Neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on striatal biopterin in BALB/c mice.

The neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on striatal total biopterin were examined both in rats and mice at different time courses. Results indicate that MPTP caused a significant decrease of total biopterin content in the striatum of mice. This effect occurred as soon as 6 h after a single acute MPTP injection (40 mg/kg). The same phenomenon was not observed in rats. Furthermore, the neurotoxic action of MPTP on striatal biopterin was prevented by pretreatment with the monoamine oxidase inhibitor pargyline at a dose of pargyline having no significant effect on biopterin alone (12 mg/kg). These results confirm previous reports of the selectivity of MPTP in certain species of animals and suggest that MPTP may also impair the biosynthesis of dopamine and possibility other monoamine neurotransmitters through its action upon biopterin. Moreover, the neurotoxicity of MPTP on biopterin is possibly mediated through its oxidative metabolite 1-methyl-4-phenylpyridinium (MPP+).