title: Comparing the effects of subchronic phencyclidine and medial prefrontal cortex dysfunction on cognitive tests relevant to schizophrenia.
abstract: BACKGROUND
  It is becoming increasingly clear that the development of treatments for cognitive symptoms of schizophrenia requires urgent attention, and that valid animal models of relevant impairments are required. With subchronic psychotomimetic agent phencyclidine (scPCP), a putative model of such impairment, the extent to which changes following scPCP do or do not resemble those following dysfunction of the prefrontal cortex is of importance.
  
  
  OBJECTIVE
  The present study carried out a comparison of the most common scPCP dosing regimen with excitotoxin-induced medial prefrontal cortex (mPFC) dysfunction in rats, across several cognitive tests relevant to schizophrenia.
  
  
  METHODS
  ScPCP subjects were dosed intraperitoneal with 5 mg/kg PCP or vehicle twice daily for 1 week followed by 1 week washout prior to behavioural testing. mPFC dysfunction was induced via fibre-sparing excitotoxin infused into the pre-limbic and infralimbic cortex. Subjects were tested on spontaneous novel object recognition, touchscreen object-location paired-associates learning and touchscreen reversal learning.
  
  
  RESULTS
  A double-dissociation was observed between object-location paired-associates learning and object recognition: mPFC dysfunction impaired acquisition of the object-location task but not spontaneous novel object recognition, while scPCP impaired spontaneous novel object recognition but not object-location associative learning. Both scPCP and mPFC dysfunction resulted in a similar facilitation of reversal learning.
  
  
  CONCLUSIONS
  The pattern of impairment following scPCP raises questions around its efficacy as a model of cognitive impairment in schizophrenia, particularly if importance is placed on faithfully replicating the effects of mPFC dysfunction.
authors.affiliation: University of Cambridge Department of Psychology, Downing Street, Cambridge, CB2 3EB, UK. kalmcallister@gmail.com.|MRC and Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, CB2 3EB, UK. kalmcallister@gmail.com.|, 20 Manchester Sq., London, W1U 3PZ, UK. kalmcallister@gmail.com.
authors.forename: K A L
authors.initials: KA
authors.lastname: McAllister
authors.affiliation: University of Cambridge Department of Psychology, Downing Street, Cambridge, CB2 3EB, UK.|MRC and Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, CB2 3EB, UK.
authors.forename: A C
authors.initials: AC
authors.lastname: Mar
authors.affiliation: University of Cambridge Department of Psychology, Downing Street, Cambridge, CB2 3EB, UK.|MRC and Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, CB2 3EB, UK.
authors.forename: D E
authors.initials: DE
authors.lastname: Theobald
authors.affiliation: University of Cambridge Department of Psychology, Downing Street, Cambridge, CB2 3EB, UK.|MRC and Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, CB2 3EB, UK.
authors.forename: L M
authors.initials: LM
authors.lastname: Saksida
authors.affiliation: University of Cambridge Department of Psychology, Downing Street, Cambridge, CB2 3EB, UK.|MRC and Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, CB2 3EB, UK.
authors.forename: T J
authors.initials: TJ
authors.lastname: Bussey
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001927:Brain Diseases / Q000139:chemically induced / Q000523:psychology*; D003071:Cognition / Q000187:drug effects*; D018690:Excitatory Amino Acid Agonists; D006213:Hallucinogens / Q000494:pharmacology*; D007051:Ibotenic Acid; D007274:Injections, Intraperitoneal; D007858:Learning / Q000187:drug effects; D008032:Limbic System; D008297:Male; D008568:Memory / Q000187:drug effects; D010622:Phencyclidine / Q000494:pharmacology*; D017397:Prefrontal Cortex; D051381:Rats; D021641:Recognition, Psychology / Q000187:drug effects; D012565:Schizophrenic Psychology
chemical_list: D018690:Excitatory Amino Acid Agonists; D006213:Hallucinogens; D007051:Ibotenic Acid; D010622:Phencyclidine
keywords: Animal model; Associative learning; Discrimination; Glutamate; Learning and memory; Object recognition; Phencyclidine; Prefrontal cortex; Rat; Schizophrenia