Cited by 110Memory and Neural MechanismsPosttraumatic Stress Disorder ResearchRenin-Angiotensin System Studies

Angiotensin type 1 receptor inhibition enhances the extinction of fear memory

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Marvar, Paul J., Goodman, Jared, Fuchs, Sebastien, Choi, Dennis C., Banerjee, Sunayana, Ressler, Kerry J.·2014·Biological Psychiatry

Abstract

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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  1. [45]Coughlin SS 2011 Post-traumatic Stress Disorder and Cardiovascular Disease Open Cardiovasc Med J 5 164 170 21792377 PMC3141329
  2. [76]Wright JW Harding JW 2008 The angiotensin AT4 receptor subtype as a target for the treatment of memory dysfunction associated with Alzheimer’s disease J Renin Angiotensin Aldosterone Syst 9 226 237 19126664

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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)
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
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

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