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Effects of D-Cycloserine on Extinction: Translation From Preclinical to Clinical Work
Abstract
Administration of benzodiazepines or serotonin reuptake inhibitors in combination with behavior therapy for the treatment of many anxiety disorders has generally lead to only modest gains. In this article we suggest that pharmacotherapy aimed not at treating the symptoms of anxiety but instead aimed at improving the learning that takes place in exposure therapy might actually improve the effectiveness of exposure therapy. This idea was based on animal work showing that the partial N-methyl-D-aspartate (NMDA) agonist D-cycloserine (DCS) facilitated extinction of fear when given either before or shortly after exposure to fearful cues, reduced return of fear that is normally seen when extinction training is followed by stress, and led to generalized extinction, where DCS given in combination with exposure to one fearful cue led to extinction to another cue previously paired with the same aversive event. These finding suggested that DCS might facilitate exposure-based psychotherapy, which was verified in a small clinical study showing that DCS facilitated exposure therapy for fear of heights in a well-controlled virtual reality environment.
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“Similar impairments of fear recall and additional enhancements of fear extinction are observed following acute antibiotic exposure in humans and rodents (Bach et al., 2018;Davis et al., 2006;Rodrigues et al., 2014).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Davis et al., 2006
In the citing paper
“Preclinical research has demonstrated that DCS facilitates extinction learning and memory in rodent models (Davis et al, 2006; Ledgerwood et al, 2003; Walker et al, 2002).”
From D-cycloserine augmentation of exposure therapy for post-traumatic stress disorder: a pilot randomized clinical trial (2014) · cites this paper as Davis et al, 2006
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Metadata
- Authors
- Davis, M., Ressler, K., Rothbaum, B. O., & Richardson, R.
- Affiliations
- Emory University (US)
- UNSW Sydney (AU)
- Corresponding author
- Davis, Michael
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2006-08
- Volume
- 60
- Issue
- 4
- Pages
- 369-375
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2162692973
- Semantic Scholar
- 4b2fc25139b7de7848a13aa43da593a50f3d77c0
- Cited by
- 498
- References
- 43
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 6 · 2023: 9 · 2022: 13 · 2021: 13 · 2020: 10 · 2019: 22 · 2018: 19 · 2017: 25 · 2016: 14 · 2015: 36 · 2014: 32 · 2013: 38 · 2012: 48
- FWCI
- 2.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r21mh055555-02)
- National Institute of Mental Health (MH55555, MH-047840, MH069884, K01MH069884)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Keywords
- D-cycloserine, fear extinction, NMDA receptor agonist, exposure therapy, anxiety disorders, fear of heights, virtual reality exposure, return of fear, phobia treatment
- MeSH terms
- Animals, Antimetabolites, Conditioning, Classical, Cycloserine, Extinction, Psychological, Fear, Humans, Phobic Disorders, Cognitive Behavioral Therapy, Receptors, N-Methyl-D-Aspartate
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