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Chronic L‐DOPA administration is not toxic to the remaining dopaminergic nigrostriatal neurons, but instead may promote their functional recovery, in rats with partial 6‐OHDA or FeCl 3 nigrostriatal lesions
Author(s) -
Datla Krishna P.,
Blunt Stavia B.,
Dexter David T.
Publication year - 2001
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.1091
Subject(s) - dopaminergic , striatum , nigrostriatal pathway , dopamine , oxidopamine , levodopa , parkinson's disease , tyrosine hydroxylase , lesion , medicine , endocrinology , neuroscience , chemistry , substantia nigra , biology , pathology , disease
In this study, we have examined the effects of chronic L‐3,4‐dihydroxyphenylalanine (L‐DOPA) administration on the remaining dopaminergic neurons in rats with 6‐hydroxydopamine (6‐OHDA) or buffered FeCl 3 partial lesions to the nigrostriatal tract. L‐DOPA administration increased the turnover of dopamine in the striatum. L‐DOPA administration for 1 week produced an increase in the level of striatal RTI‐121 binding, a specific marker for dopamine uptake sites on the dopaminergic nerve terminals in the striatum. However, longer periods of L‐DOPA treatment decreased the level of RTI‐121 binding in the striatum. In the partial 6‐OHDA lesion model, L‐DOPA treatment had a time‐dependent effect on the number of neurons demonstrating a dopaminergic phenotype i.e., neurons that are tyrosine hyrdoxylase (TH)‐immunopositive, on the lesioned side of the brain. In the first few weeks of treatment, L‐DOPA decreased the number of TH‐positive neurons but with long‐term treatment, i.e., 24 weeks, L‐DOPA increased the number of neurons demonstrating a dopaminergic phenotype. Even in the buffered FeCl 3 infusion model, where the levels of iron were increased, L‐DOPA treatment did not have any detrimental effects on the number of TH‐positive neurons on the lesioned side of the brain. Consequently, chronic L‐DOPA treatment does not have any detrimental effects to the remaining dopaminergic neurons in rats with partial lesions to the nigrostriatal tract; indeed in the 6‐OHDA lesion model, long‐term L‐DOPA may increase the number of neurons, demonstrating a dopaminergic phenotype. © 2001 Movement Disorder Society.