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Role of calcineurin in the VTA in rats behaviorally sensitized to methamphetamine
Wang, Jun; Sun, Li-Li; Zhu, Wei-Li; Sun, Yan; Liu, Jian-Feng; Lu, Lin; Shi, Jie
关键词Calcineurin Cyclosporine A Methamphetamine sensitization Synapsin GSK-3 beta
刊名PSYCHOPHARMACOLOGY
2012-03-01
DOI10.1007/s00213-011-2461-7
220期:1页:117-128
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Neurosciences ; Pharmacology & Pharmacy ; Psychiatry
研究领域[WOS]Neurosciences & Neurology ; Pharmacology & Pharmacy ; Psychiatry
关键词[WOS]VENTRAL TEGMENTAL AREA ; GLYCOGEN-SYNTHASE KINASE-3-BETA ; IN-VIVO ; LOCOMOTOR SENSITIZATION ; PROTEIN PHOSPHATASE ; SYNAPTIC PLASTICITY ; SIGNALING PATHWAY ; KNOCKOUT MICE ; COCAINE ; CELLS
英文摘要

Rationale Chronic psychostimulant administration increases locomotor activity, which is referred to as locomotor sensitization. Calcineurin has been suggested to participate in psychostimulant-induced sensitization, but the underlying neurobiological mechanism is poorly understood. Objectives This study was designed to examine whether calcineurin activity and its substrates participate in methamphetamine (METH)-induced locomotor sensitization in rats.

Materials and methods Two weeks daily METH (1 mg/kg, i.p.) was administrated to rats to induce locomotor sensitization, activity of calcineurin and its substrates Synapsin and glycogen synthase kinase-3 beta (GSK-3 beta) were detected. The initiation and expression of locomotor sensitization were tested by inhibition of calcineurin activity systematically or locally in the ventral tegmental area (VTA).

Results Expression of the calcineurin A subunit (catalytic subunit) increased in the VTA but not prefrontal cortex, nucleus accumbens, or hippocampus in rats sensitized to METH. The calcineurin inhibitor cyclosporine A, systemically administered or microinfused into the VTA, suppressed the initiation but not expression of METH-induced locomotor sensitization. Chronic METH exposure upregulated the expression of the calcineurin A subunit in the VTA, which was negatively associated with downregulation of the phosphorylation of Synapsin and GSK-3 beta. Moreover, the related molecular changes were blocked by systemically administered cyclosporine A or microinjections into the VTA.

Conclusions These data elucidate the critical role of calcineurin in the neurobiological mechanism underlying METH-induced locomotor sensitization, suggesting that calcineurin might participate in the initiation of METH-induced locomotor sensitization by negatively regulating the activity of Synapsin and GSK-3 beta in the VTA.

语种英语
WOS记录号WOS:000300780400011
项目编号2009CB522000 ; 81071079
资助机构National Basic Research Program of China ; Natural Science Foundation of China
引用统计
被引频次:4[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/400002259/60004
专题中国药物依赖性研究所
北京大学医学部管理机构_医学部
北京大学第一临床医学院_耳鼻咽喉头颈外科
作者单位Peking Univ, Natl Inst Drug Dependence, Beijing 100191, Peoples R China
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GB/T 7714
Wang, Jun,Sun, Li-Li,Zhu, Wei-Li,et al. Role of calcineurin in the VTA in rats behaviorally sensitized to methamphetamine[J]. PSYCHOPHARMACOLOGY,2012,220(1):117-128.
APA Wang, Jun.,Sun, Li-Li.,Zhu, Wei-Li.,Sun, Yan.,Liu, Jian-Feng.,...&Shi, Jie.(2012).Role of calcineurin in the VTA in rats behaviorally sensitized to methamphetamine.PSYCHOPHARMACOLOGY,220(1),117-128.
MLA Wang, Jun,et al."Role of calcineurin in the VTA in rats behaviorally sensitized to methamphetamine".PSYCHOPHARMACOLOGY 220.1(2012):117-128.
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