A study on the role of nitric oxide and iron in 3‐morpholino‐sydnonimine‐induced increases in dopamine release in the striatum of freely moving rats

1 We showed previously that interaction between NO and iron (II), both released following the decomposition of sodium nitroprusside (SNP), accounted for the late SNP-induced dopamine (DA) increase in dialysates from the striatum of freely moving rats; in addition, we showed that coinfusion of iron (II) with the NO-donor S-nitroso-N-acetylpenicillamine mimicked SNP eAects on striatal DA release. 2 In the present study, intrastriatal co-infusion of iron (II) (given as FeSO4 ,1m M for 40 min) with the NO-donor and potential peroxynitrite generator 3-morpholinosydnonimine (SIN-1) (0.2, 0.5, 1.0 or 5.0 mM for 180 min), potentiated the SIN-1-induced increase in DA concentration in dialysates from the striatum of freely moving rats. Neither alone nor associated with iron (II) did SIN-1 induce changes in dialysate ascorbic acid or uric acid concentrations. 3 Neither co-infusion of a superoxide dismutase mimetic nor uric acid aAected SIN-1-induced increases in dialysate DA concentration. 4 Infusion of the iron chelator deferoxamine (0.2 mM for 180 min) decreased dialysate DA and attenuated SIN-1-induced increases in dialysate DA concentrations. 5 These results suggest that iron plays a key role in SIN-1-induced release of striatal DA and do not support any role for either peroxynitrite or superoxide anion in SIN-1-induced release of striatal DA. British Journal of Pharmacology (2001) 134, 275‐282