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Comparing the effects of subchronic phencyclidine and medial prefrontal cortex dysfunction on cognitive tests relevant to schizophrenia.


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Authors

McAllister, KAL 
Mar, AC 
Theobald, DE 
Saksida, LM 
Bussey, TJ 

Abstract

RATIONALE: 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.

Description

Keywords

Animal model, Associative learning, Discrimination, Glutamate, Learning and memory, Object recognition, Phencyclidine, Prefrontal cortex, Rat, Schizophrenia, Animals, Behavior, Animal, Brain Diseases, Cognition, Excitatory Amino Acid Agonists, Hallucinogens, Ibotenic Acid, Injections, Intraperitoneal, Learning, Limbic System, Male, Memory, Phencyclidine, Prefrontal Cortex, Rats, Recognition, Psychology, Schizophrenic Psychology

Journal Title

Psychopharmacology (Berl)

Conference Name

Journal ISSN

0033-3158
1432-2072

Volume Title

232

Publisher

Springer Science and Business Media LLC
Sponsorship
KAL 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.