Distinct effects of intranigral L-DOPA infusion in the MPTP rat model of Parkinson's disease.
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 microM) in rats. L-DOPA elicited a 30.5% reduction in dopaminergic neurons, while 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (100 microg microL(-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.
Reksidler
Angela B
AB
Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba, PR, Brasil.
Lima
Marcelo M S
MM
Dombrowski
Patrícia A
PA
Barnabé
Gabriela F
GF
Andersen
Monica L
ML
Tufik
Sergio
S
Vital
Maria A B F
MA
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D002452:Cell Count; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects; D006719:Homovanillic Acid / Q000378:metabolism; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D009068:Movement / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D013378:Substantia Nigra / Q000187:drug effects* / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D000978:Antiparkinson Agents; D009498:Neurotoxins; D015102:3,4-Dihydroxyphenylacetic Acid; D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D006719:Homovanillic Acid