Kd. Youngren et al., Clozapine preferentially increases dopamine release in the rhesus monkey prefrontal cortex compared with the caudate nucleus, NEUROPSYCH, 20(5), 1999, pp. 403-412
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.