The influence of dose and dosing interval on MPTP-induced dopaminergic neurotoxicity in mice.

The effects of different dosing paradigms for the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were investigated in C57-black and CF-W albino mice. Several groups of mice received a total dose of 80 mg/kg of MPTP administered at different doses per injection and/or at different time intervals. In C57-black mice, the effects of MPTP administration on the neostriatal content of dopamine ranged from a 91% depletion (4 injections of 20 mg/kg per injection at 1 h intervals) to a non-significant effect (4 injections of 10 mg/kg per injection at 2 h intervals on each of 2 successive days). There was also considerable influence of the MPTP dose per injection and the dosing interval in CF-W mice, although the extent of neostriatal dopamine depletion in CF-W mice was not as great as that observed in C57-black mice. In addition, MPTP produced variable effects on neostriatal dopamine levels in different strains of mice as well as in Swiss-Webster mice obtained from different sources. Some of the strains were affected to a great extent while others were only marginally affected.