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目的:观察并比较延胡索与左旋延胡索乙素(l-THP)对吗啡诱导大鼠条件性位置偏爱(CPP)效应、谷氨酸递质含量及N-甲基-D-天冬氨酸(NMDAR)亚基NR2B表达的影响。方法:吗啡剂量递增皮下注射10d建立大鼠吗啡CPP模型,延胡索2、1、0.5g/kg水提液(分别含l-THP 0.153、0.077、0.038mg)和l-THP 3.76、1.88、0.94 mg/kg灌胃治疗6d后,CPP实验评价大鼠CPP效应;比色法和免疫组化测定纹状体中谷氨酸递质含量和NR2B的表达。结果:与生理盐水治疗组和吗啡模型组比较,延胡索2、1g/kg及l-THP 3.76、1.88mg/kg能明显减少大鼠在白箱的停留时间(P<0.01),同时纹状体中谷氨酸递质含量和NR2B表达均显著降低(P<0.01)。结论:延胡索和有效成分l-THP单体对吗啡CPP效应均具有明显的抑制作用,逆转纹状体中升高的谷氨酸递质含量和下调NR2B的表达,可能是二者有效抑制吗啡CPP效应的机制之一;含1倍量l-THP单体的延胡索不但在抑制吗啡CPP行为学方面相当于单独应用约24倍l-THP单体的效果,而且,在对纹状体中谷氨酸递质和NR2B的药理作用机制方面也具有很大的相似性。
OBJECTIVE: To observe and compare the effects of coturnum and leuprolide (l-THP) on morphine induced conditioned place preference (CPP), glutamate neurotransmitter and N-methyl-D-aspartate ) Subunit NR2B expression. METHODS: Morphine CPP model was established by subcutaneous injection of morphine for 10 days. The aqueous solution of 2, 1 and 0.5 g / kg of Corydalis japonicus (l-THP 0.153,0.077 and 0.038 mg, respectively) and l-THP 3.76,1.88 and 0.94 mg / kg for 6 days, CPP was evaluated by CPP in rats. The content of glutamate and the expression of NR2B in striatum were determined by colorimetry and immunohistochemistry. Results: Compared with saline group and morphine model group, fumaric 2, 1g / kg and l-THP3.76,1.88mg / kg could significantly reduce the residence time of white rats (P <0.01) Glutamate neurotransmitter content and NR2B expression were significantly lower (P <0.01). CONCLUSION: Corydalis and l-THP can significantly inhibit the CPP effect of morphine. The reversal of glutamate up-regulation in striatum and the down-regulation of NR2B expression may be the result of both inhibition of morphine CPP Effect of one dose of l-THP monomer fumarate not only inhibits morphine CPP behavior is equivalent to the application of about 24-fold l-THP monomer effect, and, in the striatum glutamate Neurotransmitters and NR2B pharmacological mechanisms also have a great similarity.