Resistance of golden hamster to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: relationship with low levels of regional monoamine oxidase B.
Effects of acute and chronic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were investigated for dopamine (DA) and its metabolites, 3,4-dihydroxyphenylacetic acid and 4-hydroxy-3-methoxyphenylacetic acid, in nucleus caudatus putamen (NCP), limbic system, and substantia nigra (SN) of golden hamster and BALB/c and C57/BL mice to obtain a clue for the variance of MPTP toxicity between the strains and species. Regional differences in the levels of monoamine oxidase (MAO) and the in vitro effects of MAO inhibitors were also determined and correlated with MPTP neurotoxicity. Concentrations of MPTP in the brains of mice and golden hamster at 10 min were comparable. Golden hamster was found to be resistant to the administration of MPTP as indicated by a lack of any alteration from the normal content of DA in NCP, limbic system, and SN. Both strains of mice exhibited > 50% and > 75% depletion of DA (C57/BL and BALB/c, respectively). The metabolites-to-DA ratios were decreased and increased in golden hamster and mouse strains, respectively, after acute or chronic treatment. Whereas the content of total MAO in golden hamster was one-third to one-sixth of any nuclei or mitochondria of both strains of mice, the ratio of MAO A to B was significantly higher in the former species.(ABSTRACT TRUNCATED AT 250 WORDS)
Mitra
N
N
Division of Pharmacology and Experimental Therapeutics, Indian Institute of Chemical Biology, Calcutta.
Mohanakumar
K P
KP
Ganguly
D K
DK
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D006224:Cricetinae; D004298:Dopamine / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism*; D020267:MPTP Poisoning; D008647:Mesocricetus; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008995:Monoamine Oxidase / Q000378:metabolism*; D009928:Organ Specificity; D012044:Regression Analysis; D013045:Species Specificity
D007527:Isoenzymes; D015102:3,4-Dihydroxyphenylacetic Acid; D008995:Monoamine Oxidase; D004298:Dopamine