Subchronic vortioxetine treatment –but not escitalopram- enhances pyramidal neuron activity in the rat prefrontal cortex

Vortioxetine (VOR) is a multimodal antidepressant drug. VOR is a 5-HT3-R, 5-HT7-R and 5-HT1D-R antagonist, 5-HT1B-R partial agonist, 5-HT1A-R agonist, and serotonin transporter (SERT) inhibitor. VOR shows pro-cognitive activity in animal models and beneficial effects on cognitive dysfunction in majo...

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Autores: Riga, Maurizio, Teruel-Martí, Vicent, Sánchez, Connie, Celada, Pau, Artigas, Francesc
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2016
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/137580
Acceso en línea:http://hdl.handle.net/10261/137580
Access Level:acceso abierto
Palabra clave:5-hydroxytryptamine (serotonin)
5-HT3 receptors
Antidepressants
Medial prefrontal cortex
pyramidal neurons
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spelling Subchronic vortioxetine treatment –but not escitalopram- enhances pyramidal neuron activity in the rat prefrontal cortexSubchronic vortioxetine enhances cortical activityRiga, MaurizioTeruel-Martí, VicentSánchez, ConnieCelada, PauArtigas, Francesc5-hydroxytryptamine (serotonin)5-HT3 receptorsAntidepressantsMedial prefrontal cortexpyramidal neuronsVortioxetine (VOR) is a multimodal antidepressant drug. VOR is a 5-HT3-R, 5-HT7-R and 5-HT1D-R antagonist, 5-HT1B-R partial agonist, 5-HT1A-R agonist, and serotonin transporter (SERT) inhibitor. VOR shows pro-cognitive activity in animal models and beneficial effects on cognitive dysfunction in major depressive patients. Here we compared the effects of 14-day treatments with VOR and escitalopram (ESC, selective serotonin reuptake inhibitor) on neuronal activity in the medial prefrontal cortex (mPFC). Ten groups of rats (5 standard, 5 depleted of 5-HT with p-chlorophenylalanine-pCPA-, used as model of cognitive impairment) were fed with control food or with two doses of VOR-containing food. Four groups were implanted with minipumps delivering vehicle or ESC 10 mg/kg·day s.c. The two VOR doses enable occupation by VOR of SERT+5-HT3-R and all targets, respectively, and correspond to SERT occupancies in patients treated with 5 and 20 VOR mg/day, respectively. Putative pyramidal neurons (n=985) were recorded extracellularly in the mPFC of anesthetized rats. Sub-chronic VOR administration (but not ESC) significantly increased neuronal discharge in standard and 5-HT-depleted conditions, with a greater effect of the low VOR dose in standard rats. VOR increased neuronal discharge in infralimbic (IL) and prelimbic (PrL) cortices. Hence, oral VOR doses evoking SERT occupancies similar to those in treated patients increase mPFC neuronal discharge. The effect in 5-HT-depleted rats cannot be explained by an antagonist action of VOR at 5-HT3-R and suggests a non-canonical interaction of VOR with 5-HT3-R. These effects may underlie the superior pro-cognitive efficacy of VOR compared with SSRIs in animal modelsSupported by Lundbeck A/S and grants: SAF2015-68346-P (Spanish Ministry of Economy and Competitiveness, co-financed by European Regional Development Fund (ERDF)) and PI12/00156 (Instituto de Salud Carlos III, co-financed by European Regional Development Fund (ERDF)). Support from the Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) and Generalitat de Catalunya Grup de Recerca Consolidat, 2014SGR798 is also acknowledgedPeer reviewedElsevierMinisterio de Economía y Competitividad (España)European CommissionInstituto de Salud Carlos IIICentro de Investigación Biomédica en Red Salud Mental (España)Generalitat de CatalunyaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]201620162016info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/137580reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2015-68346-Phttp://dx.doi.org/10.1016/j.neuropharm.2016.09.024Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1375802026-05-22T06:33:51Z
dc.title.none.fl_str_mv Subchronic vortioxetine treatment –but not escitalopram- enhances pyramidal neuron activity in the rat prefrontal cortex
