Dexmedetomidine-induced decreases in accumbal dopamine in the rat are partly mediated via the locus coeruleus.
We have demonstrated previously that the systemic administration of the selective alpha2-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 microM (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 alpha2-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.
Whittington
Robert A
RA
Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA. raw9@columbia.edu
Virág
László
L
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D020927:Dexmedetomidine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D008125:Locus Coeruleus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000316:Adrenergic alpha-Agonists; D020927:Dexmedetomidine; D004298:Dopamine