title: Proteomic analysis of the nucleus accumbens in rhesus monkeys of morphine dependence and withdrawal intervention.
abstract: It has been known that the reinforcing effects and long-term consequences of morphine are closely associated with nucleus accumbens (NAc) in the brain, a key region of the mesolimbic dopamine pathway. However, the proteins involved in neuroadaptive processes and withdrawal symptom in primates of morphine dependence have not been well explored. In the present study, we performed proteomes in the NAc of rhesus monkeys of morphine dependence and withdrawal intervention with clonidine or methadone. Two-dimensional electrophoresis was used to compare changes in cytosolic protein abundance in the NAc. We found a total of 46 proteins differentially expressed, which were further identified by mass spectrometry analysis. The identified proteins can be classified into 6 classes: metabolism and mitochondrial function, synaptic transmission, cytoskeletal proteins, oxidative stress, signal transduction and protein synthesis and degradation. Importantly, we discovered 14 proteins were significantly but similarly altered after withdrawal therapy with clonidine or methadone, revealing potential pharmacological strategies or targets for the treatment of morphine addiction. Our study provides a comprehensive understanding of the neuropathophysiology associated with morphine addiction and withdrawal therapy in primate, which is helpful for the development of opiate withdrawal pharmacotherapies.
authors: National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
authors: Qian
authors: Q
authors: Bu
authors: Yanzhu
authors: Y
authors: Yang
authors: Guangyan
authors: G
authors: Yan
authors: Zhengtao
authors: Z
authors: Hu
authors: Chunyan
authors: C
authors: Hu
authors: Jiachuan
authors: J
authors: Duan
authors: Lei
authors: L
authors: Lv
authors: Jiaqing
authors: J
authors: Zhou
authors: Jinxuan
authors: J
authors: Zhao
authors: Xue
authors: X
authors: Shao
authors: Yi
authors: Y
authors: Deng
authors: Yan
authors: Y
authors: Li
authors: Hongyu
authors: H
authors: Li
authors: Ruiming
authors: R
authors: Zhu
authors: Yinglan
authors: Y
authors: Zhao
authors: Xiaobo
authors: X
authors: Cen
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001835:Body Weight; D003600:Cytosol / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D005786:Gene Expression Regulation; D008253:Macaca mulatta; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D009020:Morphine / Q000378:metabolism*; D009021:Morphine Dependence / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
chemical_list: D009020:Morphine