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Biol Psychiatry. 2015 Aug 1;78(3):194-202. doi: 10.1016/j.biopsych.2014.10.015. Epub 2014 Oct 30.

Oxytocin facilitates the extinction of conditioned fear in humans.

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Department of Psychiatry, University of Bonn, Bonn, Germany.; Division of Medical Psychology, University of Bonn, Bonn, Germany.
Department of Psychiatry, University of Bonn, Bonn, Germany.; Departments of Psychiatry and Mental Health, The Johns Hopkins University, Baltimore, Maryland.
German Cancer Research Center, Heidelberg, Germany.
Key Laboratory for Neuroinformation, School of Life Science & Technology, University of Electronic Science & Technology of China, Chengdu, China.
Department of Psychiatry, University of Bonn, Bonn, Germany.; German Center for Neurodegenerative Diseases, Bonn, Germany.
Department of Psychiatry, University of Bonn, Bonn, Germany.; Division of Medical Psychology, University of Bonn, Bonn, Germany.. Electronic address:



Current neurocircuitry models of anxiety disorders posit a lack of inhibitory tone in the amygdala during acquisition of Pavlovian fear responses and deficient encoding of extinction responses in amygdala-medial prefrontal cortex circuits. Competition between these two responses often results in a return of fear, limiting control over anxiety. However, one hypothesis holds that a pharmacologic strategy aimed at reducing amygdala activity while simultaneously augmenting medial prefrontal cortex function could facilitate the extinction of conditioned fear.


Key among the endogenous inhibitors of amygdala activity in response to social fear signals is the hypothalamic peptide oxytocin. To address the question whether oxytocin can strengthen Pavlovian extinction beyond its role in controlling social fear, we conducted a functional magnetic resonance imaging experiment with 62 healthy male participants in a randomized, double-blind, parallel-group, placebo-controlled design. Specifically, subjects were exposed to a Pavlovian fear conditioning paradigm before receiving an intranasal dose (24 IU) of synthetic oxytocin or placebo.


Oxytocin, when administered intranasally after Pavlovian fear conditioning, was found to increase electrodermal responses and prefrontal cortex signals to conditioned fear in the early phase of extinction and to enhance the decline of skin conductance responses in the late phase of extinction. Oxytocin also evoked an unspecific inhibition of amygdalar responses in both phases.


Collectively, our findings identify oxytocin as a differentially acting modulator of neural hubs involved in Pavlovian extinction. This specific profile of oxytocin action may open up new avenues for enhancing extinction-based therapies for anxiety disorders.


Fear extinction; Oxytocin; Psychophysiology; Skin conductance; fMRI

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