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 acetylcholinesterase 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.
Laboratoire de Neurophysiologie et Biologie des Comportements, Centre de Neurochimie du CNRS, Strasbourg, France.
L
L
Danober
A
A
Depaulis
C
C
Marescaux
M
M
Vergnes
D000818:Animals; D018680:Cholinergic Antagonists; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects; D004832:Epilepsy, Absence / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D010275:Parasympathetic Nervous System / Q000187:drug effects; D010277:Parasympathomimetics / Q000494:pharmacology*; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects; D011978:Receptors, Nicotinic / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects
D018680:Cholinergic Antagonists; D010277:Parasympathomimetics; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic