MPTP toxicity in relation to age, dopamine uptake and MAO-B activity in two rodent species.
The effects of single and multidose 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) treatment on mice (NMRI and C-57bl) and rats of different ages have been investigated by using the reduction of striatal dopamine uptake rate as a measure of the neurotoxic effect. The possibility that differences in MAO-B activity or in dopamine (DA) uptake rate might explain differences in MPTP toxicity between species, strains or animals of different age was investigated. Single dose MPTP treatment (45 mg/kg) had no effect on 10 day and 3 week old mice, while there was a significant reduction of DA uptake rate at the age of 12 and 40 weeks (both strains). No neurotoxicity of single dose MPTP treatment was observed in the rats, irrespective of their age. Multidose treatment with MPTP (3 x 20-45 mg/kg) caused a reduction of DA uptake rates both in the mice and in the rats at all dose regimens used. The effect of MPTP increased with increasing doses and was most pronounced in the C-57bl mice. Both DA uptake rate and monoamine oxidase B (MAO-B) activity increased with age. The increase in MAO-B activity was highest between 10 days and 3 weeks both in the mice and in the rats. Rats had higher (MAO-B) activity than the mice, while the two species had about the same DA uptake rates. No obvious correlations were found either between MAO-B activities or DA uptake rates and the neurotoxic effect of MPTP.
Jossan
S S
SS
Department of Pharmacology, University of Uppsala, Sweden.
Sakurai
E
E
Oreland
L
L
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000375:Aging / Q000502:physiology*; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008995:Monoamine Oxidase / Q000378:metabolism*; D011725:Pyridines / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013997:Time Factors
D011725:Pyridines; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D008995:Monoamine Oxidase; D004298:Dopamine