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

Kenneth D. Youngren, Fiona M. Inglis, Philip J. Pivirotto, Hank P. Jedema, Charles W. Bradberry, Patricia S. Goldman-Rakic, Robert H. Roth, Bita Moghaddam

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

Despite substantial differences between species in the organization and elaboration of the cortical dopamine innervation, little is known about the pharmacological response of cortical or striatal sites to antipsychotic medications in nonhuman primates. To examine this issue, rhesus monkeys were chronically implanted with guide cannulae directed at the principal sulcus, medial prefrontal cortex, premotor cortex, and caudate nucleus. Alterations in dopamine release in these discrete brain regions were measured in response to administration of clozapine or haloperidol. Clozapine produced significant and long-lasting increases in dopamine release in the principal sulcus, and to a lesser extent, in the caudate nucleus. Haloperidol did not produce a consistent effect on dopamine release in the principal sulcus, although it increased dopamine release in the caudate. Clozapine's preferential augmentation of dopamine release in the dorsolateral prefrontal cortex supports the idea that clozapine exerts its therapeutic effects in part by increasing cortical dopamine neurotransmission. Copyright (C) 1999 American College of Neuropsychopharmacology.

Original languageEnglish (US)
Pages (from-to)403-412
Number of pages10
JournalNeuropsychopharmacology
Volume20
Issue number5
DOIs
StatePublished - May 1999
Externally publishedYes

Fingerprint

Caudate Nucleus
Clozapine
Prefrontal Cortex
Macaca mulatta
Dopamine
Haloperidol
Corpus Striatum
Motor Cortex
Therapeutic Uses
Synaptic Transmission
Primates
Antipsychotic Agents
Pharmacology
Brain

Keywords

  • Antipsychotic drugs
  • Haloperidol
  • Microdialysis
  • Schizophrenia
  • Striatum

ASJC Scopus subject areas

  • Pharmacology

Cite this

Clozapine preferentially increases dopamine release in the rhesus monkey prefrontal cortex compared with the caudate nucleus. / Youngren, Kenneth D.; Inglis, Fiona M.; Pivirotto, Philip J.; Jedema, Hank P.; Bradberry, Charles W.; Goldman-Rakic, Patricia S.; Roth, Robert H.; Moghaddam, Bita.

In: Neuropsychopharmacology, Vol. 20, No. 5, 05.1999, p. 403-412.

Research output: Contribution to journalArticle

Youngren, Kenneth D. ; Inglis, Fiona M. ; Pivirotto, Philip J. ; Jedema, Hank P. ; Bradberry, Charles W. ; Goldman-Rakic, Patricia S. ; Roth, Robert H. ; Moghaddam, Bita. / Clozapine preferentially increases dopamine release in the rhesus monkey prefrontal cortex compared with the caudate nucleus. In: Neuropsychopharmacology. 1999 ; Vol. 20, No. 5. pp. 403-412.
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