N-G-MONOMETHYL-L-ARGININE, AN INHIBITOR OF NITRIC-OXIDE SYNTHASE, INCREASES EXTRACELLULAR GABA IN THE STRIATUM OF THE FREELY MOVING RAT

WE INVESTIGATED the effect of an NO synthase inhibitor, NG-monomethyl- L-arginine (L-NMMA), on the levels of endogenous GABA in the rat stria tum using in vivo microdialysis. Rats were perfused with the artificia l CSF containing L-NMMA (0.1, 0.3 and 1.0 mM) or its inactive isomer D -NMMA (1.0 mM) for 1 h. Infusion of L-NMMA, but not its D-isomer, dose -dependently increased GABA concentration. Co-infusion with tetrodotox in (1 mu M) did not antagonize the increase of GABA induced by L-NMMA. These results show that decreased NO activity enhances GABA release e ven in the absence of depolarization of GABA neurones. We conclude tha t NO may be directly acting on GABA nerve terminals and tonically inhi biting GABA release or synthesis under basal conditions.