PNU-120596, a positive allosteric modulator of alpha 7 nicotinic acetylcholine receptors, reverses a sub-chronic phencyclidine-induced cognitive deficit in the attentional set-shifting task in female rats

The alpha 7 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) (2 mg/kg) or vehicle i.p. twice daily for 7 days, followed by 7 days' washout. PCP-treate...

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Published in:Journal of psychopharmacology (Oxford) 2012-09, Vol.26 (9), p.1265-1270
Main Authors: McLean, Samantha L, Idris, Nagi F, Grayson, Ben, Gendle, David F, Mackie, Claire, Lesage, Anne S, Pemberton, Darrel J, Neill, Jo C
Format: Article
Language:English
Subjects:
Acetylcholine receptors (nicotinic)
Allosteric properties
Animal models
Attention
Cognitive ability
Data processing
Mental disorders
Phencyclidine
Schizophrenia
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Summary:The alpha 7 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) (2 mg/kg) or vehicle i.p. twice daily for 7 days, followed by 7 days' washout. PCP-treated rats then received PNU-120596 (10 mg/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 alpha 7 nACh receptors.
ISSN:0269-8811
DOI:10.1177/0269881111431747