title: 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.
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) (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 α7 nACh receptors.
authors.affiliation: Bradford School of Pharmacy, University of Bradford, Bradford, UK.
authors.forename: Samantha L
authors.initials: SL
authors.lastname: McLean
authors.forename: Nagi F
authors.initials: NF
authors.lastname: Idris
authors.forename: Ben
authors.initials: B
authors.lastname: Grayson
authors.forename: David F
authors.initials: DF
authors.lastname: Gendle
authors.forename: Claire
authors.initials: C
authors.lastname: Mackie
authors.forename: Anne S
authors.initials: AS
authors.lastname: Lesage
authors.forename: Darrel J
authors.initials: DJ
authors.lastname: Pemberton
authors.forename: Jo C
authors.initials: JC
authors.lastname: Neill
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D001288:Attention / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D004193:Discrimination Learning / Q000187:drug effects; D004195:Disease Models, Animal; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006213:Hallucinogens / Q000008:administration & dosage / Q000633:toxicity; D007555:Isoxazoles / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D020258:Neurotoxicity Syndromes / Q000188:drug therapy* / Q000503:physiopathology; D018722:Nicotinic Agonists / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010622:Phencyclidine / Q000008:administration & dosage / Q000633:toxicity*; D010671:Phenylurea Compounds / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D011978:Receptors, Nicotinic / Q000737:chemistry*; D014018:Tissue Distribution; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C508388:1-(5-chloro-2,4-dimethoxyphenyl)-3-(5-methylisoxazol-3-yl)urea; C579165:Chrna7 protein, rat; D006213:Hallucinogens; D007555:Isoxazoles; D018696:Neuroprotective Agents; D018722:Nicotinic Agonists; D010671:Phenylurea Compounds; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D010622:Phencyclidine