Fear-enhancing effects of septal oxytocin receptors
Open accessAbstract
The nonapeptide oxytocin is considered beneficial to mental health due to its anxiolytic, prosocial and antistress effects, but evidence for anxiogenic actions of oxytocin in humans has recently emerged. Using region-specific manipulations of the mouse oxytocin receptor (Oxtr) gene (Oxtr), we identified the lateral septum as the brain region mediating fear-enhancing effects of Oxtr. These effects emerge after social defeat and require Oxtr specifically coupled to the extracellular signal-regulated protein kinase pathway.
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There is mounting evidence that oxytocin has anxiogenic and fear-enhancing effects.
“However, against the background of mounting evidence for anxiogenic and fearenhancing OXT effects (33,43,44), it is necessary that the mechanisms determining the outcome of an OXT treatment are completely identified.”
From Oxytocin enhances brain reward system responses in men viewing the face of their female partner (2013) · cites this paper as [43]
OTR activation in the lateral septum enhanced conditioned fear responses in mice exposed to acute social defeat.
“Moreover, OTR activation in the lateral septum enhanced conditioned fear responses in mice exposed to acute social defeat (Guzman et al., 2013).”
From Sex-specific modulation of juvenile social play behavior by vasopressin and oxytocin depends on social context (2014) · cites this paper as Guzman et al., 2013
These findings were surprising given typically pro-social effects of OT, although recent studies suggest a role for the OTR in the LS in reducing pro-social behaviors and enhancing anxiety in rodents.
“These findings were a bit surprising, given the typically pro-social behavior effects of OT, although recent studies suggest a role for the OTR in the LS in reducing pro-social behaviors and enhancing anxiety in rodents”
From Vasopressin and oxytocin receptor systems in the brain: Sex differences and sex-specific regulation of social behavior (2016) · cites this paper as Guzman et al., 2013
More recent studies have demonstrated some antisocial effects of OT in both humans and other animals.
“Additionally, more recent studies have demonstrated some antisocial effects of OT in both humans (De Dreu et al., 2010, De Dreu et al., 2011, Eckstein et al., 2014, Shamay-Tsoory et al., 2009) and other animals (Duque-Wilckens et al., 2018, Guzmán et al., 2013, Huang et al., 2014).”
From Wireless Optogenetic Stimulation of Oxytocin Neurons in a Semi-natural Setup Dynamically Elevates Both Pro-social and Agonistic Behaviors (2020) · cites this paper as Guzmán et al., 2013
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- Authors
- Guzmán, Y. F., Tronson, N. C., Jovasevic, V., Sato, K., Guedea, A. L., Mizukami, H., Nishimori, K., & Radulovic, J.
- Affiliations
- Northwestern University (US)
- Tohoku University (JP)
- Jichi Medical University (JP)
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2013-07-21
- Volume
- 16
- Issue
- 9
- Pages
- 1185-1187
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC3758455
- OpenAlex
- W2024049038
- Cited by
- 215
- References
- 26
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 15 · 2023: 9 · 2022: 9 · 2021: 19 · 2020: 19 · 2019: 21 · 2018: 18 · 2017: 17 · 2016: 20 · 2015: 24 · 2014: 22 · 2013: 9
- FWCI
- 37.42
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Japan Society for the Promotion of Science (23240057, 23380055)
- National Institute of Mental Health (R01MH073669, F31MH092065, MH092065, R01MH078064)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- oxytocin receptor, lateral septum, fear conditioning, stress, social defeat, ERK signaling, anxiogenic effects, oxytocin
- MeSH terms
- Analysis of Variance, Animals, Butadienes, Fear, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Nitriles, Oxytocin, Protein Kinase C, Proteins, Social Behavior, Stress, Psychological, Transduction, Genetic, Vasotocin, Signal Transduction, Receptors, Oxytocin, Septum of Brain, RNA, Untranslated, Mitogen-Activated Protein Kinase 3, Green Fluorescent Proteins, CREB-Binding Protein, Mice
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