Coordinated and spatial upregulation of arc in striatonigral neurons correlates with L-dopa-induced behavioral sensitization in dyskinetic rats.
Although oral administration of L-Dopa remains the best therapy for Parkinson disease, its long-term administration causes the appearance of abnormal involuntary movements such as dyskinesia. Although persistent striatal induction of some genes has already been associated with such pathologic profiles in hemiparkinsonian rats, molecular and cellular mechanisms underlying such long-term adaptations remain to be elucidated. In this study, using a rat model of L-Dopa-induced dyskinesia, we report that activity regulated cytoskeletal (Arc)-associated protein is strongly upregulated in the lesioned striatum and that the extent of its induction further varies according to the occurrence or absence of locomotor sensitization. Moreover, Arc is preferentially induced, along with FosB, nur77, and homer-1a, in striatonigral neurons, which express mRNA encoding the precursor of dynorphin. Given the likely importance of Arc in the regulation of cytoskeleton during synaptic plasticity, its upregulation supports the hypothesis that a relationship exists between cytoskeletal modifications and the longlasting action of chronically administrated L-Dopa.
Sgambato-Faure
Véronique
V
Inserm U318, Laboratoire de Neurosciences Précliniques, CHU Pavillon B, Grenoble, France. veronique.sgambato@ujf-grenoble.fr
Buggia
Virginie
V
Gilbert
François
F
Lévesque
Daniel
D
Benabid
Alim-Louis
AL
Berger
François
F
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000386:AIDS-Related Complex / Q000235:genetics / Q000378:metabolism*; D018663:Adrenergic Agents / Q000009:adverse effects; D000661:Amphetamine / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001522:Behavior, Animal; D002352:Carrier Proteins / Q000235:genetics; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003342:Corpus Striatum / Q000166:cytology; D004195:Disease Models, Animal; D004347:Drug Interactions; D004399:Dynorphins / Q000235:genetics; D004409:Dyskinesia, Drug-Induced / Q000209:etiology* / Q000378:metabolism; D007839:Functional Laterality; D000072233:Homer Scaffolding Proteins; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D007980:Levodopa / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D016627:Oxidopamine / Q000009:adverse effects; D011498:Protein Precursors / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013239:Stereotyped Behavior / Q000187:drug effects; D013378:Substantia Nigra / Q000166:cytology*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D018663:Adrenergic Agents; D018712:Analgesics, Non-Narcotic; D000978:Antiparkinson Agents; D002352:Carrier Proteins; D000697:Central Nervous System Stimulants; D000072233:Homer Scaffolding Proteins; D009292:Narcotic Antagonists; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; C036448:pre-prodynorphin; D009270:Naloxone; C051844:norbinaltorphimine; D007980:Levodopa; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D004399:Dynorphins; D016627:Oxidopamine; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase