EFFECTS OF CHOLINERGIC DRUGS ON GENETIC ABSENCE SEIZURES IN RATS

Wistar rats of a selected strain show spontaneous generalized non-convulsive seizures with bilateral synchronous spike-wave discharges on the cortical electroencephalograph (EEG). The 7 to 9 c/s spike-wave discharges occur predominantly in waking states of inactivity. The effects of cholinergic drugs on the cumulated duration of spike-wave discharges were investigated in this rat model of absence epilepsy. I.p. injections of drugs which potentiate cholinergic neurotransmission, namely the acetyl-cholinesterase inhibitor, physostigmine (0.1-0.5 mg/kg), the muscarinic receptor agonists, oxotremorine (0.25-1 mg/kg) and pilocarpine (0.125-2 mg/kg), and the nicotinic receptor agonist, nicotine (0.062-2 mg/kg), suppressed discharges in a dose-dependent manner and induced an arousal-like cortical EEG. The muscarinic receptor antagonist, scopolamine, increased the spike-wave discharges at doses below 0.05 mg/kg; at higher doses (0.05-1 mg/kg) it decreased discharges and induced a sleep-like EEG. The nicotinic receptor antagonist, mecamylamine (0.5-6 mg/kg), had no effect on spike-wave discharges or the EEG. These results suggest that cholinergic activity accounts for the preferential occurrence of absence seizures in states of reduced arousal.