PMID- 16428541
OWN - NLM
STAT- MEDLINE
DCOM- 20060221
LR  - 20131121
IS  - 1526-7598 (Electronic)
IS  - 0003-2999 (Linking)
VI  - 102
IP  - 2
DP  - 2006 Feb
TI  - Dexmedetomidine-induced decreases in accumbal dopamine in the rat are partly 
      mediated via the locus coeruleus.
PG  - 448-55
AB  - 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.
FAU - Whittington, Robert A
AU  - Whittington RA
AD  - Department of Anesthesiology, College of Physicians and Surgeons, Columbia 
      University, New York, New York 10032, USA. raw9@columbia.edu
FAU - Virag, Laszlo
AU  - Virag L
LA  - eng
GR  - K08-GM00681/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Anesth Analg
JT  - Anesthesia and analgesia
JID - 1310650
RN  - 0 (Adrenergic alpha-Agonists)
RN  - 67VB76HONO (Dexmedetomidine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Adrenergic alpha-Agonists/*pharmacology
MH  - Animals
MH  - Chromatography, High Pressure Liquid
MH  - Dexmedetomidine/*pharmacology
MH  - Dopamine/*metabolism
MH  - Locus Coeruleus/*drug effects/physiology
MH  - Male
MH  - Microdialysis
MH  - Nucleus Accumbens/drug effects/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2006/01/24 09:00
MHDA- 2006/02/24 09:00
CRDT- 2006/01/24 09:00
PHST- 2006/01/24 09:00 [pubmed]
PHST- 2006/02/24 09:00 [medline]
PHST- 2006/01/24 09:00 [entrez]
AID - 102/2/448 [pii]
AID - 10.1213/01.ane.0000195234.07413.5a [doi]
PST - ppublish
SO  - Anesth Analg. 2006 Feb;102(2):448-55. doi: 10.1213/01.ane.0000195234.07413.5a.