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Dopaminergic Neurotoxicity of 1-Methyl-4-Phenyl-1,2,5,6-Tetrahydropyridine in Mice

Heikkila, Richard E., Hess, Arthur, Duvoisin, Roger C.·1984·Science

Abstract

1-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) is known to cause an irreversible destruction of the dopaminergic nigrostriatal pathway and symptoms of parkinsonism in humans and in monkeys. However, MPTP has been reported to act only minimally or not at all in several other animal species. When MPTP (30 milligrams per kilogram of body weight) was administered parenterally to mice, a decrease in concentrations of neostriatal dopamine and its metabolites, a decrease in the capacity of neostriatal synaptosomal preparations to accumulate [ 3 H]dopamine, and a disappearance of nerve cells in the zona compacta of the substantia nigra were observed. In contrast, MPTP administration had no effect on neostriatal concentrations of serotonin and its metabolites. MPTP administration thus results in biochemical and histological changes in mice similar to those reported in humans and monkeys and similar to those seen in Parkinson's disease in humans. The mouse should prove to be a useful small animal with which to study the mode of action of MPTP.

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Research works printed but not linked: 7

  1. Burns, R. S., Proceedings of the National Academy of Sciences of the United States of America 80: 4546 (1983).
  2. CHIUEH, C.C., PHARMACOLOGIST 25: 131 (1983).
  3. DAVIS, G.C., CHRONIC PARKINSONISM SECONDARY TO INTRAVENOUS-INJECTION OF MEPERIDINE ANALOGS, PSYCHIATRY RESEARCH 1: 249 (1979). · DOI · Paper page
  4. GERSHANIK, O.S., ASYMMETRIC ACTION OF INTRA-VENTRICULAR MONO-AMINE NEUROTOXINS, BRAIN RESEARCH 174: 345 (1979). · DOI
  5. 10.1126/science.6823561 · DOI · Paper page
  6. MAYER, G.S., SIMULTANEOUS MULTIPLE ELECTRODE LIQUID-CHROMATOGRAPHIC ELECTROCHEMICAL ASSAY FOR CATECHOLAMINES, INDOLEAMINES AND METABOLITES IN BRAIN-TISSUE, JOURNAL OF CHROMATOGRAPHY 255: 533 (1983). · DOI
  7. WARD, C.D., PARKINSONS-DISEASE IN 65 PAIRS OF TWINS AND IN A SET OF QUADRUPLETS, NEUROLOGY 33: 815 (1983). · DOI · Paper page

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Metadata

Authors
Heikkila, R. E., Hess, A., & Duvoisin, R. C.
Venue
Science
Published
1984-06-29
Volume
224
Issue
4656
Pages
1451-1453
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2023211111
Cited by
1,009
References
0
FWCI
54.19
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: Dopaminergic Neurotoxicity of 1-Methyl-4-Phenyl-1,2,5,6-Tetrahydropyridine in Mice. https://app.cochat.ai/papers/10.1126/science.6610213
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Heikkila, R. E., Hess, A., & Duvoisin, R. C. (1984). Dopaminergic Neurotoxicity of 1-Methyl-4-Phenyl-1,2,5,6-Tetrahydropyridine in Mice. Science. https://doi.org/10.1126/science.6610213

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