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 striatal glutamate induced by local infusion of N-methyl-D-aspartate (NMDA) was investigated using microdialysis in freely moving rats. At concentrations of 0.1, 0.25, 0.5 or 1 mM NMDA induced concentration-dependent increases in striatal glutamate release. This effect of NMDA (0.5 mM) was significantly inhibited by tetrodotoxin (10 mu M), by striatal perfusion with Ca2+-free medium containing EGTA (5 mM), or by the putative 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 methyl ester (L-NAME) or N-G-monomethyl-L-arginine (L-NMMA) (both at concentrations 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 NOS inhibition was stereospecific, inasmuch as N-G-nitro-D-arginine methyl ester (D-NAME) (0.5 or 1 mM) failed to affect NMDA-induced glutamate release. These findings suggest that increased NO production following NMDA receptor activation mediates the increase in release of neurotransmitter glutamate triggered by activation of striatal NMDA receptors. (C) 1997 Elsevier Science Ireland Ltd.