, Volume 233, Issue 23–24, pp 3905–3919 | Cite as

Oxytocin modulates hemodynamic responses to monetary incentives in humans

  • Brian J. Mickey
  • Joseph Heffernan
  • Curtis Heisel
  • Marta Peciña
  • David T. Hsu
  • Jon-Kar Zubieta
  • Tiffany M. LoveEmail author
Original Investigation



Oxytocin is a neuropeptide widely recognized for its role in regulating social and reproductive behavior. Increasing evidence from animal models suggests that oxytocin also modulates reward circuitry in non-social contexts, but evidence in humans is lacking.


We examined the effects of oxytocin administration on reward circuit function in 18 healthy men as they performed a monetary incentive task.


The blood oxygenation level-dependent (BOLD) signal was measured using functional magnetic resonance imaging in the context of a randomized, double-blind, placebo-controlled, crossover trial of intranasal oxytocin.


We found that oxytocin increases the BOLD signal in the midbrain (substantia nigra and ventral tegmental area) during the late phase of the hemodynamic response to incentive stimuli. Oxytocin’s effects on midbrain responses correlated positively with its effects on positive emotional state. We did not detect an effect of oxytocin on responses in the nucleus accumbens. Whole-brain analyses revealed that oxytocin attenuated medial prefrontal cortical deactivation specifically during anticipation of loss.


Our findings demonstrate that intranasal administration of oxytocin modulates human midbrain and medial prefrontal function during motivated behavior. These findings suggest that endogenous oxytocin is a neurochemical mediator of reward behaviors in humans—even in a non-social context—and that the oxytocinergic system is a potential target of pharmacotherapy for psychiatric disorders that involve dysfunction of reward circuitry.


Oxytocin Reward FMRI 



This research was supported by the National Center for Research Resources (UL1 RR 024986), now the National Center for Advancing Translational Sciences (UL1 TR 000433). BJM was supported by the NIMH (K23 MH 092648). The authors thank Thomas Chenevert, PhD, for his help and advice in scanning; technologists Suzan Lowe BA, RT(R)(MR), and Sara Easler BA, RT(R)(MR), for their assistance in collecting imaging data; and Amy Skyles, PharmD, and Mona Moore, MS, RAC, at the Michigan Institute for Clinical and Health Research for providing regulatory support and guidance.

Compliance with ethical standards

Conflict of interest

During the 5-year period prior to submission, BJM served as a consultant to Alkermes, Inc., for work unrelated to this manuscript.

Supplementary material

213_2016_4423_MOESM1_ESM.docx (113 kb)
ESM 1 (DOCX 112 kb)
213_2016_4423_Fig7_ESM.png (98 kb)
Figure S1 (PNG 97 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Brian J. Mickey
    • 1
    • 2
    • 3
  • Joseph Heffernan
    • 2
  • Curtis Heisel
    • 2
  • Marta Peciña
    • 1
    • 2
  • David T. Hsu
    • 1
    • 2
    • 4
  • Jon-Kar Zubieta
    • 1
    • 2
    • 3
  • Tiffany M. Love
    • 1
    • 2
    • 3
    Email author
  1. 1.Department of PsychiatryUniversity of Michigan Medical SchoolAnn ArborUSA
  2. 2.Molecular and Behavioral Neuroscience InstituteUniversity of MichiganAnn ArborUSA
  3. 3.Department of PsychiatryUniversity of Utah School of MedicineSalt Lake CityUSA
  4. 4.Department of PsychiatryStony Brook School of MedicineNew YorkUSA

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