Chronic opioid pretreatment potentiates the sensitization of fear learning by trauma
Open accessAbstract
Despite the large comorbidity between PTSD and opioid use disorders, as well as the common treatment of physical injuries resulting from trauma with opioids, the ability of opioid treatments to subsequently modify PTSD-related behavior has not been well studied. Using the stress-enhanced fear learning (SEFL) model for PTSD, we characterized the impact of chronic opioid regimens on the sensitization of fear learning seen following traumatic stress in mice. We demonstrate for the first time that chronic opioid pretreatment is able to robustly augment associative fear learning. Highlighting aversive learning as the cognitive process mediating this behavioral outcome, these changes were observed after a considerable period of drug cessation, generalized to learning about multiple aversive stimuli, were not due to changes in stimulus sensitivity or basal anxiety, and correlated with a marker of synaptic plasticity within the basolateral amygdala. Additionally, these changes were not observed when opioids were given after the traumatic event. Moreover, we found that neither reducing the frequency of opioid administration nor bidirectional manipulation of acute withdrawal impacted the subsequent enhancement in fear learning seen. Given the fundamental role of associative fear learning in the generation and progression of PTSD, these findings are of direct translational relevance to the comorbidity between opioid dependence and PTSD, and they are also pertinent to the use of opioids for treating pain resulting from traumas involving physical injuries.
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The potentiation of fear learning by chronic opioid pretreatment was not observed when opioids were given after the traumatic event and lasted beyond discontinuation of drug exposure.
“These changes were not observed when opioids were given after the traumatic event, and potentiation lasted beyond discontinuation of drug exposure.”
From Food Addiction and Psychosocial Adversity: Biological Embedding, Contextual Factors, and Public Health Implications (2020) · cites this paper as [185]
In animal models, chronic opioid pretreatment robustly augments associative fear learning.
“In animal models, chronic opioid pretreatment is able to robustly augment associative fear learning [185].”
From Food Addiction and Psychosocial Adversity: Biological Embedding, Contextual Factors, and Public Health Implications (2020) · cites this paper as [185]
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Cites
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“Notably, although shock was used here for the mild stressor, we have also found SEFL using a loud auditory startle stimulus [17], demonstrating that this phenomenon is not specific to the aversive stimulus employed.”
Method
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- Authors
- Pennington, Z. T., Trott, J. M., Rajbhandari, A. K., Li, K., Walwyn, W. M., Evans, C. J., & Fanselow, M. S.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Fanselow, Michael S.
- ORCID
- Venue
- Neuropsychopharmacology
- Published
- 2019-12-02
- Volume
- 45
- Issue
- 3
- Pages
- 482-490
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC6968993
- OpenAlex
- W2984823446
- Cited by
- 19
- References
- 39
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 5 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 2
- FWCI
- 2.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Neuropsychopharmacology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (DA005010, 5T32DA007135)
- U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (RO1 MH115678, F31 MH108257-02)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- opioid use disorder, post-traumatic stress disorder, stress-enhanced fear learning, traumatic stress, opioid withdrawal, synaptic plasticity, basolateral amygdala, aversive learning
- MeSH terms
- Analgesics, Opioid, Animals, Drug Implants, Fear, Female, Learning, Male, Mice, Inbred C57BL, Morphine, Opioid-Related Disorders, Stress Disorders, Post-Traumatic, Mice
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