ROLE OF NITRIC-OXIDE IN MODULATING NEUROTRANSMITTER RELEASE FROM RAT STRIATUM

The effect of the nitric oxide synthase inhibitor N-nitro-L-arginine m ethyl ester (L-NAME) on the basal and stimulation-evoked release of do pamine (DA) and acetylcholine (ACh) was investigated in rat striatum. The experiments were carried out in isolated superfused striatal slice s, loaded with either [H-3]-dopamine or [H-3]-choline. We have found t hat L-NAME reduced the electrical field stimulation-evoked release of DA, while its enantiomer N-nitro-D-arginine methyl ester (D-NAME) was ineffective. In the presence of the nitric oxide (NO) precursor L-argi nine, L-NAME failed to influence DA release. Furthermore, treatment wi th the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 complete ly reversed the effect of L-NAME on striatal DA release. In contrast, L-NAME had no effect on either the basal or the stimulation-evoked ACh release in any experimental conditions studied. Our data indicate tha t endogenously produced NO is involved in the modulation of striatal D A, but not in ACh release. Furthermore, it seems likely that the modul atory effect of NO is linked to activation of presynaptic NMDA recepto rs located on the striatal dopaminergic nerve terminals.