Nigrostriatal Dopaminergic Neurons Remain Undamaged in Rats Given High Doses of l-DOPA and Carbidopa Chronically |
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Authors: | Thomas L Perry Voon Wee Yong Masatoshi Ito James G Foulks Richard A Wall David V Godin Ronald M Clavier† |
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Institution: | Department of Pharmacology and Therapeutics, Faculty of Medicine, The University of British Columbia, Vancouver, B. C.;Clarke Institute of Psychiatry, Toronto, Ontario, Canada |
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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 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. |
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Keywords: | Parkinson's disease Nigrostriatal dopaminergic neurons Glutathione l-DOPA Carbidopa Buthionine sulfoximine |
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