title: Activation of AMPA Receptors Mediates the Antidepressant Action of Deep Brain Stimulation of the Infralimbic Prefrontal Cortex.
abstract: 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.
authors.affiliation: Department of Neurochemistry and Neuropharmacology, Instituto de Investigaciones Biomédicas de Barcelona, CSIC, IDIBAPS, Barcelona 08036, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Jiménez-Sánchez
authors.affiliation: Department of Neurochemistry and Neuropharmacology, Instituto de Investigaciones Biomédicas de Barcelona, CSIC, IDIBAPS, Barcelona 08036, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Castañé
authors.affiliation: Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain.|Neuropsychopharmacology and Psychobiology Research Group, Department of Psychology, University of Cadiz, Cadiz 11510, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Pérez-Caballero
authors.affiliation: Department of Neurochemistry and Neuropharmacology, Instituto de Investigaciones Biomédicas de Barcelona, CSIC, IDIBAPS, Barcelona 08036, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Grifoll-Escoda
authors.affiliation: Department of Neurochemistry and Neuropharmacology, Instituto de Investigaciones Biomédicas de Barcelona, CSIC, IDIBAPS, Barcelona 08036, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain.|Current address: Experimental 7T MRI Unit, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona 08036, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: López-Gil
authors.affiliation: Department of Neurochemistry and Neuropharmacology, Instituto de Investigaciones Biomédicas de Barcelona, CSIC, IDIBAPS, Barcelona 08036, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain.
authors.forename: Leticia
authors.initials: L
authors.lastname: Campa
authors.affiliation: Department of Neurochemistry and Neuropharmacology, Instituto de Investigaciones Biomédicas de Barcelona, CSIC, IDIBAPS, Barcelona 08036, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Galofré
authors.affiliation: Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain.|Neuropsychopharmacology and Psychobiology Research Group, Department of Psychology, University of Cadiz, Cadiz 11510, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Berrocoso
authors.affiliation: Department of Neurochemistry and Neuropharmacology, Instituto de Investigaciones Biomédicas de Barcelona, CSIC, IDIBAPS, Barcelona 08036, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain.|Current address: Instituto de Biomedicina y Biotecnología de Cantabria, IBBTEC (CSIC, Universidad de Cantabria), Santander 39011, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Adell
mesh_terms: D000818:Animals; D046690:Deep Brain Stimulation / Q000379:methods*; D003866:Depressive Disorder / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D017551:Microdialysis; D009638:Norepinephrine / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000473:pathology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D018091:Receptors, AMPA; D012701:Serotonin; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D004298:Dopamine; D009638:Norepinephrine
keywords: c-Fos; dorsal raphe nucleus; glutamate; microdialysis; serotonin