Subchronic vortioxetine enhances cortical activity
title Subchronic vortioxetine treatment –but not escitalopram- enhances pyramidal neuron activity in the rat prefrontal cortex
spellingShingle Subchronic vortioxetine treatment –but not escitalopram- enhances pyramidal neuron activity in the rat prefrontal cortex
Riga, Maurizio
5-hydroxytryptamine (serotonin)
5-HT3 receptors
Antidepressants
Medial prefrontal cortex
pyramidal neurons
title_short Subchronic vortioxetine treatment –but not escitalopram- enhances pyramidal neuron activity in the rat prefrontal cortex
title_full Subchronic vortioxetine treatment –but not escitalopram- enhances pyramidal neuron activity in the rat prefrontal cortex
title_fullStr Subchronic vortioxetine treatment –but not escitalopram- enhances pyramidal neuron activity in the rat prefrontal cortex
title_full_unstemmed Subchronic vortioxetine treatment –but not escitalopram- enhances pyramidal neuron activity in the rat prefrontal cortex
title_sort Subchronic vortioxetine treatment –but not escitalopram- enhances pyramidal neuron activity in the rat prefrontal cortex
dc.creator.none.fl_str_mv Riga, Maurizio
Teruel-Martí, Vicent
Sánchez, Connie
Celada, Pau
Artigas, Francesc
author Riga, Maurizio
author_facet Riga, Maurizio
Teruel-Martí, Vicent
Sánchez, Connie
Celada, Pau
Artigas, Francesc
author_role author
author2 Teruel-Martí, Vicent
Sánchez, Connie
Celada, Pau
Artigas, Francesc
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
European Commission
Instituto de Salud Carlos III
Centro de Investigación Biomédica en Red Salud Mental (España)
Generalitat de Catalunya
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv 5-hydroxytryptamine (serotonin)
5-HT3 receptors
Antidepressants
Medial prefrontal cortex
pyramidal neurons
topic 5-hydroxytryptamine (serotonin)
5-HT3 receptors
Antidepressants
Medial prefrontal cortex
pyramidal neurons
description Vortioxetine (VOR) is a multimodal antidepressant drug. VOR is a 5-HT3-R, 5-HT7-R and 5-HT1D-R antagonist, 5-HT1B-R partial agonist, 5-HT1A-R agonist, and serotonin transporter (SERT) inhibitor. VOR shows pro-cognitive activity in animal models and beneficial effects on cognitive dysfunction in major depressive patients. Here we compared the effects of 14-day treatments with VOR and escitalopram (ESC, selective serotonin reuptake inhibitor) on neuronal activity in the medial prefrontal cortex (mPFC). Ten groups of rats (5 standard, 5 depleted of 5-HT with p-chlorophenylalanine-pCPA-, used as model of cognitive impairment) were fed with control food or with two doses of VOR-containing food. Four groups were implanted with minipumps delivering vehicle or ESC 10 mg/kg·day s.c. The two VOR doses enable occupation by VOR of SERT+5-HT3-R and all targets, respectively, and correspond to SERT occupancies in patients treated with 5 and 20 VOR mg/day, respectively. Putative pyramidal neurons (n=985) were recorded extracellularly in the mPFC of anesthetized rats. Sub-chronic VOR administration (but not ESC) significantly increased neuronal discharge in standard and 5-HT-depleted conditions, with a greater effect of the low VOR dose in standard rats. VOR increased neuronal discharge in infralimbic (IL) and prelimbic (PrL) cortices. Hence, oral VOR doses evoking SERT occupancies similar to those in treated patients increase mPFC neuronal discharge. The effect in 5-HT-depleted rats cannot be explained by an antagonist action of VOR at 5-HT3-R and suggests a non-canonical interaction of VOR with 5-HT3-R. These effects may underlie the superior pro-cognitive efficacy of VOR compared with SSRIs in animal models
publishDate 2016
dc.date.none.fl_str_mv 2016
2016
2016
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/137580
url http://hdl.handle.net/10261/137580
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2015-68346-P
http://dx.doi.org/10.1016/j.neuropharm.2016.09.024
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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