延胡索和左旋延胡索乙素对大鼠吗啡CPP效应、纹状体谷氨酸含量和NR2B表达的影响及比较

Effects of Corydalis yanhusuo and L-tetrahydropalmatine on conditioned place preference and expression of Glumatic acid and NR2B in the striatum of morphine dependent rats

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 effects of conditioned place preference（CPP） of morphine dependent rats,variation of Glumatic Acid（Glu） and NMDA receptor 2B subunit（NR2B） of the striatum in rats suffered from corydalis yanhusuo and l-tetrahydropalmatine（l-THP）.Methods： Morphine dependent rats were established by dose-increasing administration for 10 days.Treatments with administration of Corydalis yanhusuo（2,1 and 0.5g/kg） and l-THP（3.76,1.88 and 0.94mg/kg） were performed for 6 days.The CPP was applied to appraise for psychological dependence in rats.The variable contents of Glu and the expression of NR2B in striatum were detected by colorimetry and immunohistochemisty,respectively.Results： Compared with the NS treatment group and the morphine dependent group,the time of animals treated with Corydalis yanhusuo（2 and 1g/kg） and l-THP（3.76 and 1.88mg/kg） staying in drug-paired compartment was significantly reduced（P 0.01）.Lower levels of NR2B and Glu were observed in striatum from those rats（P 0.01）.Conclusion： Corydalis yanhusuo and l-THP can substantially inhibit morphine induced CPP effects caused by lower levels of Glu and NR2B in striatum.Similar effects were observed between Corydalis yanhusuo（24×） and l-THP（1×）.Therefore,both Corydalis yanhusuo and l-THP could play similar pharmacological roles in the striatum of morphine dependent rats.