Idazoxan-induced reductions in cortical glucose use are accompanied by an increase in noradrenaline release: complementary [14C]2-deoxyglucose and microdialysis studies.
The autoradiographic [14C]2-deoxyglucose procedure was used to map function-related alterations in local cerebral glucose use following acute administration of the alpha 2-adrenoceptor antagonist, idazoxan (0.3-3 mg kg-1 s.c.). The most prominent feature of the results obtained was the significant reduction in glucose use in certain locus coeruleus projection areas. Thus, in various cortical, hippocampal and thalamic regions, as well as structures involved in auditory and visual function, idazoxan administration was associated with a 13-20% decrease in glucose use. In a complementary microdialysis study, the effect of idazoxan on extracellular noradrenaline levels in the frontal cortex of rats, manipulated in the same fashion as during the [14C]2-deoxyglucose procedure (i.e. following the application of surgery and partial restraint), was examined. Both surgery and restraint were associated with a modest but significant increase in basal noradrenaline release (+31% and +26%, respectively). Subsequent administration of idazoxan (3 mg kg-1 s.c.) evoked a further increase in noradrenaline release, the magnitude of which was the same as that observed following its administration to freely-moving rats (+113%). These combined data suggest that idazoxan-induced reductions in cerebral glucose use, at least in the frontal cortex, may occur as a consequence of the increase in noradrenaline release. In addition, it appears that surgery and partial restraint do not alter alpha 2-adrenoceptor tone in the frontal cortex.
French
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N
Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, U.K.
Lalies
M D
MD
Nutt
D J
DJ
Pratt
J A
JA
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects; D003847:Deoxyglucose / Q000378:metabolism*; D004146:Dioxanes / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D019329:Idazoxan; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D007093:Imidazoles; D003847:Deoxyglucose; D005947:Glucose; D009638:Norepinephrine; D019329:Idazoxan