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PNU-120596, a positive allosteric modulator of α7 nicotinic acetylcholine receptors, reverses a sub-chronic phencyclidineinduced cognitive deficit in the attentional set-shifting task in female rats
Idris, Nagi F. Grayson, Ben Gendle, D.F. Mackie, C. Lesage, A.S. Pemberton, D.J. Neill, Joanna C.
Idris, Nagi F.
Grayson, Ben
Gendle, D.F.
Mackie, C.
Lesage, A.S.
Pemberton, D.J.
Neill, Joanna C.
Publication Date
2012-09
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The final, definitive version of this paper has been published in Journal of Psychopharmacology, 26(9) by SAGE Publications Ltd, All rights reserved. © 2012 SAGE Publications Ltd.
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Abstract
The α7 nicotinic acetylcholine receptors (nAChRs) have been highlighted as a target for cognitive enhancement in schizophrenia. Adult female hooded
Lister rats received sub-chronic phencyclidine (PCP) (2mg/kg) or vehicle i.p. twice daily for 7 days, followed by 7 days’ washout. PCP-treated rats then
received PNU-120596 (10mg/kg; s.c.) or saline and were tested in the attentional set-shifting task. Sub-chronic PCP produced a significant cognitive
deficit in the extra-dimensional shift (EDS) phase of the task (p < 0.001, compared with vehicle). PNU-120596 significantly improved performance of
PCP-treated rats in the EDS phase of the attentional set-shifting task (p < 0.001). In conclusion, these data demonstrate that PNU-120596 improves
cognitive dysfunction in our animal model of cognitive dysfunction in schizophrenia, most likely via modulation of α7 nACh receptors.
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Citation
McLean SL, Idris NF, Grayson B, Gendle DF, Mackie C, Lesage AS, Pemberton DJ and Neill JC (2012) PNU-120596, a positive allosteric modulator of α7 nicotinic acetylcholine receptors, reverses a sub-chronic phencyclidine-induced cognitive deficit in the attentional set-shifting task in female rats. Journal of Psychopharmacology. 26(9): 1265-1270.
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