Facilitation of spike-wave activity by the hypnotic etomidate in a rat model for absence epilepsy.
The epileptogenic effect of the short-acting hypnotic agent etomidate was investigated in WAG/Rij rats. Animals of this inbred strain show spontaneous spike-wave discharges and are regarded as a model for absence epilepsy. A dose-dependent increase in the total amount of spike-wave activity was found, when etomidate was injected intraperitoneally in doses of 1, 2.5, 5 and 10 mg/kg. At a dose of 10 mg/kg, spike-wave activity appeared almost uninterruptedly. Beginning with a dose of 5 mg/kg, the morphology of the spike-wave complexes changed after the administration of the drug; spike frequency decreased dose dependently from about 8 till about 4 Hz at 10 mg/kg. During spike-wave activity, animals were motionless and, certainly at 10 mg/kg of etomidate, were unresponsive to stimuli. For surgical anesthesia, a still higher dose of etomidate is necessary (20 mg/kg). It is concluded that etomidate facilitates the generation of spike-wave activity in rats with spontaneous absence seizures, presumably through its GABA-mimetic action.
Department of Medical Physics and Biophysics, University of Nijmegen, The Netherlands.
J
J
Duysens
M
M
Inoue
E L
EL
Van Luijtelaar
R
R
Dirksen
A M
AM
Coenen
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D004832:Epilepsy, Absence / Q000503:physiopathology*; D005045:Etomidate / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains / Q000502:physiology
D006993:Hypnotics and Sedatives; D005045:Etomidate