title: 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.
abstract: 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.
authors.affiliation: Parkinson's Disease Research Unit, Department of Neuroinflammation, Imperial College School of Medicine at Charing Cross Campus, Fulham Palace Road, London W6 8RF, United Kingdom.
authors.forename: K P
authors.initials: KP
authors.lastname: Datla
authors.forename: S B
authors.initials: SB
authors.lastname: Blunt
authors.forename: D T
authors.initials: DT
authors.lastname: Dexter
mesh_terms: D018663:Adrenergic Agents / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage; D001545:Benserazide / Q000008:administration & dosage; D002712:Chlorides; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005290:Ferric Compounds / Q000494:pharmacology; D007124:Immunoenzyme Techniques; D007980:Levodopa / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism; D009415:Nerve Net; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000633:toxicity*; D016627:Oxidopamine / Q000494:pharmacology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism; D010302:Parkinson Disease, Secondary / Q000139:chemically induced; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
chemical_list: D018663:Adrenergic Agents; D000978:Antiparkinson Agents; D002712:Chlorides; D015259:Dopamine Agents; D005290:Ferric Compounds; D018696:Neuroprotective Agents; D007980:Levodopa; D001545:Benserazide; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; C024555:ferric chloride; D004298:Dopamine