Kappa opioid receptor in nucleus accumbens regulates depressive-like behaviors following prolonged morphine withdrawal in mice
Jinyu Zhang,
Ye Lu,
Min Jia,
Yuying Bai,
Lulu Sun,
Ziqing Dong,
Wenrong Tian,
Fangyuan Yin,
Shuguang Wei,
Yunpeng Wang
Affiliations
Jinyu Zhang
Department of Psychiatry and Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China; College of Forensic Science, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China
Ye Lu
College of Forensic Science, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China
Min Jia
Department of Psychiatry and Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China; Shaanxi Belt and Road Joint Laboratory of Precision Medicine in Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China
Yuying Bai
College of Forensic Science, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China
Lulu Sun
College of Forensic Science, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China
Ziqing Dong
Department of Psychiatry and Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China; Shaanxi Belt and Road Joint Laboratory of Precision Medicine in Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China
Wenrong Tian
College of Forensic Science, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China
Fangyuan Yin
College of Forensic Science, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China
Shuguang Wei
College of Forensic Science, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China; Corresponding author
Yunpeng Wang
Department of Psychiatry and Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China; Corresponding author
Summary: 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 antagonist norBNI improved depressive-like behaviors and reversed PSD95, synaptophysin, p-ERK, p-CREB, and BDNF in NAc. This study demonstrated the important role of striatal KOR in morphine withdrawal-related depressive-like behaviors and offered therapeutic potential for the treatment of withdrawal-related depression.
