Brain oxytocin in social fear conditioning and its extinction: involvement of the lateral septum
Open accessAbstract
Central oxytocin (OXT) has anxiolytic and pro-social properties both in humans and rodents, and has been proposed as a therapeutic option for anxiety and social dysfunctions. Here, we utilized a mouse model of social fear conditioning (SFC) to study the effects of OXT on social fear, and to determine whether SFC causes alterations in central OXT receptor (OXTR) binding and local OXT release. Central infusion of OXT, but not arginine vasopressin, prior to social fear extinction training completely abolished social fear expression in an OXTR-mediated fashion without affecting general anxiety or locomotion. SFC caused increased OXTR binding in the dorso-lateral septum (DLS), central amygdala, dentate gyrus, and cornu ammunis 1, which normalized after social fear extinction, suggesting that these areas form part of a brain network involved in the development and neural support of social fear. Microdialysis revealed that the increase in OXT release observed in unconditioned mice within the DLS during social fear extinction training was attenuated in conditioned mice. Consequently, increasing the availability of local OXT by infusion of OXT into the DLS reversed social fear. Thus, alterations in the brain OXT system, including altered OXTR binding and OXT release within the DLS, play an important role in SFC and social fear extinction. Thus, we suggest that the OXT system is adversely affected in disorders associated with social fear, such as social anxiety disorder and reinstalling an appropriate balance of the OXT system may alleviate some of the symptoms.
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The implication of CeA OXT signaling in processing threat responses and social fear suggests a specific role in detection of fear-mediated responses.
“The implication of CeA OXT signaling in processing threat responses [22,94,104] and social fear [105] would suggest a specific role in the detection of fear-mediated responses.”
From Oxytocin Signaling in the Central Amygdala Modulates Emotion Discrimination in Mice (2019) · cites this paper as [105]
In rodents, central oxytocin administration before conditioned fear extinction improved social fear extinction but impaired nonsocial fear extinction.
“in rodents, central oxytocin administration before conditioned fear extinction improved social fear extinction (68) but impaired nonsocial fear extinction (69).”
From Intranasal Oxytocin to Prevent Posttraumatic Stress Disorder Symptoms: A Randomized Controlled Trial in Emergency Department Patients (2017) · cites this paper as [68]
Findings in mice suggest that OXT specifically facilitates social fear conditioning.
“findings in mice suggesting that OXT specifically facilitates social fear conditioning (Zoicas et al, 2014).”
From Oxytocin Facilitates Pavlovian Fear Learning in Males (2016) · cites this paper as Zoicas et al, 2014
OT administration increased (recall of) extinction learning in rodents and healthy males.
“Behaviorally, OT administration resulted in decreased subjective anxiety during a public speaking stressor in healthy individuals (de Oliveira et al, 2012) and increased (recall of) extinction learning in both rodents (Zoicas et al, 2014) and healthy males (Acheson et al, 2013).”
From Intranasal oxytocin administration dampens amygdala reactivity towards emotional faces in male and female PTSD patients (2016) · cites this paper as Zoicas et al, 2014
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Neuropeptide S Activates Paraventricular Oxytocin Neurons to Induce Anxiolysis
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Maternal separation facilitates extinction of social fear in adult male mice.
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Oxytocin Promotes Accurate Fear Discrimination and Adaptive Defensive Behaviors
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Chronic oxytocin-driven alternative splicing of Crfr2α induces anxiety
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Septal oxytocin administration impairs peer affiliation via V1a receptors in female meadow voles
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Men Scare Me More: Gender Differences in Social Fear Conditioning in Virtual Reality
Reichenberger, J., Pfaller, M. A., Forster, D., Gerczuk, J., Shiban, Y., & Mühlberger, A. (2019) · Frontiers in Psychology · doi:10.3389/fpsyg.2019.01617 · Cited by 38 · see citing works
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Oxytocin and social anxiety: Interactions with sex hormones
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N-Methyl D-aspartate receptor subunit signaling in fear extinction
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Fish as a model in social neuroscience: conservation and diversity in the social brain network
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- Authors
- Zoicas, I., Slattery, D. A., & Neumann, I. D.
- Affiliations
- University of Regensburg (DE)
- Corresponding author
- Neumann, Inga D
- Venue
- Neuropsychopharmacology
- Published
- 2014-06-26
- Volume
- 39
- Issue
- 13
- Pages
- 3027-3035
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC4229574
- OpenAlex
- W1999269819
- Cited by
- 189
- References
- 56
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 20 · 2023: 10 · 2022: 13 · 2021: 19 · 2020: 17 · 2019: 15 · 2018: 18 · 2017: 16 · 2016: 20 · 2015: 17 · 2014: 2
- FWCI
- 27.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Regensburg Publication Server (University of Regensburg) (submittedVersion)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- oxytocin, lateral septum, oxytocin release, vasopressin, central amygdala, dentate gyrus, cornu ammonis, social anxiety disorder, anxiolytic effects
- MeSH terms
- Analysis of Variance, Animals, Arginine Vasopressin, Autoradiography, Conditioning, Psychological, Electric Stimulation, Extinction, Psychological, Fear, Locomotion, Male, Ornipressin, Oxytocin, Protein Binding, Septal Nuclei, Time Factors, Microdialysis, Receptors, Oxytocin, Maze Learning, Mice
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