Nitric oxide synthase inhibitor facilitates focal seizures induced by aminopyridine in rat

The effects of N-nitro-L-arginine (NA), a nitric oxide (NO) synthase inhibitor, were investigated on the focal ictal-like seizure induced by 3-aminopyridine in rat neocortex in vivo. Intraperitoneal and intracerebroventricular (i.c.v.) injections of NA markedly facilitated propagation of epileptiform events. In addition, NA injected i.c.v. increased the number/hour of individual ictal periods while decreasing their duration. In the presence of NA and an N-methyl-D-aspartate (NMDA) receptor antagonist D(-)2-amino-5-phosphonovaleric acid (APV) the number of ictal periods increased while their duration synergically decreased. APV by itself did not change the number of ictal episodes but decreased their duration. Our results suggest that NO inhibits the induction and propagation of seizure activity. We cannot distinguish the proportion of neuronal and/or vascular MO involved in our experimental conditions, but these effects seem to be independent of the NMDA receptors.