NMDA-MEDIATED TOXICITY TO STRIATAL NEURONS IS NOT REVERSED BY 7-NITROINDAZOLE, AN INHIBITOR OF NEURONAL NITRIC-OXIDE SYNTHASE

L-glutamate itself and compounds activating glutamate receptor subtype s such as N-methyl-D-aspartate (NMDA) can produce excitotoxic lesions similar to neuronal cell damage following ischemia, traumatic brain in jury or as seen in human neurodegenerative disorders. Competitive and non-competitive NMDA-receptor antagonists have neuroprotective propert ies in a number of in-vitro and in-vivo models for these disorders. Th e discovery of nitric oxide (NO) in the central nervous system (CNS) a nd the demonstration of the link between glutamate receptor activation and NO formation led to the hypothesis that NMDA toxicity may be medi ated by NO because of its ability to promote free radical generation. Three isoforms of nitric oxide synthase (NOS) have been described, one of which is expressed constitutively in neuronal tissues (nNOS) and i s perferentially inhibited by 7-nitroindazole (7-NI). One day after in trastriatal injection of NMDA, systemic pretreatment of rats with 7-NI had no effect on lesion volumes. It is concluded that formation of NO subsequent to NMDA receptor stimulation is not critically involved in excitotoxicity seen in this model.