title: The locus coeruleus is directly implicated in L-DOPA-induced dyskinesia in parkinsonian rats: an electrophysiological and behavioural study.
abstract: Despite being the most effective treatment for Parkinson's disease, L-DOPA causes a development of dyskinetic movements in the majority of treated patients. L-DOPA-induced dyskinesia is attributed to a dysregulated dopamine transmission within the basal ganglia, but serotonergic and noradrenergic systems are believed to play an important modulatory role. In this study, we have addressed the role of the locus coeruleus nucleus (LC) in a rat model of L-DOPA-induced dyskinesia. Single-unit extracellular recordings in vivo and behavioural and immunohistochemical approaches were applied in rats rendered dyskinetic by the destruction of the nigrostriatal dopamine neurons followed by chronic treatment with L-DOPA. The results showed that L-DOPA treatment reversed the change induced by 6-hydroxydopamine lesions on LC neuronal activity. The severity of the abnormal involuntary movements induced by L-DOPA correlated with the basal firing parameters of LC neuronal activity. Systemic administration of the LC-selective noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine did not modify axial, limb, and orolingual dyskinesia, whereas chemical destruction of the LC with ibotenic acid significantly increased the abnormal involuntary movement scores. These results are the first to demonstrate altered LC neuronal activity in 6-OHDA lesioned rats treated with L-DOPA, and indicate that an intact noradrenergic system may limit the severity of this movement disorder.
authors.affiliation: Department of Pharmacology, Faculty of Medicine and Dentistry, University of the Basque Country, Vizcaya, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Miguelez
authors.forename: Asier
authors.initials: A
authors.lastname: Aristieta
authors.forename: Maria Angela
authors.initials: MA
authors.lastname: Cenci
authors.forename: Luisa
authors.initials: L
authors.lastname: Ugedo
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D020820:Dyskinesias / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D004594:Electrophysiology; D005260:Female; D007051:Ibotenic Acid / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology*; D008125:Locus Coeruleus / Q000378:metabolism / Q000503:physiopathology*; D020734:Parkinsonian Disorders / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007051:Ibotenic Acid; D007980:Levodopa; D000661:Amphetamine