延胡索水提物及左旋延胡索乙素抗吗啡条件性位置偏爱效应机制研究和效果比较

目的:研究延胡索水提物及左旋延胡索乙素(L-THP)抗吗啡条件性位置偏爱(CPP)效应的机制并进行效果比较.方法:吗啡剂量递增注射10d建立大鼠吗啡CPP模型(起始剂量10 mg·kg-1,每天递增10 mg·kg-1,至注射10d时100mg·kg-1),延胡索水提液2,1,0.5 g·kg-1(分别含L-THP 0.153,0.077,0.038 mg),以及L-THP 3.76,1.88,0.94 mg·kg-1灌胃治疗6d后,检测大鼠CPP效应,用比色法和免疫组化分别测定其中脑腹侧被盖区-伏核-前额叶皮质(VTA-NAc-PFC)神经环路各脑区内谷氨酸递质含量和NR2B的表达.结果:与生理盐水治疗组比较,延胡索2,1g·kg-1及L-THP 3.76,1.88 mg·kg-1组大鼠在白箱(吗啡伴药箱)停留时间明显减少(P＜0.05或P＜0.01),同时VTA,NAc和PFC内谷氨酸含量及NR2B表达均显著降低(P＜0.05或P＜0.01).结论:延胡索与L-THP均能加速吗啡CPP效应的消退,逆转VTA-NAc-PFC神经环路中升高的谷氨酸含量和下调NR2B的表达,可能是二者加速吗啡CPP效应消退的机制之一；含1倍量L-THP单体的延胡索中药不但在抑制吗啡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VTA-NAc-PFC环路中谷氨酸递质和NR2B的药理作用机制方面也具有很大的相似性.

Study on acting mechanism of anti-morphine conditioned place preference between aqueous extract of Corydalis yanhusuo and L-THP and comparison of their effects

Objective:To study the acting mechanism of anti-morphine conditioned place preference (CPP) between aqueous extract of Corydalis yanhusuo and L-THP and compare their effects. Method:The CPP model was established by injecting morphine in rats with a increasing dose for 10 days, with the initial dose of 10 g·kg^-1 and the final dose of 100 g·kg^-1, 10 mg·kg^-1 was increased each day, thus 100 mg·kg^-1 was injected by d 10. Having been treated with differential doses (2, 1 and 0.5 g·kg^-1) of C. yanhusuo (containing L-THP: 0.153, 0.077 and 0.038 mg·kg^-1 respectively) and L-THP (3.76, 1.88 and 0.94 mg·kg^-1) for six days, the CPP effect in rats was detected. Both colorimetry and immunohistochemistry methods were adopted to detect the content of glutamate neurotransmitter in each brain region and the expression of NR2B in VTA-NAc-PFC neuroanatomical circuit. Result:Compared with the physiological saline treatment group, C. yanhusuo(2, 1 g·kg^-1) and L-THP (3.76 and 1.88 mg·kg^-1) groups showed a notably shorter retention period of rats in white boxes (morphine-accompanied boxes) (P<0.05 or P<0.01) and remarkably lower glutamic acid content in VTA, NAc and PFC and NR2B expression. Conclusion:Both C. yanhusuo and L-THP can substantially inhibit the effect of morphine CPP, reduce the increasing glutamic acid content in VTA-NAc-PFC neuroanatomical circuit and down-regulated NR2B expression, which may be one of mechanisms on reducing the effect of morphine CPP. C. yanhusuo preparations containing L-THP (1×) showed 24-fold effect of L-THP monomer of single application in terms of the behaviouristics of inhibitory effect on CPP as well as the similarity in terms of transmitter glutamic acid of in VTA-NAc-PFC neuroanatomical circuit and pharmacological mechanism of NR2B.