Tropisetron improves deficient inhibitory auditory processing in DBA/2 mice: role of alpha 7 nicotinic acetylcholine receptors

Psychopharmacology (Berl). 2005 Nov;183(1):13-9. doi: 10.1007/s00213-005-0142-0. Epub 2005 Oct 22.

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.

MeSH terms

  • Aconitine / analogs & derivatives
  • Aconitine / pharmacology
  • Animals
  • Auditory Perceptual Disorders / drug therapy*
  • Disease Models, Animal
  • Drug Interactions
  • Evoked Potentials, Auditory / drug effects
  • Indoles / administration & dosage
  • Indoles / pharmacology*
  • Male
  • Mice
  • Mice, Inbred DBA
  • Nicotinic Antagonists / pharmacology
  • Receptors, Nicotinic / drug effects*
  • Serotonin 5-HT3 Receptor Antagonists
  • Serotonin Antagonists / administration & dosage
  • Serotonin Antagonists / pharmacology*
  • Time Factors
  • Tropisetron
  • alpha7 Nicotinic Acetylcholine Receptor

Substances

  • Chrna7 protein, human
  • Chrna7 protein, mouse
  • Indoles
  • Nicotinic Antagonists
  • Receptors, Nicotinic
  • Serotonin 5-HT3 Receptor Antagonists
  • Serotonin Antagonists
  • alpha7 Nicotinic Acetylcholine Receptor
  • nicotinic receptor alpha4beta2
  • methyllycaconitine
  • Tropisetron
  • Aconitine