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.