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

Nasriya A. Witt, Benita Lee, Kaylee Ghent, Wynne Q. Zhang, Alan L. Pehrson, Connie Sánchez, Georgianna G. Gould

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Vortioxetine is a multimodal antidepressant with agonist activity at serotonin (5-HT)1A and 5-HT1B receptors that blocks the 5-HT transporter (SERT). Previously in male BTBR T+Itpr3tf/J (BTBR) mice, the 5-HT1A 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-HT1A could improve BTBR sociability and via 5-HT1B 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-HT1A, and 80 ± 5 for 5-HT1B 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-HT1B are more likely to underlie its behavioral effects than 5-HT1A. Overall, vortioxetine has great potential for suppressing restrictive-repetitive behaviors, but it appears less promising as a sociability enhancer.

Original languageEnglish
Pages (from-to)4319-4327
Number of pages9
JournalACS Chemical Neuroscience
Volume10
Issue number10
DOIs
StatePublished - 16 Oct 2019

Keywords

  • Autism
  • Lu AA21004
  • multimodal antidepressant
  • repetitive burying
  • serotonin
  • social

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