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 kinetics of the changes in rat s triatal extracellular concentrations of dopamine (DA), and its monoamine ox idase (MAO)-derived metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), foll owing administration either of nitric oxide (NO) synthase inhibitors 7-nitr oindazole (7-NI) and N-omega-nitro-L-arginine methyl ester (L-NAME) or of t he widely used MAO inhibitor pargyline. DA and DOPAC concentrations were de termined every 4 min by microdialysis combined with capillary zone electrop horesis 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 extra cellular DA and a significant decrease in extracellular DOPAC. On the other hand, administration of L-NAME (200 mg/kg, i.p.) produced a significant in crease 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 inter est for the studies on the functional role of NO in the brain, particularly in dopaminergic transmission. (C) 1999 Elsevier Science ireland Ltd. All r ights reserved.