LB100 attenuates methamphetamine-induced behavioral sensitization by inhibiting the Raf1-ERK 1/2 cascade in the caudate putamen
LB100 attenuates methamphetamine-induced behavioral sensitization by inhibiting the Raf1-ERK 1/2 cascade in the caudate putamen
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LB100 通过抑制尾壳核中的 Raf1-ERK 1/2 级联来减弱甲基苯丙胺诱导的行为敏化
DOI：
10.1097/wnr.0000000000001678
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发表时间：
2021-06
期刊：
影响因子：
1.7
通讯作者：
Xinshe Liu
中科院分区：
文献类型：
--
作者：
Qing Shang;Min Liang;Jing Xiao;Baoyao Gao;Hongyan Qian;Jing Wang;Gang Chen;Jie Fang;Tao Li;Xinshe Liu
Supplemental Digital Content is available in the text. Methamphetamine (METH) abuse has become a serious social problem. Behavioral sensitization is a common behavioral paradigm used to study the neurobiological mechanism that underlies drug addiction. Our previous study demonstrated that the activity of protein phosphatase 2A (PP2A) and the level of phosphorylated extracellular signal-related kinase 1/2 (p-ERK 1/2) are increased in the caudate putamen (CPu) of METH-sensitive mice. However, the relationship between PP2A and ERK 1/2 in METH-induced behavioral sensitization remains unknown. Some studies have indicated that Raf1 may be involved in this process. In this study, LB100, a PP2A inhibitor for treating solid tumors, was first used to clarify the relationship between PP2A and ERK 1/2. In addition, Western blot was used to examine the levels of p-Raf1 (Ser 259) and p-ERK 1/2 (Thr 202/Tyr 204) in the CPu, hippocampus (Hip) and nucleus accumbens (NAc). Our results showed that 2 mg/kg LB100 significantly attenuated METH-induced behavioral sensitization. Furthermore, Western blot analysis revealed that pretreatment with 2 mg/kg LB100 remarkably reversed METH-induced reduction of p-Raf1, as well as upregulation of p-ERK 1/2 in the CPu. Taken together, these results indicate that PP2A plays an important role in METH-induced behavioral sensitization and phosphorylates ERK 1/2 by dephosphorylating p-Raf1 in the CPu to further regulate METH-induced behavioral sensitization.
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DOI：
10.1016/bs.pmbts.2015.10.017
发表时间：
2016
影响因子：
--
作者：
Sun WL;Quizon PM;Zhu J
通讯作者：
Zhu J
DOI：
--
发表时间：
--
期刊：
--
影响因子：
--
作者：
B. Everitt;T. Robbins
通讯作者：
B. Everitt;T. Robbins
影响因子：
2.8
作者：
HOLMES, CFB
通讯作者：
HOLMES, CFB
影响因子：
10.5
作者：
D. Wassarman;N. M. Solomon;Henry C. Chang;F. Karim;M. Therrien;Gerald M. Rubin
通讯作者：
D. Wassarman;N. M. Solomon;Henry C. Chang;F. Karim;M. Therrien;Gerald M. Rubin
影响因子：
4.8
作者：
Abraham, D;Podar, K;Baccarini, M
通讯作者：
Baccarini, M