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dc.contributor.authorLópez-Gil, Xavier
dc.contributor.authorJiménez-Sánchez, Laura
dc.contributor.authorCampa, Leticia
dc.contributor.authorCastro Fernández, María Elena 
dc.contributor.authorFrago, Clara
dc.contributor.authorAdell Calduch, Albert
dc.contributor.otherUniversidad de Cantabriaes_ES
dc.date.accessioned2019-08-01T16:22:12Z
dc.date.available2019-08-01T16:22:12Z
dc.date.issued2019
dc.identifier.issn1948-7193
dc.identifier.urihttp://hdl.handle.net/10902/16651
dc.description.abstractDepression is a chronic and debilitating illness that interferes severely with many human behaviors, and is the leading cause of disability in the world. There is data suggesting that deficits in serotonin neurotransmission can contribute to the development of depression. Indeed, >90% of prescribed antidepressant drugs act by increasing serotonergic transmission at the synapse. However, this increase is offset by a negative feedback operating at the level of the cell body of the serotonin neurons in the raphe nuclei. In the present work, we demonstrate: first, the intracortical infusion of ketamine induced an antidepressant-like effect in the forced swim test, comparable to that produced by systemic ketamine; second, systemic and intracortical ketamine increased serotonin and noradrenaline efflux in the prefrontal cortex, but not in the dorsal raphe nucleus; third, systemic and intracortical administration of ketamine increased the efflux of glutamate in the prefrontal cortex and dorsal raphe nucleus; fourth, systemic ketamine did not alter the functionality of 5-HT1A receptors in the dorsal raphe nucleus. Taken together, these findings suggest that the antidepressant-like effects of ketamine are caused by the stimulation of the prefrontal projection to the dorsal raphe nucleus and locus coeruleus caused by an elevated glutamate in the medial prefrontal cortex, which would stimulate release of serotonin and noradrenaline in the same area. The impact of both monoamines in the antidepressant response to ketamine seems to have different time frames.es_ES
dc.description.sponsorshipFunding: This work was supported by the Instituto de Salud Carlos III, Subdirección General del Evaluación y Fomento de la Investigación (FIS Grants PI13-00038 and PI16-00217) that were cofunded by the European Regional Development Fund (“A way to build Europe”). Funding from the Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) is also acknowledged. We also acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).es_ES
dc.format.extent9 p.es_ES
dc.language.isoenges_ES
dc.publisherAmerican Chemical Societyes_ES
dc.rights© ACS under an ACS AuthorChoice Licensees_ES
dc.sourceACS Chem Neurosci. 2019 Jul 17;10(7):3318-3326es_ES
dc.subject.otherDepressiones_ES
dc.subject.otherRaphees_ES
dc.subject.otherSerotonines_ES
dc.subject.otherNoradrenalinees_ES
dc.subject.otherGlutamatees_ES
dc.titleRole of Serotonin and Noradrenaline in the Rapid Antidepressant Action of Ketaminees_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.relation.publisherVersionhttps://www.doi.org/10.1021/acschemneuro.9b00288es_ES
dc.rights.accessRightsopenAccesses_ES
dc.identifier.DOI10.1021/acschemneuro.9b00288
dc.type.versionpublishedVersiones_ES


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