotic drug doses and neuroleptic/ dopamine receptors. Nature 261: 717–719

    Google Scholar 

  • Stoof JC, Kebabian JW (1984) Two dopamine receptors: biochemistry, physiology and pharmacology. Life Sci 35: 2281–2296

    Google Scholar 

  • Tassin JP, Bockaert J, Blanc G, Stinus L, Thierry AM, Lavielle S, Premont G, Glowinski J (1978) Topographical distribution of dopaminergic innervation and dopaminergic receptors of the anterior cerebral cortex of the rat. Brain Res 106: 241–251

    Google Scholar 

  • Ullberg S (1977) The technique of whole-body autoradiography: cryosectioning of large specimens. Sci Tools [Suppl]: 2–29

    Google Scholar 

  • Waddington JL (1986) Behavioural correlates of the action of selective D-1 dopamine receptor antagonists. Impact of SCH23390 and SKF83566, and functionally interactive D-1∶D-2 receptor systems. Biochem Pharmacol 35: 3661–3667

    Google Scholar 

  • Wagner HN Jr, Burns HD, Dannals RF, Wong DF, Långström B, Duelfer T, Frost JJ, Ravert HT, Links JM, Rosenbloom SB, Lukas SE, Kramer AV, Kuhar MJ (1983) Imaging dopamine receptors in the human brain by positron tomography. Science 221: 1264–1266

    Google Scholar 

Download references

Author information

Author notes

  1. H. Hall

    Present address: Department of Biochemical Neuropharmacology, CNS-Drugs, Research and Development Laboratories, Astra Alab AB, SödertÄlje

Authors and Affiliations

  1. Department of Psychiatry and Psychology, Karolinska Institute, Stockholm, Sweden

    L. Farde & G. Sedvall

Authors
  1. H. Hall
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L. Farde
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. Sedvall
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hall, H., Farde, L. & Sedvall, G. Human dopamine receptor subtypes—in vitro binding analysis using3H-SCH 23390 and3H-raclopride. J. Neural Transmission 73, 7–21 (1988). https://doi.org/10.1007/BF01244618

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01244618

Keywords

Search

Navigation