Nitric oxide synthesis, epileptic seizures and kindling

• Published in: Psychopharmacology Vol. 119; no. 1; p. 115
• Main Authors: Herberg, L J, Grottick, A, Rose, I C
• Format: Journal Article
• Language: English
• Published: Germany 01.05.1995
• Subjects: Animals; Arginine - pharmacology; Epilepsy; Kindling, Neurologic; Kinetics; Long-Term Potentiation; Male; Nitric Oxide - metabolism; Rats; Rats, Inbred Strains; Seizures
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/BF02246062

Nitric oxide (NO) has been implicated in synaptic changes underlying long-term potentiation and some forms of learning. It is unclear, however, whether NO contributes to long-term changes associated with the kindling of epileptic seizures. In the present study rats were treated, on the first 6 days of kindling, with L-arginine (L-Arg), the endogenous donor from which NO derives, or with L-nitro-arginine (L-No-Arg), a competitive inhibitor of NO synthesis, or with vehicle. Drugs were given in doses previously shown to affect learning or other behaviour. L-Arg (750 mg/kg IP) did not affect kindling or seizure severity. L-No-Arg (100 mg/kg) prolonged the duration of afterdischarges and convulsions on treatment days but did not advance kindling or affect seizures on subsequent days. A second experiment examined the possible role of NO in the development of resistance to seizures following prior seizures. Six or more stimuli were administered at 10-min intervals to fully-kindled rats after injection of L-No-Arg or vehicle. Vehicle-treated rats became progressively more resistant to afterdischarges and convulsions with successive stimulations but L-No-Arg-treated rats failed to do so. Rats injected with L-NO-Arg also showed an unexpected high mortality in the ensuing 24 h. L-No-Arg appeared to have no direct effect on the course of kindling but impaired the development of postictal resistance, and increased the duration and lethal after-effects of closely repeated seizures. The results do not support suggestions that antagonists of NO might prove clinically useful as anticonvulsants.