A high dose of MPTP overcomes the protective effect of selegiline against dopaminergic neurotoxicity

Abstract
1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) at 90 mg kg−1 s.c., a dose lethal in non-pretreated mice, was well tolerated in selegiline ((—)-deprenyl)-pretreated mice and produced persistent depletion of striatal dopamine and its metabolites one week after the last of four daily injections. The protective effect of selegiline against dopaminergic neurotoxicity of MPTP can thus be overridden by a high dose of MPTP that would be lethal without selegiline pretreatment.