Serotonergic mechanisms involved in antidepressant-like responses evoked by GLT-1 blockade in rat infralimbic cortex

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• dc.contributor.author Gasull-Camós, Júlia
• dc.contributor.author Martínez-Torres, Sara
• dc.contributor.author Tarrés-Gatius, Mireia
• dc.contributor.author Ozaita Mintegui, Andrés, 1969-
• dc.contributor.author Artigas, Francesc
• dc.contributor.author Castañé Forn, Anna
• dc.date.accessioned 2019-03-26T09:37:36Z
• dc.date.issued 2018
• dc.description.abstract Novel fast-acting antidepressant strategies, such as ketamine and deep brain stimulation, enhance glutamatergic neurotransmission in medial prefrontal cortex (mPFC) regions via AMPA receptor (AMPA-R) activation. We recently reported that the regionally-selective blockade of the glial glutamate transporter-1 (GLT-1) by dihydrokainic acid (DHK) microinfusion in rat infralimbic cortex (IL), the most ventral part of the mPFC, evoked immediate (10 min) antidepressant-like responses, which involved AMPA-R activation and were associated to increased serotonin (5-hydroxytryptamine, 5-HT) release. Given the reciprocal connectivity between the mPFC and the serotonergic dorsal raphe nucleus (DR), here we examined the serotoninergic mechanisms involved in the reported antidepressant-like responses of DHK microinfusion. First, we show that antidepressant-like responses evoked by IL application of DHK and citalopram are mediated by local 5-HT1A receptors (5-HT1A-R), since they are cancelled by previous IL WAY100635 microinfusion. Second, IL DHK microinfusion increases excitatory inputs onto DR, as shown by an increased glutamate and 5-HT release in DR and by a selective increase of c-Fos expression in DR 5-HT neurons, not occurring in putative GABAergic neurons. This view is also supported by an increased 5-HT release in ventral hippocampus following IL DHK microinfusion. Interestingly, antidepressant-like responses evoked by IL DHK lasted for 2¿h and could be prolonged for up to 24¿h by attenuating self-inhibitory effects via 5-HT1A autoreceptors. In contrast, the antidepressant-like effects of S-AMPA microinfusion in IL were short-lasting. Together, our results further support a prominent role of the IL-DR pathway and of ascending 5-HT pathways in mediating antidepressant-like responses evoked by glutamatergic mechanisms.
• dc.description.sponsorship This work was supported by the Spanish Ministry of Economy and Competitiveness (SAF2015-68346 and BES2013-063241 to J.G-C; BFU2015-68568-P to A.O.) co-financed by European Regional Development Fund; Generalitat de Catalunya (CERCA Programme; 2014-SGR798, 2016FI-B00285 to M.T-G, 2016 FI-B00531 to S.M-T and ICREA Acadèmia to A.O.); Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM).
• dc.format.mimetype application/pdf
• dc.identifier.citation Gasull-Camós J, Martínez-Torres S, Tarrés-Gatius M, Ozaita A, Artigas F, Castañé A. Serotonergic mechanisms involved in antidepressant-like responses evoked by GLT-1 blockade in rat infralimbic cortex. Neuropharmacology. 2018;139:41-51. DOI: 10.1016/j.neuropharm.2018.06.029
• dc.identifier.doi http://dx.doi.org/10.1016/j.neuropharm.2018.06.029
• dc.identifier.issn 0028-3908
• dc.identifier.uri http://hdl.handle.net/10230/36960
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Neuropharmacology. 2018;139:41-51
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2015-68346
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BES2013-063241
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2015-68568-P
• dc.rights © Elsevier http://dx.doi.org/10.1016/j.neuropharm.2018.06.029
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.keyword Antidepressant effects
• dc.subject.keyword Dihydrokainic acid
• dc.subject.keyword Dorsal raphe
• dc.subject.keyword GLT-1
• dc.subject.keyword Infralimbic cortex
• dc.subject.keyword Serotonin
• dc.title Serotonergic mechanisms involved in antidepressant-like responses evoked by GLT-1 blockade in rat infralimbic cortex
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion