Induction of ΔFosB in the Periaqueductal Gray by Stress Promotes Active Coping Responses
Open accessAbstract
We analyzed the influence of the transcription factor DeltaFosB on learned helplessness, an animal model of affective disorder wherein a subset of mice exposed to inescapable stress (IS) develop a deficit in escape behavior. Repeated IS induces DeltaFosB in the ventrolateral periaqueductal gray (vlPAG), and levels of the protein are highly predictive of an individual's subsequent behavorial deficit-with the strongest DeltaFosB induction observed in the most resilient animals. Induction of DeltaFosB by IS predominates in substance P-positive neurons in the vlPAG, and the substance P gene, a direct target for DeltaFosB, is downregulated upon DeltaFosB induction. Local overexpression of DeltaFosB in the vlPAG using viral-mediated gene transfer dramatically reduces depression-like behaviors and inhibits stress-induced release of substance P. These results indicate that IS-induced accumulation of DeltaFosB in the vlPAG desensitizes substance P neurons enriched in this area and opposes behavioral despair by promoting active defense responses.
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In learned helplessness models, depending on severity and duration of inescapable foot shock, about 30% of animals develop learned helplessness while another subset escapes with latencies seen in unstressed animals.
“Depending on the severity and duration of exposure to inescapable foot shock, a subset of animals, ~30% in some studies, develop learned helplessness—they fail to escape when escape becomes possible, while another subset (termed resilient) escapes with latencies seen in unstressed animals29.”
From Neurobiology of resilience (2012) · cites this paper as [29]
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- Authors
- Berton, O., Covington, H. E., Ebner, K., Tsankova, N. M., Carle, T. L., Ulery, P., Bhonsle, A., Barrot, M., Krishnan, V., Singewald, G. M., Singewald, N., Birnbaum, S., Neve, R. L., & Nestler, E. J.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Universität Innsbruck (AT)
- Centre National de la Recherche Scientifique (FR)
- Harvard University (US)
- Corresponding author
- Nestler, Eric J.
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2007-07
- Volume
- 55
- Issue
- 2
- Pages
- 289-300
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W1990957877
- Cited by
- 129
- References
- 66
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 6 · 2023: 3 · 2022: 4 · 2021: 7 · 2020: 5 · 2019: 4 · 2018: 9 · 2017: 6 · 2016: 8 · 2015: 7 · 2014: 8 · 2013: 9 · 2012: 14
- FWCI
- 3.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2208 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- National Institute of Mental Health
- Fondation pour la Recherche Médicale
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- ΔFosB, periaqueductal gray, learned helplessness, inescapable stress, substance P, depression-like behavior, active coping, stress resilience, transcription factors, viral gene delivery, behavioral despair, mood disorders
- MeSH terms
- Adaptation, Physiological, Adaptation, Psychological, Analysis of Variance, Animals, Escape Reaction, Gene Expression Regulation, Helplessness, Learned, Male, Mice, Inbred C57BL, Neurons, Nucleus Accumbens, Periaqueductal Gray, Stress, Psychological, Substance P, Proto-Oncogene Proteins c-fos, Rats, Sprague-Dawley, Mice, Rats
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