Kenji Hashimoto1, Masaomi Iyo, Robert Freedman, Karen E Stevens. 1. Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 1-8-1 Inohana, Chiba, Chiba 260-8670, Japan. hashimoto@faculty.chiba-u.jp
Abstract
RATIONALE: Deficient inhibitory processing of the P50 auditory evoked potential is a pathophysiological feature of schizophrenia. Several lines of evidence suggest that alpha 7 nicotinic receptors play a critical role in this phenomenon. Similar to schizophrenic patients, DBA/2 mice spontaneously exhibit a deficit in inhibitory processing of the P20-N40 auditory evoked potential, which is thought to be a rodent analog of the human P50 auditory evoked potential. OBJECTIVE: The present study was undertaken to examine whether tropisetron, a partial agonist at alpha 7 nicotinic receptors and an antagonist at 5-hydroxytryptamine-3 receptors, improves this deficit in DBA/2 mice. RESULTS: Administration of tropisetron (1 mg/kg i.p.) significantly improved the deficient inhibitory processing of the P20-N40 auditory evoked potential in DBA/2 mice. Coadministration of methyllycaconitine (MLA; 3 mg/kg i.p.), a partially selective antagonist at alpha 7 nicotinic receptors, significantly blocked the normalizing effect of tropisetron. Furthermore, MLA alone did not alter the deficient inhibitory processing of the P20-N40 auditory evoked potential in DBA/2 mice. CONCLUSIONS: The data suggest that tropisetron improves the deficient inhibitory processing of the P20-N40 auditory evoked potential in DBA/2 mice by effects on alpha 7 and perhaps alpha 4 beta 2 nicotinic receptors. Tropisetron may be useful for the treatment of deficient inhibitory processing in schizophrenia.
RATIONALE: Deficient inhibitory processing of the P50 auditory evoked potential is a pathophysiological feature of schizophrenia. Several lines of evidence suggest that alpha 7 nicotinic receptors play a critical role in this phenomenon. Similar to schizophrenicpatients, DBA/2mice spontaneously exhibit a deficit in inhibitory processing of the P20-N40 auditory evoked potential, which is thought to be a rodent analog of the humanP50 auditory evoked potential. OBJECTIVE: The present study was undertaken to examine whether tropisetron, a partial agonist at alpha 7 nicotinic receptors and an antagonist at 5-hydroxytryptamine-3 receptors, improves this deficit in DBA/2mice. RESULTS: Administration of tropisetron (1 mg/kg i.p.) significantly improved the deficient inhibitory processing of the P20-N40 auditory evoked potential in DBA/2mice. Coadministration of methyllycaconitine (MLA; 3 mg/kg i.p.), a partially selective antagonist at alpha 7 nicotinic receptors, significantly blocked the normalizing effect of tropisetron. Furthermore, MLA alone did not alter the deficient inhibitory processing of the P20-N40 auditory evoked potential in DBA/2mice. CONCLUSIONS: The data suggest that tropisetron improves the deficient inhibitory processing of the P20-N40 auditory evoked potential in DBA/2mice by effects on alpha 7 and perhaps alpha 4 beta 2 nicotinic receptors. Tropisetron may be useful for the treatment of deficient inhibitory processing in schizophrenia.
Authors: Sherry Leonard; Judith Gault; Jan Hopkins; Judith Logel; Ruby Vianzon; Margaret Short; Carla Drebing; Ralph Berger; Diana Venn; Pinkhas Sirota; Gary Zerbe; Ann Olincy; Randal G Ross; Lawrence E Adler; Robert Freedman Journal: Arch Gen Psychiatry Date: 2002-12
Authors: C M Cullum; J G Harris; M C Waldo; E Smernoff; A Madison; H T Nagamoto; J Griffith; L E Adler; R Freedman Journal: Schizophr Res Date: 1993-08 Impact factor: 4.939
Authors: R Freedman; L E Adler; P Bickford; W Byerley; H Coon; C M Cullum; J M Griffith; J G Harris; S Leonard; C Miller Journal: Harv Rev Psychiatry Date: 1994 Nov-Dec Impact factor: 3.732
Authors: Christina R Maxwell; Yuling Liang; Bryanne D Weightman; Stephen J Kanes; Ted Abel; Raquel E Gur; Bruce I Turetsky; Warren B Bilker; Robert H Lenox; Steven J Siegel Journal: Neuropsychopharmacology Date: 2004-04 Impact factor: 7.853
Authors: L E Adler; A Olincy; M Waldo; J G Harris; J Griffith; K Stevens; K Flach; H Nagamoto; P Bickford; S Leonard; R Freedman Journal: Schizophr Bull Date: 1998 Impact factor: 9.306
Authors: R Freedman; L E Adler; G A Gerhardt; M Waldo; N Baker; G M Rose; C Drebing; H Nagamoto; P Bickford-Wimer; R Franks Journal: Schizophr Bull Date: 1987 Impact factor: 9.306
Authors: Indrani Poddar; Patrick M Callahan; Caterina M Hernandez; Xiangkun Yang; Michael G Bartlett; Alvin V Terry Journal: Biochem Pharmacol Date: 2017-11-24 Impact factor: 5.858
Authors: Karen E Stevens; Brandon Cornejo; Catherine E Adams; Lijun Zheng; Joan Yonchek; Keith L Hoffman; Uwe Christians; William R Kem Journal: Brain Res Date: 2010-07-03 Impact factor: 3.252
Authors: Noam D Rudnick; Andrew A Strasser; Jennifer M Phillips; Christopher Jepson; Freda Patterson; Joseph M Frey; Bruce I Turetsky; Caryn Lerman; Steven J Siegel Journal: Nicotine Tob Res Date: 2010-04-15 Impact factor: 4.244