ROLE OF IRON AND ASCORBIC ACID IN NO-DONOR-INDUCED RELEASE OF STRIATAL DOPAMINE IN FREELY MOVING RATS

The effects of sodium nitroprusside (SNP), 3-morfolinosydnonimine (SIN-1), or S-nitroso-Nacetylpenicillamine (SNAP), on striatal dopamine release in freely moving rats, were evaluated using microdialysis 1 . When infused (1 mM) for 180 min, both SNP (n=3) and SIN-1 (n=3) increased DA dialysate concentrations (baseline levels 6.73±1.02 and 7.15±1.12 nM, respectively). The SNP-induced DA increase was inhibited by deferoxamine co-infusion, thus suggesting a key role for iron in SNP-induced increases in DA release. SNAP 1 mM 180 min infusion decreased dialysate DA (baseline levels 5.34±0.80 nM, n=3). The decrease was a consequence of SNAP-induced non-enzymatic oxidation of extracellular DA; in fact, the decrease was inhibited by N-acetyl-cysteine or uric acid co-infusion. Both SNP and SNAP greatly decreased dialysate ascorbic acid (AA, baseline values 10.82±2.5 and 8.55±2.62 μM, respectively); on the contrary, SIN-1 did not affect dialysate AA (baseline levels 7.90±0.73 μM). These finding are consistent with the role of endogenous ascorbic acid as an active promoter of both SNAP and SNP degradation in vivo 2 . Co-infusion of iron(II) (given as FeSO4, 1 mM for 40 min) with SIN-1 or SNAP greatly potentiated the increase in dialysate DA. These results suggest that exogenous iron(II) may react with NO generated from SNAP or SIN-1 decomposition, with a consequent increase in dialysate DA, therefore mimicking SNP effects on striatal DA release.