MPTP PRODUCES DIFFERENTIAL OXIDATIVE STRESS AND ANTIOXIDATIVE RESPONSES IN THE NIGROSTRIATAL AND MESOLIMBIC DOPAMINERGIC PATHWAYS

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is known to produc e a differential toxicity in the nigrostriatal and mesolimbic dopamine rgic pathways with the nigrostriatal pathway being more vulnerable. We , therefore, investigated whether oxidative stress and the antioxidant system play a role in this phenomenon. Balb/c mice were treated with either saline or MPTP (30 mg/kg/d) for 7 d, and were sacrificed on the next day. Results revealed that MPTP increased lipid peroxidation in the striatum (ST) and decreased glutathione concentration in the subst antia nigra (SN) without markedly affecting these measures in the nucl eus accumbens (NAc) and ventral tegmental area (VTA). Further, MPTP pr oduced approximately twofold increases in both manganese superoxide di smutase (MnSOD) and copper-zinc superoxide dismutase (CuZnSOD) activit ies in the VTA while it only increased MnSOD activity in the SN. Both catalase and glutathione peroxidase (GPx) activities were not markedly altered by MPTP in both systems. However, the basal levels of catalas e and GPx activities were higher in the VTA and NAc than in the SN and ST. These results together suggest that a lesser degree of oxidative damage and a more inducible CuZnSOD activity observed in the mesolimbi c dopaminergic pathway may partially explain the differential toxicity MPTP produced in these two dopaminergic systems. (C) 1997 Elsevier Sc ience Inc.