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.
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Acknowledgements
We thank Terri Beattie for expert technical assistance and Dr. Nicolas Hengartner (Dept. of Statistics, Yale University) for assistance in analyzing data. Support for these studies came from National Institutes of Health grants MH44866, MH48404, and MH14092.
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Youngren, K., Inglis, F., Pivirotto, P. et al. Clozapine Preferentially Increases Dopamine Release in the Rhesus Monkey Prefrontal Cortex Compared with the Caudate Nucleus. Neuropsychopharmacol 20, 403–412 (1999). https://doi.org/10.1016/S0893-133X(98)00082-7
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DOI: https://doi.org/10.1016/S0893-133X(98)00082-7
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