Brain Imaging and Behavior

, Volume 10, Issue 2, pp 581–593 | Cite as

Effects of oxytocin and vasopressin on the neural response to unreciprocated cooperation within brain regions involved in stress and anxiety in men and women

  • Xu Chen
  • Patrick D. Hackett
  • Ashley C. DeMarco
  • Chunliang Feng
  • Sabrina Stair
  • Ebrahim Haroon
  • Beate Ditzen
  • Giuseppe Pagnoni
  • James K. RillingEmail author
Original Research


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.


Amygdala Anterior insula Anxiety Oxytocin Social cooperation Functional magnetic resonance imaging (fMRI) 



This study was partially supported by NIMH Grant R01 MH084068-01A1 and the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR000454. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

We thank Susan Rogers, Jianguo Xu and Larry Young for assistance with various aspects of this study.

Financial disclosures

None of the authors (Xu Chen, Patrick D. Hackett, Ashley C. DeMarco, Chunliang Feng, Sabrina Stair, Ebrahim Haroon, Beate Ditzen, Giuseppe Pagnoni, and James K. Rilling) has any biomedical financial interests or potential conflicts of interests to declare.

Informed consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, and the applicable revisions at the time of the investigation. Informed consent was obtained from all patients for being included in the study.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Xu Chen
    • 1
    • 2
  • Patrick D. Hackett
    • 1
  • Ashley C. DeMarco
    • 6
  • Chunliang Feng
    • 1
  • Sabrina Stair
    • 2
  • Ebrahim Haroon
    • 2
  • Beate Ditzen
    • 2
    • 3
    • 7
  • Giuseppe Pagnoni
    • 8
  • James K. Rilling
    • 1
    • 2
    • 3
    • 4
    • 5
    Email author
  1. 1.Department of AnthropologyEmory UniversityAtlantaUSA
  2. 2.Department of Psychiatry and Behavioral SciencesEmory UniversityAtlantaUSA
  3. 3.Center for Behavioral NeuroscienceEmory UniversityAtlantaUSA
  4. 4.Yerkes National Primate Research CenterEmory UniversityAtlantaUSA
  5. 5.Center for Translational Social NeuroscienceEmory UniversityAtlantaUSA
  6. 6.Department of PsychologyUniversity of KansasLawrenceUSA
  7. 7.Department of PsychologyUniversity of ZurichZurichSwitzerland
  8. 8.Department of Neural, Biomedical, and Metabolic SciencesUniversity of Modena and Reggio EmiliaModenaItaly

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