title: The subchronic phencyclidine rat model: relevance for the assessment of novel therapeutics for cognitive impairment associated with schizophrenia.
abstract: BACKGROUND
  Current treatments for schizophrenia have modest, if any, efficacy on cognitive dysfunction, creating a need for novel therapies. Their development requires predictive animal models. The N-methyl-D-aspartate (NMDA) hypothesis of schizophrenia indicates the use of NMDA antagonists, like subchronic phencyclidine (scPCP) to model cognitive dysfunction in adult animals.
  
  
  OBJECTIVE
  The objective of this study was to assess the scPCP model by (1) reviewing published findings of scPCP-induced neurochemical changes and effects on cognitive tasks in adult rats and (2) comparing findings from a multi-site study to determine scPCP effects on standard and touchscreen cognitive tasks.
  
  
  METHODS
  Across four research sites, the effects of scPCP (typically 5 mg/kg twice daily for 7 days, followed by at least 7-day washout) in adult male Lister Hooded rats were studied on novel object recognition (NOR) with 1-h delay, acquisition and reversal learning in Morris water maze and touchscreen-based visual discrimination.
  
  
  RESULTS
  Literature findings showed that scPCP impaired attentional set-shifting (ASST) and NOR in several labs and induced a variety of neurochemical changes across different labs. In the multi-site study, scPCP impaired NOR, but not acquisition or reversal learning in touchscreen or water maze. Yet, this treatment regimen induced locomotor hypersensitivity to acute PCP until 13-week post-cessation.
  
  
  CONCLUSIONS
  The multi-site study confirmed that scPCP impaired NOR and ASST only and demonstrated the reproducibility and usefulness of the touchscreen approach. Our recommendation, prior to testing novel therapeutics in the scPCP model, is to be aware that further work is required to understand the neurochemical changes and specificity of the cognitive deficits.
authors.affiliation: CNS Research, Research and Development, Orion Pharma, Orion Corporation, Tengstrominkatu 8, P.O. Box 425, 20101, Turku, Finland. sanna.janhunen@orionpharma.com.
authors.forename: Sanna K
authors.initials: SK
authors.lastname: Janhunen
authors.affiliation: CNS Research, Research and Development, Orion Pharma, Orion Corporation, Tengstrominkatu 8, P.O. Box 425, 20101, Turku, Finland.
authors.forename: Heta
authors.initials: H
authors.lastname: Svärd
authors.affiliation: Janssen Research and Development, Turnhoutseweg 30, 2340, Beerse, Belgium.
authors.forename: John
authors.initials: J
authors.lastname: Talpos
authors.affiliation: Janssen Research and Development, Turnhoutseweg 30, 2340, Beerse, Belgium.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Kumar
authors.affiliation: Janssen Research and Development, Turnhoutseweg 30, 2340, Beerse, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Steckler
authors.affiliation: Synaptic Transmission, H. Lundbeck A/S, Ottiliavej 9, 2500, Valby, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Plath
authors.affiliation: Synaptic Transmission, H. Lundbeck A/S, Ottiliavej 9, 2500, Valby, Denmark.
authors.forename: Linda
authors.initials: L
authors.lastname: Lerdrup
authors.affiliation: Synaptic Transmission, H. Lundbeck A/S, Ottiliavej 9, 2500, Valby, Denmark.
authors.forename: Trine
authors.initials: T
authors.lastname: Ruby
authors.affiliation: Neuroscience, Ophthalmology and Rare Diseases, Roche Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070, Basel, Switzerland.
authors.forename: Marie
authors.initials: M
authors.lastname: Haman
authors.affiliation: Neuroscience, Ophthalmology and Rare Diseases, Roche Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070, Basel, Switzerland.
authors.forename: Roger
authors.initials: R
authors.lastname: Wyler
authors.affiliation: Neuroscience, Ophthalmology and Rare Diseases, Roche Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070, Basel, Switzerland.
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Ballard
mesh_terms: D000818:Animals; D001288:Attention / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced* / Q000150:complications / Q000188:drug therapy; D004195:Disease Models, Animal; D008297:Male; D010622:Phencyclidine; D051381:Rats; D012193:Reversal Learning / Q000187:drug effects*; D012559:Schizophrenia / Q000139:chemically induced* / Q000150:complications / Q000188:drug therapy
chemical_list: D010622:Phencyclidine
keywords: Adult rat; Cognition; Schizophrenia; Subchronic phencyclidine; Touchscreen; Visual discrimination; Water maze