Serotonin2 (5-HT2) receptor binding in the frontal cortex of schizophrenic patients

  • R. C. Arora
  • H. Y. Meltzer
Full Papers


Serotonin2 (5-HT2) receptor binding was studied, using3H-spiperone as the ligand, in post-mortem brain specimens obtained from schizophrenic patients (N=11) and non-psychiatric controls (N=11). The maximum number of binding sites (Bmax) was significantly decreased in schizophrenic patients as compared to normal controls. This difference did not appear to be due to neuroleptic treatment. No difference in Kd (an inverse measure of the affinity of3H-spiperone to its binding sites) was observed between the two groups. However, studies with unmedicated schizophrenic patients are needed to draw any definite conclusion. The role of serotonergic processes in the psychobiology of schizophrenia is discussed.


5-HT2 receptor human postmortem brain schizophrenia 


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  1. Altar CA, Wasley AM, Neale RF, Stone GA (1986) Typical and atypical antipsychotic occupancy of D2 and S2 receptors: an autoradiographic analysis in rat brain. Brain Res Bull 16: 517–525Google Scholar
  2. Andorn AC, Huang EH, Warren AE (1984) Specific [3H]-spiroperidol binding sites in human prefrontal cortex: potential site multiplicity and overall serotonin-like selectively. Life Sci 34: 2461–2466Google Scholar
  3. Andreé TH, Mikuni M, Tong CY, Koenig JI, Meltzer HY (1986) Differential effect of subchronic treatment with various neuroleptic agents on serotonin2 receptors in rat cerebral cortex. J Neurochem 46: 191–197Google Scholar
  4. Arora RC, Meltzer HY (1989) Serotonergic measures in the brains of suicide victims: 5-HT2 binding sites in the frontal cortex of suicide victims and control subjects. Am J Psychiatry 146: 730–736Google Scholar
  5. Bennett JP, Enna SJ, Bylund DB, Gillin JC, Wyatt RJ, Snyder SH (1979) Neurotransmitter receptors in frontal cortex of schizophrenics. Arch Gen Psychiatry 36: 927–934Google Scholar
  6. Biegon A, Kargman S, Snyder L, McEwen BS (1986) Characterisation and localisation of serotonin receptors in human brain postmortem. Brain Res 353: 91–98Google Scholar
  7. Bleich A, Brown S, Kahn R, van Praag H (1988) The role of serotonin in schizophrenia. Schizophr Bull 14: 297–315Google Scholar
  8. Burt DR, Creese I, Snyder SH (1976) Binding interactions of lyseric acid diethylamide and related agents with dopamine receptors in the brain. Mol Pharmacol 12: 631–638Google Scholar
  9. Camus A, Javoy-Agid F, Dubois A, Scatton B (1986) Autoradiographic localization and quantification of dopamine D2 receptors in normal human brain with [3H]N-n-propylnorapomorphine. Brain Res 375: 135–149Google Scholar
  10. Camps M, Cortes R, Gueye B, Probst A, Palacios JM (1989) Dopamine receptors in human brain: autoradiographic distribution of D2 sites. Neuroscience 28: 275–290Google Scholar
  11. Cheetham SC, Crompton MR, Katona CLE, Horton RW (1988) Brain 5-HT2 receptor binding sites in depressed suicide victims. Brain Res 443: 272–280Google Scholar
  12. Chivers J, Jenner P, Marsden CD (1987) Pharmacological chracterization of binding sites identified in rat brain following in vivo administration of [3H]-spiperone. Br J Pharmacol 90: 467–478Google Scholar
  13. De Keyser J, De Backer J-P, Ebinger G, Vauqueline G (1985) Regional distribution of the dopamine D2 receptors in the mesotelencephalic dopamine neurons systems of human brain. J Neurol Sci 71: 119–127Google Scholar
  14. De Keyser J, Claeys A, De-Backer J-P, Ebinger G, Roels F, Vanquelin G (1988) Autoradiographic localization of D1 and D2 dopamine receptors in the human brain. Neurosci Lett 91: 142–147Google Scholar
  15. Engel G, Muller-Schweinitzer E, Palacios JM (1984) 2-[125Iodo]LSD, a new ligand for the characterization and localization of 5-HT2 receptors. Naunyn-Schiedebergs Arch Pharmacol 325: 328–336Google Scholar
  16. Gross-Isseroff R, Salama D, Israeli M, Biegon A (1990) Autoradiographic analysis of agedependent changes in serotonin 5-HT2 receptors of the human brain postmortem. Brain Res 519: 223–227Google Scholar
  17. Kraepelin E (1919) Lectures of clinical insanity (translated by T Johnstone). William Word and Co, Gryphon Editions Inc, Alabama, pp 357–359Google Scholar
  18. Lee T, Tang SW (1984) Loxapine and clozpaine decrease serotonin (S2) but do not elevate dopamine (D2) receptor numbers in the rat brain. Psychiatry Res 12: 277–285Google Scholar
  19. Levin S (1984) Frontal lobe dysfunctions in schizophrenia. II. Impairments of psychological and brain functions. J Psychiatry Res 18: 57–72Google Scholar
  20. Leysen JE, Niemegeers CJE, van Nueten JM, Laduron PM (1982) [3H]Ketanserin (R 41468), a selective3H-ligand for serotonin2 receptor binding sites. Mol Pharmacol 21: 301–314Google Scholar
