Evidence that the neuronal nitric oxide synthase inhibitor 7 -nitroindazole inhibits monoamine oxidase in the rat: in vivo effects on extracellular striatal dopamine and 3,4-dihydroxyphenylacetic acid

Abstract

The present study investigated in vivo the kinetics of the changes in rat striatal extracellular concentrations of dopamine (DA), and its monoamine oxidase (MAO)-derived metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), following administration either of nitric oxide (NO) synthase inhibitors 7-nitroindazole (7-NI) and N ω -nitro- l-arginine methyl ester ( l-NAME) or of the widely used MAO inhibitor pargyline. DA and DOPAC concentrations were determined every 4 min by microdialysis combined with capillary zone electrophoresis coupled with laser-induced fluorescence detection (CZE-LIFD) and by differential normal pulse voltammetry (DNPV), respectively. Administration of 7-NI, both systemic (30 mg/kg, i.p.) or intrastriatal (1 mM through the microdialysis probe), as well as administration of pargyline (75 mg/kg, i.p.), induced simultaneously in the striatum a significant increase in extracellular DA and a significant decrease in extracellular DOPAC. On the other hand, administration of l-NAME (200 mg/kg, i.p.) produced a significant increase in striatal extracellular DA without changes in extracellular DOPAC. These data suggest a possible MAO inhibitory effect of 7-NI which seems to be restricted to this NOS inhibitor. These results may be of special interest for the studies on the functional role of NO in the brain, particularly in dopaminergic transmission.