title: Effects of acute phencyclidine administration on arginine metabolism in the hippocampus and prefrontal cortex in rats.
abstract: Phencyclidine (PCP), a non-competitive N-methyl-d-aspartate glutamate receptor antagonist, induces schizophrenic symptoms in healthy individuals, and altered arginine metabolism has been implicated in schizophrenia. The present study investigated the effects of a single subcutaneous injection of PCP (2, 5 or 10 mg/kg) on arginine metabolism in the sub-regions of the hippocampus and prefrontal cortex in male young adult Sprague-Dawley rats. Animals' general behaviour was assessed in the open field apparatus 30 min after the treatment, and the brain tissues were collected at the time point of 60 min post-treatment. Behaviourally, PCP resulted in reduced exploratory activity in a dose-dependent manner, and severe stereotype behaviour and ataxia at the highest dose. Neurochemically, PCP significantly altered the nitric oxide synthase and arginase activities, the l-arginine, agmatine, spermine, glutamate and GABA levels, and the glutamine/glutamate and glutamate/GABA ratios in a dose-dependent and/or region-specific manner. Cluster analyses showed that l-arginine and its main metabolites l-citrulline, l-ornithine and agmatine formed distinct groups, which changed as a function of PCP mainly in the hippocampus. Multiple regression analysis revealed significant neurochemical-behavioural correlations. These results demonstrate, for the first time, that a single acute administration of PCP affects animals' behaviour and arginine metabolism in the brain.
authors.affiliation: Department of Anatomy, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand; Brain Health Research Centre, University of Otago, Dunedin, New Zealand.
authors.forename: Logan T
authors.initials: LT
authors.lastname: Knox
authors.affiliation: Department of Anatomy, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand; Brain Health Research Centre, University of Otago, Dunedin, New Zealand.
authors.forename: Yu
authors.initials: Y
authors.lastname: Jing
authors.affiliation: Department of Anatomy, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand; Brain Health Research Centre, University of Otago, Dunedin, New Zealand.
authors.forename: Nicola D
authors.initials: ND
authors.lastname: Collie
authors.affiliation: School of Pharmacy, University of Otago, Dunedin, New Zealand; Brain Health Research Centre, University of Otago, Dunedin, New Zealand.
authors.forename: Hu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Anatomy, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand; Brain Health Research Centre, University of Otago, Dunedin, New Zealand. Electronic address: ping.liu@otago.ac.nz.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D006213:Hallucinogens / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010622:Phencyclidine / Q000633:toxicity*; D011073:Polyamines / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014316:Tritium / Q000378:metabolism
chemical_list: D000596:Amino Acids; D006213:Hallucinogens; D011073:Polyamines; D014316:Tritium; D001120:Arginine; D019001:Nitric Oxide Synthase; D010622:Phencyclidine
keywords: Arginine metabolism; Glutamate; Hippocampus; Phencyclidine; Prefrontal cortex; Schizophrenia