Mar 4, 2008

Modelling prefrontal cortex deficits in schizophrenia: implications for treatment

British Journal of Pharmacology
Judith A PrattBrian J Morris

Abstract

Current treatments of schizophrenia are compromised by their inability to treat all symptoms of the disease and their side-effects. Whilst existing antipsychotic drugs are effective against positive symptoms, they have negligible efficacy against the prefrontal cortex (PFC)-associated cognitive deficits and negative symptoms. New models that reproduce core pathophysiological features of schizophrenia are more likely to have improved predictive validity in identifying new treatments. We have developed a NMDA receptor antagonist model that reproduces core PFC deficits of schizophrenia and discuss this in relation to pathophysiology and treatments. Subchronic and chronic intermittent PCP (2.6 mg/kg i.p.) was administered to rats. PFC activity was assessed by 2-deoxyglucose imaging, parvalbumin and Kv3.1 mRNA expression, and the attentional set-shifting test (ASST) of executive function. Affymetrix gene array technology was employed to examine gene expression profile patterns. PCP treatment reduced glucose utilization in the PFC (hypofrontality). This was accompanied by a reduction in markers of GABAergic interneurones (parvalbumin and Kv3.1 mRNA expression) and deficits in the extradimensional shift dimension of the ASST. Consiste...Continue Reading

Mentioned in this Paper

Antipsychotic Effect
Microarray Analysis
Adrenal Cortex Diseases
Neurologic Manifestations
Assay OF Haloperidol
Prefrontal Cortex
Schizophrenia
Phencyclidine Hydrobromide
Clozapine
Transcription, Genetic

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