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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.00804

Chronic fluoxetine treatment induces maturation-compatible changes in the dendritic arbor and in synaptic responses in the auditory cortex.

  • 1Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Chile
  • 2SCIAN-Lab, CIMT, Biomedical Neuroscience Institute (BNI), Institute of Biomedical Sciences, University of Chile, Chile
  • 3National Center for Health Information Systems (CENS), Chile
  • 4University of the Andes, Chile, Chile
  • 5Institute of Biomedical Sciences, Faculty of Health Sciences, Autonomous University of Chile, Chile
  • 6Laboratorio de Neurociencias, University of the Andes, Chile, Chile
  • 7Department of Biomedical Sciences, Faculty of Medicine, Catholic University of the North, Chile

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) used to treat mood and anxiety disorders. Chronic treatment with this antidepressant drug is thought to favor functional recovery by promoting structural and molecular changes in several forebrain areas. At the synaptic level, chronic fluoxetine induces an increased size and density of dendritic spines and an increased ratio of GluN2A over GluN2B N-methyl-D-aspartate (NMDA) receptor subunits. The “maturation”-promoting molecular changes observed after chronic fluoxetine should also induce structural remodeling of the neuronal dendritic arbor and changes in the synaptic responses. We treated adult rats with fluoxetine (0.7 mg/kg i.p. for 28 days) and performed a morphometric analysis using Golgi stain in limbic and non limbic cortical areas. Then, we focused especially on the auditory cortex, where we evaluated the dendritic morphology of pyramidal neurons using a 3-dimensional reconstruction of neurons expressing mRFP after in utero electroporation. With both methodologies, a shortening and decreased complexity of the dendritic arbors was observed, which is compatible with an increased GluN2A over GluN2B ratio. Recordings of extracellular excitatory postsynaptic potentials in the auditory cortex revealed an increased synaptic response after fluoxetine and were consistent with an enrichment of GluN2A-containing NMDA receptors. Our results confirm that fluoxetine favors maturation and refinement of extensive cortical networks, including the auditory cortex. The fluoxetine-induced receptor switch may decrease GluN2B-dependent toxicity and thus could be applied in the future to treat neurodegenerative brain disorders characterized by glutamate toxicity and/or by an aberrant network connectivity.

Keywords: Dendritic architecture, Auditory Cortex, Neuronal segmentation, antidepressant, structural plasticity

Received: 09 Feb 2019; Accepted: 21 Jun 2019.

Edited by:

Javier A. Bravo, Pontificia Universidad Católica de Valparaíso, Chile

Reviewed by:

Luigia Trabace, University of Foggia, Italy
Camila González Arancibia, University of Valparaíso, Chile  

Copyright: © 2019 Ampuero, Cerda, Hartel, Rubio, Massa, Cubillos, Abarzua, Sandoval and Wyneken. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
PhD. Estibaliz M. Ampuero, Universidad Autónoma de Chile, Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Santiago, Chile, estibaliz.ampuero@uautonoma.cl
PhD. Ursula Wyneken, University of the Andes, Chile, Laboratorio de Neurociencias, Las Condes, Santiago Metropolitan Region (RM), Chile, uwyneken@uandes.cl