Effects of intranasal oxytocin and vasopressin on cooperative behavior and associated brain activity in men
Open accessAbstract
The neural mechanisms supporting social bonds between adult men remain uncertain. In this double-blind, placebo-controlled study, we investigate the impact of intranasally administered oxytocin (OT) and vasopressin (AVP) on behavior and brain activity among men in the context of an iterated Prisoner's Dilemma game, which models a real-life social situation. fMRI results show that, relative to both AVP and placebo, OT increases the caudate nucleus response to reciprocated cooperation, which may augment the reward of reciprocated cooperation and/or facilitate learning that another person can be trusted. OT also enhances left amygdala activation in response to reciprocated cooperation. Behaviorally, OT was associated with increased rates of cooperation following unreciprocated cooperation in the previous round compared with AVP. AVP strongly increased cooperation in response to a cooperative gesture by the partner compared with both placebo and OT. In response to reciprocated cooperation, AVP increased activation in a region spanning known vasopressin circuitry implicated in affiliative behaviors in other species. Finally, both OT and AVP increase amygdala functional connectivity with the anterior insula relative to placebo, which may increase the amygdala's ability to elicit visceral somatic markers that guide decision making. These findings extend our knowledge of the neural and behavioral effects of OT and AVP to the context of genuine social interactions.
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Human studies show that the behavioral effects of AVP and OXT depend on social contextual factors.
“There are also human studies showing that the behavioral effects of AVP and OXT depend on social contextual factors (Declerck et al., 2010; Bartz et al., 2011; Rilling et al., 2012; Olff 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 Rilling et al., 2012
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 [84]
Peptides administered via the intranasal route produce significant alterations in cognition and neuronal activity whether they are acting peripherally and/or centrally.
“It is clear, however, that peptides administered via the intranasal route produce significant alterations in cognition and neuronal activity whether they are acting peripherally and/or centrally.”
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 [84]
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 [84]
Other studies have reported that oxytocin effects on amygdala responses often occur with concurrent changes in its connections with, and activation of, the insula.
“Indeed, other studies have also reported that OXT effects on amygdala responses often occur with concurrent changes in its connections with, and activation of, the insula (27 -29).”
From Oxytocin, the peptide that bonds the sexes also divides them (2016) · cites this paper as [27]
Although not statistically significant in a comparison between sexes, OT lowered rates of cooperation with computer partners following defection in women only.
“Although not statistically significant in a comparison between sex, OT lowered rates of cooperation with computer partners following defection in women only (Rilling et al., 2012; 2014).”
From Vasopressin and oxytocin receptor systems in the brain: Sex differences and sex-specific regulation of social behavior (2016) · cites this paper as Rilling et al., 2012
Intranasal OT had opposite effects on brain activation during reciprocated cooperation in humans.
“intranasal OT had opposite effects on brain activation during reciprocated cooperation in humans (Rilling et al., 2012; 2014)”
From Vasopressin and oxytocin receptor systems in the brain: Sex differences and sex-specific regulation of social behavior (2016) · cites this paper as Rilling et al., 2012
fMRI techniques require study subjects to be restrained during examination, rendering them impractical for examining natural triggers or effects of oxytocin on animals and humans when engaged in contexts representative of natural social and environmental life.
“fMRI techniques are also not yet at a point where study subjects can be anything other than restrained during the examination (e.g., Bethlehem et al., 2012; Rilling et al., 2012), rendering them impractical for examining natural triggers or effects of oxytocin on animals and humans when engaged in contexts representative of natural social and environmental life.”
From Endogenous peripheral oxytocin measures can give insight into the dynamics of social relationships: a review (2014) · cites this paper as Rilling et al., 2012
During an interpersonal cooperation task, OXT increased functional connectivity between the amygdala and the anterior insula.
“For example, during an interpersonal cooperation task, Rilling et al (2012) found that OXT increased functional connectivity between the amygdala and the anterior insula.”
From Oxytocin modulation of amygdala functional connectivity to fearful faces in generalized social anxiety disorder (2015) · cites this paper as Rilling et al, 2012
Oxytocin enhanced amygdala-insula functional connectivity and this reflected an increased ability to assess internal states to guide decision-making.
“Rilling et al (2012) also found that OXT enhanced amygdala-insula functional connectivity and posited that this reflected an increased ability to assess internal states (eg, somatic markers) to guide decision-making.”
From Oxytocin modulation of amygdala functional connectivity to fearful faces in generalized social anxiety disorder (2015) · cites this paper as Rilling et al (2012)
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- Authors
- Rilling, J. K., DeMarco, A. C., Hackett, P. D., Thompson, R., Ditzen, B., Patel, R., & Pagnoni, G.
- Affiliations
- Emory University (US)
- Bowdoin College (US)
- University of Modena and Reggio Emilia (IT)
- Corresponding author
- Rilling, James K.
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2012-04
- Volume
- 37
- Issue
- 4
- Pages
- 447-461
- ISSN
- 0306-4530 (ISSN-L)
- PMC
- PMC3251702
- OpenAlex
- W2098974252
- Cited by
- 303
- References
- 66
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 9 · 2023: 10 · 2022: 18 · 2021: 10 · 2020: 13 · 2019: 22 · 2018: 25 · 2017: 35 · 2016: 31 · 2015: 32 · 2014: 36 · 2013: 26 · 2012: 18
- FWCI
- 36.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Funders
- National Institutes of Health (UL1TR000454)
- National Institute of Mental Health (R01MH084068)
- National Center for Advancing Translational Sciences
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Social Sciences › Safety Research › Experimental Behavioral Economics Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- oxytocin, vasopressin, intranasal administration, cooperation, prisoner's dilemma, social bonding, caudate nucleus, amygdala, anterior insula, functional connectivity, trust, reward, affiliative behavior, men
- MeSH terms
- Administration, Intranasal, Adolescent, Arginine Vasopressin, Brain, Cooperative Behavior, Double-Blind Method, Game Theory, Humans, Magnetic Resonance Imaging, Male, Oxytocin, Young Adult, Functional Neuroimaging
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