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 glutamatergic neurotransmission and the regulation of cerebral blood flow in epileptic seizures. This study examines the effect of an inhibitor of NO synthesis, NG-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg), on the extracellular concentration of glutamate during seizures induced by kainic acid (KA; 10 mg/kg), both drugs being administered systemically. L-NAME was injected 40 min before KA. The extracellular glutamate concentration was measured in the hippocampus of awake, spontaneously breathing rats using microdialysis combined with HPLC. The arterial blood gases and glycemia were periodically checked. The arterial blood pressure, the electrocorticogram and the body temperature were continuously monitored. In basal conditions, the systemic injection of L-NAME increased arterial blood pressure but did not significantly change the hippocampal glutamate level. In seizure conditions, the hippocampal glutamate concentration was either slightly increased or not significantly 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 hippocampal glutamate concentration was significantly lower in L-NAME-treated rats than in saline-treated rats. Unlike saline-treated rats, L-NAME-treated rats died during status epilepticus. This study shows that acute systemic injection of L-NAME reduces the extracellular concentration of glutamate in the rat hippocampus during seizures induced by KA.