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

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Vortioxetine Reduces Marble Burying but Only Transiently Enhances Social Interaction Preference in Adult Male BTBR T+Itpr3tf/J Mice. / Witt, Nasriya A.; Lee, Benita; Ghent, Kaylee; Zhang, Wynne Q.; Pehrson, Alan L.; Sánchez, Connie; Gould, Georgianna G.

In: ACS Chemical Neuroscience, Vol. 10, No. 10, 10.2019, p. 4319-4327.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Witt, NA, Lee, B, Ghent, K, Zhang, WQ, Pehrson, AL, Sánchez, C & Gould, GG 2019, 'Vortioxetine Reduces Marble Burying but Only Transiently Enhances Social Interaction Preference in Adult Male BTBR T+Itpr3tf/J Mice', ACS Chemical Neuroscience, vol. 10, no. 10, pp. 4319-4327. https://doi.org/10.1021/acschemneuro.9b00386

APA

Witt, N. A., Lee, B., Ghent, K., Zhang, W. Q., Pehrson, A. L., Sánchez, C., & Gould, G. G. (2019). Vortioxetine Reduces Marble Burying but Only Transiently Enhances Social Interaction Preference in Adult Male BTBR T+Itpr3tf/J Mice. ACS Chemical Neuroscience, 10(10), 4319-4327. https://doi.org/10.1021/acschemneuro.9b00386

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Author

Witt, Nasriya A. ; Lee, Benita ; Ghent, Kaylee ; Zhang, Wynne Q. ; Pehrson, Alan L. ; Sánchez, Connie ; Gould, Georgianna G. / Vortioxetine Reduces Marble Burying but Only Transiently Enhances Social Interaction Preference in Adult Male BTBR T+Itpr3tf/J Mice. In: ACS Chemical Neuroscience. 2019 ; Vol. 10, No. 10. pp. 4319-4327.

Bibtex

@article{75ca21bb258e4d9aba6c6b99649aaec2,
title = "Vortioxetine Reduces Marble Burying but Only Transiently Enhances Social Interaction Preference in Adult Male BTBR T+Itpr3tf/J Mice",
abstract = "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. ",
keywords = "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",
author = "Witt, {Nasriya A.} and Benita Lee and Kaylee Ghent and Zhang, {Wynne Q.} and Pehrson, {Alan L.} and Connie S{\'a}nchez and Gould, {Georgianna G.}",
year = "2019",
month = oct,
doi = "10.1021/acschemneuro.9b00386",
language = "English",
volume = "10",
pages = "4319--4327",
journal = "A C S Chemical Neuroscience",
issn = "1948-7193",
publisher = "American Chemical Society",
number = "10",

}

RIS

TY - JOUR

T1 - Vortioxetine Reduces Marble Burying but Only Transiently Enhances Social Interaction Preference in Adult Male BTBR T+Itpr3tf/J Mice

AU - Witt, Nasriya A.

AU - Lee, Benita

AU - Ghent, Kaylee

AU - Zhang, Wynne Q.

AU - Pehrson, Alan L.

AU - Sánchez, Connie

AU - Gould, Georgianna G.

PY - 2019/10

Y1 - 2019/10

N2 - 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.

AB - 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.

KW - Autism

KW - Lu AA21004

KW - multimodal antidepressant

KW - repetitive burying

KW - serotonin

KW - social

KW - SEROTONIN TRANSPORTER

KW - 5-HT1A RECEPTORS

KW - AUTISM SPECTRUM DISORDERS

KW - PERVASIVE DEVELOPMENTAL DISORDERS

KW - REPETITIVE BEHAVIORS

KW - MULTIMODAL ANTIDEPRESSANT

KW - MOUSE MODEL

KW - ANTIDEPRESSANT VORTIOXETINE

KW - OXYTOCIN

KW - LU AA21004

UR - http://www.scopus.com/inward/record.url?scp=85073311100&partnerID=8YFLogxK

U2 - 10.1021/acschemneuro.9b00386

DO - 10.1021/acschemneuro.9b00386

M3 - Journal article

C2 - 31468969

AN - SCOPUS:85073311100

VL - 10

SP - 4319

EP - 4327

JO - A C S Chemical Neuroscience

JF - A C S Chemical Neuroscience

SN - 1948-7193

IS - 10

ER -