|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|
|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|
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.
|项目编号||2009CB522000 ; 81071079|
|资助机构||National Basic Research Program of China ; Natural Science Foundation of China|
|作者单位||Peking Univ, Natl Inst Drug Dependence, Beijing 100191, Peoples R China|
|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.|