Distinct Effects of Intranigral L-DOPA Infusion in the MPTP Rat Model of Parkinson's Disease

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.