Psychopharmacology

, Volume 112, Supplement 1, pp S35–S39

Differential changes in serotonin 5-HT1A and 5-HT2 receptor binding in patients with chronic schizophrenia

  • Takeshi Hashimoto
  • Noboru Kitamura
  • Yasuo Kajimoto
  • Yutaka Shirai
  • Osamu Shirakawa
  • Tatsuo Mita
  • Naoki Nishino
  • Chikako Tanaka
Article

Abstract

Serotonin 5-HT1A and 5-HT2 receptors were examined in the postmortem brains of controls and patients with chronic schizophrenia. In the prefrontal cortex from patients with schizophrenia, 5-HT1A receptor binding was increased, while 5-HT2 receptor binding was decreased, when compared to controls. The increased 5-HT1A receptor binding or the decreased 5-HT2 receptor binding was observed in both the patients who had been medicated with neuroleptics at time of death and those who had not, at least 2 months prior to death. Thus, abnormalities of 5-HT receptor subtypes seem to exist in the brains of patients with chronic schizophrenia. 5-HT related agents might be beneficial for the treatment of schizophrenia.

Key words

Serotonin Serotonin1A(5-HT1A) receptor Serotonin2(5-HT2) receptor Schizophrenia Postmortem brain 

References

  1. Andrée 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
  2. Arnt J, Hyttel J (1989) Facilitation of 8-OH-DPAT-induced forepaw treading of rats by the 5-HT2 agonist DOI. Eur J Pharmacol 161:45–51Google Scholar
  3. Arora RC, Meltzer HY (1991) Serotonin2 (5-HT2) receptors binding in the frontal cortex of schizophrenic patients. J Neural Transm 85:19–29CrossRefGoogle Scholar
  4. Azmitia EC, Whitaker-Azmitia PM (1991) Awaking the sleeping giant: anatomy and plasticity of the brain serotonergic system. J Clin Psychiatry 52 [12, suppl]:4–16Google Scholar
  5. Bachus LI, Sharp T, Grahame-Smith DG (1990) Behavioral evidence for a functional interaction between central 5-HT2 and 5-HT1A receptors. Br J Pharmacol 100:793–799PubMedGoogle Scholar
  6. Barnes NM, Costall B, Ironside JW, Naylor RJ (1988) Identification of 5-HT3 recognition sites in human brain tissue using [3H]zacopride. J Pharm Pharmacol 40:668PubMedGoogle Scholar
  7. Benes FM, McSparren J, Bird ED, SanGiovanni JP, Vincent SL (1991) Deficits in small interneurons in prefrontal and cingulate cortices of schizophrenic and schizoaffective patients. Arch Gen Psychiatry 48:996–1001PubMedGoogle Scholar
  8. Bennett JP, Enna SJ, Bylund DB, Gillin JC, Wyatt RJ, Snyder SH (1979) Neurotransmitter receptors in frontal cortex of schizophrenics. Arch Gen Psychiatry 36:927–934PubMedGoogle Scholar
  9. Berendsen HHG, Broekkamp CLE, van Delft AML (1991) Depletion of brain serotonin differently affects behaviors induced by 5HT1A, 5HT1C and 5HT2 receptor activation. Behav Neural Biol 55:214–226CrossRefPubMedGoogle Scholar
  10. Bleich A, Brown S, Kahn R, van Praag H (1988) The role of serotonin in schizophrenia. Schizophr Bull 14:297–315PubMedGoogle Scholar
  11. Brody D, Adler LA, Kim T, Angrist B, Rotrosen J (1990) Effects of buspirone in seven schizophrenic subjects. J Clin Psychopharmacol 10[1]:68–69PubMedGoogle Scholar
  12. Conn PJ, Sanders-Bush E (1985) Serotonin-stimulated phosphoinositide turnover: mediation by the S2 binding site in rat cerebral cortex but not in subcortical regions. J Pharmacol Exp Ther 234:195–203PubMedGoogle Scholar
