Antagonism of central but not peripheral cholinergic receptors retards amygdala kindling in rats

The effects of antagonism of muscarinic cholinergic receptors on the development of seizures produced by electrical stimulation of the amygdala (kindling) were assessed in three experiments. Rats pretreated with the muscarinic antagonist scopolamine developed seizures more slowly than did untreated rats. Whereas scopolamine retarded the development of seizures in a dose-dependent manner, it did not affect the intensity or duration of seizures when administered to kindled control rats. Pretreatment with methylscopolamine, a quaternary derivative of scopolamine that does not readily cross the blood-brain barrier, did not affect the rate of development of seizures, nor did it affect established seizures. Thus the prophylactic effects of scopolamine are produced in the central nervous system and not in the periphery. The results from these experiments are consistent with the idea that central cholinergic or cholinoceptive neurons are critically involved in amygdala kindling.