A randomized controlled trial of the effect of D-cycloserine on extinction and fear conditioning in humans
Abstract
Previous research has shown that D-cycloserine (DCS) facilitates extinction of Pavlovian fear conditioning in rats and enhances exposure therapy in humans. The aim of this study was to test the effect of DCS on extinction of fear conditioning in humans. In three experiments, 238 participants were given either DCS (50 or 500 mg) or placebo 2-3 h before extinction training following a differential shock conditioning paradigm. Clear extinction and recovery (return of fear) effects were observed on both skin conductance and self-reported shock expectancy measures in three studies. DCS had no influence on these effects. The same pattern was observed when the analysis was restricted to aware participants or to good conditioners, when fear-relevant cues (pictures of snakes) were used as the conditioned stimuli, or when analysis was restricted to heightened snake-fearful participants. These results suggest that DCS may not enhance the extinction, or prevent the recovery, of learned fear in a differential Pavlovian conditioning paradigm in humans. Further experimental research is needed to better understand the mechanisms underlying the therapeutic effects of DCS.
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D-cycloserine (DCS), an NMDA receptor partial agonist, facilitated extinction learning in rats; this finding was replicated in rodents but not replicated using skin conductance and expectancy ratings in humans.
“Walker et al. (64) found that d-cycloserine (DCS), an NMDA receptor partial agonist, facilitated extinction learning in rats; a finding that was later replicated by several other groups employing multiple types of fear learning paradigms in rodents [e.g., Ref. (65)] but not replicated using skin conductance and expectancy ratings in humans (66).”
From Conditioned fear associated phenotypes as robust, translational indices of trauma-, stressor-, and anxiety-related behaviors (2014) · cites this paper as [66]
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- Authors
- Guastella, A. J., Lovibond, P. F., Dadds, M. R., Mitchell, P., & Richardson, R.
- Affiliations
- UNSW Sydney (AU)
- Corresponding author
- Guastella, Adam J.
- Venue
- Behaviour Research and Therapy
- Publisher
- Elsevier BV
- Published
- 2007-04
- Volume
- 45
- Issue
- 4
- Pages
- 663-672
- ISSN
- 0005-7967 (ISSN-L)
- OpenAlex
- W2096494352
- Semantic Scholar
- 0698d51b56bea8b166c28594522d7bceeeba4089
- Cited by
- 106
- References
- 24
- Citations by year
- 2026: 2 · 2025: 1 · 2023: 4 · 2022: 3 · 2021: 7 · 2019: 2 · 2018: 5 · 2017: 3 · 2016: 2 · 2015: 7 · 2014: 11 · 2013: 6 · 2012: 15
- FWCI
- 3.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Behaviour Research and Therapy (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- D-cycloserine, fear extinction, fear conditioning, post-extinction recovery, skin conductance, fear of snakes, phobia treatment
- MeSH terms
- Adult, Conditioning, Classical, Cycloserine, Dose-Response Relationship, Drug, Electroshock, Extinction, Psychological, Fear, Female, Galvanic Skin Response, Humans, Male
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