Nigrostriatal Dopaminergic Neurons Remain Undamaged in Rats Given High Doses of l‐DOPA and Carbidopa Chronically

  • Perry T
  • Yong V
  • Ito M
 et al. 
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Rats were fed maximally tolerated doses of L-3,4-Dihydroxyphenylalanine (L-DOPA) and carbidopa daily for 120 days in order to achieve a sustained elevation in brain dopamine levels. Some animals were also given buthionine sulfoximine, a gamma-glutamylcysteine synthetase inhibitor, in an unsuccessful effort to reduce brain glutathione contents. L-DOPA- and carbidopa-treated animals displayed no behavioral changes suggestive of nigrostriatal dopaminergic neuronal loss. When sacrificed 60 days after L-DOPA treatment ended, all rats had normal tyrosine hydroxylase activities and dopamine contents in their striata, and cell counts were normal in the substantia nigra. It therefore seems unlikely that a model of Parkinson's disease, suitable for exploring the etiological importance of glutathione deficiency, can be produced in rats merely by administering the largest tolerable doses of L-DOPA.

Author-supplied keywords

  • Buthionine sulfoximine
  • Carbidopa
  • Glutathione
  • Nigrostriatal dopaminergic neurons
  • Parkinson's disease
  • l‐DOPA

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  • Thomas L. Perry

  • Voon Wee Yong

  • Masatoshi Ito

  • James G. Foulks

  • Richard A. Wall

  • David V. Godin

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