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dc.contributor.authorMcAllister, KAL
dc.contributor.authorMar, AC
dc.contributor.authorTheobald, DE
dc.contributor.authorSaksida, LM
dc.contributor.authorBussey, TJ
dc.date.accessioned2015-07-13T15:52:35Z
dc.date.available2015-07-13T15:52:35Z
dc.date.issued2015-11
dc.identifier.citationPsychopharmacology 2015, 232(21):3883-3897. doi: 10.1007/s00213-015-4018-7
dc.identifier.issn0033-3158
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/248912
dc.description.abstractRATIONALE: 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. OBJECTIVES: 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.
dc.description.sponsorshipKAL McAllister received funding from the Cambridge Commonwealth Trusts and University of Cambridge Overseas Studentship Programme. LM Saksida and TJ Bussey also received funding from the Innovative Medicines Initiative Joint Undertaking (IMI) under grant agreement n° 115008. IMI is a public-private partnership between the European Union and the European Federation of Pharmaceutical Industries and Associations.
dc.languageEnglish
dc.language.isoen
dc.publisherSpringer Science and Business Media LLC
dc.subjectSchizophrenia
dc.subjectPhencyclidine
dc.subjectPrefrontal cortex
dc.subjectObject recognition
dc.subjectRat
dc.subjectAnimal model
dc.subjectAssociative learning
dc.subjectGlutamate
dc.subjectLearning and memory
dc.subjectDiscrimination
dc.titleComparing the effects of subchronic phencyclidine and medial prefrontal cortex dysfunction on cognitive tests relevant to schizophrenia.
dc.typeArticle
dc.description.versionThis is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s00213-015-4018-7
prism.endingPage3897
prism.publicationDate2015
prism.publicationNamePsychopharmacology (Berl)
prism.startingPage3883
prism.volume232
dcterms.dateAccepted2015-07-01
rioxxterms.versionofrecord10.1007/s00213-015-4018-7
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2015-07-21
dc.identifier.eissn1432-2072
rioxxterms.typeJournal Article/Review
cam.issuedOnline2015-07-21
rioxxterms.freetoread.startdate2016-07-21


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