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  Augmenting extinction learning with d-cycloserine reduces return of fear: A randomized, placebo-controlled fMRI study

Ebrahimi, C., Gechter, J., Lueken, U., Schlagenhauf, F., Wittchen, H.-U., Hamm, A. O., et al. (2020). Augmenting extinction learning with d-cycloserine reduces return of fear: A randomized, placebo-controlled fMRI study. Neuropsychopharmacology, 45(3), 499-506. doi:10.1038/s41386-019-0552-z.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0005-BEFE-8 Version Permalink: http://hdl.handle.net/21.11116/0000-0005-BF0B-9
Genre: Journal Article

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 Creators:
Ebrahimi, Claudia1, Author
Gechter, Johanna1, Author
Lueken, Ulrike2, Author
Schlagenhauf, Florian1, 3, Author              
Wittchen, Hans-Ulrich4, 5, Author
Hamm, Alfons O.6, Author
Ströhle, Andreas1, Author
Affiliations:
1Charité University Medicine Berlin, Germany, ou_persistent22              
2Department of Psychology, Humboldt University Berlin, Germany, ou_persistent22              
3Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549              
4Department of Psychiatry and Psychotherapy, TU Dresden, Germany, ou_persistent22              
5Department of Psychiatry and Psychotherapy, Ludwig Maximilians University Munich, Germany, ou_persistent22              
6Institute of Physiological and Clinical Psychology, Ernst Moritz Arndt University of Greifswald, Germany, ou_persistent22              

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Free keywords: Consolidation; Extinction; Fear conditioning
 Abstract: d-cycloserine (DCS), a partial NMDA-receptor agonist, seems to be a promising enhancer for exposure therapy in anxiety disorders. It has been tested successfully in animal models of fear extinction, where DCS enhanced extinction learning. Applied in clinical studies, results of DCS-augmented exposure therapy remain ambiguous, calling for a deeper understanding of the underlying mechanisms of DCS and its exact effect on extinction learning and return of fear (ROF) in humans. In the present study, we investigated the effect of DCS-augmented extinction learning on behavioral, psychophysiological, and neural indices of ROF during a 24-h delayed recall test. Thirty-seven participants entered a randomized, placebo-controlled, double-blind, 3-day fear conditioning and delayed extinction fMRI design. One hour before extinction training, participants received an oral dose of 50 mg of DCS or a placebo. Behavioral arousal ratings revealed a generalized ROF during extinction recall in the placebo but not DCS group. Furthermore, participants receiving DCS compared to placebo showed attenuated differential BOLD responses in left posterior hippocampus and amygdala from extinction learning to extinction recall, due to increased hippocampal recruitment in placebo and trendwise decreased amygdala responding in DCS subjects. Our finding that DCS reduces ROF in arousal ratings and neural structures subserving defensive reactions support a role for NMDA receptors in extinction memory consolidation and encourage further translational research.

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Language(s): eng - English
 Dates: 2019-09-222019-05-252019-10-142019-10-212020-02
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1038/s41386-019-0552-z
Other: Epub 2019
PMID: 31634897
PMC: PMC6969173
 Degree: -

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Title: Neuropsychopharmacology
Source Genre: Journal
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Publ. Info: New York, NY
Pages: - Volume / Issue: 45 (3) Sequence Number: - Start / End Page: 499 - 506 Identifier: ISSN: 0893-133X
CoNE: https://pure.mpg.de/cone/journals/resource/954925558485