Oxytocin and vasopressin effects on the neural response to social cooperation are modulated by sex in humans
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Recent research has examined the effects of oxytocin (OT) and vasopressin (AVP) on human social behavior and brain function. However, most participants have been male, while previous research in our lab demonstrated sexually differentiated effects of OT and AVP on the neural response to reciprocated cooperation. Here we extend our previous work by significantly increasing the number of participants to enable the use of more stringent statistical thresholds that permit more precise localization of OT and AVP effects in the brain. In a double-blind, placebo-controlled study, 153 men and 151 women were randomized to receive 24 IU intranasal OT, 20 IU intranasal AVP or placebo. Afterwards, they were imaged with fMRI while playing an iterated Prisoner's Dilemma Game with same-sex partners. Sex differences were observed for effects of OT on the neural response to reciprocated cooperation, such that OT increased the caduate/putamen response among males, whereas it decreased this response among females. Thus, 24 IU OT may increase the reward or salience of positive social interactions among men, while decreasing their reward or salience among women. Similar sex differences were also observed for AVP effects within bilateral insula and right supramarginal gyrus when a more liberal statistical threshold was employed. While our findings support previous suggestions that exogenous nonapeptides may be effective treatments for disorders such as depression and autism spectrum disorder, they caution against uniformly extending such treatments to men and women alike.
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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 [89]
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 [89]
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“divergent in men and women, as a line of research ultimately including a sample size of over 300 participants determined that OT increases activation in the ventral striatum inmen but decreases activation in the same region in women during the canonical prisoner's dilemma game (Feng et al., 2015; Rilling et al., 2012,…”
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- Authors
- Feng, C., Hackett, P. D., DeMarco, A. C., Chen, X., 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
- 2014-11-22
- Volume
- 9
- Issue
- 4
- Pages
- 754-764
- ISSN
- 1931-7557 (ISSN-L)
- 1931-7565
- OpenAlex
- W2042444366
- Cited by
- 157
- References
- 69
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 14 · 2023: 11 · 2022: 10 · 2021: 16 · 2020: 15 · 2019: 16 · 2018: 23 · 2017: 13 · 2016: 14 · 2015: 10
- FWCI
- 18.30
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Brain Imaging and Behavior (publishedVersion)
- PubMed (publishedVersion)
- 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 › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Keywords
- oxytocin, vasopressin, sex differences, social cooperation, iterated prisoner's dilemma, caudate nucleus, putamen, insula, supramarginal gyrus, intranasal administration, social reward, nonapeptide, autism spectrum disorder, depression
- MeSH terms
- Prisoner Dilemma, Administration, Intranasal, Adolescent, Brain, Brain Mapping, Cerebrovascular Circulation, Cooperative Behavior, Double-Blind Method, Female, Humans, Magnetic Resonance Imaging, Male, Oxygen, Oxytocin, Psychotropic Drugs, Reward, Sex Characteristics, Vasopressins, Young Adult
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