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Chaperone heat shock protein 70 in nucleus accumbens core: a novel biological target of behavioural sensitization to morphine in rats
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
2014-03-01
DOI10.1017/S1461145713001429
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
WOS记录号WOS:000332958200009
项目编号30870894 ; 2009CB522000 ; 2011BAK04B08
资助机构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
引用统计
被引频次:7[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/59652
专题中国药物依赖性研究所
北京大学药学院_分子与细胞药理学系
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
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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.
APA Wang, Yan-Ting.,Qin, Wang-Jun.,Liu, Qing.,Li, Yu-Ling.,Liang, Hui.,...&Liang, Jian-Hui.(2014).Chaperone heat shock protein 70 in nucleus accumbens core: a novel biological target of behavioural sensitization to morphine in rats.INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY,17(3),469-484.
MLA Wang, Yan-Ting,et al."Chaperone heat shock protein 70 in nucleus accumbens core: a novel biological target of behavioural sensitization to morphine in rats".INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY 17.3(2014):469-484.
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