The role of central amygdala corticotropin-releasing factor in predator odor stress-induced avoidance behavior and escalated alcohol drinking in rats
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Abstract
Post-traumatic stress disorder (PTSD) is characterized by avoidance of trauma-associated stimuli and amygdala hyperreactivity, and is highly co-morbid with alcohol use disorder (AUD). Our lab uses a predator odor (bobcat urine) stress model that produces conditioned avoidance of an odor-paired context in a subset of rats, mirroring avoidance symptoms that manifest in some but not all humans exposed to trauma. We previously showed that after predator odor stress, Avoiders exhibit escalated operant alcohol self-administration (SA), higher aversion-resistant operant alcohol responding, hyperalgesia, and greater anxiety-like behavior compared to unstressed Controls. We also showed previously that systemic antagonism of corticotropin-releasing factor-1 receptors (CRFR1) reduced escalation of operant alcohol SA in rats not indexed for avoidance, that corticotropin-releasing factor (CRF) infusions into the central amygdala (CeA) produced conditioned place avoidance in stress-naïve rats, and that intra-CeA infusion of a CRFR1 antagonist reduced hyperalgesia in Avoiders. Here, we show that avoidance behavior is persistent after repeated predator odor exposure. In addition, Avoiders showed lower weight gain than Controls after predator odor re-exposure. In the brain, higher avoidance was correlated with higher number of c-Fos + cells and CRF immunoreactivity in the CeA. Finally, we show that intra-CeA CRFR1 antagonism reversed post-stress escalation of alcohol SA and reduced avoidance behavior in Avoiders. Collectively, these findings suggest that elucidation of the mechanisms by which CRFR1-gated CeA circuits regulate avoidance behavior and alcohol SA may lead to better understanding of the neural mechanisms underlying co-morbid PTSD and AUD.
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The central amygdala is particularly implicated in compulsive drug seeking and drug seeking after extended use, dependence and withdrawal, or stress.
“The central amygdala is particularly implicated in compulsive drug seeking and drug seeking after extended use, dependence and withdrawal, or stress66,76.”
From A dual-pathway architecture for stress to disrupt agency and promote habit (2025) · cites this paper as [76]
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A dual-pathway architecture for stress to disrupt agency and promote habit
Giovanniello, J. R., Paredes, N., Wiener, A., Ramírez-Armenta, K., Oragwam, C., Uwadia, H. O., Yu, A. L., Lim, K., Pimenta, J. S., Vilchez, G. E., et al. (2025) · Nature · doi:10.1038/s41586-024-08580-w · Cited by 30 · see citing works
- Authors
- Weera, M. M., Schreiber, A. L., Avegno, E. M., & Gilpin, N. W.
- Affiliations
- Louisiana State University Health Sciences Center New Orleans (US)
- Southeast Louisiana Veterans Health Care System (US)
- Corresponding author
- Weera, Marcus M.
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2020-04
- Volume
- 166
- Pages
- 107979
- ISSN
- 0028-3908 (ISSN-L)
- PMC
- PMC7442223
- OpenAlex
- W3001103562
- Cited by
- 54
- References
- 38
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 9 · 2023: 8 · 2022: 9 · 2021: 8 · 2020: 5
- FWCI
- 4.19
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Neuropharmacology (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Keywords
- central amygdala, corticotropin-releasing factor, avoidance conditioning, alcohol self-administration, alcoholism, post-traumatic stress disorder, c-fos, weight gain, hyperalgesia, anxiety-like behavior
- MeSH terms
- Alcohol Drinking, Animals, Avoidance Learning, Corticotropin-Releasing Hormone, Male, Odorants, Predatory Behavior, Stress, Psychological, Rats, Wistar, Lynx, Rats, Central Amygdaloid Nucleus
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