Nitric oxide synthesis, epileptic seizures and kindling.
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.
Herberg
L J
LJ
Institute of Neurology, London, UK.
Grottick
A
A
Rose
I C
IC
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D004827:Epilepsy; D007696:Kindling, Neurologic; D007700:Kinetics; D017774:Long-Term Potentiation; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures
D009569:Nitric Oxide; D001120:Arginine