The neurotoxin MPTP does not affect striatal superoxide dismutase activity in mice

Intraneuronal superoxide generation may be a possible mechanism of the dopaminergic (DA) neurotoxicity of MPTP. In such case, MPTP might theoretically affect superoxide dismutase (SOD) activity. We determined SOD activity and DA levels in striata of mice at 0.5, 1, 4, 16, 24 h or 7 days after an acute single injection of MPTP (40 mg/kg, s.c.). MPTP produced marked striatal DA depletions from 4 h post-treatment but SOD activity remained unaltered and similar to controls at all time points. Intrastriatal injections of purified SOD 15 min prior to systemic administration of MPTP did not attenuate the MPTP-induced striatal DA depletions in mice at 7 days post-treatment. Combined administration of MPTP with the SOD inhibitor diethyldithiocarbamate markedly enhanced striatal DA decreases produced by MPTP alone. Findings suggest that MPTP does not act via inhibition of SOD. Therefore, potentiation of MPTP toxicity by diethyldithiocarbamate may be due to interference with other enzymatic systems.