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目的:探讨左旋四氢巴马汀(l-THP)对MA引起的小鼠行为敏化的影响及脑内细胞外信号调节激酶(ERK)磷酸化程度的影响。方法:采用甲基苯丙胺(methamphetamine,MA)2mg·kg-1连续给药5d,戒断2d,并以相同剂量MA诱导小鼠(C57BL)敏化表达,同时设立l-THP(5,10mg·kg-1)伴随给药组,l-THP在MA给药前30min给予,观察l-THP(5,10mg·kg-1)对MA(2mg·kg-1)引起的小鼠行为敏化的影响。采用Westernblot方法检测前额叶皮质、伏隔核及尾壳核内细胞外信号调节激酶(ERK)磷酸化程度的改变。结果:MA(2mg·kg-1)可诱导小鼠产生行为敏化,同时可引起脑内伏隔核和尾壳核内ERK磷酸化表达增加,在前额叶皮质内并未发现磷酸化表达的改变。l-THP(5,10mg·kg-1)伴随MA给药,对MA诱导的行为敏化的形成和表达有不同程度的影响。同时,l-THP可抑制伏隔核及尾壳核内MA诱导的磷酸化ERK表达的增加。结论:这些研究结果表明,l-THP可能通过影响伏隔核及尾壳核内ERK的磷酸化来抑制MA引起的行为敏化。
Objective: To investigate the effects of l-tetrahydropalmatine (l-THP) on behavioral sensitization induced by MA in mice and the phosphorylation of extracellular signal-regulated kinase (ERK) in brain. Methods: Mice were continuously treated with methamphetamine (MA) 2 mg · kg-1 for 5 days and were sacrificed for 2 days. Mice were sensitized with the same dose of MA and the concentrations of l-THP (5, 10 mg · kg- kg-1) with administration group, l-THP was administered 30 min before MA administration, and the mice sensitized with l-THP (5 and 10 mg · kg -1) to MA influences. The changes of phosphorylation of extracellular signal-regulated kinase (ERK) in prefrontal cortex, nucleus accumbens and caudate putamen were detected by Western blot. Results: MA (2mg · kg-1) induced behavioral sensitization in mice and increased the phosphorylation of ERK in nucleus accumbens and caudate putamen. No phosphorylation was found in prefrontal cortex change. Administration of MA with l-THP (5, 10 mg · kg -1) had some effects on the formation and expression of MA-induced behavioral sensitization. In the meantime, l-THP inhibited the MA-induced increase of MA-induced phosphorylated ERK expression in nucleus accumbens and caudate putamen. CONCLUSIONS: These findings suggest that l-THP may inhibit behavioral sensitization induced by MA by affecting the phosphorylation of ERK in nucleus accumbens and caudate putamen.