期刊
BIOLOGICAL PSYCHIATRY
卷 78, 期 3, 页码 194-202出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2014.10.015
关键词
Fear extinction; fMRI; Oxytocin; Psychophysiology; Skin conductance
资金
- Starting Independent Researcher Grant (Neuromodulation of Emotion research group)
- Ministry of Innovation, Science, Research & Technology of the German State of North Rhine-Westphalia [91132720]
- University of Bonn [91132720]
- National Natural Science Foundation of China [91132720]
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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