Tetrahydropalmatine protects against methamphetamine-induced spatial learning and memory impairment in mice
Tetrahydropalmatine protects against methamphetamine-induced spatial learning and memory impairment in mice
复制标题
四氢延胡索乙素可预防甲基苯丙胺引起的小鼠空间学习和记忆障碍
DOI：
10.1007/s12264-012-1236-4
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发表时间：
2012-06-01
影响因子：
5.6
通讯作者：
Chen, Teng
中科院分区：
文献类型：
--
作者：
Chen, Yan-Jiong;Liu, Yan-Ling;Chen, Teng
目的探讨甲基苯丙胺(MA)对小鼠空间学习记忆的影响及延胡索乙素(THP)在MA诱导的小鼠空间学习记忆改变中的作用。方法雄性C57BL/6小鼠随机分为8组，分别给予不同剂量的MA、不同剂量的THP、MA+THP联合治疗和生理盐水对照组。用Morris水迷宫评估大鼠的空间学习和记忆能力。免疫印迹法检测细胞外信号调节蛋白激酶(ERK)在小鼠前额叶皮质(PFC)和海马区的表达。结果重复MA治疗可显著延长小鼠在学习阶段的逃避潜伏期，减少记忆测试阶段的平台穿越次数。在MA处理的小鼠中，ERK1/2的表达在PFC中降低，但在海马区不表达。单独重复THP治疗不影响逃避潜伏期、跨越平台的次数或脑内ERK1/2的总表达。与MA组相比，MA+THP组小鼠的逃避潜伏期明显缩短，跨越平台的次数明显增多。结论MA重复给药可损害小鼠的空间学习记忆能力，与THP联合给药可阻止这种损害，这可能与其在PFC中ERK1/2表达的改变有关。这项研究有助于揭示MA滥用的机制，并探索潜在的治疗方法。
ObjectiveThe purpose of this study was to investigate the effect of methamphetamine (MA) on spatial learning and memory and the role of tetrahydropalmatine (THP) in MA-induced changes in these phenomena in mice.MethodsMale C57BL/6 mice were randomly divided into eight groups, according to different doses of MA, different doses of THP, treatment with both MA and THP, and saline controls. Spatial learning and memory were assessed using the Morris water maze. Western blot was used to detect the expression of extracellular signal-regulated protein kinase (ERK) in the mouse prefrontal cortex (PFC) and hippocampus.ResultsRepeated MA treatment significantly increased the escape latency in the learning phase and decreased the number of platform site crossings in the memory-test phase. ERK1/2 expression was decreased in the PFC but not in the hippocampus of the MA-treated mice. Repeated THP treatment alone did not affect the escape latency, the number of platform site crossings or the total ERK1/2 expression in the brain. Statistically significantly shorter escape latencies and more platform site crossings occurred in MA+THP-treated mice than in MA-treated mice.ConclusionRepeated MA administration impairs spatial learning and memory in mice, and its co-administration with THP prevents this impairment, which is probably attributable to changed ERK1/2 expression in the PFC. This study contributes to uncovering the mechanism underlying MA abuse, and to exploring potential therapies.