The Effect of 5-HT1A Receptor Agonists on the Entopeduncular Nucleus is Modified in 6-Hydroxydopamine-Lesioned Rats

Background and Purpose l-DOPA prolonged treatment leads to disabling motor complications as dyskinesia that could be decreased by drugs acting on 5-HT1A receptors. Since the internal segment of the globus pallidus, homologous to the entopeduncular nucleus in rodents, seems to be involved in the etio...

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Authors: Vegas Suárez, Sergio, Aristieta Arbelaiz, Asier, Requejo Rodríguez, Catalina, Bengoetxea Odriozola, Harkaitz, Lafuente Sánchez, José Vicente, Miguélez Palomo, Cristina, Ugedo Urruela, Luisa
Format: article
Publication Date:2021
Country:España
Institution:Universidad del País Vasco
Repository:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/51844
Online Access:http://hdl.handle.net/10810/51844
Access Level:Open access
Keyword:8-OH-DPAT
basal ganglia
buspirone
dyskinesia
electrophysiology
Parkinson's disease
5-hyroxytryptamine
serotonin
high-frequency stimulation
deep brain-stimulation
abnormal involuntary movements
dopa-induced dyskinesia
dorsal raphe nucleus
globus-pallidus
nigrostriatal pathway
parkinsons-disease
id ES_dc4be12cecc98c69010bee77a5d55044
oai_identifier_str oai:addi.ehu.eus:10810/51844
network_acronym_str ES
network_name_str España
repository_id_str
spelling The Effect of 5-HT1A Receptor Agonists on the Entopeduncular Nucleus is Modified in 6-Hydroxydopamine-Lesioned RatsVegas Suárez, SergioAristieta Arbelaiz, AsierRequejo Rodríguez, CatalinaBengoetxea Odriozola, HarkaitzLafuente Sánchez, José VicenteMiguélez Palomo, CristinaUgedo Urruela, Luisa8-OH-DPATbasal gangliabuspironedyskinesiaelectrophysiologyParkinson's disease5-hyroxytryptamineserotoninhigh-frequency stimulationdeep brain-stimulationabnormal involuntary movementsdopa-induced dyskinesiadorsal raphe nucleusglobus-pallidusnigrostriatal pathwayparkinsons-diseasebasal gangliaBackground and Purpose l-DOPA prolonged treatment leads to disabling motor complications as dyskinesia that could be decreased by drugs acting on 5-HT1A receptors. Since the internal segment of the globus pallidus, homologous to the entopeduncular nucleus in rodents, seems to be involved in the etiopathology of l-DOPA-induced dyskinesia, we investigated whether the entopeduncular nucleus is modulated by the 5-HT1A receptor partial and full agonists, buspirone, and 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) in control and 6-hydroxydopamine (6-OHDA)-lesioned rats with or without long-term l-DOPA treatment. Experimental Approach Extracellular single-unit electrocorticogram and local field potential recordings under anaesthesia, immunostaining assays and optogenetic manipulation coupled to electrophysiological recordings were performed. Key Results Systemic buspirone reduced the entopeduncular nucleus firing rate in the sham animals and burst activity in the 6-OHDA-lesioned rats (with or without l-DOPA treatment), while local administration reduced entopeduncular nucleus activity in all the groups, regardless of DA integrity. Systemic 8-OH-DPAT also induced inhibitory effects only in the sham animals. Effects triggered by buspirone and 8-OH-DPAT were reversed by the 5-HT1A receptor antagonist, WAY-100635. Neither buspirone nor 8-OH-DPAT modified the low-frequency oscillatory activity in the entopeduncular nucleus or its synchronization with the motor cortex. Buspirone did not alter the response induced by subthalamic nucleus opto-stimulation in the entopeduncular nucleus. Conclusion and Implications Systemic 5-HT1A receptor activation elicits different effects on the electrophysiological properties of the entopeduncular nucleus depending on the integrity of the nigrostriatal pathway and it does not alter the relationship between subthalamic nucleus and entopeduncular nucleus neuron activity.Euskal Herriko Unibertsitatea, Grant/Award Number: GIU19/092; Basque Government, Grant/Award Numbers: PIBA 2019-38, T747-13; Spanish Ministry of Economy and Competitiveness, Grant/Award Number: SAF2016-77758-R AEI/FEDER, UEWiley202120212021info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/51844reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoInglésinfo:eu-repo/grantAgreement/MICINN/SAF2016-77758-R/https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.15437info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/3.0/es/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0)Atribución 3.0 Españaoai:addi.ehu.eus:10810/518442026-06-18T09:23:17Z
dc.title.none.fl_str_mv The Effect of 5-HT1A Receptor Agonists on the Entopeduncular Nucleus is Modified in 6-Hydroxydopamine-Lesioned Rats
title The Effect of 5-HT1A Receptor Agonists on the Entopeduncular Nucleus is Modified in 6-Hydroxydopamine-Lesioned Rats
