Angiotensin type 1 receptor inhibition enhances the extinction of fear memory
Open accessAbstract
Background The current effective treatment options for posttraumatic stress disorder (PTSD) are limited, and therefore the need to explore new treatment strategies is critical. Pharmacological inhibition of the renin-angiotensin system is a common approach to treat hypertension, and emerging evidence highlights the importance of this pathway in stress and anxiety. A recent clinical study from our laboratory provides evidence supporting a role for the renin-angiotensin system in the regulation of the stress response in patients diagnosed with PTSD.Methods With an animal model of PTSD and the selective angiotensin receptor type 1 (AT1) antagonist losartan, we investigated the acute and long-term effects of AT1 receptor inhibition on fear memory and baseline anxiety. After losartan treatment, we performed classical Pavlovian fear conditioning pairing auditory cues with footshocks and examined extinction behavior, gene expression changes in the brain, as well as neuroendocrine and cardiovascular responses.Results After cued fear conditioning, both acute and 2-week administration of losartan enhanced the consolidation of extinction memory but had no effect on fear acquisition, baseline anxiety, blood pressure, and neuroendocrine stress measures. Gene expression changes in the brain were also altered in mice treated with losartan for 2 weeks, in particular reduced amygdala AT1 receptor and bed nucleus of the stria terminalis c-Fos messenger RNA levels.Conclusions These data suggest that AT1 receptor antagonism enhances the extinction of fear memory and therefore might be a beneficial therapy for PTSD patients who have impairments in extinction of aversive memories.
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Angiotensin receptor AT1 antagonism with losartan enhances fear extinction learning (extinction recall) in mice.
“In addition, recent evidence from mouse studies implicates the renin–angiotensin system in the regulation of fear and anxiety responses as angiotensin receptor AT1 antagonism with the anti-hypertension drug losartan has been shown to enhance fear extinction learning [extinction recall; (87)].”
From Conditioned fear associated phenotypes as robust, translational indices of trauma-, stressor-, and anxiety-related behaviors (2014) · cites this paper as [87]
The renin-angiotensin system is implicated in the regulation of fear and anxiety responses.
“In addition, recent evidence from mouse studies implicates the renin–angiotensin system in the regulation of fear and anxiety responses as angiotensin receptor AT1 antagonism with the anti-hypertension drug losartan has been shown to enhance fear extinction learning [extinction recall; (87)].”
From Conditioned fear associated phenotypes as robust, translational indices of trauma-, stressor-, and anxiety-related behaviors (2014) · cites this paper as [87]
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- Authors
- Marvar, P. J., Goodman, J., Fuchs, S., Choi, D. C., Banerjee, S., & Ressler, K. J.
- Affiliations
- Emory University (US)
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2014-06
- Volume
- 75
- Issue
- 11
- Pages
- 864-872
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC3975818
- OpenAlex
- W2053674362
- Cited by
- 110
- References
- 82
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 6 · 2023: 9 · 2022: 11 · 2021: 17 · 2020: 4 · 2019: 19 · 2018: 5 · 2017: 7 · 2016: 5 · 2015: 11 · 2014: 7 · 2013: 1
- FWCI
- 4.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (P51OD011132)
- National Heart, Lung, and Blood Institute (K99HL107675, R00HL107675)
- National Institute of Mental Health (R01MH096764)
- National Center for Research Resources (P51RR000165)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Keywords
- angiotensin II type 1 receptor, losartan, fear extinction, post-traumatic stress disorder, renin-angiotensin system, fear conditioning, amygdala, bed nucleus of the stria terminalis, c-fos, anxiety, stress response, cardiovascular response, neuroendocrine response
- MeSH terms
- Animals, Disease Models, Animal, Extinction, Psychological, Fear, Male, Memory, Mice, Inbred C57BL, Stress Disorders, Post-Traumatic, Losartan, Angiotensin II Type 1 Receptor Blockers, Mice
About these checks
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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