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学科主题: 药物依赖
题名:
Chaperone heat shock protein 70 in nucleus accumbens core: a novel biological target of behavioural sensitization to morphine in rats
作者: Wang, Yan-Ting1; Qin, Wang-Jun2; Liu, Qing1; Li, Yu-Ling1; Liang, Hui1; Chen, Feng3; Lawrence, Andrew J.3; Zhang, Xiang-Lin2; Liang, Jian-Hui1
关键词: heat shock protein 70 ; nucleus accumbens core ; chaperone ; behavioural sensitization ; morphine
刊名: INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
发表日期: 2014-03-01
DOI: 10.1017/S1461145713001429
卷: 17, 期:3, 页:469-484
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Clinical Neurology ; Neurosciences ; Pharmacology & Pharmacy ; Psychiatry
研究领域[WOS]: Neurosciences & Neurology ; Pharmacology & Pharmacy ; Psychiatry
关键词[WOS]: HEAT-SHOCK-PROTEIN ; COCAINE-SEEKING BEHAVIOR ; TRANSGENIC MOUSE MODEL ; INCENTIVE-SENSITIZATION ; MOLECULAR CHAPERONES ; SINGLE EXPOSURE ; NEUROCHEMICAL SENSITIZATION ; DIFFERENTIAL CHANGES ; HSP70 CHAPERONE ; GENE-EXPRESSION
英文摘要:

Drug addiction is a major public health issue, yet the underlying adaptation of neural networks by drugs of abuse is not fully understood. We have previously linked chaperone heat shock protein 70 (Hsp70) to drug-induced adaptations. Focusing on the NAc core and shell, the present study aims to provide further findings for our understanding of the relation between behavioural sensitization to morphine and Hsp70 at transcriptional and functional levels in rats. Firstly, we delineated the characteristics of behavioural sensitization induced by a single morphine exposure (1-10mg/kg, s.c.). Secondly, Hsp70 protein expression in the NAc core was time- and dose-relatedly induced during the development of behavioural sensitization to a single morphine exposure in rats, and Pearson analysis indicated a positive correlation between behavioural sensitization and Hsp70 expression in NAc core. Thirdly, at the transcriptional level, intra-NAc core injection of the specific heat shock factor-I (HSF-I) inhibitor N-Formyl-3,4-methylenedioxy-benzylidine-gamma-butyrolactam (KNK437) suppressed Hsp70 expression and the development of behavioural sensitization, while the HSF-I specific inducer geranylgeranylacetone (GGA) promoted both of them. Interestingly, intra-NAc shell injection of KNK437 or GGA did not affect the development of behavioural sensitization. Finally, both the functional inhibition of Hsp70 ATPase activity by methylene blue (MB), and the antagonism of Hsp70 substrate binding site (SBD) activity by pifithrin-mu (PES) impaired the development of behavioural sensitization when they were microinjected into the NAc core. Taken together, the critical involvement of chaperone Hsp70 in behavioural sensitization to morphine identifies a biological target for long-lasting adaptations with relevance to addiction.

语种: 英语
所属项目编号: 30870894 ; 2009CB522000 ; 2011BAK04B08
项目资助者: National Nature Science Foundation of China ; National Basic Research Programme of China ; National Key Technology R&amp ; D Programme of China ; National Health &amp ; Medical Research Council (Australia) ; Victorian Government&prime ; s Operational Infrastructure Support Programme
WOS记录号: WOS:000332958200009
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/59652
Appears in Collections:中国药物依赖性研究所_期刊论文

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作者单位: 1.Peking Univ, Natl Inst Drug Dependence, Beijing 100191, Peoples R China
2.China Japan Friendship Hosp, Dept Pharm, Beijing 100029, Peoples R China
3.Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Parkville, Vic 3010, Australia

Recommended Citation:
Wang, Yan-Ting,Qin, Wang-Jun,Liu, Qing,et al. Chaperone heat shock protein 70 in nucleus accumbens core: a novel biological target of behavioural sensitization to morphine in rats[J]. INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY,2014,17(3):469-484.
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