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

The present study investigated in vivo the kinetic of the changes in rat st riatal extracellular concentrations of dopamine (DA), and its monoamine oxi dase (MAO)-derived metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), follo wing administration either of nitric oxide (NO) synthase (NOS) inhibitors 7 -nitroindazole (7-NI) and N-omega-nitro-1-arginine methyl ester (L-NAME) or of the widely used MAO inhibitor pargyline. DA and DOPAC concentrations we re determined every 4 min by microdialysis combined with capillary zone ele ctrophoresis coupled with laser-induced fluorescence detection (CZE-LIFD) a nd by differential normal pulse voltammetry (DNPV), respectively. Administr ation of 7-NI, both systemic (30 mg/kg, intraperitoneally, i.p.) or intrast riatal (1 mM through the microdialysis probe), as well as administration of pargyline (75 mg/kg, i.p.), induced simultaneously in the striatum a signi ficant increase in extracellular DA and a significant decrease in extracell ular DOPAC, However, administration of L-NAME (200 mg/kg, i.p,) produced a significant increase in striatal extracellular DA without changes in extrac ellular 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 functional role of NO in the brain, pa rticularly in dopaminergic transmission. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.