Journal Article

Activation of AMPA Receptors Mediates the Antidepressant Action of Deep Brain Stimulation of the Infralimbic Prefrontal Cortex

Laura Jiménez-Sánchez, Anna Castañé, Laura Pérez-Caballero, Marc Grifoll-Escoda, Xavier López-Gil, Leticia Campa, Mireia Galofré, Esther Berrocoso and Albert Adell

in Cerebral Cortex

Volume 26, issue 6, pages 2778-2789
Published in print June 2016 | ISSN: 1047-3211
Published online June 2015 | e-ISSN: 1460-2199 | DOI: http://dx.doi.org/10.1093/cercor/bhv133
Activation of AMPA Receptors Mediates the Antidepressant Action of Deep Brain Stimulation of the Infralimbic Prefrontal Cortex

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Although deep brain stimulation (DBS) has been used with success in treatment-resistant depression, little is known about its mechanism of action. We examined the antidepressant-like activity of short (1 h) DBS applied to the infralimbic prefrontal cortex in the forced swim test (FST) and the novelty-suppressed feeding test (NSFT). We also used in vivo microdialysis to evaluate the release of glutamate, γ-aminobutyric acid, serotonin, dopamine, and noradrenaline in the prefrontal cortex and c-Fos immunohistochemistry to determine the brain regions activated by DBS. One hour of DBS of the infralimbic prefrontal cortex has antidepressant-like effects in FST and NSFT, and increases prefrontal efflux of glutamate, which would activate AMPA receptors (AMPARs). This effect is specific of the infralimbic area since it is not observed after DBS of the prelimbic subregion. The activation of prefrontal AMPARs would result in a stimulation of prefrontal output to the brainstem, thus increasing serotonin, dopamine, and noradrenaline in the prefrontal cortex. Further, the activation of prefrontal AMPARs is necessary and sufficient condition for the antidepressant response of 1 h DBS.

Keywords: c-Fos; dorsal raphe nucleus; glutamate; microdialysis; serotonin

Journal Article.  7727 words.  Illustrated.

Subjects: Neurology ; Clinical Neuroscience ; Neuroscience

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