  13. De Bleeker E, Verslegers W (1990) Ritanserin in the treatment of negative symptoms in chronic schizophrenic patients. Abstracts of 17th congress of CINP, vol II, Kyoto, Japan, p 221Google Scholar
  14. De Vivo M, Maayani S (1986) Characterization of the 5-hydroxytryptamine1A receptor-mediated inhibition of forskolin-stimulated adenylate cyclase activity in guinea pig and rat hippocampal membranes J Pharmacol Exp Ther 238:248–253PubMedGoogle Scholar
  15. Eison AS, Yocca FD (1985) reduction in cortical 5-HT2 receptor sensitivity after continuous gepirone treatment. Eur J Pharmacol 111:389–392CrossRefPubMedGoogle Scholar
  16. Gerlach J (1991) New antipsychotics: classification, efficacy, and adverse effects. Schizophr Bull 17[2]:289–309PubMedGoogle Scholar
  17. Glennon RA, Darmani NA, Martin BR (1991) Multiple populations of serotonin receptors may modulate the behavioral effects of serotonergic agents. Life Sci 48:2493–2498CrossRefPubMedGoogle Scholar
  18. Goff DC, Midha KK, Brotman AW, Mccormick S, Waites M, Amico ET (1991) An open trial of buspirone added to neuroleptics in schizophrenic patients. J Clin Psychopharmacol 11:193–197PubMedGoogle Scholar
  19. Gozlan H, Mestikaway SEI, Pichat L, Glowinski, Hamon M (1983) Identification of presynaptic serotonin autoreceptors using a new ligand:3H-PAT. Nature 305:140–142CrossRefPubMedGoogle Scholar
  20. Hall MD, Mestikawy SE, Emerit MB, Pitchat L, Hamon M, Gozlan H (1985) [3H]8-hydroxy-2-(di-n-propylamino)tetralin binding to pre- and postsynaptic 5-hydroxytryptamine sites in various regions of the rat brain. J Neurochem 44:1685–1696PubMedGoogle Scholar
  21. Hashimoto T, Nishino N, Nakai H, Tanaka C (1991) Increase in serotonin 5-HT1A receptors in prefrontal and temporal cortices of brains from patients with schizophrenia. Life Sci 48:355–363CrossRefPubMedGoogle Scholar
  22. Hoyer D, Paroz A, Probst A, Palacios JN (1986a) Serotonin receptors in the human brain. I. Characterization and autoradiographic localization of 5-HT1A recognition sites. Apparent absence of 5-HT1B recognition sites. Brain Res 376:85–96CrossRefPubMedGoogle Scholar
  23. Hoyer D, Pazos A, Probst A and Palacios JN (1986b) Serotonin receptors in the human brain. II. Characterization and autoradiographic localization of 5-HT1C and 5-HT2 recognition sites. Brain Res 376:97–107CrossRefPubMedGoogle Scholar
  24. Jann MW (1988) Buspirone: an update on a unique anxiolytic agent. Pharmacotherapy 8:100–116PubMedGoogle Scholar
  25. Julius D (1991) Molecular biology of serotonin receptors. Annu Rev Neurosci 14:335–360CrossRefPubMedGoogle Scholar
  26. Kane A, Honigfeld G, Singer J, Meltzer HY (1988) Clozapine to the treatment-resistant schizophrenic: a double-blind comparison versus chlorpromazine/benztropine. Arch Gen Psychiatry 45:789–796PubMedGoogle Scholar
  27. Lee T, Seeman P, Tourtellotte WW, Hornykiewicz O (1978) Binding of3H-neuroleptics and3H-apomorphine in schizophrenic brains. Nature 274:897–900CrossRefPubMedGoogle Scholar
  28. Leysen JE, van Gompel P, Verwimp M, Niemegeers CJE (1983) Role and localization of serotonin (S2)-receptor-binding sites: effects of neuronal lesions. In: Mandel P, DeFeudis FV (eds) CNS receptors — from molecular pharmacology to behavior. Raven Press, New York, pp 373–383Google Scholar
