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Author Notes:

Department of Anthropology, Department of Psychiatry and Behavioral Sciences, Emory University, 1557 Dickey Drive, Atlanta, GA, 30322 United States. Email: jrillin@emory.edu (J.K. Rilling)

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

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

The opinions expressed in this publication are those of the author(s) and do not necessarily reflect the views of the John Templeton Foundation.


Research Funding:

This research was made possible through the support of a grant from the John Templeton Foundation.

This study was also 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.


  • Science & Technology
  • Life Sciences & Biomedicine
  • Endocrinology & Metabolism
  • Neurosciences
  • Psychiatry
  • Neurosciences & Neurology
  • Oxytocin
  • Ventral tegmental area (VTA)
  • Within-subject design
  • Social cooperation
  • Functional magnetic resonance imaging (fMRI)
  • Prisoner dilemma

Within vs. between-subject effects of intranasal oxytocin on the neural response to cooperative and non-cooperative social interactions


Journal Title:



Volume 78


, Pages 22-30

Type of Work:

Article | Post-print: After Peer Review


The neuropeptide oxytocin (OT) plays a critical role in modulating social behavior across a wide range of vertebrate species. In humans, intranasal oxytocin (INOT) has been shown to modulate various aspects of social behavior, such as empathy, trust, in-group preference, and memory of socially relevant cues. Most INOT studies employ cross-sectional designs despite the enhanced statistical power and reduction in error variance associated with individual differences characteristic of within-subject designs. Using the Prisoner Dilemma task, which models a real-life dyadic social interaction, our group has systematically explored the effect of INOT on social cooperation and non-cooperation using a cross-sectional design. In the current study, we investigated if the main findings from our cross-sectional study could be replicated in a within-subject design using the same paradigm and whether new findings would emerge. We found OT to attenuate the ventral tegmental area response to reciprocated cooperation in women, an effect that is also present in our cross-sectional sample. However, other cross-sectional findings, especially those found in men, were not observed in this within-subject study. We hypothesize that the discrepancy can be explained by differing OT effects based on the degree of stimulus novelty/familiarity. Our within-subject study also revealed new effects not found previously in our cross-sectional study. Most importantly, OT treatment on scan 2 blocked amygdala habituation to unreciprocated cooperation found in a group that received placebo on both scans among men. Our results suggest that exogenous OT reduces the salience of positive social interactions among women and prevents habituation to negative social interactions among men. These findings may have implications for the potential clinical utility of OT as a treatment for psychiatric disorders.

Copyright information:

© 2017 Elsevier Ltd

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