A novel approach to PTSD modeling in rats reveals alternating patterns of limbic activity in different types of stress reaction
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Human reactions to trauma exposure are extremely diverse, with some individuals exhibiting only time-limited distress and others qualifying for posttraumatic stress disorder diagnosis (PTSD). Furthermore, whereas most PTSD patients mainly display fear-based symptoms, a minority of patients display a co-morbid anhedonic phenotype. We employed an individual profiling approach to model these intriguing facets of the psychiatric condition in underwater-trauma exposed rats. Based on long-term assessments of anxiety-like and anhedonic behaviors, our analysis uncovered three separate phenotypes of stress response; an anxious, fear-based (38%), a co-morbid, fear-anhedonic (15%), and an exposed-unaffected group (47%). Immunohistochemical assessments for cellular activation (c-Fos) and activation of inhibition (c-Fos+GAD67) revealed a differential involvement of limbic regions and distinct co-activity patterns for each of these phenotypes, validating the behavioral categorization. In accordance with recent neurocognitive hypotheses for posttraumatic depression, we show that enhanced pretrauma anxiety predicts the progression of posttraumatic anhedonia only in the fear-anhedonic phenotype.
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The stratification approach followed is in line with an emerging trend in the literature, taking into account individual differences in behavioral outcomes when examining underlying neurobiology.
“We should briefly note that the stratification approach that we have followed is in line with an emerging trend in the literature, taking into account individual differences in behavioral outcomes when examining underlying neurobiology36,39–44.”
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- Authors
- Ritov, G., Boltyansky, B., & Richter-Levin, G.
- Affiliations
- University of Haifa (IL)
- Venue
- Molecular Psychiatry
- Published
- 2015-11-10
- Volume
- 21
- Issue
- 5
- Pages
- 630-641
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC5414084
- OpenAlex
- W2137703000
- Cited by
- 92
- References
- 44
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 7 · 2023: 6 · 2022: 9 · 2021: 8 · 2020: 11 · 2019: 11 · 2018: 16 · 2017: 10 · 2016: 3
- FWCI
- 12.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Psychiatry (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense (W81XWH)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- post-traumatic stress disorder, anhedonia, fear, anxiety-like behavior, limbic system, c-fos, GAD67, post-traumatic depression, stress response
- MeSH terms
- Animals, Anxiety, Disease Models, Animal, Fear, Glutamate Decarboxylase, Immunohistochemistry, Limbic System, Male, Phenotype, Random Allocation, Stress Disorders, Post-Traumatic, Proto-Oncogene Proteins c-fos, Rats, Sprague-Dawley, Rats, Anhedonia
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