NDLI: A possible substrate for dopamine-related changes in mood and behavior: prefrontal and limbic effects of a D3-preferring dopamine agonist.

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A possible substrate for dopamine-related changes in mood and behavior: prefrontal and limbic effects of a D3-preferring dopamine agonist.

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A possible substrate for dopamine-related changes in mood and behavior: prefrontal and limbic effects of a D3-preferring dopamine agonist.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Hershey, Tamara Black, Kevin J. Perlmutter, Joel S. Koller, Jonathan M. Mintun, Mark A. Price, Joseph L. Videen, Tom O.
Description	Author Affiliation: Black KJ ( Departments of Psychiatry, School of Medicine, Washington University, 660 South Euclid Avenue, St. Louis, MO 63110, USA. kevin@npg.wustl.edu);
Abstract	Dopamine can induce fascinating, complex human behavioral states, including disinhibition, euphoria, or elaborate stereotypies, whereas dopamine deficiency can cause anxiety or sadness. Limited data suggest that these phenomena may involve dysfunction of orbital frontal cortex, cingulate cortex, or ventral striatum. The dopamine D3 receptor (D3R) has an anatomic distribution that suggests it could mediate these effects, but almost no data directly demonstrate the regional functional effects of D3R activation. We used quantitative positron emission tomography (PET), [15O]water, and the D3-preferring dopamine agonist pramipexole to identify D3-mediated regional cerebral blood flow (rCBF) responses in living primates. We studied seven normal baboons ventilated with 70% nitrous oxide, and analyzed results voxelwise in a common atlas space. At clinically relevant doses, pramipexole produced statistically robust decreases in rCBF in bilateral orbitofrontal cortex, thalamus, operculum, posterior and anterior (subgenual) cingulate cortex, and insula (in decreasing order of significance). Cortical areas related to movement were relatively unaffected, and rCBF did not change in cerebellum or visual cortex. The dose-response curve and duration of pramipexole's effects suggest that these rCBF responses indicate functional effects of a D3-preferring agonist. A D2-preferring agonist studied under the same conditions produced a quantitatively different pattern of responses. We conclude that a dopamine D3 receptor agonist preferentially affects brain activity in prefrontal and limbic cortex, and speculate that dopamine's effects on these regions via D3Rs may mediate some of the known psychiatric complications of dopamine deficiency or excess.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	26
Volume Number	99
Language	English
Publisher	National Academy of Sciences
Publisher Date	2002-12-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Dopamine Agonists Pharmacology Dopamine Physiology Limbic System Drug Effects Mental Disorders Etiology Mood Disorders Prefrontal Cortex Receptors, Dopamine D2 Agonists Animals Benzothiazoles Cerebrovascular Circulation Papio Receptors, Dopamine D3 Thiazoles Tomography, Emission-Computed Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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