Possible involvement of nitric oxide in NMDA-induced glutamate release in the rat striatum: an in vivo microdialysis study

Abstract

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 μM), by striatal perfusion with Ca 2+-free medium containing EGTA (5 mM), or by the putative antagonist of intracellular Ca 2+, 8-( N, N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8) (1, 10 or 100 μM). 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.