biostudies-literatureZhang JNational Natural Science Foundation of ChinaNatural Science Basic Research Program of Shaanxi Province107536https://www.ebi.ac.uk/biostudies/studies/S-EPMC10448166biostudies-literatureUnknown26(9)Prolonged withdrawal from opioids leads to negative emotions. Kappa opioid receptor (KOR) plays an important role in opioid addiction and affective disorders. However, the underlying mechanism of KOR in withdrawal-related depression is still lacking. We found that escitalopram treatment had a limited effect in improving depression symptoms in heroin-dependent patients. In mice, we demonstrated prolonged (4 weeks) but not acute (24 h) withdrawal from morphine induced depressive-like behaviors. The number of c-Fos positive cells and the expression of KOR in the nucleus accumbens (NAc), were significantly increased in the prolonged morphine withdrawal mice. Conditional KOR knockdown in NAc significantly improved depressive-like behaviors. Repeated but not acute treatment with the KOR antagoniiScienceKappa opioid receptor in nucleus accumbens regulates depressive-like behaviors following prolonged morphine withdrawal in mice.PMC104481662021JM-027821718802022JQ-783Sun LYin FZhang JTian WLu YDong ZWei SJia MBai YWang YfalseKappa opioid receptor in nucleus accumbens regulates depressive-like behaviors following prolonged morphine withdrawal in mice.Prolonged withdrawal from opioids leads to negative emotions. Kappa opioid receptor (KOR) plays an important role in opioid addiction and affective disorders. However, the underlying mechanism of KOR in withdrawal-related depression is still lacking. We found that escitalopram treatment had a limited effect in improving depression symptoms in heroin-dependent patients. In mice, we demonstrated prolonged (4 weeks) but not acute (24 h) withdrawal from morphine induced depressive-like behaviors. The number of c-Fos positive cells and the expression of KOR in the nucleus accumbens (NAc), were significantly increased in the prolonged morphine withdrawal mice. Conditional KOR knockdown in NAc significantly improved depressive-like behaviors. Repeated but not acute treatment with the KOR antagoni2023-01-01T00:00:00Z2023 Sep2025-04-19T23:16:01.213Z2025-04-19T23:16:01.213ZS-EPMC104481663763607310.1016/j.isci.2023.107536