Activation of α7 nicotinic receptors improves phencyclidine-induced deficits in cognitive tasks in rats: implications for therapy of cognitive dysfunction in schizophrenia.

RATIONALE Nicotinic α7 acetylcholine receptors (nAChRs) have been highlighted as a target for cognitive enhancement in schizophrenia. AIM To investigate whether the deficits induced by sub-chronic phencyclidine (PCP) in reversal learning and novel object recognition could be attenuated by the selective α7 nAChR full agonist, PNU-282987. METHODS Adult female hooded-Lister rats received sub-chronic PCP (2mg/kg) or vehicle i.p. twice daily for 7days, followed by 7 days washout. In cohort 1, PCP-treated rats then received PNU-282987 (5, 10, 20mg/kg; s.c.) or vehicle and were tested in the reversal-learning task. In cohort 2, PCP-treated rats received PNU-282987 (10mg/kg; s.c.) or saline for 15days and were tested in the novel object recognition test on day 1 and on day 15, to test for tolerance. RESULTS Sub-chronic PCP produced significant deficits in both cognitive tasks (P<0.01-0.001). PNU-282987 attenuated the PCP-induced deficits in reversal learning at 10mg/kg (P<0.01) and 20mg/kg (P<0.001), and in novel object recognition at 10mg/kg on day 1 (P<0.01) and on day 15 (P<0.001). CONCLUSIONS These data show that PNU-282987 has efficacy to reverse PCP-induced deficits in two paradigms of relevance to schizophrenia. Results further suggest that 15-day once daily dosing of PNU-282987 (10mg/kg s.c.) does not cause tolerance in the rat. This study suggests that activation of α7 nAChRs, may represent a suitable strategy for improving cognitive deficits of relevance to schizophrenia.

• Publication year

  2011

• Venue

  European Neuropsychopharmacology

• Publication date

  2011-04-01

• Fields of study

  Medicine, Psychology

• Identifiers
  DOI 10.1016/j.euroneuro.2010.06.003PMID 20630711
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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