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

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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

DOI 10.1016/j.biopsych.2013.08.024PMC PMC3975818

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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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Authors: Marvar, P. J., Goodman, J., Fuchs, S., Choi, D. C., Banerjee, S., & Ressler, K. J.
Affiliations: Emory University (US)
ORCID: Marvar, Paul J.
Goodman, Jared
Ressler, Kerry J.
Venue: Biological Psychiatry
Publisher: Elsevier BV
Published: 2014-06
Volume: 75
Issue: 11
Pages: 864-872
ISSN: 0006-3223 (ISSN-L)
DOI: 10.1016/j.biopsych.2013.08.024
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
FWCI: 4.37
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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Angiotensin Type 1 Receptor Inhibition Enhances the Extinction of Fear Memory

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