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Anesth Analg 2006;102:448-455
© 2006 International Anesthesia Research Society
doi: 10.1213/01.ane.0000195234.07413.5a


ANESTHETIC PHARMACOLOGY

Dexmedetomidine-Induced Decreases in Accumbal Dopamine in the Rat Are Partly Mediated via the Locus Coeruleus

Robert A. Whittington, MD, and László Virág, MS

Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, New York

Address correspondence and reprint requests to Robert A. Whittington, MD, Columbia University College of Physicians and Surgeons, Department of Anesthesiology, 622 West 168th Street, PH 5, New York, NY 10032. Address e-mail to raw9{at}columbia.edu

We have demonstrated previously that the systemic administration of the selective {alpha}2-adrenoceptor agonist dexmedetomidine (Dex) decreases extracellular dopamine (DA) levels in the rat nucleus accumbens (NAcc). Because the locus ceruleus (LC) is a noradrenergic center linked to several of the pharmacological effects of Dex, we investigated the role of the LC in Dex-induced modulation of accumbal DA. Microdialysis probes were implanted in the NAcc and LC of Sprague-Dawley rats, and Dex 5 mM (Dex-High, n = 6), Dex 0.5 mM (Dex-Mid, n = 5), Dex 5 µM (Dex-Low, n = 6), or artificial cerebrospinal fluid (control, n = 5) was administered in the LC via retrograde microdialysis for 45 min. Extracellular DA levels were continuously measured in the NAcc dialysates using high-performance liquid chromatography coupled to electrochemical detection. Dex produced significant decreases in extracellular DA in the NAcc. Accumbal DA decreased maximally to 68.9% ± 8.8%, 75.1% ± 6.5%, and 77.04% ± 12.8% of baseline in the Dex-High, Dex-Mid, and Dex-Low groups, respectively. No significant decrease in extracellular DA was observed in the control group. The coadministration of the highly selective {alpha}2-adrenoceptor antagonist (n = 6) RS 79948 20 mM prevented the Dex-induced decrease in accumbal DA. These data suggest that the LC plays a role in Dex-induced modulation of mesolimbic DA and support the hypothesis that noradrenergic systems can regulate remote dopaminergic sites in the central nervous system.







Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2006 by the International Anesthesia Research Society.