The locus coeruleus Is Directly Implicated in L-DOPA-Induced Dyskinesia in Parkinsonian Rats: An Electrophysiological and Behavioural Study

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 noradrenerg...

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Autores: Miguélez Palomo, Cristina, Aristieta Arbelaiz, Asier, Cenci, María Angela, Ugedo Urruela, Luisa
Tipo de recurso: artículo
Fecha de publicación:2011
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/11595
Acceso en línea:http://hdl.handle.net/10810/11595
Access Level:acceso abierto
Palabra clave:abnormal involuntary movements
nigra pars reticulata
adrenoceptor antagonist idazoxan
coeruleus noradrenergic neurons
levdopa induced dyskineia
lesioned primate model
substantia nigra
dopaminergic neurons
subthalamic nucleus
in vivo
AGRICULTURAL AND BIOLOGICAL SCIENCES
MEDICINE
BIOCHEMISTRY AND MOLECULAR BIOLOGY
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spelling The locus coeruleus Is Directly Implicated in L-DOPA-Induced Dyskinesia in Parkinsonian Rats: An Electrophysiological and Behavioural StudyMiguélez Palomo, CristinaAristieta Arbelaiz, AsierCenci, María AngelaUgedo Urruela, Luisaabnormal involuntary movementsnigra pars reticulataadrenoceptor antagonist idazoxancoeruleus noradrenergic neuronslevdopa induced dyskineialesioned primate modelsubstantia nigradopaminergic neuronssubthalamic nucleusin vivoAGRICULTURAL AND BIOLOGICAL SCIENCESMEDICINEBIOCHEMISTRY AND MOLECULAR BIOLOGYDespite 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.This study was supported by the Ministry of Science and Technology (SAF 2009-08664) and the Basque Government (SAIOTEK SA 2010/00033 and GIC07/143-IT-201-07). CM has a fellowship from the Basque Government and AA a grant from the University of the Basque Country (UPV/EHU)Public Library Science201420142011info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/11595reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoIngléshttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0024679info:eu-repo/semantics/openAccess© 2011 Miguelez et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.oai:addi.ehu.eus:10810/115952026-06-18T09:23:17Z
dc.title.none.fl_str_mv The locus coeruleus Is Directly Implicated in L-DOPA-Induced Dyskinesia in Parkinsonian Rats: An Electrophysiological and Behavioural Study
title The locus coeruleus Is Directly Implicated in L-DOPA-Induced Dyskinesia in Parkinsonian Rats: An Electrophysiological and Behavioural Study
spellingShingle The locus coeruleus Is Directly Implicated in L-DOPA-Induced Dyskinesia in Parkinsonian Rats: An Electrophysiological and Behavioural Study
Miguélez Palomo, Cristina
abnormal involuntary movements
nigra pars reticulata
adrenoceptor antagonist idazoxan
coeruleus noradrenergic neurons
levdopa induced dyskineia
lesioned primate model
substantia nigra
dopaminergic neurons
subthalamic nucleus
in vivo
AGRICULTURAL AND BIOLOGICAL SCIENCES
MEDICINE
BIOCHEMISTRY AND MOLECULAR BIOLOGY
title_short The locus coeruleus Is Directly Implicated in L-DOPA-Induced Dyskinesia in Parkinsonian Rats: An Electrophysiological and Behavioural Study
title_full The locus coeruleus Is Directly Implicated in L-DOPA-Induced Dyskinesia in Parkinsonian Rats: An Electrophysiological and Behavioural Study
title_fullStr The locus coeruleus Is Directly Implicated in L-DOPA-Induced Dyskinesia in Parkinsonian Rats: An Electrophysiological and Behavioural Study
title_full_unstemmed The locus coeruleus Is Directly Implicated in L-DOPA-Induced Dyskinesia in Parkinsonian Rats: An Electrophysiological and Behavioural Study
title_sort The locus coeruleus Is Directly Implicated in L-DOPA-Induced Dyskinesia in Parkinsonian Rats: An Electrophysiological and Behavioural Study
dc.creator.none.fl_str_mv Miguélez Palomo, Cristina
Aristieta Arbelaiz, Asier
Cenci, María Angela
Ugedo Urruela, Luisa
author Miguélez Palomo, Cristina
author_facet Miguélez Palomo, Cristina
Aristieta Arbelaiz, Asier
Cenci, María Angela
Ugedo Urruela, Luisa
author_role author
author2 Aristieta Arbelaiz, Asier
Cenci, María Angela
Ugedo Urruela, Luisa
author2_role author
author
author
dc.subject.none.fl_str_mv abnormal involuntary movements
nigra pars reticulata
adrenoceptor antagonist idazoxan
coeruleus noradrenergic neurons
levdopa induced dyskineia
lesioned primate model
substantia nigra
dopaminergic neurons
subthalamic nucleus
in vivo
AGRICULTURAL AND BIOLOGICAL SCIENCES
MEDICINE
BIOCHEMISTRY AND MOLECULAR BIOLOGY
topic abnormal involuntary movements
nigra pars reticulata
adrenoceptor antagonist idazoxan
coeruleus noradrenergic neurons
levdopa induced dyskineia
lesioned primate model
substantia nigra
dopaminergic neurons
subthalamic nucleus
in vivo
AGRICULTURAL AND BIOLOGICAL SCIENCES
MEDICINE
BIOCHEMISTRY AND MOLECULAR BIOLOGY
description 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.
publishDate 2011
dc.date.none.fl_str_mv 2011
2014
2014
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10810/11595
url http://hdl.handle.net/10810/11595
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0024679
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Public Library Science
publisher.none.fl_str_mv Public Library Science
dc.source.none.fl_str_mv reponame:Addi. Archivo Digital para la Docencia y la Investigación
instname:Universidad del País Vasco
instname_str Universidad del País Vasco
reponame_str Addi. Archivo Digital para la Docencia y la Investigación
collection Addi. Archivo Digital para la Docencia y la Investigación
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300719

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