Effects of atropine, reserpine, 6-hydroxydopamine, and handling on seizure development in the rat

Repeated electrical stimulation in the limbic system causes permanent changes in the susceptibility to epileptiform afterdischarge and motor seizure; the present study examined the involvement of cholinergic and catecholaminergic neural circuits in the mechanism underlying these changes. The cholinergic blocking agent atropine retarded the rate of seizure development without altering the local afterdischarge threshold. Atropine appeared to suppress propagation of epileptiform afterdischarge to other structures within the limbic system. By contrast, attenuation of catecholaminergic activity by intraperitoneal injections of reserpine or intraventricular applications of 6-hydroxydopamine facilitated seizure development, while stress, which elevates catecholaminergic activity, retarded seizure development. These studies suggest that cholinergic circuits in the limbic system play an important role in propagating epileptiform discharge within the limbic system, and raise the possibility that noradrenergic or dopaminergic circuits act in antagonism to these cholinergic “seizure circuits”.