Chronic dexmedetomidine, a selective alpha 2-agonist, decreases serotonin but not noradrenaline turnover in rat brainstem nuclei.
The effects of a chronic treatment with dexmedetomidine, the active d-isomer of a selective alpha 2-agonist, medetomidine, on the metabolism and turnover of catecholamines and indoleamines in discrete rat brain stem and mesencephalic nuclei were investigated. Chronic dexmedetomidine (3 or 10 micrograms/kg per h for 14 days, delivered by osmotic minipumps) did not change the basal concentrations of noradrenaline, dopamine or 3,4-dihydroxyphenylacetic acid, or the rates of accumulation of 3,4-dihydroxyphenylalanine after inhibition of decarboxylase by NSD 1015. In contrast, the concentrations of 5-hydroxyindoleacetic acid (5-HIAA) and/or 5-HIAA/5-HT were significantly reduced in the nucleus tractus solitarii, raphe dorsalis, locus coeruleus, A1-C1 area, A9 and A10 areas after 10 micrograms/kg per h of dexmedetomidine. The accumulation of 5-hydroxytryptophan was significantly reduced in the locus coeruleus and nucleus tractus solitarii. It is concluded that chronic dexmedetomidine treatment significantly decreases the turnover of 5-hydroxytryptamine in discrete brainstem and mesencephalic nuclei, while the rate of synthesis of noradrenaline in the same areas is not changed.
Department of Pharmacology, University of Turku, Finland.
M
M
Koulu
U
U
Pesonen
R
R
Virtanen
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism*; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D020926:Medetomidine; D009043:Motor Activity / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D015306:Biogenic Monoamines; D007093:Imidazoles; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D004295:Dihydroxyphenylalanine; D020926:Medetomidine; D009638:Norepinephrine