Clozapine preferentially increases dopamine release in the rhesus monkey prefrontal cortex compared with the caudate nucleus

Despite substantial differences between species in the organization and ela boration of the cortical dopamine innervation, little is known about the ph armacological response of cortical or striatal sites to antipsychotic medic ations in nonhuman primates. To examine this issue, rhesus monkeys were chr onically implanted with guide cannulae directed at the principal sulcus, me dial prefrontal cortex, premotor cortex, and caudate nucleus. Alterations i n dopamine release in these discrete brain regions were measured in respons e to administration of clozapine or haloperidol. Clozapine produced signifi cant and long-lasting increases in dopamine release in the principal sulcus , and to a lesser extent, in the caudate nucleus. Haloperidol did not produ ce a consistent effect on dopamine release in the principal sulcus, althoug h it increased dopamine release in the caudate. Clozapine's preferential au gmentation of dopamine release in the dorsolateral prefrontal cortex suppor ts the idea that clozapine exerts its therapeutic effects in part by increa sing cortical dopamine neurotransmission. (C) 1999 American College of Neur opsychopharmacology. Published by Elsevier Science Inc.