title: Nitric oxide synthase inhibition attenuates phencyclidine-induced disruption of cognitive flexibility.
abstract: Schizophrenia encompasses, amongst other symptoms, a heavy load of cognitive dysfunctionality. Using the psychotomimetic agent, phencyclidine (PCP), we have previously found that PCP-induced disruptions of cognitive function in translational rodent models of schizophrenia are dependent on nitric oxide (NO) production. In the present study, male Sprague-Dawley rats were subjected to a Morris water maze task designed to assess cognitive flexibility (i.e. the ability to cope with an increasingly demanding cognitive task) by means of a "constant reversal learning paradigm". Experiments were conducted to evaluate the effects of the NO synthase inhibitor, L-NAME (10 mg/kg), on PCP-induced (2 mg/kg) impairments. Control animals significantly improved their learning over the first 3 consecutive days, whereas PCP-treated animals failed to show any significant learning. Pretreatment with L-NAME normalized the PCP-induced disruption of learning to control levels. These findings suggest that PCP-induced disruptions of cognitive flexibility (i.e. ability to modify behaviour according to an increasingly demanding cognitive task) are dependent upon NO production. These observations, together with accumulated clinical findings, suggest that the NO system is a potential treatment target for cognitive dysfunctions in schizophrenia.
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden. caroline.wass@pharm.gu.se
authors.forename: Caroline
authors.initials: C
authors.lastname: Wass
authors.forename: Lennart
authors.initials: L
authors.lastname: Svensson
authors.forename: Kim
authors.initials: K
authors.lastname: Fejgin
authors.forename: Erik
authors.initials: E
authors.lastname: Pålsson
authors.forename: Trevor
authors.initials: T
authors.lastname: Archer
authors.forename: Jörgen A
authors.initials: JA
authors.lastname: Engel
authors.forename: Daniel
authors.initials: D
authors.lastname: Klamer
mesh_terms: D000818:Animals; D003071:Cognition / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013239:Stereotyped Behavior / Q000187:drug effects; D013550:Swimming
chemical_list: D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D010622:Phencyclidine; D019331:NG-Nitroarginine Methyl Ester