Sub-chronic psychotomimetic phencyclidine induces deficits in reversal learning and alterations in parvalbumin-immunoreactive expression in the rat

Abstract

Acute administration of the psychotomimetic phencyclidine (PCP) can mimic some features of schizophrenia, while a repeated treatment regimen of PCP may provide a more effective way to model in animals the enduring cognitive dysfunction observed in many schizophrenic patients. The present study aims to investigate behavioural and neuropathological effects of sub-chronic PCP administration. The cognitive deficit induced by sub-chronic PCP was examined using a previously established operant reversal-learning paradigm. Subsequently, the effect of sub-chronic PCP on parvalbumin-immunoreactive (parvalbumin-IR) neurons was assessed using immunohistochemical techniques. Rats were trained to respond for food in an operant reversal-learning paradigm for approximately 6 weeks, followed by sub-chronic administration of PCP (2mg/kg) or vehicle twice daily for 7 days followed 7 days later by behavioural testing. Six weeks post PCP, brains were analysed using immunohistochemical techniques to determine the size and density of parvalbumin-IR in the frontal cortex and hippocampus. Sub-chronic PCP significantly reduced (p p p p p <0.001). These results parallel findings of profound hippocampal and more subtle cortical deficits of parvalbumin-IR neurons in schizophrenia, and provide evidence to suggest that sub-chronic PCP can induce a lasting cognitive deficit, an effect that may be related to the observed neuronal deficits.