Distinct Effects of Intranigral L-DOPA Infusion in the MPTP Rat Model of Parkinson's Disease
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2009-01-01
Authors
Reksidler, Angela B.
Lima, Marcelo M. S.
Dombrowski, Patricia A.
Barnabe, Gabriela F. [UNIFESP]
Andersen, Monica L. [UNIFESP]
Tufik, Sergio [UNIFESP]
Vital, Maria A. B. F.
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Abstract
The potential neuroprotective or neurotoxic effects of 3,4-dihydroxyphenylalanine (L-DOPA) are yet to be understood. We examined the behavioral, immunohistochemical, tyrosine hydroxylase (TH) expression and neurochemical parameters after an intranigral administration of L-DOPA (10 mu M) in rats.. L-DOPA elicited a 30.5% reduction in dopaminergic neurons, while 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (100 mu g mu L(-1)) produced a 53.6% reduction. A combined infusion of MPTP and L-DOPA generated a 42% reduction of nigral neurons. Motor parameters revealed that both the MPTP and L-DOPA groups presented impairments; however, the concomitant administration evoked a partial restorative effect. in addition, MPTP and L-DOPA separately induced reductions of TH protein expression within the substantia nigra. in contrast, the coadministration of MPTP and L-DOPA did not demonstrate such difference. the striatal levels of dopamine were reduced after MPTP or L-DOPA, with an increased turnover only for the MPTP group. in view of such results, it seems reasonable to suggest that L-DOPA could potentially produce dopaminergic neurotoxicity.
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Journal of Neural Transmission-supplement. New York: Springer, n. 73, p. 259-268, 2009.