Tropisetron improves deficient inhibitory auditory processing in DBA/2 mice: role of alpha 7 nicotinic acetylcholine receptors.
BACKGROUND
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.
Hashimoto
Kenji
K
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
Iyo
Masaomi
M
Freedman
Robert
R
Stevens
Karen E
KE
D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001308:Auditory Perceptual Disorders / Q000188:drug therapy*; D004195:Disease Models, Animal; D004347:Drug Interactions; D005072:Evoked Potentials, Auditory / Q000187:drug effects; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects*; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D000077526:Tropisetron; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579167:Chrna7 protein, human; C579166:Chrna7 protein, mouse; D007211:Indoles; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2; C054634:methyllycaconitine; D000077526:Tropisetron; D000157:Aconitine