1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in mice is enhanced by ethanol or acetaldehyde.
Persistent neurochemical changes consistent with parkinsonism have been reported in brains of mice treated with repeated high doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We now report that ethanol or acetaldehyde potentiate MPTP-induced damage to mouse striatum. One hour after the combined treatments (ethanol and MPTP or acetaldehyde and MPTP), the animals exhibited a marked and long-lasting catatonic posture and then returned gradually to apparently normal locomotion. Seven days after MPTP administration, depletion of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in mouse striatum were further potentiated in the group of animals treated with ethanol. This effect was more evident when the treatment was repeated twice and was dose-dependent. Acetaldehyde was more potent than ethanol in enhancing MPTP neurotoxicity. A single exposure to acetaldehyde before and during MPTP treatment produced a very consistent fall of DA, DOPAC and HVA but not serotonin (5HT) or 5-hydroxyindoleacetic acid (5HIAA) in the striatum. This suggests that ethanol effects on MPTP neurotoxicity might be related to acetaldehyde formation.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000079:Acetaldehyde / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004298:Dopamine / Q000378:metabolism; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009498:Neurotoxins; D011725:Pyridines / Q000633:toxicity*; D012701:Serotonin / Q000378:metabolism
D009498:Neurotoxins; D011725:Pyridines; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D000431:Ethanol; D006897:Hydroxyindoleacetic Acid; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000079:Acetaldehyde; D004298:Dopamine; D006719:Homovanillic Acid