The effect of intranasal oxytocin treatment on conditioned fear extinction and recall in a healthy human sample
Open accessAbstract
Rationale To improve outcomes for patients undergoing extinction-based therapies (e.g., exposure therapy) for anxiety disorders such as post-traumatic stress disorder (PTSD), there has been interest in identifying pharmaceutical compounds that might facilitate fear extinction learning and recall. Oxytocin (OT) is a mammalian neuropeptide that modulates activation of fear extinction-based neural circuits and fear responses. Little is known, however, about the effects of OT treatment on conditioned fear responding and extinction in humans.Objectives The purpose of the present study was to assess the effects of OT in a fear-potentiated startle task of fear conditioning and extinction.Methods A double-blind, placebo-controlled study of 44 healthy human participants was conducted. Participants underwent a conditioned fear acquisition procedure, after which they were randomized to treatment group and delivered OT (24 IU) or placebo via intranasal (IN) spray. Forty-five minutes after treatment, participants underwent extinction training. Twenty-four hours later, subjects were tested for extinction recall.Results Relative to placebo, the OT group showed increased fear-potentiated startle responding during the earliest stage of extinction training relative to placebo; however, all treatment groups showed the same level of reduced responding by the end of extinction training. Twenty-four hours later, the OT group showed significantly higher recall of extinction relative to placebo.Conclusions The current study provides preliminary evidence that OT may facilitate fear extinction recall in humans. These results support further study of OT as a potential adjunctive treatment for extinction-based therapies in fear-related disorders.
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Oxytocin has demonstrated the ability to enhance fear extinction in preclinical models and among healthy individuals.
“Oxytocin has demonstrated the ability to enhance fear extinction in preclinical models (Eskandarian et al., 2013) and among healthy individuals (Acheson et al., 2013; Eckstein et al., 2014).”
From Augmenting Prolonged Exposure therapy for PTSD with intranasal oxytocin: a randomized, placebo-controlled pilot trial (2018) · cites this paper as Acheson et al., 2013
In healthy participants, intranasal OXT has been shown to facilitate the extinction of conditioned fear.
“In healthy participants, intranasal OXT has been shown to facilitate the extinction of conditioned fear (Acheson et al., 2013;Eckstein et al., 2015).”
From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Acheson et al., 2013
Three studies investigated the effects of oxytocin on startle response to learned threat cues after conditioning and on learned threat following extinction.
“Three studies investigated the effects of oxytocin on startle response to learned threat cues after conditioning and on learned threat following extinction (Acheson et al., 2013;Eckstein et al., 2015;Eckstein et al., 2016).”
From Meta-analytic review of the effects of a single dose of intranasal oxytocin on threat processing in humans (2018) · cites this paper as Acheson et al., 2013
OT administration increased (recall of) extinction learning in rodents and healthy males.
“Behaviorally, OT administration resulted in decreased subjective anxiety during a public speaking stressor in healthy individuals (de Oliveira et al, 2012) and increased (recall of) extinction learning in both rodents (Zoicas et al, 2014) and healthy males (Acheson et al, 2013).”
From Intranasal oxytocin administration dampens amygdala reactivity towards emotional faces in male and female PTSD patients (2016) · cites this paper as Acheson et al, 2013
Extinction of fear-potentiated startle in healthy humans could be enhanced with intranasal administration of oxytocin.
“For example, Acheson and colleagues showed that the extinction of fear-potentiated startle in healthy humans could be enhanced with the intranasal administration of oxytocin (86).”
From Conditioned fear associated phenotypes as robust, translational indices of trauma-, stressor-, and anxiety-related behaviors (2014) · cites this paper as [86]
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Acheson, D. T., Feifel, D., Kamenski, M., Mckinney, R., & Risbrough, V. B. (2015) · Depression and Anxiety · doi:10.1002/da.22362 · Cited by 44 · see citing works
Self-citationA precision medicine approach to oxytocin trials
Andari, E., Hurlemann, R., & Young, L. J. (2017) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2017_29 · Cited by 40 · see citing works
Acheson, D. T., Twamley, E. W., & Young, J. W. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00103 · Cited by 26 · see citing works
Self-citation
- Authors
- Acheson, D., Feifel, D., de Wilde, S., Mckinney, R., Lohr, J., & Risbrough, V.
- Affiliations
- University of California San Diego (US)
- Veterans Health Administration (US)
- Corresponding author
- Risbrough, Victoria
- Venue
- Psychopharmacology
- Published
- 2013-05-05
- Volume
- 229
- Issue
- 1
- Pages
- 199-208
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- PMC
- PMC5458114
- OpenAlex
- W2024925365
- Cited by
- 141
- References
- 65
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 5 · 2023: 5 · 2022: 6 · 2021: 10 · 2020: 11 · 2019: 11 · 2018: 19 · 2017: 14 · 2016: 12 · 2015: 16 · 2014: 17 · 2013: 7
- FWCI
- 9.47
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R34MH091285)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- oxytocin, fear extinction, extinction recall, fear conditioning, fear-potentiated startle, intranasal administration, post-traumatic stress disorder, anxiety disorders, adjunctive therapy
- MeSH terms
- Adult, Conditioning, Psychological, Extinction, Psychological, Fear, Female, Humans, Male, Oxytocin, Mental Recall, Reflex, Startle, Treatment Outcome, Young Adult
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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