McLean, SamanthaGrayson, BenIdris, Nagi F.Lesage, A.S.Pemberton, D.J.Mackie, C.Neill, Joanna C.2016-06-082016-06-082011-04McLean SL, Grayson B, Idris NF, Lesage AS, Pemberton DJ, Mackie C and Neill JC (2011) Activation of α7 nicotinic receptors improves phencyclidine-induced deficits in cognitive tasks in rats: implications for therapy of cognitive dysfunction in schizophrenia. European Neuropsychopharmacology. 21(4): 333-343.http://hdl.handle.net/10454/8464YesRationale: 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 (2 mg/kg) or vehicle i.p. twice daily for seven days, followed by 7-days washout. In cohort 1, PCP-treated rats then received PNU-282987 (5, 10, 20 mg/kg; s.c.) or vehicle and were tested in the reversal learning task. In cohort 2, PCP-treated rats received PNU-282987 (10 mg/kg; s.c.) or saline for 15 days 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 10 mg/kg (P<0.01) and 20 mg/kg (P<0.001), and in novel object recognition at 10 mg/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 daily dosing of PNU-282987 (10 mg/kg s.c.) does not cause tolerance in rat. This study suggests that activation of α7 nAChRs, may represent a suitable strategy for improving cognitive deficits of relevance to schizophrenia.en© 2011 Elsevier. Reproduced in accordance with the publisher's self-archiving policy. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Reversal learningNovel object recognitionα7 nACh receptorPhencyclidineFemale ratCognitionSchizophreniaArticlehttps://doi.org/10.1016/j.euroneuro.2010.06.003CC-BY-NC-ND