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Cited by 27Neuroendocrine regulation and behaviorNeuropeptides and Animal PhysiologyNeurotransmitter Receptor Influence on Behavior

Oxytocin receptor behavioral effects and cell types in the bed nucleus of the stria terminalis

Open access
Luo, Pei X., Zakharenkov, Hannah Cortez, Torres, Lisette Y., Rios, Roberto A., Gegenhuber, Bruno, Black, Alexis M., Xu, Christine K., Minie, Vanessa A. +3 more·2022·Hormones and Behavior
DOI 10.1016/j.yhbeh.2022.105203PMC PMC9827713
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Abstract

Oxytocin is a neuropeptide that can produce anxiolytic effects and promote social approach. However, emerging evidence shows that under some conditions, oxytocin can instead induce anxiety-related behaviors. These diverse effects of oxytocin appear to be mediated by circuit-specific actions. Recent data showed that inhibition of oxytocin receptors (OTRs) in the bed nucleus of the stria terminalis (BNST) was sufficient to increase social approach and decrease social vigilance in female California mice (Peromyscus californicus) exposed to social defeat stress. As a member of the G-protein coupled receptor family, OTRs can induce distinct downstream pathways by coupling to different G-protein isoforms. We show that infusion of carbetocin, a biased OTR-Gq agonist, in the BNST reduced social approach in both female and male California mice. In both females and males, carbetocin also increased social vigilance. To gain insight into cell types that could be mediating this effect, we analyzed previously published single-cell RNAseq data from the BNST and nucleus accumbens (NAc). In the NAc, we and others showed that OTR activation promotes social approach behaviors. In the BNST, Oxtr was expressed in over 40 cell types, that span both posterior and anterior subregions of the BNST. The majority of Oxtr-expressing neurons were GABAergic. In the anterior regions of BNST targeted in our carbetocin experiments, Cyp26b1-expressing neurons had high average Oxtr expression. In the NAc, most Oxtr+ cells were D1 dopamine receptor-expressing neurons and interneurons. These differences in Oxtr cell type distribution may help explain how activation of OTR in BNST versus NAc can have different effects on social approach and social vigilance.

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  • The BNST plays a key role in modulating stress-induced social avoidance and social vigilance in males and females.

    “The BNST plays a key role in modulating stress-induced social avoidance and social vigilance in males and females (38, 40, 41).”

    From Sexual differentiation of neural mechanisms of stress sensitivity during puberty (2023) · cites this paper as [41]

    The Discussion (page not provided) reports that activating oxytocin receptors in the BNST reduced social approach and increased social vigilance in both male and female mice. Those mice were stress-naïve; the paper discusses a BNST finding in stressed females, but does not establish the claimed stress-induced effects in both sexes. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Previous work in California mice shows changes in BNST drive stress-induced social avoidance and social vigilance.

    “Previous work in California mice (Peromyscus californicus) shows that social defeat stress has stronger effects on BNST structure and function in adult females than males (37, 38) and that these changes drive stress-induced social avoidance and social vigilance (39–41).”

    From Sexual differentiation of neural mechanisms of stress sensitivity during puberty (2023) · cites this paper as [41]

    The Discussion reports that activating oxytocin receptors in the BNST reduced social approach and increased social vigilance in California mice, while BNST receptor blockade had the opposite effects in stressed females. This supports a role for BNST function in those behaviors, but the paper does not show that stress-induced changes in BNST structure drive them; its carbetocin experiments used stress-naïve mice. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • In California mice, OXTR is expressed in different cell types depending on the brain region.

    “In California mice, OXTR is expressed in different cell types depending on the brain region (72).”

    From Oxytocin, Vasopressin, and Social Behavior: From Neural Circuits to Clinical Opportunities (2022) · cites this paper as [72]

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Authors
Luo, P. X., Zakharenkov, H. C., Torres, L. Y., Rios, R. A., Gegenhuber, B., Black, A. M., Xu, C. K., Minie, V. A., Tran, A. M., Tollkuhn, J., & Trainor, B. C.
Affiliations
  • University of California, Davis (US)
  • Cold Spring Harbor Laboratory (US)
Corresponding author
Trainor, Brian C.
ORCID
Venue
Hormones and Behavior
Publisher
Elsevier BV
Published
2022-07
Volume
143
Pages
105203
ISSN
0018-506X (ISSN-L)
DOI
10.1016/j.yhbeh.2022.105203
PMC
PMC9827713
OpenAlex
W4282016948
Cited by
27
References
85
Citations by year
2026: 5 · 2025: 9 · 2024: 4 · 2023: 7 · 2022: 2
FWCI
5.19
Type
journal article
Language
en
Open access
Licence
Locations
  • Hormones and Behavior (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
National Institute of Mental Health (R01MH113628, R01MH121829)
Topics
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
oxytocin receptor, bed nucleus of the stria terminalis, carbetocin, social approach, social vigilance, social defeat stress, Gq-coupled receptors, biased agonists, GABAergic neurons, CYP26B1, dopamine D1 receptor, nucleus accumbens, single-cell RNA sequencing, Peromyscus californicus
MeSH terms
Animals, Female, Male, Nucleus Accumbens, Oxytocin, Septal Nuclei, Social Behavior, Receptors, Dopamine D1, Receptors, Oxytocin

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