Analysis of S-nitroso-N-acetylpenicillamine effects on dopamine release inthe striatum of freely moving rats: role of endogenous ascorbic acid and oxidative stress
Pa. Serra et al., Analysis of S-nitroso-N-acetylpenicillamine effects on dopamine release inthe striatum of freely moving rats: role of endogenous ascorbic acid and oxidative stress, BR J PHARM, 132(4), 2001, pp. 941-949
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.