Evidence that L-arginine possesses proconvulsant effects mediated through nitric oxide

Increasing evidence suggests a neurotransmitter role for NO in the mammalian CNS. We have now studied the behavioural and electrocortical (ECoG) profile of rats injected into the lateral cerebral ventricle (ICV) with L-arginine (L-arg), the endogenous donor of the guanidino group from which NO physiologically originates. Rats treated with L-arg (up to 300 micrograms) showed behavioural stimulation, ECoG desynchronization with occasional isolated high voltage spikes but not motor seizures. In rats receiving a subconvulsive dose (0.5 microgram) of N-methyl-D-aspartic acid, (NMDA; ICV) the microinjection of L-arg (300 micrograms; 1 min before) resulted in behavioural and ECoG seizures. The latter effects were prevented by co-administrating L-arg with N-nitro-L-arginine (L-NAME), an inhibitor of NO synthesis. In conclusion, L-arg possesses proconvulsant effects probably mediated by an increase in NO synthesis.