spellingShingle The Effect of 5-HT1A Receptor Agonists on the Entopeduncular Nucleus is Modified in 6-Hydroxydopamine-Lesioned Rats
Vegas Suárez, Sergio
8-OH-DPAT
basal ganglia
buspirone
dyskinesia
electrophysiology
Parkinson's disease
5-hyroxytryptamine
serotonin
high-frequency stimulation
deep brain-stimulation
abnormal involuntary movements
dopa-induced dyskinesia
dorsal raphe nucleus
globus-pallidus
nigrostriatal pathway
parkinsons-disease
basal ganglia
title_short The Effect of 5-HT1A Receptor Agonists on the Entopeduncular Nucleus is Modified in 6-Hydroxydopamine-Lesioned Rats
title_full The Effect of 5-HT1A Receptor Agonists on the Entopeduncular Nucleus is Modified in 6-Hydroxydopamine-Lesioned Rats
title_fullStr The Effect of 5-HT1A Receptor Agonists on the Entopeduncular Nucleus is Modified in 6-Hydroxydopamine-Lesioned Rats
title_full_unstemmed The Effect of 5-HT1A Receptor Agonists on the Entopeduncular Nucleus is Modified in 6-Hydroxydopamine-Lesioned Rats
title_sort The Effect of 5-HT1A Receptor Agonists on the Entopeduncular Nucleus is Modified in 6-Hydroxydopamine-Lesioned Rats
dc.creator.none.fl_str_mv Vegas Suárez, Sergio
Aristieta Arbelaiz, Asier
Requejo Rodríguez, Catalina
Bengoetxea Odriozola, Harkaitz
Lafuente Sánchez, José Vicente
Miguélez Palomo, Cristina
Ugedo Urruela, Luisa
author Vegas Suárez, Sergio
author_facet Vegas Suárez, Sergio
Aristieta Arbelaiz, Asier
Requejo Rodríguez, Catalina
Bengoetxea Odriozola, Harkaitz
Lafuente Sánchez, José Vicente
Miguélez Palomo, Cristina
Ugedo Urruela, Luisa
author_role author
author2 Aristieta Arbelaiz, Asier
Requejo Rodríguez, Catalina
Bengoetxea Odriozola, Harkaitz
Lafuente Sánchez, José Vicente
Miguélez Palomo, Cristina
Ugedo Urruela, Luisa
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv 8-OH-DPAT
basal ganglia
buspirone
dyskinesia
electrophysiology
Parkinson's disease
5-hyroxytryptamine
serotonin
high-frequency stimulation
deep brain-stimulation
abnormal involuntary movements
dopa-induced dyskinesia
dorsal raphe nucleus
globus-pallidus
nigrostriatal pathway
parkinsons-disease
basal ganglia
topic 8-OH-DPAT
basal ganglia
buspirone
dyskinesia
electrophysiology
Parkinson's disease
5-hyroxytryptamine
serotonin
high-frequency stimulation
deep brain-stimulation
abnormal involuntary movements
dopa-induced dyskinesia
dorsal raphe nucleus
globus-pallidus
nigrostriatal pathway
parkinsons-disease
basal ganglia
description Background and Purpose l-DOPA prolonged treatment leads to disabling motor complications as dyskinesia that could be decreased by drugs acting on 5-HT1A receptors. Since the internal segment of the globus pallidus, homologous to the entopeduncular nucleus in rodents, seems to be involved in the etiopathology of l-DOPA-induced dyskinesia, we investigated whether the entopeduncular nucleus is modulated by the 5-HT1A receptor partial and full agonists, buspirone, and 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) in control and 6-hydroxydopamine (6-OHDA)-lesioned rats with or without long-term l-DOPA treatment. Experimental Approach Extracellular single-unit electrocorticogram and local field potential recordings under anaesthesia, immunostaining assays and optogenetic manipulation coupled to electrophysiological recordings were performed. Key Results Systemic buspirone reduced the entopeduncular nucleus firing rate in the sham animals and burst activity in the 6-OHDA-lesioned rats (with or without l-DOPA treatment), while local administration reduced entopeduncular nucleus activity in all the groups, regardless of DA integrity. Systemic 8-OH-DPAT also induced inhibitory effects only in the sham animals. Effects triggered by buspirone and 8-OH-DPAT were reversed by the 5-HT1A receptor antagonist, WAY-100635. Neither buspirone nor 8-OH-DPAT modified the low-frequency oscillatory activity in the entopeduncular nucleus or its synchronization with the motor cortex. Buspirone did not alter the response induced by subthalamic nucleus opto-stimulation in the entopeduncular nucleus. Conclusion and Implications Systemic 5-HT1A receptor activation elicits different effects on the electrophysiological properties of the entopeduncular nucleus depending on the integrity of the nigrostriatal pathway and it does not alter the relationship between subthalamic nucleus and entopeduncular nucleus neuron activity.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10810/51844
url http://hdl.handle.net/10810/51844
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/MICINN/SAF2016-77758-R/
https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.15437
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/3.0/es/
Atribución 3.0 España
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/3.0/es/
Atribución 3.0 España
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
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 15,198674

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