Facilitation of Spike-Wave Activity by the Hypnotic Etomidate in a Rat Model for Absence Epilepsy

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Abstract
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 10mg/kg. At a dose of 10mg/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.