The neuropeptide oxytocin facilitates pro-social behavior and prevents social avoidance in rats and mice
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Social avoidance and social phobia are core symptoms of various psychopathologies but their underlying etiology remains poorly understood. Therefore, this study aims to reveal pro-social effects of the neuropeptide oxytocin (OT), under both basal and stress-induced social avoidance conditions in rodents using a social preference paradigm. We initially show that intracerebroventricular (i.c.v.) application of an OT receptor antagonist (OTR-A) in naïve male rats (0.75 μg/5 μl), or mice (20 μg/2 μl), reduced social exploration of a novel con-specific indicative of attenuated social preference. Previous exposure of male rats to a single social defeat resulted in loss of their social preference and social avoidance, which could be restored by i.c.v. infusion of synthetic OT (0.1 μg/5 μl) 20 min before the social preference test. Although the amygdala has been implicated in both social and OT-mediated actions, bilateral OTR-A (0.1 μg/1 μl) or OT (0.01 μg/1 μl) administration into various subnuclei of the amygdala did not affect basal or stress-induced social preference behavior, respectively. Finally, we demonstrate the social specificity of these OT-mediated effects by showing that neither an arginine vasopressin V1a receptor antagonist (0.75 μg/5 μl, i.c.v.) nor the anxiogenic drug pentylenetetrazol (15 mg/kg, i.p.) altered social preference, with OTR-A not affecting non-social anxiety on the elevated plus-maze. Overall, the data indicate that the basal activity of the endogenous brain OT system is sufficient to promote natural occurring social preference in rodents while synthetic OT shows potential to reverse stress-induced social avoidance and might thus be of use for treating social phobia and social dysfunction in humans.
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Following a single episode of social defeat, male rats exhibited social avoidance, but their innate social preference could be reinstated by i.c.v. infusion of synthetic OXT.
“Moreover, following a single episode of social defeat, male rats exhibited social avoidance, but their innate social preference could be reinstated by i.c.v. infusion of synthetic OXT (Lukas et al., 2011).”
From Convergence of oxytocin and dopamine signalling in neuronal circuits: Insights into the neurobiology of social interactions across species (2024) · cites this paper as Lukas et al., 2011
In rodents, where high sociability is typical, OXT promotes pro-social behaviour and counteracts social avoidance.
“In rodents, where high sociability is typical, OXT promotes pro-social behaviour and counteracts social avoidance.”
From Convergence of oxytocin and dopamine signalling in neuronal circuits: Insights into the neurobiology of social interactions across species (2024) · cites this paper as Lukas et al., 2011
Seminal studies in male-male and male-female rodent pairs have contributed to the notion of OT as a facilitator of affiliative behaviors.
“While seminal studies in male-male and male-female rodent pairs have contributed to the notion of OT as a facilitator of affiliative behaviors (Lukas et al., 2011, Williams et al., 1994, Witt et al., 1992), recent findings also provide evidence of antisocial effects of OT (van Anders et al., 2013, Bartz et al., 2011, Beery, 2015).”
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 Lukas et al., 2011
Oxytocin exhibits very limited penetration across the blood-brain barrier.
“oxytocin, despite exhibiting very limited penetration across the blood-brain barrier, 75”
From Beyond the hype and hope: critical considerations for intranasal oxytocin research in autism spectrum disorder (2017) · cites this paper as [75]
Play fighting in rats, unlike serious fighting, typically does not involve biting or threat postures, but is based on trying to reach the opponent's nape or protecting one's own.
“This type of social interactioncontrary to serious fighting-typically does not involve any biting nor threat postures, but instead is based on trying to reach opponent's nape or protecting one's own.54 (see also Reference 107).”
From Ecological validity of social interaction tests in rats and mice (2019) · cites this paper as [54]
Animal studies reported that OT abolished the impact of negative outcomes on subsequent behaviors in rats and mice.
“Animal studies also reported that OT abolished the impact of negative outcomes (such as traumatic events and aversive conditioning) on subsequent behaviors in rats and mice (57, 58).”
From Distinct oxytocin effects on belief updating in response to desirable and undesirable feedback (2016) · cites this paper as [57]
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- Authors
- Lukas, M., Toth, I., Reber, S. O., Slattery, D. A., Veenema, A. H., & Neumann, I. D.
- Affiliations
- University of Regensburg (DE)
- Boston College (US)
- Corresponding author
- Neumann, Inga D
- Venue
- Neuropsychopharmacology
- Published
- 2011-06-15
- Volume
- 36
- Issue
- 11
- Pages
- 2159-2168
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3176581
- OpenAlex
- W2081762124
- Cited by
- 403
- References
- 75
- Citations by year
- 2026: 12 · 2025: 17 · 2024: 24 · 2023: 20 · 2022: 28 · 2021: 33 · 2020: 29 · 2019: 28 · 2018: 26 · 2017: 35 · 2016: 34 · 2015: 37 · 2014: 33 · 2013: 19 · 2012: 20
- FWCI
- 34.92
- 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) (acceptedVersion)
- HAL (submittedVersion, other-oa)
- Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
- Funders
- Bundesministerium für Bildung und Forschung
- 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, social avoidance, social preferences, social anxiety disorder, social defeat, oxytocin receptor antagonist, amygdala, pentylenetetrazole, prosocial behavior, intracerebroventricular infusion
- MeSH terms
- Animals, Behavior, Animal, Male, Mice, Inbred C57BL, Neuropeptides, Oxytocin, Social Behavior, Social Facilitation, Rats, Wistar, Mice, Rats
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