Social Defeat Stress-Induced Behavioral Responses are Mediated by the Endogenous Kappa Opioid System
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Previous studies have demonstrated that repeated forced-swim stress-induced behaviors (including analgesia, immobility, and increased drug reward) were mediated by the release of endogenous prodynorphin-derived opioid peptides and subsequent activation of the kappa opioid receptor (KOR). We tested the generality of these effects using a different type of stressful situation: repeated social defeat. C57Bl/6 mice subjected to social defeat stress (SDS) over 3 days showed a characteristic stress-induced immobility and defeated-postural response, as well as stress-induced analgesia (SIA). Daily pretreatment with the KOR antagonist nor-binaltorphimine (nor-BNI, 10 mg/kg, i.p.) blocked the SIA and significantly reduced the stress-induced immobility on the second and third days of SDS exposure. In contrast, prodynorphin gene-disrupted mice showed no significant increase in immobility, socially defeated postures, or SIA following repeated exposure to SDS. Since both stress and the kappa opioid system can modulate the response to drugs of abuse, we tested the effects of SDS on cocaine-conditioned place preference (CPP). SDS-exposed mice conditioned with cocaine (15 mg/kg, s.c.) showed significant potentiation of place-preference for the drug-paired chamber over the responses of unstressed mice. Nor-BNI pretreatment blocked stress-induced potentiation of cocaine-CPP. Consistent with this result, mice lacking the prodynorphin gene did not show stress-induced potentiation of cocaine-CPP, whereas wild-type littermates did. The findings suggest that chronic SDS may activate the kappa opioid system to produce analgesia, immobility, social defeat postures, and resulting in a potentiation of the acute rewarding properties of cocaine.
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In some species or strains within species, tonic immobility may be the front-line defense response to extreme threat, even when the animal is not restrained.
“In some species or strains within species, however, tonic immobility may be the front-line defense response to extreme threat, even when the animal is not restrained.8,26,86”
From Fear and the Defense Cascade (2015) · cites this paper as [86]
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- Authors
- McLaughlin, J. P., Li, S., Valdez, J., Chavkin, T. A., & Chavkin, C.
- Affiliations
- Northeastern University (US)
- University of Washington (US)
- Corresponding author
- Chavkin, Charles
- Venue
- Neuropsychopharmacology
- Published
- 2005-08-17
- Volume
- 31
- Issue
- 6
- Pages
- 1241-1248
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC2096774
- OpenAlex
- W2023872238
- Cited by
- 253
- References
- 43
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 5 · 2023: 11 · 2022: 11 · 2021: 9 · 2020: 16 · 2019: 10 · 2018: 26 · 2017: 12 · 2016: 10 · 2015: 17 · 2014: 12 · 2013: 14 · 2012: 21
- FWCI
- 3.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5p01da015916-05)
- U.S. Public Health Service
- National Institute on Drug Abuse (R01DA11672, P01DA15916, R01DA016898, P01-DA015916, R03DA016656, R01DA011672, R03 DA 16656)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- social defeat stress, kappa opioid receptor, nor-binaltorphimine, prodynorphin, stress-induced analgesia, immobility, cocaine conditioned place preference, endogenous opioids, chronic stress
- MeSH terms
- Analysis of Variance, Anesthetics, Local, Animals, Behavior, Animal, Cocaine, Conditioning, Operant, Enkephalins, Male, Mice, Inbred C57BL, Naltrexone, Narcotic Antagonists, Pain Measurement, Protein Precursors, Reaction Time, Social Behavior, Stress, Psychological, Receptors, Opioid, kappa, Mice, Knockout, Immobility Response, Tonic, Mice
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