title: Antagonism of κ opioid receptor in the nucleus accumbens prevents the depressive-like behaviors following prolonged morphine abstinence.
abstract: The association between morphine withdrawal and depressive-like symptoms is well documented, however, the role of dynorphin/κ opioid receptor system and the underlying neural substrates have not been fully understood. In the present study, we found that four weeks morphine abstinence after a chronic escalating morphine regimen significantly induced depressive-like behaviors in mice. Prodynorphin mRNA and protein levels were increased in the nucleus accumbens (NAc) after four weeks of morphine withdrawal. Local injection of κ opioid receptor antagonist nor-Binaltorphimine (norBNI) in the NAc significantly blocked the expression of depressive-like behaviors without influencing general locomotor activity. Thus, the present study extends previous findings by showing that prolonged morphine withdrawal-induced depressive-like behaviors are regulated by dynorphin/κ opioid receptor system, and shed light on the κ opioid receptor antagonists as potential therapeutic agents for the treatment of depressive-like behaviors induced by opiate withdrawal.
authors.affiliation: Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica and Collaborative Innovation Center for Brain Science, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Gui-Ying
authors.initials: GY
authors.lastname: Zan
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian 116044, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica and Collaborative Innovation Center for Brain Science, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Yu-Jun
authors.initials: YJ
authors.lastname: Wang
authors.affiliation: Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Ai
authors.initials: A
authors.lastname: Hang
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian 116044, China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Shu
authors.affiliation: Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica and Collaborative Innovation Center for Brain Science, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: jgliu@mail.shcnc.ac.cn.
authors.forename: Jing-Gen
authors.initials: JG
authors.lastname: Liu
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D003866:Depressive Disorder / Q000378:metabolism / Q000517:prevention & control*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004745:Enkephalins / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000494:pharmacology / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology / Q000633:toxicity*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000378:metabolism / Q000517:prevention & control* / Q000523:psychology
chemical_list: D000928:Antidepressive Agents; D004745:Enkephalins; D009292:Narcotic Antagonists; D009294:Narcotics; D011498:Protein Precursors; D012333:RNA, Messenger; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D009271:Naltrexone; D009020:Morphine; C033660:preproenkephalin
keywords: Depression; Morphine withdrawal; Nucleus accumbens; Prodynorphin; κ Opioid receptor