Comparing the effects of subchronic phencyclidine and medial prefrontal cortex dysfunction on cognitive tests relevant to schizophrenia
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McAllister, K., Mar, A., Theobald, D., Saksida, L., & Bussey, T. (2015). Comparing the effects of subchronic phencyclidine and medial prefrontal cortex dysfunction on cognitive tests relevant to schizophrenia. Psychopharmacology, 232 3883-3897. https://doi.org/10.1007/s00213-015-4018-7
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 PCP (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 the rat, across several cognitive tests relevant to schizophrenia. Methods ScPCP subjects were dosed i.p. with 5mg/kg PCP or vehicle twice daily for one week followed by 1 week washout prior to behavioural testing. mPFC dysfunction was induced via fibre-sparing excitotoxin infused into the prelimbic 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 pairedassociates 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.
Schizophrenia, Phencyclidine, Prefrontal cortex, Object recognition, Rat, Animal model, Associative learning, Glutamate, Learning and memory, Discrimination
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.
External DOI: https://doi.org/10.1007/s00213-015-4018-7
This record's URL: https://www.repository.cam.ac.uk/handle/1810/248912