Analysis of S-nitroso-N-acetylpenicillamine effects on dopamine release inthe striatum of freely moving rats: role of endogenous ascorbic acid and oxidative stress

1 We showed previously that interaction between NO and iron(II), both relea sed following decomposition of sodium nitroprusside (SNP), accounted for th e late SNP-induced dopamine (DA) increase in dialysates from the striatum o f freely moving rats. 2 In this study, intrastriatal infusion of the NO-donor S-nitroso-N-acetylp enicillamine (SNAP) (0.2 mM for 180 min) induced a moderate increase in dia lysate DA and decreases in ascorbic acid dialysate concentrations; in contr ast, SNAP 1 mM infusion induced a long-lasting decrease in both DA and asco rbic acid dialysate concentrations. 3-Methoxy-tyramine (3-MT), dihydroxyphe nylacetic acid (DOPAC), homovanillic acid (HVA), and uric acid levels were unaffected. 3 Co-infusion of ferrous sulphate [iron(II), 1 mM for 40 min] with SNAP eit her 1 or 0.2 mM (for 180 min), produced a significant increase in both DA a nd 3-MT dialysate concentrations, but it did not affect decreases in dialys ate ascorbic acid levels. All other dialysate neurochemicals were unaffecte d. 4 Co-infusion of ascorbic acid (0.1 mM) with SNAP (1 mM) for 180 min did no t modify SNAP-induced decreases in dialysate DA levels. In contrast, co-inf usion of uric acid (1 mM) reversed SNAP-induced decreases in dialysate DA, co-infusion of a superoxide dismutase mimetic delayed SNAP-induced DA decre ases For a short period, while co-infusion of the antioxidant N-acetylcyste ine (NAC, 0.1 mM) significantly increased dialysate DA. 5 The results of this study show that SNAP induces concentration-related ch anges in DA dialysate levels. At higher concentrations. SNAP induces non-en zymatic DA oxidation, which is inhibited by uric acid and NAG: ascorbic aci d failed to protect dialysate DA from oxidation, probably owing to its prom oting effect on SNAP decomposition: exogenous iron(II) may react with NO ge nerated from SNAP decomposition, with a consequent increase in dialysate DA and 3-MT, therefore mimicking SNP effects on striatal DA release.