THE ROLE OF NITRIC-OXIDE IN MODULATING BRAIN ACTIVITY AND BLOOD-FLOW DURING SEIZURE

THE role played by nitric oxide (NO) in modulating seizure activity and cerebral blood flow (CBF) during seizures was investigated in rats. Seizures were induced with bicuculline (a GABA antagonist, 1.2 mg kg(-1), i.v.). Each animal was subjected to an initial bicuculline-induced seizure followed by treatment with either L-nitroarginine (L-NA, a NO synthase inhibitor) or its less active enantiomer D-NA as a 50 mg kg(-1) bolus followed by an infusion of 1 mg kg(-1) min(-1). The animals then received a second bicuculline treatment. Seizure duration was monitored using EEG and CBF was measured with laser-Doppler. There was no difference in seizure duration before or after D-NA administration. Seizure duration doubled from (6 +/- 1 to 12 +/- 2 min p < 0.05) following inhibition of NO synthase with L-NA. The increase in CBF that accompanied the seizure activity paralleled the seizure duration. Our data support the concept that (1) NO acts as an endogenous anticonvulsant, with seizure duration doubling when NO synthase is acutely inhibited, and (2) that NO is not the messenger that couples CBF to metabolism during bicuculline-induced seizures.