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Acta Psychiatr Scand. 2010 Jan;121(1):11-21. doi: 10.1111/j.1600-0447.2009.01455.x.

The prefrontal cortex: a target for antipsychotic drugs.

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1
Department of Neurochemistry and Neuropharmacology, Institut d' Investigacions Biomèdiques de Barcelona (CSIC), IDIBAPS,08036 Barcelona, Spain. fapnqi@iibb.csic.es

Abstract

OBJECTIVE:

At therapeutic doses, classical antipsychotic drugs occupy a large proportion of subcortical dopamine D2 receptors, whereas atypical antipsychotics preferentially occupy cortical 5-HT(2) receptors. However, the exact cellular and network basis of their therapeutic action is not fully understood.

METHOD:

To review the mechanism of action of antipsychotic drugs with a particular emphasis on their action in the prefrontal cortex (PFC).

RESULTS:

The PFC controls a large number of higher brain functions altered in schizophrenia. Histological studies indicate the presence of a large proportion of PFC neurons expressing monoaminergic receptors sensitive to the action of atypical- and to a lesser extentclassical antipsychotic drugs. Functional studies also indicate that both drug families act at PFC level.

CONCLUSION:

Atypical antipsychotic drugs likely exert their therapeutic activity by a preferential action on PFC neurons, thus modulating the PFC output to basal ganglia circuits. Classical antipsychotics also interact with these PFC targets in addition to blocking massively striatal D2 receptors.

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