Glial GLT-1 blockade in infralimbic cortex as a new strategy to evoke rapid antidepressant-like effects in rats

Ketamine and deep brain stimulation produce rapid antidepressant effects in humans and rodents. An increased AMPA receptor (AMPA-R) signaling in medial prefrontal cortex (mPFC) has been suggested to mediate these responses. However, little research has addressed the direct effects of enhancing gluta...

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Autores: Gasull-Camós, Júlia, Tarrés-Gatius, Mireia, Artigas, Francesc, Castañé, Anna
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/177376
Acceso en línea:http://hdl.handle.net/10261/177376
Access Level:acceso abierto
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spelling Glial GLT-1 blockade in infralimbic cortex as a new strategy to evoke rapid antidepressant-like effects in ratsGasull-Camós, JúliaTarrés-Gatius, MireiaArtigas, FrancescCastañé, AnnaKetamine and deep brain stimulation produce rapid antidepressant effects in humans and rodents. An increased AMPA receptor (AMPA-R) signaling in medial prefrontal cortex (mPFC) has been suggested to mediate these responses. However, little research has addressed the direct effects of enhancing glutamate tone or AMPA-R stimulation in mPFC subdivisions. The current study investigates the behavioral and neurochemical consequences of glutamate transporter-1 (GLT-1) blockade or s-AMPA microinfusion in the infralimbic (IL) and prelimbic (PrL) cortex. Owing to the connectivity between the mPFC and raphe nuclei, the role of serotonin is also explored. The bilateral microinfusion of the depolarizing agent veratridine into IL -but not PrL- of rats evoked immediate antidepressant-like responses. The same regional selectivity was observed after microinfusion of dihydrokainic acid (DHK), a selective inhibitor of GLT-1, present in astrocytes. The DHK-evoked antidepressant-like responses appear to be mediated by an AMPA-R-driven enhancement of serotonergic activity, as (i) they were prevented by NBQX 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide disodium salt) and mimicked by s-AMPA; (ii) DHK and s-AMPA elevated similarly extracellular glutamate in IL and PrL, although extracellular 5-HT and c-fos expression in the midbrain dorsal raphe increased only when these agents were applied in IL; and (iii) DHK antidepressant-like responses were prevented by 5-HT synthesis inhibition and mimicked by citalopram microinfusion in IL. These results indicate that an acute increase of glutamatergic neurotransmission selectively in IL triggers immediate antidepressant-like responses in rats, likely mediated by the activation of IL–raphe pathways, which then results in a fast increase of serotonergic activity.This work was supported by the Spanish Ministry of Economy and Competitiveness (grant numbers SAF2012-35183; SAF2015-68346; and BES2013-063241 to JG-C), co-financed by European Regional Development Fund (ERDF); Generalitat de Catalunya (grant number 2014-SGR798 and 2016FI-B00285 to MT-G) and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM).Peer reviewedSpringer NatureMinisterio de Economía y Competitividad (España)European CommissionGeneralitat de CatalunyaCentro de Investigación Biomédica en Red Salud Mental (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]201920192017info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/177376reponame: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/SAF2015-68346https://doi.org/10.1038/tp.2017.7Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1773762026-05-22T06:33:51Z
dc.title.none.fl_str_mv Glial GLT-1 blockade in infralimbic cortex as a new strategy to evoke rapid antidepressant-like effects in rats
title Glial GLT-1 blockade in infralimbic cortex as a new strategy to evoke rapid antidepressant-like effects in rats
spellingShingle Glial GLT-1 blockade in infralimbic cortex as a new strategy to evoke rapid antidepressant-like effects in rats
Gasull-Camós, Júlia
title_short Glial GLT-1 blockade in infralimbic cortex as a new strategy to evoke rapid antidepressant-like effects in rats
title_full Glial GLT-1 blockade in infralimbic cortex as a new strategy to evoke rapid antidepressant-like effects in rats
title_fullStr Glial GLT-1 blockade in infralimbic cortex as a new strategy to evoke rapid antidepressant-like effects in rats
title_full_unstemmed Glial GLT-1 blockade in infralimbic cortex as a new strategy to evoke rapid antidepressant-like effects in rats
title_sort Glial GLT-1 blockade in infralimbic cortex as a new strategy to evoke rapid antidepressant-like effects in rats
dc.creator.none.fl_str_mv Gasull-Camós, Júlia
Tarrés-Gatius, Mireia
Artigas, Francesc
Castañé, Anna
author Gasull-Camós, Júlia
author_facet Gasull-Camós, Júlia
Tarrés-Gatius, Mireia
Artigas, Francesc
Castañé, Anna
author_role author
author2 Tarrés-Gatius, Mireia
Artigas, Francesc
Castañé, Anna
author2_role author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
European Commission
Generalitat de Catalunya
Centro de Investigación Biomédica en Red Salud Mental (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
description Ketamine and deep brain stimulation produce rapid antidepressant effects in humans and rodents. An increased AMPA receptor (AMPA-R) signaling in medial prefrontal cortex (mPFC) has been suggested to mediate these responses. However, little research has addressed the direct effects of enhancing glutamate tone or AMPA-R stimulation in mPFC subdivisions. The current study investigates the behavioral and neurochemical consequences of glutamate transporter-1 (GLT-1) blockade or s-AMPA microinfusion in the infralimbic (IL) and prelimbic (PrL) cortex. Owing to the connectivity between the mPFC and raphe nuclei, the role of serotonin is also explored. The bilateral microinfusion of the depolarizing agent veratridine into IL -but not PrL- of rats evoked immediate antidepressant-like responses. The same regional selectivity was observed after microinfusion of dihydrokainic acid (DHK), a selective inhibitor of GLT-1, present in astrocytes. The DHK-evoked antidepressant-like responses appear to be mediated by an AMPA-R-driven enhancement of serotonergic activity, as (i) they were prevented by NBQX 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide disodium salt) and mimicked by s-AMPA; (ii) DHK and s-AMPA elevated similarly extracellular glutamate in IL and PrL, although extracellular 5-HT and c-fos expression in the midbrain dorsal raphe increased only when these agents were applied in IL; and (iii) DHK antidepressant-like responses were prevented by 5-HT synthesis inhibition and mimicked by citalopram microinfusion in IL. These results indicate that an acute increase of glutamatergic neurotransmission selectively in IL triggers immediate antidepressant-like responses in rats, likely mediated by the activation of IL–raphe pathways, which then results in a fast increase of serotonergic activity.
publishDate 2017
dc.date.none.fl_str_mv 2017
2019
2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/177376
url http://hdl.handle.net/10261/177376
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
https://doi.org/10.1038/tp.2017.7
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
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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