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Full-Text Articles in Social and Behavioral Sciences
Neuroplasticity Pathways And Protein-Interaction Networks Are Modulated By Vortioxetine In Rodents, Jessica A. Waller, Sara Holm Nygaard, Yan Li, Kristian Gaarn Jardin, Joseph A. Tamm, Aicha Abdourahman, Betina Elfving, Alan Pehrson, Connie Sánchez, Rasmus Wernersson
Neuroplasticity Pathways And Protein-Interaction Networks Are Modulated By Vortioxetine In Rodents, Jessica A. Waller, Sara Holm Nygaard, Yan Li, Kristian Gaarn Jardin, Joseph A. Tamm, Aicha Abdourahman, Betina Elfving, Alan Pehrson, Connie Sánchez, Rasmus Wernersson
Department of Psychology Faculty Scholarship and Creative Works
Background: The identification of biomarkers that predict susceptibility to major depressive disorder and treatment response to antidepressants is a major challenge. Vortioxetine is a novel multimodal antidepressant that possesses pro-cognitive properties and differentiates from other conventional antidepressants on various cognitive and plasticity measures. The aim of the present study was to identify biological systems rather than single biomarkers that may underlie vortioxetine's treatment effects. Results: We show that the biological systems regulated by vortioxetine are overlapping between mouse and rat in response to distinct treatment regimens and in different brain regions. Furthermore, analysis of complexes of physically-interacting proteins reveal that …
A Study Of Time- And Sex-Dependent Effects Of Vortioxetine On Rat Sexual Behavior: Possible Roles Of Direct Receptor Modulation, Yan Li, Alan Pehrson, Ronald S. Oosting, Maria Gulinello, Berend Olivier, Connie Sanchez
A Study Of Time- And Sex-Dependent Effects Of Vortioxetine On Rat Sexual Behavior: Possible Roles Of Direct Receptor Modulation, Yan Li, Alan Pehrson, Ronald S. Oosting, Maria Gulinello, Berend Olivier, Connie Sanchez
Department of Psychology Faculty Scholarship and Creative Works
Treatment-related sexual dysfunction is a common side effect of antidepressants and contributes to patient non-compliance or treatment cessation. However, the multimodal antidepressant, vortioxetine, demonstrates low sexual side effects in depressed patients. To investigate the mechanisms involved, sexual behavior was assessed in male and female rats after acute, and repeated (7 and 14 days) treatment with vortioxetine, flesinoxan (a 5-HT1A agonist), CP-94253 (a 5-HT1B agonist), or ondansetron (a 5-HT3 antagonist). These selective ligands were chosen to simulate vortioxetine's direct modulation of these receptors. Paroxetine was also included in the male study. Acute and repeated treatment with vortioxetine at doses corresponding to …
Serotonin Transporter-Independent Actions Of The Antidepressant Vortioxetine As Revealed Using The Sert Met172 Mouse, Alex G. Nackenoff, Linda D. Simmler, Nicole L. Baganz, Alan Pehrson, Connie Sánchez, Randy D. Blakely
Serotonin Transporter-Independent Actions Of The Antidepressant Vortioxetine As Revealed Using The Sert Met172 Mouse, Alex G. Nackenoff, Linda D. Simmler, Nicole L. Baganz, Alan Pehrson, Connie Sánchez, Randy D. Blakely
Department of Psychology Faculty Scholarship and Creative Works
Selective serotonin (5-HT, SERT) reuptake inhibitors (SSRIs) are the most commonly prescribed treatments for depression. However, they have delayed efficacy and can induce side-effects that can encourage discontinuation. Recently, agents have been developed, including vortioxetine (Trintellix), that augment SERT blockade with interactions at other targets. At therapeutic doses, vortioxetine interacts with SERT as well as 5-HT1A, 5-HT1B, 5-HT3, and 5-HT7 receptors. We assessed the SERT-dependency of vortioxetine action using the SERT Met172 mouse model, which disrupts high-affinity interactions of many antidepressants with the transporter. We demonstrate that the SERT Met172 substitution induces an ∼19-fold loss in vortioxetine potency for SERT …
In Vivo And In Vitro Effects Of Vortioxetine On Molecules Associated With Neuroplasticity, Pirathiv Kugathasan, Jessica Waller, Ligia Westrich, Aicha Abdourahman, Joseph A. Tamm, Alan Pehrson, Elena Dale, Maria Gulinello, Connie Sanchez, Yan Li
In Vivo And In Vitro Effects Of Vortioxetine On Molecules Associated With Neuroplasticity, Pirathiv Kugathasan, Jessica Waller, Ligia Westrich, Aicha Abdourahman, Joseph A. Tamm, Alan Pehrson, Elena Dale, Maria Gulinello, Connie Sanchez, Yan Li
Department of Psychology Faculty Scholarship and Creative Works
Neuroplasticity is fundamental for brain functions, abnormal changes of which are associated with mood disorders and cognitive impairment. Neuroplasticity can be affected by neuroactive medications and by aging. Vortioxetine, a multimodal antidepressant, has shown positive effects on cognitive functions in both pre-clinical and clinical studies. In rodent studies, vortioxetine increases glutamate neurotransmission, promotes dendritic branching and spine maturation, and elevates hippocampal expression of the activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) at the transcript level. The present study aims to assess the effects of vortioxetine on several neuroplasticity-related molecules in different experimental systems. Chronic (1 month) vortioxetine increased Arc/Arg3.1 protein levels in the …