The effects of alpha 2-adrenoceptor stimulation on neocortical EEG activity in control and 6-hydroxydopamine dorsal noradrenergic bundle-lesioned rats.
The present study investigated the effects of a alpha 2-adrenoceptor agonist, D-medetomidine (0.3, 3.0, 30.0 and 300.0 micrograms/kg, s.c.), on neocortical EEG activity in control and 6-hydroxydopamine dorsal noradrenergic bundle-lesioned rats. D-Medetomidine at 0.3, 3.0, and 30.0 micrograms/kg dose dependently increased waking-immobility-related high-voltage spike and wave spindles. Movement and waking-immobility-related slow wave activity was increased at doses of 3.0, 30.0 and 300.0 micrograms/kg. D-Medetomidine at 300.0 micrograms/kg produced continuous 1-2 Hz slow wave activity and the animals were markedly sedated. In rats injected with D-medetomidine at 0.3, 3.0 and 30.0, micrograms/kg EEG activity could be desynchronized (block of high-voltage spindles and slow waves) by pinching the tail. However, rats injected with D-medetomidine at 300.0 micrograms/kg showed no change in EEG activity or behavior following tail pinching. D-Medetomidine induced similar EEG activity (high-voltage spindles and slow waves) and behavioral changes (sedation) in 6-hydroxydopamine dorsal noradrenergic bundle-lesioned rats. Atipamezole, an alpha 2-adrenoceptor antagonist, blocked D-medetomidine-induced EEG and behavioral changes in control and 6-hydroxydopamine dorsal noradrenergic bundle-lesioned rats. Based on the present results we suggest that stimulation of presynaptic noradrenergic fibers is not a prerequisite for the increase of high-voltage spindle and slow wave activity induced by an alpha 2-adrenoceptor agonist and that the magnitude of EEG slowing induced by D-medetomidine correlates with the decreased behavioral response to sensory stimulation.
Riekkinen
P
P
University of Kuopio, Department of Neurology, A.I. Virtanen Institute, Finland.
Lammintausta
R
R
Ekonsalo
T
T
Sirviö
J
J
D000320:Adrenergic Fibers / Q000502:physiology; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects*; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D008125:Locus Coeruleus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D020926:Medetomidine; D016627:Oxidopamine / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; C050701:atipamezole; D016627:Oxidopamine; D020926:Medetomidine