The prefrontal cortex: a target for antipsychotic drugs.
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.


METHODS
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.


CONCLUSIONS
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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Department of Neurochemistry and Neuropharmacology, Institut d' Investigacions Biomèdiques de Barcelona (CSIC), IDIBAPS,08036 Barcelona, Spain. fapnqi@iibb.csic.es
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001479:Basal Ganglia / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects; D000882:Haplorhini; D006801:Humans; D009434:Neural Pathways / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology; D012559:Schizophrenia / Q000188:drug therapy; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2