Vortioxetine Reduces Marble Burying but Only Transiently Enhances Social Interaction Preference in Adult Male BTBR T+Itpr3tf/J Mice

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  • Nasriya A. Witt, University of Texas Health Science Center at San Antonio, The University of Texas at San Antonio
  • ,
  • Benita Lee, University of Texas Health Science Center at San Antonio, University of Texas at Austin
  • ,
  • Kaylee Ghent, University of Texas Health Science Center at San Antonio, Trinity University
  • ,
  • Wynne Q. Zhang, University of Texas Health Science Center at San Antonio, Baylor College of Medicine
  • ,
  • Alan L. Pehrson, Monclair State University
  • ,
  • Connie Sánchez
  • Georgianna G. Gould, University of Texas Health Science Center at San Antonio

Vortioxetine is a multimodal antidepressant with agonist activity at serotonin (5-HT) 1A and 5-HT 1B receptors that blocks the 5-HT transporter (SERT). Previously in male BTBR T +Itpr3 tf/J (BTBR) mice, the 5-HT 1A partial agonist buspirone and SERT blocker fluoxetine enhanced social interaction but did not reduce marble burying. We hypothesized that vortioxetine through its actions at SERT and 5-HT 1A could improve BTBR sociability and via 5-HT 1B could reduce burying better than sertraline, a selective SERT blocker. Vortioxetine (5-10 mg/kg) or sertraline (2 mg/kg) was administered 30 min presociability and 75 min prior to marble burying tests. Vortioxetine (10 mg/kg) occupancy (%) was 84 ± 1 for SERT, 31 ± 12 for 5-HT 1A, and 80 ± 5 for 5-HT 1B in brain at 110 min postinjection, and serum oxytocin was 24% lower (p < 0.01) in vortioxetine-treated mice. Vortioxetine reduced novel object investigation, whereas sertraline enhanced overall sociability. However, the vortioxetine-induced increase in social sniffing was transient, as it was lost with 60-120 min presociability test delays in subsequent experiments. Vortioxetine and sertraline both reduced BTBR marble burying. Based on vortioxetine occupancy, actions at SERT and/or 5-HT 1B are more likely to underlie its behavioral effects than 5-HT 1A. Overall, vortioxetine has great potential for suppressing restrictive-repetitive behaviors, but it appears less promising as a sociability enhancer.

Original languageEnglish
JournalACS Chemical Neuroscience
Volume10
Issue10
Pages (from-to)4319-4327
Number of pages9
ISSN1948-7193
DOIs
Publication statusPublished - Oct 2019

    Research areas

  • Autism, Lu AA21004, multimodal antidepressant, repetitive burying, serotonin, social, SEROTONIN TRANSPORTER, 5-HT1A RECEPTORS, AUTISM SPECTRUM DISORDERS, PERVASIVE DEVELOPMENTAL DISORDERS, REPETITIVE BEHAVIORS, MULTIMODAL ANTIDEPRESSANT, MOUSE MODEL, ANTIDEPRESSANT VORTIOXETINE, OXYTOCIN, LU AA21004

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