Schizophrenia Research
Volume 76, Issue 1 , Pages 67-72 , 1 July 2005

Tropisetron improves deficits in auditory P50 suppression in schizophrenia

  • Kaori Koike

      Affiliations

    • Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba, Chiba 260-8670, Japan
    • ,
  • Kenji Hashimoto

      Affiliations

    • Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba, Chiba 260-8670, Japan
    • Corresponding Author InformationCorresponding author. Tel.: +81 43 226 2147; fax: +81 43 226 2150.
    • ,
  • Nobuyuki Takai

      Affiliations

    • Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba, Chiba 260-8670, Japan
    • ,
  • Eiji Shimizu

      Affiliations

    • Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba, Chiba 260-8670, Japan
    • ,
  • Naoya Komatsu

      Affiliations

    • Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba, Chiba 260-8670, Japan
    • ,
  • Hiroyuki Watanabe

      Affiliations

    • Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba, Chiba 260-8670, Japan
    • ,
  • Michiko Nakazato

      Affiliations

    • Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba, Chiba 260-8670, Japan
    • ,
  • Naoe Okamura

      Affiliations

    • Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba, Chiba 260-8670, Japan
    • ,
  • Karen E. Stevens

      Affiliations

    • Department of Psychiatry, University of Colorado Health Science Center and the Denver Veterans Affairs Medical Center, Denver, CO 80262, USA
    • ,
  • Robert Freedman

      Affiliations

    • Department of Psychiatry, University of Colorado Health Science Center and the Denver Veterans Affairs Medical Center, Denver, CO 80262, USA
    • ,
  • Masaomi Iyo

      Affiliations

    • Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba, Chiba 260-8670, Japan

Received 13 October 2004 ,Revised 18 December 2004 ,Accepted 27 December 2004.

