The role of 5-HT 1A receptors in phencyclidine (PCP)-induced novel object recognition (NOR) deficit in rats

M. Horiguchi, H. Y. Meltzer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

Rationale: Atypical antipsychotic drugs (APDs), many of which are direct or indirect serotonin (5-HT) 1A agonists, and tandospirone, a 5-HT 1A partial agonist, have been reported to improve cognition in schizophrenia. Objectives and methods: We tested the effect of 5-HT 1A agonism, alone, and in combination with other psychotropic agents, including the atypical APD, lurasidone, in reversing the deficit in novel object recognition (NOR) induced by subchronic treatment with the non-competitive NMDA receptor antagonist, phencyclidine (PCP) (2 mg/kg, b.i.d., for 7 days). Results: Subchronic treatment with PCP induced a persistent NOR deficit. Lurasidone (0.1 mg/kg), a potent 5-HT 1A partial agonist, 5-HT 2A antagonist, and weaker D 2 antagonist, tandospirone (0.6 mg/kg), and the selective postsynaptic 5-HT 1A agonist, F15599 (0.16 mg/kg), ameliorated the subchronic PCP-induced-NOR deficit. The 5-HT 1A antagonist, WAY100635 (0.6 mg/kg), blocked the ameliorating effects of tandospirone and lurasidone. The combination of sub-effective doses of tandospirone (0.2 mg/kg) and lurasidone (0.03 mg/kg) also reversed the PCP-induced NOR-deficit. Buspirone, a less potent partial 5-HT 1A agonist than tandospirone, was less effective. Co-administration of tandospirone (0.2 mg/kg) and pimavanserin (3 mg/kg), a relatively selective 5-HT 2A receptor inverse agonist, did not reverse the effect of sub-chronic PCP on NOR. The D 2 antagonist, haloperidol, blocked the ameliorating effect of tandospirone on the PCP-induced deficit in NOR. Conclusions: These results indicate that 5-HT 1A agonism is adequate to ameliorate the PCP-induced impairment in NOR and suggest further study of utilizing the combination of a 5-HT 1A agonist and an atypical APD to ameliorate some types of cognitive impairment in schizophrenia.

Original languageEnglish (US)
Pages (from-to)205-215
Number of pages11
JournalPsychopharmacology
Volume221
Issue number2
DOIs
StatePublished - May 2012

Keywords

  • 5-HT
  • Buspirone
  • Cognition
  • F15599
  • Lurasidone
  • Novel object recognition
  • Phencyclidine
  • Schizophrenia
  • Tandospirone

ASJC Scopus subject areas

  • Pharmacology

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