Effects of L- and D-enantiomers of N omega-nitro-arginine on NMDA-evoked striatal dopamine overflow.

The microdialysis method was utilized to study the effects of N omega-nitro-L-arginine (L-NNA) and N omega-nitro-D-arginine (D-NNA), an inhibitor of nitric oxide (NO) synthesis from L-arginine and its D-enantiomer, on spontaneous and N-methyl-D-aspartate (NMDA)-evoked overflow of striatal extracellular dopamine (DA) in unanesthetized, freely moving rats. Perfusion of 3-10 mM NMDA through the microdialysis probe resulted in a dose-dependent increase in striatal DA overflow. Perfusion of 500 microM L-NNA alone did not change the DA level significantly, but when added to 3 mM NMDA, it substantially suppressed the NMDA-evoked increase of DA. Perfusion of 500 microM D-NNA altered neither the basal nor the NMDA-evoked DA level. Data suggest that the stimulatory effect of NMDA in DA release involves activation of the L-arginine-NO pathway in the striatum.