Luteolin Inhibits Behavioral Sensitization by Blocking Methamphetamine-Induced MAPK Pathway Activation in the Caudate Putamen in Mice
Luteolin Inhibits Behavioral Sensitization by Blocking Methamphetamine-Induced MAPK Pathway Activation in the Caudate Putamen in Mice
复制标题
木犀草素通过阻断甲基苯丙胺诱导的小鼠尾壳核 MAPK 通路激活来抑制行为敏化
DOI：
10.1371/journal.pone.0098981
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发表时间：
2014-06-05
期刊：
影响因子：
3.7
通讯作者：
Liu, Xinshe
中科院分区：
文献类型：
--
作者：
Yan, Tinglin;Li, Lu;Liu, Xinshe
目的探讨毛地黄黄酮对甲基苯丙胺（MA）诱导的小鼠行为敏化及丝裂原活化蛋白激酶（MAPK）信号转导通路的影响。方法采用单次给予MA诱导小鼠多动或多次间断腹腔注射MA建立MA诱导的行为敏化小鼠模型。研究了毛地黄黄酮对MA诱导的多动和行为敏化的发展和表达的影响。Western blot检测尾壳核（CPu）中ΔFosB的表达和活性，以及磷酸化细胞外信号调节激酶1/2（pERK 1/2）、磷酸化c-Jun N-末端激酶（pJNK）和磷酸化p38丝裂原活化蛋白激酶（pp 38）的水平。结果木犀草素能显著降低MA诱导的小鼠多动性及行为敏化的发生和表达。MA处理小鼠CPu中的ΔFosB、pERK 1/2和pJNK水平高于对照小鼠，而pp 38水平没有变化。注射毛地黄黄酮可抑制MA诱导的ΔFosB、pERK 1/2和pJNK水平的升高，但不影响pp 38水平。结论木犀草素通过ERK 1/2/ΔFosB通路抑制MA诱导的小鼠多动和行为敏感化。此外，JNK信号通路可能参与MA诱导的CPu神经元变性，毛地黄黄酮抑制这一过程。
Goal To investigate the effect of luteolin on methamphetamine (MA)-induced behavioral sensitization and mitogen-activated protein kinase (MAPK) signal transduction pathway activation in mice. Methods Mice received a single dose of MA to induce hyperactivity or repeated intermittent intraperitoneal injections of MA to establish an MA-induced behavioral sensitization mouse model. The effect of luteolin on the development and expression of MA-induced hyperactivity and behavioral sensitization was examined. The expression and activity of ΔFosB and the levels of phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2), phosphorylated c-Jun N-terminal kinase (pJNK), and phosphorylated p38 mitogen-activated protein kinase (pp38) in the caudate putamen (CPu) were measured by western blot. Results Luteolin significantly decreased hyperactivity as well as the development and expression of MA-induced behavioral sensitization in mice. ΔFosB, pERK1/2, and pJNK levels in the CPu were higher in MA-treated mice than in control mice, whereas the pp38 level did not change. Injection of luteolin inhibited the MA-induced increase in ΔFosB, pERK1/2, and pJNK levels, but did not affect the pp38 level. Conclusions Luteolin inhibits MA-induced hyperactivity and behavioral sensitization in mice through the ERK1/2/ΔFosB pathway. Furthermore, the JNK signaling pathway might be involved in MA-induced neurodegeneration in the CPu, and luteolin inhibits this process.