  21. Leysen JE, Niemegeers CJE, Tollenaere JP, Laduron PM (1978) Serotonergic component of neuroleptic receptors. Nature 272: 168–171Google Scholar
  22. Liskowsky DR, Potter LT (1985) D-2 dopamine receptors in the frontal cortex of rat and human. Life Sci 36: 1551–1559Google Scholar
  23. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin Phenol reagent. J Biol Chem 193: 265–275Google Scholar
  24. Luabeya MK, Maloteaux J-M, Laduron PM (1984) Regional and cortical laminar distributions of serotonin S2 benzodiazepine, muscarinic, and dopamine D2 receptor in human brain. J Neurochem 43: 1068–1071Google Scholar
  25. Mackay AVP, Doble A, Bird ED, Spokes EG, Ouik M, Iversen LL (1978)3H-Spiperone binding in normal and schizophrenic post-mortem human brain. Life Sci 23: 527–532Google Scholar
  26. Mann JJ, Stanley M, McBride PA, McEwen BS (1986) Increased serotonin2 and β-adrenergic receptor binding in frontal cortex of suicide victims. Arch J Psychiatry 43: 954–959Google Scholar
  27. Matsubara S, Meltzer HY (1989) Effect of typical and atypical antipsychotic drugs on 5-HT2 receptor density in rat cerebral cortex. Life Sci 45: 1397–1406Google Scholar
  28. Meltzer HY (1989) Clinical studies on the mechanism of action of clozapine: the dopamine-serotonin hypothesis of schizophrenia. Psychopharmacology 99: S 18-S 27Google Scholar
  29. Meltzer HY, Matsubara S, Lee J-C (1989) Classification of typical and atypical antipsychotic drugs on the basis of dopamine D-1, D-2 and serotonin2 pKi values. J Pharmacol Exp Ther 251: 238–246Google Scholar
  30. Meltzer HY (1987) Biological studies in schizophrenia. Schizophr Bull 13: 77–111Google Scholar
  31. Mita T, Kuno T, Nakai H, Tanaka C (1982) Evidence for the presence of D2 and 5-HT2 receptors in the human prefrontal cortex. Jap J Pharmacol 32: 1027–1032Google Scholar
  32. Mita T, Hanada S, Nishimo N, Kuno T, Nakai H, Yamadori R, Mizoi Y, Tanaka C (1986) Decreased serotonin S2 and increased dopamine D2 receptors in chronic schizophrenics. Biol Psychiatry 21: 1407–1414Google Scholar
  33. O'Dell SJ, La Hoste GJ, Widmark CB, Shapiro RM, Potkin SG, Marshall JF (1990) Chronic treatment with clozapine or haloperidol differentially regulates dopamine and serotonin receptor in rat brain. Synapse 6: 146–153Google Scholar
  34. Owen F, Cross AJ, Crow TJ, Lofthouse R, Poulter M (1981) Neurotransmitter receptors in brain in schizophrenia. Acta Psychiatr Scand 63: 20–28Google Scholar
  35. Owen F, Crow TJ, Poulter M, Cross AJ, Longden A, Riley GJ (1978) Increased dopaminereceptor sensitivity in schizophrenia. Lancet ii: 223–225Google Scholar
  36. Peroutka SJ, Snyder SH (1980) Relationship of neuroleptic drug effects at brain dopamine, serotonin, α-adrenergic, and histamine to clinical potency. Am J Psychiatry 137: 1518–1522Google Scholar
  37. Peroutka SJ, Snyder SH (1979) Multiple serotonin receptors: differential binding on [3H]5-hydroxytryptamine, [3H]lysergic acid diethylamide and [3H]spiroperidol. Mol Pharmacol 16: 687–699Google Scholar
  38. Reynolds GP, Rossor MN, Iversen LL (1983) Preliminary studies of human cortical 5-HT2 receptors and their involvement in schizophrenia and neuroleptic drug action. J Neural Transm [Suppl 18]: 273–277Google Scholar
  39. Scatchard G (1949) The attraction of proteins for small molecules and ions. Ann NY Acad Sci 51: 660–672Google Scholar
  40. Schmidt AW, Peroutka SJ (1989) 5-Hydroxytryptamine receptor “families”. FASEB J 3: 2242–2249Google Scholar
  41. Van Nueten JM, Janssen PAJ, Van Beek J, Xhonneux R, Verbeuren TJ, Vanhoutee PM (1981) Vascular effects of ketanserin (R-41468), a novel antagonist of 5-HT2 serotonergic receptors. J Pharmacol Exp Ther 218: 217–230Google Scholar
  42. Weinberger DR, Berman KF, Zec RF (1986) Physiological dysfunction of dorsolateral prefrontal cortex in schizophrenia. 1. Regional cerebral blood flow evidence. Arch Gen Psychiatry 43: 114–124Google Scholar
  43. Whitaker PM, Crow TJ, Ferrier IN (1981) Triatiated LSD binding in frontal cortex in schizophrenia. Arch Gen Psychiatry 38: 278–280Google Scholar
  44. Whitaker PM, Seeman P (1978) Selective labelling of serotonin receptors by D-3H-lysergic acid diethylamide in calf caudate. Proc Natl Acad Sci USA 75: 5783–5787Google Scholar
  45. Wilmot CA, Szczepanik AM (1989) Effects of acute and chronic treatments with clozapine and haloperidol on serotonin (5-HT2) and dopamine (D2) receptors in the rat brain. Brain Res 487: 288–298Google Scholar

Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • R. C. Arora
    • 1
  • H. Y. Meltzer
    • 1
  1. 1.Laboratory of Biological Psychiatry, Department of Psychiatry, School of MedicineCase Western Reserve UniversityClevelandUSA

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