Nicotinic receptors and lurasidone-mediated reversal of phencyclidine-induced deficit in novel object recognition

Masanori Miyauchi, Nichole M. Neugebauer, Yoshihiro Oyamada, Herbert Y. Meltzer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Background: Enhancement of cholinergic function via nicotinic acetylcholine (ACh) receptor (nAChR) agonism is a potential approach for the treatment of cognitive impairment associated with schizophrenia (CIAS). Some atypical antipsychotic drugs (AAPDs) enhance ACh release in rodent brain, indirectly stimulating these receptors. Here, we elucidate which nAChR subtypes mediate novel object recognition (NOR) in normal rats and contribute to the ability of the AAPD, lurasidone, to improve the NOR deficit in sub-chronic (sc) phencyclidine (PCP)-treated rats, a model for CIAS. Methods: The ability of lurasidone and nAChR ligands to reverse the scPCP-induced deficit in NOR was assessed in female, Long-Evans rats. Results: The broad acting nAChR antagonist, mecamylamine (MEC), induced a NOR deficit in normal rats. The NOR deficit secondary to scPCP was reversed by either selective α4β2* nAChR agonism (A-85380) or α7 nAChRs agonism (PNU-282987); these effects were blocked by DHβE and MLA, selective antagonists of α4β2* and α7 nAChR, respectively. The ability of lurasidone to reverse the scPCP-induced NOR deficit was blocked by MEC, but not MLA or DHβE. However, sub-effective doses (SED) of either A-85380 or PNU-282987 potentiated the ability of SED lurasidone to reverse the scPCP-induced NOR deficit. Conclusions: These results identify both α4β2* and α7 nAChRs as candidates for enhancing the ability of lurasidone and other AAPDs, which increase the release of ACh, to improve CIAS.

Original languageEnglish (US)
Pages (from-to)204-212
Number of pages9
JournalBehavioural Brain Research
Volume301
DOIs
StatePublished - Mar 15 2016

Keywords

  • Acetylcholine
  • Atypical antipsychotic drug
  • Nicotinic acetylcholine receptors
  • Novel object recognition
  • Phencyclidine

ASJC Scopus subject areas

  • Behavioral Neuroscience

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