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

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.

The effect of atypical and classical antipsychotics on sub-chronic PCP-induced cognitive deficits in a reversal-learning paradigm.

Phencyclidine (PCP), an NMDA antagonist, has been shown to mimic some aspects of schizophrenia including positive, negative and cognitive symptoms. Previous studies in this laboratory have shown a selective reversal-learning deficit following acute PCP administration, a deficit that is attenuated by atypical, but not classical, antipsychotic treatment. However, acute PCP has limitations for modelling the chronic psychotic illness and persistent cognitive deficits observed in many schizophrenic patients.

Calcium binding protein markers of GABA deficits in schizophrenia--postmortem studies and animal models.

As quantitative neuroimaging continues to elucidate the gross neuropathology of schizophrenia, neurochemical and histological studies have contributed to defining this pathology in terms of neurotransmitter dysfunction. Increasingly, there is evidence implicating neurons containing the major inhibitory neurotransmitter of the brain--gamma-aminobutyric acid (GABA). Benes was the first to demonstrate deficits in some morphological subtypes of interneurons in the frontal cortex in schizophrenia.

The atypical antipsychotic ziprasidone, but not haloperidol, improves phencyclidine-induced cognitive deficits in a reversal learning task in the rat.

The glutamate/N-methyl-D-aspartate receptor antagonist phencyclidine (PCP) has been shown to induce both positive and negative symptoms of schizophrenia, as well as cognitive deficits, thus providing a relatively valid model of psychosis. Isolation rearing from weaning in the rat has been proposed as a non-pharmacological model of psychosis. The aim of the present study was to explore the validity of a combination of these techniques to model cognitive dysfunction associated with schizophrenia.