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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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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.

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Acknowledgments

KAL McAllister received funding from the Cambridge Commonwealth Trusts and University of Cambridge Overseas Studentship Programme. The work leading to these results has 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.

Conflict of interest

LMS and TJB are consultants for Campden Instruments Ltd.

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Authors and Affiliations

  1. University of Cambridge Department of Psychology, Downing Street, Cambridge, CB2 3EB, UK

    K. A. L. McAllister, A. C. Mar, D. E. Theobald, L. M. Saksida & T. J. Bussey

  2. MRC and Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, CB2 3EB, UK

    K. A. L. McAllister, A. C. Mar, D. E. Theobald, L. M. Saksida & T. J. Bussey

  3. 20 Manchester Sq., London, W1U 3PZ, UK

    K. A. L. McAllister

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  1. K. A. L. McAllister
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  2. A. C. Mar
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  3. D. E. Theobald
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  4. L. M. Saksida
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  5. T. J. Bussey
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Correspondence to K. A. L. McAllister.

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McAllister, K.A.L., Mar, A.C., Theobald, D.E. et al. Comparing the effects of subchronic phencyclidine and medial prefrontal cortex dysfunction on cognitive tests relevant to schizophrenia. Psychopharmacology 232, 3883–3897 (2015). https://doi.org/10.1007/s00213-015-4018-7

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  • DOI: https://doi.org/10.1007/s00213-015-4018-7

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