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.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011725:Pyridines / Q000008:administration & dosage / Q000633:toxicity*; D013045:Species Specificity; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism
D011725:Pyridines; D015102:3,4-Dihydroxyphenylacetic Acid; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine; D006719:Homovanillic Acid