Effects of oxytocin and vasopressin on the neural response to unreciprocated cooperation within brain regions involved in stress and anxiety in men and women.
Open accessAbstract
Anxiety disorders are characterized by hyperactivity in both the amygdala and the anterior insula. Interventions that normalize activity in these areas may therefore be effective in treating anxiety disorders. Recently, there has been significant interest in the potential use of oxytocin (OT), as well as vasopressin (AVP) antagonists, as treatments for anxiety disorders. In this double-blind, placebo-controlled, pharmaco- fMRI study, 153 men and 151 women were randomized to treatment with either 24 IU intranasal OT, 20 IU intranasal AVP, or placebo and imaged with fMRI as they played the iterated Prisoner's Dilemma game with same-sex human and computer partners. In men, OT attenuated the fMRI response to unreciprocated cooperation (CD), a negative social interaction, within the amygdala and anterior insula. This effect was specific to interactions with human partners. In contrast, among women, OT unexpectedly attenuated the amygdala and anterior insula response to unreciprocated cooperation from computer but not human partners. Among women, AVP did not significantly modulate the response to unreciprocated cooperation in either the amygdala or the anterior insula. However, among men, AVP attenuated the BOLD response to CD outcomes with human partners across a relatively large cluster including the amygdala and the anterior insula, which was contrary to expectations. Our results suggest that OT may decrease the stress of negative social interactions among men, whereas these effects were not found in women interacting with human partners. These findings support continued investigation into the possible efficacy of OT as a treatment for anxiety disorders.
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The few studies that have compared the effects of intranasally administered OT and AVP in humans have reported that these peptides do not have opposing roles.
“The few studies that have compared the effects of intranasally administered OT and AVP in humans have reported that these peptides do not have opposing roles.”
From Cross-talk among oxytocin and arginine-vasopressin receptors: Relevance for basic and clinical studies of the brain and periphery (2018) · cites this paper as [86]
OT and AVP can have differential effects on neural activity (BOLD fMRI responses) and cognition, at least in some cases, although the effects of OT are more robust.
“These data have, however, found OT and AVP can have differential effects on neural activity (i.e., BOLD fMRI responses) and cognition, at least in some cases although the effects of OT are more robust [84; 86; 87; 88; 89; 90].”
From Cross-talk among oxytocin and arginine-vasopressin receptors: Relevance for basic and clinical studies of the brain and periphery (2018) · cites this paper as [86]
A growing number of findings suggest sex-dependent effects of oxytocin on social cognition.
“Based on a growing number of findings suggesting sex-dependent effects of OXT on social cognition (Chen et al., 2016; Gao et al., 2016; Luo et al., 2017), the second experiment additionally explored whether OXT differentially affects empathic processing in men and women.”
From Oxytocin Enhancement of Emotional Empathy: Generalization Across Cultures and Effects on Amygdala Activity (2018) · cites this paper as Chen et al., 2016
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References 73 · Cited by 81
- Authors
- Chen, X., Hackett, P. D., DeMarco, A. C., Feng, C., Stair, S., Haroon, E., Ditzen, B., Pagnoni, G., & Rilling, J. K.
- Affiliations
- Emory University (US)
- University of Kansas (US)
- University of Modena and Reggio Emilia (IT)
- Corresponding author
- Rilling, James K.
- ORCID
- Venue
- Brain Imaging and Behavior
- Published
- 2015-06-04
- Volume
- 10
- Issue
- 2
- Pages
- 581-593
- ISSN
- 1931-7557 (ISSN-L)
- 1931-7565
- PMC
- PMC4670292
- OpenAlex
- W597545024
- Cited by
- 81
- References
- 73
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 6 · 2023: 3 · 2022: 4 · 2021: 11 · 2020: 9 · 2019: 14 · 2018: 13 · 2017: 7 · 2016: 3 · 2015: 2
- FWCI
- 13.63
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Brain Imaging and Behavior (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- Funders
- National Institutes of Health (UL1TR000454)
- National Institute of Mental Health (MH084068-01A1, R01MH084068, MH084068)
- National Center for Advancing Translational Sciences
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- oxytocin, vasopressin, anxiety disorders, amygdala, anterior insula, stress response, sex differences, iterated prisoner's dilemma, social stress, intranasal administration, pharmacological treatment of anxiety
- MeSH terms
- Administration, Intranasal, Adolescent, Amygdala, Anxiety, Brain, Cerebral Cortex, Cooperative Behavior, Double-Blind Method, Female, Humans, Interpersonal Relations, Magnetic Resonance Imaging, Male, Oxytocin, Social Behavior, Stress, Psychological, Vasopressins, Young Adult
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