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Antipsychotic Drugs Normalize Prefrontal Cortex Activity

Study used a rat model of schizophrenia

TUESDAY, Sept. 11 (HealthDay News) -- Antipsychotic drugs such as haloperidol may act by normalizing disrupted activity in the prefrontal cortex, according to the results of a study in a rat model of schizophrenia published in the Sept. 11 issue of the Proceedings of the National Academy of Sciences.

As a model of schizophrenia, Francesc Artigas, Ph.D., and colleagues from Institut d'Investigacions Biomediques de Barcelona in Spain examined the effect of phencyclidine (PCP), an NMDA-receptor antagonist, on the function of the prefrontal cortex in rats.

The researchers found that PCP increased the activity of 45 percent of pyramidal neurons in the prefrontal cortex, decreased the function of 33 percent, and had no effect in 22 percent. This was reversed by the antipsychotic drugs haloperidol and clozapine. PCP also increased the expression of a marker of neuronal activity in the prefrontal cortex, which was blocked by clozapine. PCP also enhanced the expression of this marker in areas of the thalamus, which provide input into the prefrontal cortex.

"These results shed light on the involvement of prefrontal cortex in the schizomimetic action of NMDA-receptor antagonists and show that antipsychotic drugs may partly exert their therapeutic effect by normalizing a disrupted prefrontal cortex activity, an effect that may add to subcortical dopamine receptor blockade," Artigas and colleagues conclude.

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