Prevention of ethanol-induced sympathetic overactivity and degeneration by dexmedetomidine.
The effects of dexmedetomidine, a selective alpha 2-adrenoceptor agonist, on rat sympathetic neurons were studied during a 12-day, heavy ethanol exposure. Adult male Wistar rats were given ethanol or isocaloric sucrose three times a day by intragastric intubation. Both acute (a single dose of 300 micrograms/kg p.o.) and chronic (100 micrograms/kg x 2 P.O. throughout the experiment) effects of dexmedetomidine were tested. The superior cervical ganglia (SCG) of the ethanol-exposed, non-dexmedetomidine-treated rats showed an abnormally high overall level of tyrosine hydroxylase immunoreactivity (TH-IR) and catecholamine histofluorescence. However, a subpopulation of neurons had apparently lost their catecholamine synthetic activity, as they exhibited no TH-IR or catecholamine fluorescence. The ethanol-exposed ganglia also showed structural alterations (e.g., decreased neuronal size and increased occurrence of vacuolated neurons). In the ethanol-exposed, chronically dexmedetomidine-treated group, by contrast, the SCG exhibited TH-IR and catecholamine fluorescence intensities comparable to those seen in the control ganglia. All the structural parameters studied, as well, were at the control level in the chronically dexmedetomidine-treated group. The single dose of dexmedetomidine offered only marginal protection against the ethanol-induced alterations. These results suggest that chronic dexmedetomidine treatment may prevent ethanol-induced overactivity and degeneration of catecholaminergic neurons.
University of Tampere, School of Public Health, Finland.
P
P
Jaatinen
P
P
Riihioja
A
A
Haapalinna
E
E
Heinonen
K
K
Kiianmaa
A
A
Hervonen
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002492:Central Nervous System Depressants / Q000097:blood / Q000633:toxicity*; D000431:Ethanol / Q000097:blood / Q000633:toxicity*; D006651:Histocytochemistry; D007091:Image Processing, Computer-Assisted; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D020926:Medetomidine; D009410:Nerve Degeneration / Q000187:drug effects*; D009638:Norepinephrine / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017783:Superior Cervical Ganglion / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D002492:Central Nervous System Depressants; D007093:Imidazoles; D000431:Ethanol; D014446:Tyrosine 3-Monooxygenase; D020926:Medetomidine; D009638:Norepinephrine