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

Abstract

Abstract: 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 γ‐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. Copyright © 1984, Wiley Blackwell. All rights reserved