IN primary cultures of rat cerebral cortex, N-methyl-D-aspartate cause
s widespread neurotoxicity. Inhibitors of the nitric oxide generating
the enzyme nitric oxide synthase has been shown to attenuate the effec
ts of N-methyl-D-aspartate in a number of neuronal systems both in viv
o and in vitro. In our experiments, the nitric oxide synthase inhibito
r N-nitroarginine was ineffective at blocking neurotoxicity induced by
N-methyl-D-aspartate. Cyclic guanine monophosphate, known to be synth
esized in response to nitric oxide was demonstrably inhibited by ident
ical treatments with N-nitroarginine in sister cultures. We conclude t
hat although nitric oxide is produced in response to N-methyl-D-aspart
ate, it is neither necessary nor sufficient for neurotoxicity.