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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10 d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10 d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6 d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2,1 g·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。
Objective: To study the mechanism of anti-morphine conditioned place preference (CPP) effect of aqueous extract of Rhizoma Corydalis and L-THP and to compare the effects. METHODS: Morphine CPP model was established on the 10th day after morphine injection (initial dose 10 mg · kg-1, increasing 10 mg · kg-1 every day, till 100 mg · kg-1 on the 10th day after injection) 2, 1, 0.5 g · kg-1 (L-THP 0.153,0.077, 0.038 mg, respectively) and L-THP 3.76,1.88,0.94 mg · kg- The contents of glutamate transmitter and the expression of NR2B in brain regions of ventral tegular area - nucleus accumbens - prefrontal cortex (VTA-NAc-PFC) were determined by colorimetry and immunohistochemistry respectively. Results: Compared with saline group, the dwell time in white box (morphine with medicine box) of 2, 1 g · kg-1 and L-THP 3.76 and 1.88 mg · kg-1 groups decreased significantly (P <0.05 Or P <0.01). Meanwhile, glutamate content and NR2B expression in VTA, NAc and PFC were significantly decreased (P <0.05 or P <0.01). CONCLUSION: Both fumarate and L-THP can accelerate the regression of morphine CPP effect, reversing the increase of glutamate content and NR2B expression in the VTA-NAc-PFC neural circuit may be the mechanism of both accelerating CPP effect of morphine Clove, which contains 1 times the amount of L-THP monomer, not only reduced the morphine CPP behavior by about 24 times the L-THP monomer alone, but also increased the activity of VTA-NAc-PFC loop There are also similarities in the mechanism of pharmacological action between neurotransmitter and NR2B.