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学科主题: 药物依赖
题名:
The mammalian target of rapamycin pathway in the basolateral amygdala is critical for nicotine-induced behavioural sensitization
作者: Gao, Yang1,2; Peng, Shuxian1,2; Wen, Quan1,2; Zheng, Chunming1,2; Lin, Jue1,2; Tan, Yalun1,2; Ma, Yan1,2; Luo, Yixiao3; Xue, Yanxue3; Wu, Ping3; Ding, Zengbo3; Lu, Lin3; Li, Yanqin1,2
关键词: Amygdala ; locomotor sensitization ; mTORC1 ; nicotine ; rapamycin
刊名: INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
发表日期: 2014-11-01
DOI: 10.1017/S1461145714000650
卷: 17, 期:11, 页:1881-1894
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]: INDUCED PLACE PREFERENCE ; NUCLEUS-ACCUMBENS ; SIGNALING PATHWAY ; ACETYLCHOLINE-RECEPTORS ; HORSERADISH-PEROXIDASE ; NEURONAL DEVELOPMENT ; AXONAL-TRANSPORT ; STIMULANT-DRUGS ; FEAR MEMORY ; RAT-BRAIN
英文摘要:

Repeated exposure to nicotine increases psychomotor activity. Long-lasting neural plasticity changes that contribute to the nicotine-induced development of locomotor sensitization have been identified. The mammalian target of rapamycin complex 1 (mTORC1) signalling pathway is involved in regulating the neuroplasticity of the central nervous system. In this study, we examined the role of mTORC1 in the amygdala in nicotine-induced locomotor sensitization. Rapamycin, an inhibitor of mTORC1, was infused into the basolateral amygdala (BLA) and central amygdala (CeA) or systemically administered to investigate the role of the mTORC1 in the development and expression of nicotine-induced locomotor sensitization. We found that locomotor activity progressively increased during the initiation of nicotine-induced locomotor sensitization and the expression of nicotine sensitization was induced by nicotine challenge injection (0.35 mg/kg s.c.) after five days of withdrawal. The initiation of nicotine-induced locomotor sensitization was accompanied by the increased phosphorylated level of mTORC1 downstream target proteins including p-p70s6k and p-4EBP in the BLA, but not CeA. Intra-BLA infusion or systemic administration of rapamycin blocked locomotor activity. Increased p-p70s6k and p-4EBP were also observed in the expression of nicotine sensitization, which was demonstrated to be inhibited by systemic rapamycin administration. Our findings indicated that mTORC1 activity in the BLA, but not the CeA, mediated the initiation and expression of nicotine-induced locomotor sensitization, and may become a potential target for the treatment of nicotine addiction.

语种: 英语
所属项目编号: 81000574 ; 313040 ; 2011CDB475 ; 4103004 ; 306271203
项目资助者: National Scientific Foundation of China ; Key Project of Chinese Ministry of Education ; &prime ; Chen-Guang&prime ; Plan of Wuhan Science and Technology Bureau ; Fundamental Research Funds for the Central Universities ; Start-up Funds for Young Investigator of Wuhan University ; Research Funds for &prime ; CHUTIAN&prime ; Young Investigator of the Hubei Provincial Department of Education
WOS记录号: WOS:000345005400014
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内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/54938
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.Wuhan Univ, Sch Pharmaceut Sci, Wuhan 430071, Peoples R China
2.Wuhan Univ, Key Lab Combinatorial Biosynth & Drug Discovery, Minist Educ, Wuhan 430071, Peoples R China
3.Peking Univ, Natl Inst Drug Dependence, Beijing 100871, Peoples R China

Recommended Citation:
Gao, Yang,Peng, Shuxian,Wen, Quan,et al. The mammalian target of rapamycin pathway in the basolateral amygdala is critical for nicotine-induced behavioural sensitization[J]. INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY,2014,17(11):1881-1894.
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