Synergistic effect of intrastriatal co-administration of L-NAME and quinolinic acid.

Chronic dialytic intrastriatal co-administration of quinolinic acid (QUIN) and four concentrations of the nitric oxide synthase (NOS) inhibitor NG nitro-L-arginine methyl ester (L-NAME) produced variable results. Low concentrations of L-NAME (1 microM and 50 microM) co-administered with 15 mM QUIN produced lesions not significantly different from those produced by 15 mM QUIN alone. In contrast, higher concentrations of L-NAME (1 mM and 100 mM) co-administered with 15 mM QUIN produced striatal lesions significantly larger than those produced by 15 mM QUIN alone. Administered by itself, 100 mM L-NAME produced little striatal damage. These findings suggest that low levels of NOS inhibition have little or no effect on NMDA neurotoxicity in the striatum, whereas high levels of NOS inhibition increase NMDA-induced striatal lesion volume.