  29. Lucki I (1991) Behavioral studies of serotonin receptor agonists as antidepressant drugs. J Clin Psychiatry 52[suppl 12]:24–31Google Scholar
  30. Meltzer HY (1989) Clinical studies on the mechanism of action of clozapine: the dopamine-serotonin hypothesis of schizophrenia. Psychopharmacology 99:S18-S27CrossRefPubMedGoogle Scholar
  31. Mita T, Hanada S, Nishino N, Kuno T, Nakai H, Yamadori T, Mizoi Y, Tanaka C (1986) Decreased serotonin S2 and increased dopamine D2 receptors in chronic schizophrenics. Biol Psychiatry 21:1407–1414CrossRefPubMedGoogle Scholar
  32. O'Boyle KM, Waddington JL (1985) Striatal [3H]-spiperone binding after long-term depot neuroleptic treatment: interaction with age. Br J Pharmacol [March suppl]:p 73Google Scholar
  33. Owen F, Cross AJ, Crow TJ, Longden A, Poulter M, Riley GJ (1978) Increased dopamine-receptor sensitivity in schizophrenia. Lancet II:223–225CrossRefGoogle Scholar
  34. Pazos A, Probst A, Palacios JM (1987) Serotonin receptors in the human brain III. autoradiographic mapping of serotonin-1 receptors. Neuroscience 21:97–122CrossRefPubMedGoogle Scholar
  35. Pompeiano M, Palacios JM, Mengod G (1992) Distribution and cellular localization of mRNA coding for 5-HT1A receptor in the rat brain: correlation with receptor binding. J Neurosci 12[2]:442–453Google Scholar
  36. Reynolds GP, Rossor MN, Iversen LL (1983) Preliminary studies of human cortical 5-HT2 receptors and their involvement in schizophrenia. J Neural Transm [Suppl 18]:273–277Google Scholar
  37. Sathananthan GL, Sanghvi I, Phillips N, Gershon S (1975) MJ9022: correlation between neuroleptic potential and stereotypy. Curr Ther Res 18:701–705PubMedGoogle Scholar
  38. Seeman P, Ulpian C, Bergeron C, Riederer P, Jellinger K, Gabriel E, Reynolds GP, Tourtellotte WW (1984) Bimodal distribution of dopamine receptor densities in brains of schizophrenics. Science 225:728–731PubMedGoogle Scholar
  39. Sovner R, Parnell-Sovner N (1989) Use of buspirone in the treatment of schizophrenia. J Clin Psychopharmacol 9:61–62PubMedGoogle Scholar
  40. Traber J, Glaser T (1987) 5-HT1A receptor-related anxiolytics. TIPS 8:432–437Google Scholar
  41. Van Kammen DP, Gelernter J (1987) Biochemical instability in schizophrenia II: the serotonin and γ-aminobutyric acid systems. In: Meltzer HY (ed) Psychopharmacology: the third generation of progress. Raven Press, New York, pp 753–758Google Scholar
  42. Whitaker PM, Crow TJ, Ferrier IN (1981) Tritiated LSD binding in frontal cortex in schizophrenia. Arch Gen Psychiatry 38:278–280PubMedGoogle Scholar
  43. Wieland S, Fischette CT, Lucki I (1990) Chronic infusion of tandospirone and imipramine alters 5-HT-mediated behaviors and 5-HT receptors. Soc Neurosci Abstr 16:530Google Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • Takeshi Hashimoto
    • 1
  • Noboru Kitamura
    • 1
  • Yasuo Kajimoto
    • 2
  • Yutaka Shirai
    • 2
  • Osamu Shirakawa
    • 1
  • Tatsuo Mita
    • 3
  • Naoki Nishino
    • 1
  • Chikako Tanaka
    • 2
  1. 1.Department of Psychiatry and NeurologyKobe University School of MedicineKobeJapan
  2. 2.Department of PharmacologyKobe University School of MedicineKobeJapan
  3. 3.Department of PsychiatrySaiseikai Nakatsu HospitalOsakaJapan

Personalised recommendations