, Volume 236, Issue 1, pp 293–301 | Cite as

Post-retrieval oxytocin facilitates next day extinction of threat memory in humans

  • Jingchu Hu
  • Zijie Wang
  • Xiaoyi Feng
  • Cheng LongEmail author
  • Daniela SchillerEmail author
Original Investigation



Memories can return to a labile state and become amenable to modification by pharmacological and behavioral manipulations after retrieval. This process may reduce the impact of aversive memories and provide a promising therapeutic technique for the treatment of anxiety disorders. A growing body of evidence suggests that the mammalian neuropeptide oxytocin (OT) plays a role in the regulation of emotional memories in animals. However, the effects of OT on threat memory in humans remain largely unknown.


This study aimed to investigate the effects of OT administration following threat memory retrieval on subsequent memory expression in human participants.


In a double-blind, randomized, placebo-controlled, between-subject design, 61 healthy human individuals completed a 3-day experiment. All the participants underwent threat conditioning on day 1. On day 2, the participants were randomized to receive an intranasal dose of OT (40 IU) or placebo after memory retrieval, or an intranasal dose of OT (40 IU) without retrieval. On day 3, the participants were tested for extinction and reinstatement.


On day 3, all groups showed equivalent stimulus discrimination during the early phase of extinction. However, the group that received OT following a memory reminder showed a greater decline in stimulus discrimination by the late phase of extinction relative to the two other groups.


The results indicate that OT did not block reconsolidation to prevent the return of threat memory but rather interacted with post-retrieval processes to facilitate next day extinction. The study provides novel preliminary evidence for the role of OT in human threat memory.


Oxytocin Fear conditioning Extinction Reactivation Reconsolidation 



The authors thank Xiaoting Chen for the assistance with data collection and Xifu Zheng and Li Yang for the helpful discussions.

Author contributions

J.H., C.L., and D.S. designed the study. Z.W. and X.F. collected and scored the data. J.H. analyzed the data. D.S. contributed to data analysis; J.H. and D.S. wrote the first draft of the manuscript. All the authors contributed to the final version of the manuscript.

Funding information

Funding was provided by the NIH MH105535 R01 grant and a Klingenstein-Simons Fellowship Award in the Neurosciences to D.S.; a grant from the National Natural Science Foundation of China (31871170) to C.L.; and the PhD Research Startup Foundation of Guangdong province to J.H.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

213_2018_5074_MOESM1_ESM.docx (210 kb)
Figure S1 (DOCX 210 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of Life SciencesSouth China Normal UniversityGuangzhouChina
  2. 2.School of Psychology and Center for Studies of Psychological ApplicationSouth China Normal UniversityGuangzhouChina
  3. 3.Department of PsychiatryIcahn School of Medicine at Mount SinaiNew YorkUSA
  4. 4.Department of NeuroscienceIcahn School of Medicine at Mount SinaiNew YorkUSA
  5. 5.Friedman Brain InstituteIcahn School of Medicine at Mount SinaiNew YorkUSA

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