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

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Abstract
Rats were fed maximally tolerated odses of (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.