References 

  1. Adler LE, Pachtman E, Franks RD, Pecevich M, Waldo MC, Freedman R. Neurophysiological evidence for a defect in neuronal mechanisms involved in sensory gating in schizophrenia. Biol. Psychiatry. 1982;17:639–654
  2. Adler LE, Hoffer LJ, Griffith J, Waldo MC, Freedman R. Normalization by nicotine of deficient auditory sensory gating in the relatives of schizophrenics. Biol. Psychiatry. 1992;32:607–616
  3. Adler LE, Hoffer LD, Wiser A, Freedman R. Normalization of auditory physiology by cigarette smoking in schizophrenic patients. Am. J. Psychiatry. 1993;150:1856–1861
  4. Adler, L.E., Cawthra, E., Donovan, K.A., Harris, J.G., Nagamoto, H., Olincy, A., Waldo, M., in press. Ondansetron improves P50 auditory gating in medicated schizophrenic patients. Am. J. Psychiatry.
  5. Adler LE, Olincy A, Cawthra EC, McRae KA, Harris JG, Nagamoto HT, et al. The varied effects of atypical medications on P50 auditory gating in schizophrenic patients. Am. J. Psychiatry. 2004;161:1822–1828
  6. Braff DL, Freedman R. Endophenotypes in studies of the genetics of schizophrenia. In:  Davis KL,  Coyle JT,  Nemeroff C editor. Neuropsychopharmacology: the fifth generation of progress. New York: Lippincott, Williams and Wilkins; 2002;p. 703–716
  7. Braff DL, Geyer MA. Sensorimotor gating and schizophrenia. Human and animal model studies. Arch. Gen. Psychiatry. 1990;47:181–188
  8. Clementz BA, Geyer MA, Braff DL. Poor P50 suppression among schizophrenia patients and their first-degree biological relatives. Am. J. Psychiatry. 1998;155:1691–1694
  9. Consolo S, Bertorelli R, Russi G, Zambelli M, Ladinsky H. Serotonergic facilitation of acetylcholine release in vivo from rat dorsal hippocampus via serotonin 5-HT3 receptors. J. Neurochem. 1994;62:2254–2261
  10. Court J, Spurden D, Lloyd S. Neuronal nicotinic receptors in dementia with Lewy bodies and schizophrenia: alpha-bungarotoxin and nicotine binding in the thalamus. J. Neurochem. 1999;73:1590–1597
  11. Cullum CM, Harris JG, Waldo MC, Smernoff E, Madison A, Nagamoto HT, et al. Neurophysiological and neuropsychological evidence for attentional dysfunction in schizophrenia. Schizophr. Res. 1993;10:131–141
  12. Freedman R, Hall M, Adler LE, Leonard S. Evidence in postmortem brain tissue for decreased numbers of hippocampal nicotinic receptors in schizophrenia. Biol. Psychiatry. 1995;38:22–33
  13. Freedman R, Coon H, Myles-Worsley M, Orr-Urtreger A, Olincy A, Davis A, et al. Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus. Proc. Natl. Acad. Sci. U. S. A. 1997;94:587–592
  14. Freedman R, Adams CE, Leonard S. The alpha7-nicotinic acetylcholine receptor and the pathology of hippocampal interneurons in schizophrenia. J. Chem. Neuroanat. 2000;20:299–306
  15. Giovannini MG, Ceccarelli I, Molinari B, Cecchi M, Goldfarb J, Blandina P. Serotonergic modulation of acetylcholine release from cortex of freely moving rats. J. Pharmacol. Exp. Ther. 1998;285:1219–1225
  16. Green MF. What are the functional consequences of neurocognitive deficits in schizophrenia?. Am. J. Psychiatry. 1996;153:321–330
  17. Guan ZZ, Zhang X, Blennow K, Nordberg A. Decreased protein level of nicotinic receptor alpha7 subunit in the frontal cortex from schizophrenic brain. NeuroReport. 1999;10:1779–1782
  18. Harris JG, Kongs S, Allensworth D, Martin L, Tregellas J, Sullivan B, et al. Effects of nicotine on cognitive deficits in schizophrenia. Neuropsychopharmacology. 2004;29:1378–1385
  19. Ichikawa J, Dai J, O'Laughlin IA, Fowler WL, Meltzer HY. Atypical, but not typical, antipsychotic drugs increase cortical acetylcholine release without an effect in the nucleus accumbens or striatum. Neuropsychopharmacology. 2002;26:325–339
  20. Jacobsen LK, D'Souza DC, Menci WE, Pugh KR, Skudlarski P, Krystal JH. Nicotine effects on brain function and functional connectivity in schizophrenia. Biol. Psychiatry. 2004;55:850–858
  21. Kees F, Farber L, Bucher M, Mair G, Morike K, Grobecker H. Pharmacokinetics of therapeutic doses of tropisetron in healthy volunteers. Br. J. Clin. Pharmacol. 2001;52:705–707
  22. Leysen JE, Gommeren W, Schotte A. Serotonin receptor subtypes: possible roles and implications in antipsychotic drug action. In:  Awounters M editors. Serotonin in antipsychotic treatment—mechanism and clinical practice. New York: Marcel Dekker Inc.; 1996;p. 51–75
  23. Light GA, Geyer MA, Clementz BA, Cadenhead KS, Braff DL. Normal P50 suppression in schizophrenia patients treated with atypical antipsychotic medications. Am. J. Psychiatry. 2000;157:767–771
  24. Macor JE, Gurley D, Lanthorn T, Loch J, Mack RA, Mullen G, et al. The 5-HT3 antagonist tropisetron (ICS 205–930) is a potent and selective alpha7 nicotinic receptor partial agonist. Bioorg. Med. Chem. Lett. 2001;11:319–321
  25. Maricq AV, Peterson AS, Brake AJ, Myers RM, Julius D. Primary structure and functional expression of the 5HT3 receptor, a serotonin-gated ion channel. Science. 1991;254:432–437
  26. Maura G, Andrioli GC, Cavazzani P, Raiteri M. 5-Hydroxytryptamine3 receptors sited on cholinergic axon terminals of human cerebral cortex mediate inhibition of acetylcholine release. J. Neurochem. 1992;58:2334–2337
  27. Myers CS, Robles O, Kakoyannis AN, Sherr JD, Avila MT, Blaxton TA, et al. Nicotine improves delayed recognition in schizophrenic patients. Psychopharmacology. 2004;174:334–340
  28. Papke RL, Porter-Papke JK, Rose GM. Activity of alpha7-selective agonists at nicotinic and serotonin 5HT3 receptors expressed in Xenopus oocytes. Bioorg. Med. Chem. Lett. 2004;14:1849–1853
  29. Raux G, Bonnet-Brilhault F, Louchart S. The −2 bp deletion in exon 6 of the ‘alpha 7-like’ nicotinic receptor subunit gene is a risk factor for the P50 sensory gating deficit. Mol. Psychiatry. 2002;7:1006–1011
  30. Simosky JK, Stevens KE, Freedman R. Nicotinic agonists and psychosis. Curr. Drug Target CNS Neurol. Disord. 2002;1:149–162
  31. Simosky JK, Stevens KE, Adler LE, Freedman R. Clozapine improves deficient inhibitory auditory processing in DBA/2 mice, via a nicotinic cholinergic mechanism. Psychopharmacology (Berl.). 2003;165:386–396
  32. Simpson K, Spencer CM, McClellan KJ. Tropisetron: an update of its use in the prevention of chemotherapy-induced nausea and vomiting. Drugs. 2000;59:1297–1315
  33. Smith RC, Singh A, Infante M, Khandat A, Kloos A. Effects of cigarette smoking and nicotine nasal spray on psychiatric symptoms and cognition in schizophrenia. Neuropsychopharmacology. 2002;27:479–497
  34. Venables PH. Input dysfunction in schizophrenia. In:  Maher BA editors. Progress in experimental personality research. Orlando, FL: Academic Press; 1967;p. 1–64

PII: S0920-9964(04)00477-3

doi: 10.1016/j.schres.2004.12.016

Schizophrenia Research
Volume 76, Issue 1 , Pages 67-72 , 1 July 2005

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