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Dopamine dysregulation in the prefrontal cortex relates to cognitive deficits in the sub-chronic PCP-model for schizophrenia: a preliminary investigation
Harte, Michael K. Neill, Joanna C. Young, A.M.J.
Harte, Michael K.
Neill, Joanna C.
Young, A.M.J.
Publication Date
2017
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© 2017 The Authors. Published by SAGE. Reproduced in accordance with the publisher's self-archiving policy.
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openAccess
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2017-03-12
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Abstract
Rationale: Dopamine dysregulation in the prefrontal cortex (PFC) plays an important role in cognitive dysfunction in schizophrenia. Sub-chronic phencyclidine (scPCP) treatment produces cognitive impairments in rodents and is a thoroughly validated animal model for cognitive deficits in schizophrenia. The aim of our study was to investigate the role of PFC dopamine in scPCP-induced deficits in a cognitive task of relevance to the disorder, novel object recognition (NOR).
Methods: Twelve adult female Lister Hooded rats received scPCP (2 mg/kg) or vehicle via the intraperitoneal route twice daily for seven days, followed by seven days washout. In vivo microdialysis was carried out prior to, during and following the NOR task.
Results: Vehicle rats successfully discriminated between novel and familiar objects and this was accompanied by a significant increase in dopamine in the PFC during the retention trial (P<0.01). scPCP produced a significant deficit in NOR (P<0.05 vs. control) and no PFC dopamine increase was observed. Conclusions: These data demonstrate an increase in dopamine during the retention trial in vehicle rats that was not observed in scPCP-treated rats accompanied by cognitive disruption in the scPCP group. This novel finding suggests a mechanism by which cognitive deficits are produced in this animal model and support its use for investigating disorders in which PFC dopamine is central to the pathophysiology.
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Citation
McLean SL, Harte MK, Neill JC and Young AMJ (2017) Dopamine dysregulation in the prefrontal cortex relates to cognitive deficits in the sub-chronic PCP-model for schizophrenia: a preliminary investigation. Journal of Psychopharmacology. 31(6): 660-666.
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Article