Evidence for a muscarinic inhibitory mechanism in the cerebral cortex

Abstract The development of spontaneous electrical activity and of prolonged epileptiform afterdischarges has been studied in chronically neuronally isolated slabs of cerebral cortex in the suprasylvian gyrus of unanesthetized, unrestrained cats. Sessions of electrical stimulation at twice-weekly intervals prevented the development of both the spontaneous activity and the prolonged epileptiform response. Isolated slabs in animals that were left unstimulated for a period of 1 month exhibited a bursting form of spontaneous activity and responded to electrical stimulation with afterdischarges lasting for up to 5 hours. The ability of cholinergic agents to alter the duration of epileptiform afterdischarges in the chromically isolated slabs was tested. The cholinergic drugs—pilocarpine, arecoline, eserine, and oxotremorine—all significantly decreased the duration of afterdischarge. The antimuscarinic drugs atropine and scopolamine antagonized the anticonvulsant effects of the muscarinic agents. Methylatropine, in doses which blocked all the visible peripheral effects of the muscarinic drugs, neither altered the duration of afterdischarge nor antagonized the central effects of the muscarinic drugs. Nicotine and the antinicotinic agents mecamylamine and dihydrobeta-erythroidine, had no effect on duration of afterdischarge. It is proposed that the common basis for convulsive activity in the cerebral cortex is a defect in some as yet undefined pathway which includes a muscarinic inhibitory site.