EFFECT OF INHIBITING NO SYNTHESIS ON HIPPOCAMPAL EXTRACELLULAR GLUTAMATE CONCENTRATION IN SEIZURES INDUCED BY KAINIC ACID

It has been suggested that nitric oxide (NO) interferes with both glut amatergic neurotransmission and the regulation of cerebral blood flow in epileptic seizures. This study examines the effect of an inhibitor of NO synthesis, N-G-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg), on the extracellular concentration of glutamate during seizures induc ed by kainic acid (KA; 10 mg/kg), both drugs being administered system ically. r-NAME was injected 40 min before KA. The extracellular glutam ate concentration was measured in the hippocampus of awake, spontaneou sly breathing rats using microdialysis combined with HPLC. The arteria l blood gases and glycemia were periodically checked. The arterial blo od pressure, the electrocorticogram and the body temperature were cont inuously monitored. In basal conditions, the systemic injection of L-N AME increased arterial blood pressure but did not significantly change the hippocampal glutamate level. In seizure conditions, the hippocamp al glutamate concentration was either slightly increased or not signif icantly changed in saline-treated rats (n = 6) but it was decreased in L-NAME-treated rats (n = 6). At all times after KA injection, the hip pocampal glutamate concentration was significantly lower in L-NAME-tre ated rats than in saline-treated rats. Unlike saline-treated rats, L-N AME-treated rats died during status epilepticus. This study shows that acute systemic injection of L-NAME reduces the extracellular concentr ation of glutamate in the rat hippocampus during seizures induced by K A.