Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/132548
COMPARTIR / EXPORTAR:
logo share SHARE logo core CORE BASE
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE

Invitar a revisión por pares abierta
Título

Involvement of 5-HT3 receptors in the action of vortioxetine in rat brain: focus on glutamatergic and GABAergic neurotransmission

AutorRiga, Maurizio CSIC ORCID; Sánchez, Connie; Celada, Pau CSIC ORCID; Artigas, Francesc CSIC ORCID
Palabras clave5-HT3 receptors
Medial prefrontal cortex
Pyramidal neurons
Serotonin transporter
Ventral hippocampus
Serotonin release
Fecha de publicación20-abr-2016
EditorElsevier
CitaciónNeuropharmacology 108:73-81 (2016)
ResumenThe antidepressant vortioxetine is a 5-HT3-R, 5-HT7-R and 5-HT1D-R antagonist, 5-HT1B-R partial agonist, 5-HT1A-R agonist, and serotonin (5-HT) transporter (SERT) inhibitor. Vortioxetine occupies all targets at high therapeutic doses and only SERT and 5-HT3-R at low doses. Vortioxetine increases extracellular monoamine concentrations in rat forebrain more than selective serotonin reuptake inhibitors (SSRI) and shows pro-cognitive activity in preclinical models. Given its high affinity for 5-HT3-R (Ki = 3.7 nM), selectively expressed in GABA interneurons, we hypothesized that vortioxetine may disinhibit glutamatergic and monoaminergic neurotransmission following 5-HT3-R blockade. Here we assessed vortioxetine effect on pyramidal neuron activity and extracellular 5-HT concentration using in vivo extracellular recordings of rat medial prefrontal cortex (mPFC) pyramidal neurons and microdialysis in mPFC and ventral hippocampus (vHPC). Vortioxetine, but not escitalopram, increased pyramidal neuron discharge in mPFC. This effect was prevented by SR57227A (5-HT3-R agonist) and was mimicked by ondansetron (5-HT3-R antagonist) and by escitalopram/ondansetron combinations. In microdialysis experiments, ondansetron augmented the 5-HT-enhancing effect of escitalopram in mPFC and vHPC. Local ondansetron in vHPC augmented escitalopram effect, indicating the participation of intrinsic mechanisms. Since 5-HT neurons express GABAB receptors, we examined their putative involvement in controlling 5-HT release after 5-HT3-R blockade. Co-perfusion of baclofen (but not muscimol) reversed the increased 5-HT levels produced by vortioxetine and escitalopram/ondansetron combinations in vHPC. The present results suggest that vortioxetine increases glutamatergic and serotonergic neurotransmission in rat forebrain by blocking 5-HT3 receptors in GABA interneurons.
Versión del editorhttp://dx.doi.org/10.1016/j.neuropharm.2016.04.023
URIhttp://hdl.handle.net/10261/132548
DOI10.1016/j.neuropharm.2016.04.023
Aparece en las colecciones: (IIBB) Artículos




Ficheros en este ítem:
Fichero Descripción Tamaño Formato
Riga_MS_Sanchez_C_et_al_Neuropharmacol_Postprint.pdf1,06 MBAdobe PDFVista previa
Visualizar/Abrir
Mostrar el registro completo

CORE Recommender

SCOPUSTM   
Citations

58
checked on 28-mar-2024

WEB OF SCIENCETM
Citations

59
checked on 25-feb-2024

Page view(s)

391
checked on 28-mar-2024

Download(s)

332
checked on 28-mar-2024

Google ScholarTM

Check

Altmetric

Altmetric


Este item está licenciado bajo una Licencia Creative Commons Creative Commons