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目的:研究延胡索及左旋延胡索乙素(L-THP)对吗啡条件性位置偏爱(CPP)模型大鼠奖赏环路各脑区多巴胺递质与D2受体的影响及比较。方法:吗啡剂量递增颈背部皮下注射CPP训练10 d(起始剂量10 mg·kg-1,每天递增10 mg·kg-1,至注射10 d时为100 mg·kg-1),末次训练后48 h CPP检测确认模型建立成功,即日(12 d)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,共6 d,第18天再次CPP检测,次日取材用高效液相法测定其中脑腹侧被盖区-伏核-前额叶皮质(VTA-NAc-PFC)奖赏神经环路各脑区多巴胺递质含量,免疫组化和Western blotting检测D2受体的表达。结果:与生理盐水治疗组比较,延胡索2,1 g·kg-1,以及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<0.01或P<0.05),同时VTA,NAc和PFC内多巴胺含量降低,D2受体表达显著增加(P<0.01或P<0.05)。结论:下调奖赏神经环路中升高的多巴胺含量和上调D2受体的表达,可能是延胡索与L-THP加速吗啡CPP效应消退的机制之一;对于抑制吗啡CPP效应以及对多巴胺系统的影响,含1倍量L-THP单体的延胡索中药相当于单独应用约24倍L-THP单体的效果。
AIM: To investigate the effects of danshensu and L-tetrahydropalmatine (L-THP) on dopamine transporter and D2 receptor in reward loop brain regions in morphine-conditioned place preference (CPP) model rats. METHODS: Morphine was injected subcutaneously in the back of the neck for 10 days (10 mg · kg-1 starting dose 10 mg · kg-1, CPP 100 mg · kg-1 every 10 d after injection) 48 h CPP test confirmed the successful establishment of the model, that day (12 d) Corylus apetala extract 2,1,0.5 g · kg-1 (containing L-THP 0.153,0.077,0.038 mg), and L-THP 3.76,1.88, 0.94 mg · kg-1 intragastrically for 6 days. On the 18th day, CPP test was again performed. The next day, the ventral tegmental area covered with VTA-NAc-PFC ) Reward dopamine neurotransmitters in the brain regions of the neural circuit, and immunohistochemistry and Western blotting to detect D2 receptor expression. Results: Compared with the saline group, the dwell time of rats in the two compartments (morphine with medicine box) was significantly decreased at 2,1 g · kg-1 and 3.76 and 1.88 mg · kg-1 of L-THP group (P < 0.01 or P <0.05). At the same time, the contents of dopamine in VTA, NAc and PFC decreased and the expression of D2 receptor increased significantly (P <0.01 or P <0.05). CONCLUSIONS: Down-regulation of elevated dopamine levels in the neural circuit and upregulation of D2 receptors may be one of the mechanisms by which corydalis and L-THP accelerate the CPP effect of morphine. To suppress the CPP effect of morphine and its effect on dopamine system, Corydalis medicine containing 1-fold amount of L-THP monomer is equivalent to about 24-fold L-THP monomer alone.