POSSIBLE INVOLVEMENT OF NITRIC-OXIDE IN NMDA-INDUCED GLUTAMATE RELEASE IN THE RAT STRIATUM - AN IN-VIVO MICRODIALYSIS STUDY

The involvement of nitric oxide (NO) production in the release of stri atal glutamate induced by local infusion of N-methyl-D-aspartate (NMDA ) was investigated using microdialysis in freely moving rats. At conce ntrations of 0.1, 0.25, 0.5 or 1 mM NMDA induced concentration-depende nt increases in striatal glutamate release. This effect of NMDA (0.5 m M) was significantly inhibited by tetrodotoxin (10 mu M), by striatal perfusion with Ca2+-free medium containing EGTA (5 mM), or by the puta tive antagonist of intracellular Ca2+, 8-(N,N-diethylamino)octyl-3,4,5 -trimethoxybenzoate (TMB-8) (1, 10 or 100 mu M). Local infusion of the competitive inhibitors of NO synthase (NOS), N-G-nitro-L-arginine met hyl ester (L-NAME) or N-G-monomethyl-L-arginine (L-NMMA) (both at conc entrations 0.1, 0.25, 0.5 or 1 mM) caused the concentration-dependent inhibition of the glutamate response to 0.5 mM NMDA. This effect of NO S inhibition was stereospecific, inasmuch as N-G-nitro-D-arginine meth yl ester (D-NAME) (0.5 or 1 mM) failed to affect NMDA-induced glutamat e release. These findings suggest that increased NO production followi ng NMDA receptor activation mediates the increase in release of neurot ransmitter glutamate triggered by activation of striatal NMDA receptor s. (C) 1997 Elsevier Science Ireland Ltd.