N-METHYL-D-ASPARTATE-INDUCED NITRIC-OXIDE RELEASE - AN IN-VIVO MICRODIALYSIS STUDY

Increasing evidence indicates that nitric oxide acts as an intercellul ar signal transduction molecule in the nervous system. In particular, in vitro studies have demonstrated that nitric oxide is produced in th e cerebellar cortex and is responsible for the increases in cyclic GMP seen in response to glutamate receptor activation. In this study, we have combined the technique of intracerebellar microdialysis with a se nsitive assay for nitric oxide oxidation products nitrate and nitrite, to assess nitric oxide release directly in awake, freely moving anima ls. We have found that infusion of N-methyl-D-aspartate via the microd ialysis probe results in a dose-dependent increase in cerebellar nitri c oxide release. This increase was prevented by prior administration o f an N-methyl-D-aspartate receptor antagonist, or the nitric oxide syn thase inhibitor N-G-nitroarginine. Both these pretreatments also reduc ed the basal extracellular nitrite and nitrate levels, suggesting that there is a tonic glutamate-induced nitric oxide production in the cer ebellum of awake, freely moving animals. These results provide direct evidence for nitric oxide release in response to N-methyl-D-aspartate receptor activation in the adult cerebellar cortex, in vivo. This new approach, coupling microdialysis with the azo dye detection method of Griess, should thus prove useful for the in vivo study of nitric oxide release from various brain regions in response to pharmacological, ph ysiological or behavioral manipulations.