title: Chronic vortioxetine treatment in rodents modulates gene expression of neurodevelopmental and plasticity markers.
abstract: The multimodal antidepressant vortioxetine displays an antidepressant profile distinct from those of conventional selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) and possesses cognitive-enhancing properties in preclinical and clinical studies. Recent studies have begun to investigate molecular mechanisms that may differentiate vortioxetine from other antidepressants. Acute studies in adult rats and chronic studies in a middle-aged mouse model reveal upregulation of several markers that play a central role in synaptic plasticity. However, the effect of chronic vortioxetine treatment on expression of neuroplasticity and neurodevelopmental biomarkers in naïve rats has not been evaluated. In the present study, we demonstrate that vortioxetine at a range of doses regulates expression of genes associated with plasticity in the frontal cortex, hippocampus, region encompassing the amygdala, as well as in blood, and displays similar effects relative to the SSRI fluoxetine in adult naïve rats. These genes encode immediate early genes (IEGs), translational regulators, and the neurodevelopmental marker Sema4g. Similar findings detected in brain regions and in blood provide a potential translational impact, and vortioxetine appears to consistently regulate signaling in these networks of neuroplasticity and developmental markers.
authors.affiliation: External Sourcing and Scientific Excellence, Lundbeck Research USA, Paramus, NJ 07652, USA. Electronic address: wallerjessica14@gmail.com.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Waller
authors.affiliation: In Vitro Biology, Lundbeck Research USA, Paramus, NJ 07652, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Tamm
authors.affiliation: In Vitro Biology, Lundbeck Research USA, Paramus, NJ 07652, USA.
authors.forename: Aicha
authors.initials: A
authors.lastname: Abdourahman
authors.affiliation: External Sourcing and Scientific Excellence, Lundbeck Research USA, Paramus, NJ 07652, USA.
authors.forename: Alan L
authors.initials: AL
authors.lastname: Pehrson
authors.affiliation: External Sourcing and Scientific Excellence, Lundbeck Research USA, Paramus, NJ 07652, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Molecular Pharmacology, Lundbeck Research USA, Paramus, NJ 07652, USA.
authors.forename: Manuel
authors.initials: M
authors.lastname: Cajina
authors.affiliation: External Sourcing and Scientific Excellence, Lundbeck Research USA, Paramus, NJ 07652, USA. Electronic address: connie_sanchez@clin.au.dk.
authors.forename: Connie
authors.initials: C
authors.lastname: Sánchez
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood; D005473:Fluoxetine; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013440:Sulfides / Q000494:pharmacology*; D000078784:Vortioxetine
chemical_list: D000928:Antidepressive Agents; D015415:Biomarkers; D005473:Fluoxetine; D010879:Piperazines; D012333:RNA, Messenger; D017367:Selective Serotonin Reuptake Inhibitors; D013440:Sulfides; D000078784:Vortioxetine
keywords: Immediate early gene; Multimodal; Neurodevelopment; Neuroplasticity; Transcription regulation