Chronic stress enhanced fear memories are associated with increased amygdala zif268 mRNA expression and are resistant to reconsolidation
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The chronically stressed brain may present a vulnerability to develop maladaptive fear-related behaviors in response to a traumatic event. In rodents, chronic stress leads to amygdala hyperresponsivity and dendritic hypertrophy and produces a post traumatic stress disorder (PTSD)-like phenotype that includes exaggerated fear learning following Pavlovian fear conditioning and resistance to extinction. It is unknown whether chronic stress-induced enhanced fear memories are vulnerable to disruption via reconsolidation blockade, as a novel therapeutic approach for attenuating exaggerated fear memories. We used a chronic stress procedure in a rat model (wire mesh restraint for 6h/d/21d) to create a vulnerable brain that leads to a PTSD-like phenotype. We then examined freezing behavior during acquisition, reactivation and after post-reactivation rapamycin administration (i.p., 40mg/kg) in a Pavlovian fear conditioning paradigm to determine its effects on reconsolidation as well as the subsequent functional activation of limbic structures using zif268 mRNA. Chronic stress increased amygdala zif268 mRNA during fear memory retrieval at reactivation. Moreover, these enhanced fear memories were unaffected by post reactivation rapamycin to disrupt long-term fear memory. Also, post-reactivation long term memory processing was also associated with increased amygdala (LA and BA), and decreased hippocampal CA1 zif268 mRNA expression. These results suggest potential challenges for reconsolidation blockade as an effective approach in treating exaggerated fear memories, as in PTSD. Our findings also support chronic stress manipulations combined with fear conditioning as a useful preclinical approach to study a PTSD-like phenotype.
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Older and stronger memories may require additional retrieval procedures for updating to take place, as do individual differences such as exposure to chronic stress and high trait anxiety.
“Similarly, older and stronger memories may require additional retrieval procedures for updating to take place (e.g. [135,136]), as do individual differences such as exposure to chronic stress and high trait anxiety [130,137].”
From Multiple memory systems, multiple time points: How science can inform treatment to control the expression of unwanted emotional memories (2018) · cites this paper as [137]
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Additional file 3 of Lack of drug-induced post-retrieval amnesia for auditory fear memories in rats
Luyten, L., Schnell, A. E., Schroyens, N., & Beckers, T. (2021) · Figshare · doi:10.6084/m9.figshare.13646953
Additional file 2 of Lack of drug-induced post-retrieval amnesia for auditory fear memories in rats
Luyten, L., Schnell, A. E., Schroyens, N., & Beckers, T. (2021) · Figshare · doi:10.6084/m9.figshare.13646950
Additional file 1 of Lack of drug-induced post-retrieval amnesia for auditory fear memories in rats
Luyten, L., Schnell, A. E., Schroyens, N., & Beckers, T. (2021) · Figshare · doi:10.6084/m9.figshare.13646947
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- Authors
- Hoffman, A. N., Parga, A., Paode, P. R., Watterson, L. R., Nikulina, E. M., Hammer, R. P., & Conrad, C. D.
- Affiliations
- University of California, Los Angeles (US)
- University of Arizona College of Medicine- Phoenix (US)
- Arizona State University (US)
- Corresponding author
- Conrad, Cheryl D.
- Venue
- Neurobiology of Learning and Memory
- Publisher
- Elsevier BV
- Published
- 2015-04
- Volume
- 120
- Pages
- 61-68
- ISSN
- 1074-7427 (ISSN-L)
- PMC
- PMC4397163
- OpenAlex
- W1984829191
- Cited by
- 45
- References
- 57
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 5 · 2023: 2 · 2022: 3 · 2021: 7 · 2020: 5 · 2019: 4 · 2018: 5 · 2017: 5 · 2016: 2 · 2015: 1
- FWCI
- 2.61
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Learning and Memory (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (MH073930, R01MH073930)
- National Institute on Drug Abuse (R01DA026451, DA026451)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Keywords
- chronic stress, fear memory, reconsolidation blockade, Zif268, amygdala, post-traumatic stress disorder, fear conditioning, rapamycin, hippocampal CA1, fear extinction, freezing behavior, memory reactivation
- MeSH terms
- Memory Consolidation, Amygdala, Animals, Conditioning, Classical, Fear, Male, Memory, RNA, Messenger, Stress, Psychological, Rats, Sprague-Dawley, In Situ Hybridization, Rats, Early Growth Response Protein 1
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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