Dissociative role for dorsal hippocampus in mediating heroin self-administration and relapse through CDK5 and RhoB signaling revealed by proteomic analysis

doi:10.1111/adb.12435

	Dissociative role for dorsal hippocampus in mediating heroin self-administration and relapse through CDK5 and RhoB signaling revealed by proteomic analysis
	Chen, Zhong-Guo 1,6; Liu, Xing 1,6; Wang, Weisheng 1,6; Geng, Fan 2; Gao, Jing 1,6; Gan, Chen-Ling 4; Chai, Jing-Rui 1,6; He, Ling 4; Hu, Gang 2; Zhou, Hu1,3,5,6
刊名	ADDICTION BIOLOGY
	2017-11
卷号	22 期号:6 页码:1731-1742
关键词	CDK5 dorsal hippocampus heroin self-administration label-free proteomic analysis RhoB the centrifugal proteomic reactor
ISSN号	1355-6215
DOI	10.1111/adb.12435
文献子类	Article
英文摘要	Addiction is characterized by drug craving, compulsive drug taking and relapse, which is attributed to aberrant neuroadaptation in brain regions implicated in drug addiction, induced by changes in gene and protein expression in these regions after chronic drug exposure. Accumulating evidence suggests that the dorsal hippocampus (DH) plays an important role in mediating drug-seeking and drug-taking behavior and relapse. However, the molecular mechanisms underlying these effects of the DH are unclear. In the present study, we employed a label-free quantitative proteomic approach to analyze the proteins altered in the DH of heroin self-administering rats. A total of 4015 proteins were quantified with high confidence, and 361 proteins showed significant differences compared with the saline control group. Among them, cyclin-dependent kinase 5 (CDK5) and ras homolog family member B (RhoB) were up-regulated in rats with a history of extended access to heroin. Functionally, inhibition of CDK5 in the DH enhanced heroin self-administration, indicating that CDK5 signaling in the DH acts as a homeostatic compensatory mechanism to limit heroin-taking behavior, whereas blockade of the Rho-Rho kinase (ROCK) pathway attenuated context-induced heroin relapse, indicating that RhoB signaling in the DH is required for the retrieval (recall) of addiction memory. Our findings suggest that manipulation of CDK5 signaling in the DH may be essential in determining vulnerability to opiate taking, whereas manipulation of RhoB signaling in the DH may be essential in determining vulnerability to relapse. Overall, the present study suggests that the DH can exert dissociative effects on heroin addiction through CDK5 and RhoB signaling.
资助项目	Ministry of Science and Technology of China[2013CB835100] ; Ministry of Science and Technology of China[2015CB553502] ; Ministry of Science and Technology of China[2013ZX09507001] ; National Natural Science Foundation of China[81130087] ; National Natural Science Foundation of China[91232716] ; National Natural Science Foundation of China[21375138] ; Committee of Science and Technology of Shanghai[13JC140680] ; 'one hundred talent program' of Chinese Academy of Sciences[00000000] ; China Postdoctoral Science Foundation[2015M570392] ; Open Project Program of Jiangsu Key Laboratory of Pediatric Respiratory Disease, Nanjing University of Chinese Medicine[JKLPRD201404]
WOS关键词	NUCLEUS-ACCUMBENS ; REGULATED KINASE ; SYNAPTIC DEPRESSION ; ENERGY-METABOLISM ; PLACE PREFERENCE ; CHRONIC EXPOSURE ; COCAINE-SEEKING ; RATS ; MORPHINE ; MEMORY
WOS研究方向	Biochemistry & Molecular Biology ; Substance Abuse
语种	英语
出版者	WILEY
WOS记录号	WOS:000413904600022
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272425]
专题	分析化学研究室药理学第二研究室
通讯作者	Zhou, Hu; Liu, Jing-Gen
作者单位	1.Chinese Acad Sci, Collaborat Innovat Ctr Brain Sci, Shanghai, Peoples R China; 2.Nanjing Med Univ, Dept Pharmacol, Jiangsu Key Lab Neurodegenerat, Nanjing, Jiangsu, Peoples R China; 3.Chinese Acad Sci, SIMMUOMICS Lab, Joint Res Lab Translat OMICS Shanghai Inst Mat Me, Shanghai, Peoples R China; 4.China Pharmaceut Univ, Dept Pharmacol, Nanjing, Jiangsu, Peoples R China; 5.Univ Ottawa, Ottawa, ON, Canada 6.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai, Peoples R China;
推荐引用方式 GB/T 7714	Chen, Zhong-Guo,Liu, Xing,Wang, Weisheng,et al. Dissociative role for dorsal hippocampus in mediating heroin self-administration and relapse through CDK5 and RhoB signaling revealed by proteomic analysis[J]. ADDICTION BIOLOGY,2017,22(6):1731-1742.
APA	Chen, Zhong-Guo.,Liu, Xing.,Wang, Weisheng.,Geng, Fan.,Gao, Jing.,...&Liu, Jing-Gen.(2017).Dissociative role for dorsal hippocampus in mediating heroin self-administration and relapse through CDK5 and RhoB signaling revealed by proteomic analysis.ADDICTION BIOLOGY,22(6),1731-1742.
MLA	Chen, Zhong-Guo,et al."Dissociative role for dorsal hippocampus in mediating heroin self-administration and relapse through CDK5 and RhoB signaling revealed by proteomic analysis".ADDICTION BIOLOGY 22.6(2017):1731-1742.