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Chronic NO synthase inhibition fails to protect hippocampal neurones against NMDA toxicity.

Since nitric oxide (NO) is supposed to mediate excitotoxicity in various brain structures, the effects of two NO synthase inhibitors were studied on rat hippocampal lesions induced by the focal injection of N-methyl-D-aspartate (NMDA). Although both drugs (NG-nitro-L-arginine methyl ester: L-NAME and L-NG-nitroarginine: L-NOARG) were given twice daily for 4 days before NMDA injection, at doses which are known to profoundly inhibit NO synthase activity, no significant decrease of NMDA-induced damage could be observed. These results do not confirm the current hypothesis of a NO involvement in NMDA toxicity at least on hippocampal neurons, in vivo.