A sheep model for MPTP induced parkinson-like symptoms

Bruce D. Hammock, Allison M. Beale, Thierry Work, Shirley J. Gee, Robert Gunther, Robert Higgins, Toshihivo Shinka, Neal Castagnoli

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11 Scopus citations

Abstract

Administration of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) causes behaviors reminiscent of idiopathic Parkinson's disease in man and other primates, but development of such symptomology has not been reported to date in other species. We now report a sheep model which responds to administration of low levels of the compound with well defined, apparently permanent symptomology very similar to that seen in primates. Histological examination indicates drug dependent destruction of the substantia nigra which, in sheep, lacks the high levels of neuromelanin present in primates. Following infusion of either MPTP or MPP+, only the metabolite MPP+ was detected in serum with this metabolite demonstrating a very long half life. The rapid disappearance of MPTP suggests that its potency will be directly related to a function of body size and inversely related to heart rate.

Original languageEnglish (US)
Pages (from-to)1601-1608
Number of pages8
JournalLife Sciences
Volume45
Issue number17
DOIs
StatePublished - 1989

ASJC Scopus subject areas

  • Pharmacology

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    Hammock, B. D., Beale, A. M., Work, T., Gee, S. J., Gunther, R., Higgins, R., Shinka, T., & Castagnoli, N. (1989). A sheep model for MPTP induced parkinson-like symptoms. Life Sciences, 45(17), 1601-1608. https://doi.org/10.1016/0024-3205(89)90427-X