Mt. Silva et al., INCREASED STRIATAL DOPAMINE EFFLUX IN-VIVO FOLLOWING INHIBITION OF CEREBRAL NITRIC-OXIDE SYNTHASE BY THE NOVEL MONOSODIUM SALT OF 7-NITRO INDAZOLE, British Journal of Pharmacology, 114(2), 1995, pp. 257-258
The role of nitric oxide (NO) in striatal dopamine release has been co
ntroversial. Most NO synthase inhibitors affect more than one isoform
of the enzyme and exert vasoconstrictor effects which may also affect
striatal dopamine function. We now report on the effect of a soluble m
onosodium salt of the selective brain NO synthase inhibitor 7-nitro in
dazole (7-NINA). Using 7-NINA the first study of selective inhibition
of the brain isoform of NO synthase on dopamine efflux in rat striatum
was undertaken by use of in vivo microdialysis. Perfusion with 7-NINA
(1 mM) increased striatal dopamine efflux. The effect of 7-NINA was p
artially antagonized (67%) by co-perfusion with L-arginine (1 mM), the
precursor of NO formation in vivo. This suggests that 7-NINA induces
a competitive inhibition of NO synthase activity. These data show that
endogenous NO has an inhibitory effect on striatal dopamine efflux in
vivo.