Abstract
Rationale
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.
Objectives
This study aimed to investigate the effects of OT administration following threat memory retrieval on subsequent memory expression in human participants.
Methods
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.
Results
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.
Conclusions
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.
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Acknowledgments
The authors thank Xiaoting Chen for the assistance with data collection and Xifu Zheng and Li Yang for the helpful discussions.
Funding
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.
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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.
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This article belongs to a Special Issue on Psychopharmacology of Extinction.
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Hu, J., Wang, Z., Feng, X. et al. Post-retrieval oxytocin facilitates next day extinction of threat memory in humans. Psychopharmacology 236, 293–301 (2019). https://doi.org/10.1007/s00213-018-5074-6
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DOI: https://doi.org/10.1007/s00213-018-5074-6