Abstract
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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Acknowledgements
Dr Uwe Hochgeschwender generously provided the prodynorphin knockout mice. Joe Novak performed the mouse genotyping. The work was supported by USPHS grants and RO1-DA11672 and PO1-DA15916 to CC and RO3 DA16656 to JPM from the National Institute on Drug Abuse. JV was supported by the Physician Scientist Summer Training Program.
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McLaughlin, J., Li, S., Valdez, J. et al. Social Defeat Stress-Induced Behavioral Responses are Mediated by the Endogenous Kappa Opioid System. Neuropsychopharmacol 31, 1241–1248 (2006). https://doi.org/10.1038/sj.npp.1300872
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DOI: https://doi.org/10.1038/sj.npp.1300872
