title: Vortioxetine promotes early changes in dendritic morphology compared to fluoxetine in rat hippocampus.
abstract: Preclinical studies reveal that the multimodal antidepressant vortioxetine enhances long-term potentiation and dendritic branching compared to a selective serotonin reuptake inhibitor (SSRI). In the present study, we investigated vortioxetine׳s effects on spines and dendritic morphology in rat hippocampus at two time points compared to the SSRI, fluoxetine. Rats were dosed for 1 and 4 weeks with vortioxetine and fluoxetine at doses relevant for antidepressant activity. Dendritic morphology of pyramidal neurons (i.e., dendritic length, dendritic branch, spine number and density, and Sholl analysis) was examined in Golgi-stained sections from hippocampal CA1. After 1 week of treatment, vortioxetine significantly increased spine number (apical and basal dendrites), spine density (only basal), dendritic length (only apical), and dendritic branch number (apical and basal), whereas fluoxetine had no effect. After 4 weeks of treatment, vortioxetine significantly increased all measures of dendritic spine morphology as did fluoxetine except for spine density of basal dendrites. The number of intersections in the apical and basal dendrites was also significantly increased for both treatments after 4 weeks compared to control. In addition, 4 weeks of vortioxetine treatment, but not fluoxetine, promoted a decrease in spine neck length. In conclusion, 1-week vortioxetine treatment induced changes in spine number and density and dendritic morphology, whereas an equivalent dose of fluoxetine had no effects. Decreased spine neck length following 4-week vortioxetine treatment suggests a transition to mature spine morphology. This implies that vortioxetine׳s effects on spine and dendritic morphology are mediated by mechanisms that go beyond serotonin reuptake inhibition.
authors.affiliation: Stereology and Electron Microscopy Laboratory, Centre for Stochastic Geometry and Advanced Bioimaging, Aarhus University Hospital, DK-8000 Aarhus C, Denmark; Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, DK-8240 Risskov, Denmark. Electronic address: fenghua.chen@clin.au.dk.
authors.forename: Fenghua
authors.initials: F
authors.lastname: Chen
authors.affiliation: Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, DK-8240 Risskov, Denmark.
authors.forename: Kristian Gaarn
authors.initials: KG
authors.lastname: du Jardin
authors.affiliation: Sourcing and Scientific Excellence at Lundbeck Research USA, Inc., Paramus, NJ 07652-1431, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Waller
authors.affiliation: Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, DK-8240 Risskov, Denmark; Sourcing and Scientific Excellence at Lundbeck Research USA, Inc., Paramus, NJ 07652-1431, USA.
authors.forename: Connie
authors.initials: C
authors.lastname: Sanchez
authors.affiliation: Stereology and Electron Microscopy Laboratory, Centre for Stochastic Geometry and Advanced Bioimaging, Aarhus University Hospital, DK-8000 Aarhus C, Denmark.
authors.forename: Jens R
authors.initials: JR
authors.lastname: Nyengaard
authors.affiliation: Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, DK-8240 Risskov, Denmark; Centre for Pharmaceutical Excellence, School of Pharmacy, North-West University, Potchefstroom 2520, South Africa.
authors.forename: Gregers
authors.initials: G
authors.lastname: Wegener
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D003712:Dendrites / Q000187:drug effects*; D049229:Dendritic Spines / Q000187:drug effects / Q000648:ultrastructure; D005473:Fluoxetine / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000648:ultrastructure*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016622:Silver Staining; D013440:Sulfides / Q000494:pharmacology*; D013997:Time Factors; D000078784:Vortioxetine
chemical_list: D000928:Antidepressive Agents; D010879:Piperazines; D013440:Sulfides; D005473:Fluoxetine; D000078784:Vortioxetine
keywords: Antidepressant; Dendrite; Length; Number; Spine