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为了观察延胡索和左旋延胡索乙素(L-tetrahydropalmatine,L-THP)对吗啡条件性位置偏爱(conditioned place preference,CPP)大鼠学习记忆相关脑区海马(Hip)和纹状体(Str)内多巴胺递质含量,多巴胺转运体(dopamine transporter,DAT)和多巴胺D2受体(D2R)表达的影响。对各组大鼠颈背部皮下注射生理盐水或吗啡后(吗啡起始剂量为10 mg·kg-1,逐日递增,至第10天为100 mg·kg-1),末次训练48 h进行CPP测试确认模型建立成功,立即处死生理盐水对照组和模型组大鼠,分别取海马、纹状体脑组织。延胡索高、中、低剂量组大鼠则分别给予延胡索2,1,0.5 g·kg-1水提液(内含L-THP的量分别为0.274,0.137,0.069 mg),L-THP高、中、低剂量组分别给予L-THP 3.76,1.88,0.94 mg·kg-1灌胃治疗,生理盐水治疗组灌胃生理盐水,持续治疗6 d,再次CPP测试后处死,同前取材。采用高效液相色谱法检测多巴胺递质含量;Western blot技术检测DAT和D2R的表达。结果显示,与生理盐水治疗组比较,延胡索和L-THP高、中剂量组大鼠在白箱停留的时间显著减少(P<0.01),同时海马和纹状体脑区内多巴胺递质含量明显降低(P<0.01或P<0.05),DAT表达上调(P<0.01),D2R表达上调(P<0.01)。学习记忆相关脑区海马和纹状体是延胡索和L-THP治疗精神依赖的又一神经解剖学作用位点,其机制与下调其升高的DA递质含量以及上调DAT和D2R的表达有关;对吗啡CPP效应消退的药效作用,以及对学习记忆相关脑区海马、纹状体中DA递质含量、DAT和D2R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14倍L-THP单体的效果。
In order to observe the effect of fumarate and L-tetrahydropalmatine (L-THP) on dopamine in hippocampus and striatum of brain related to learning and memory in conditioned place preference (CPP) Neurotransmitter content, dopamine transporter (DAT) and dopamine D2 receptor (D2R) expression. After subcutaneous injection of normal saline or morphine in the back of the neck of the rats, the initial dose of morphine was 10 mg · kg-1, increasing day by day until 100 mg · kg-1 on the 10th day. CPP test Confirmed the successful establishment of the model, immediately killed saline control group and model group rats, respectively, hippocampus, striatum brain tissue. The rats in high, middle and low doses of Corydalis japonicus were given 2,1,0.5 g · kg-1 aqueous solution of corydalis (the content of L-THP was 0.274,0.137 and 0.069 mg, respectively), L-THP was high, Medium and low dose groups were given L-THP 3.76,1.88,0.94 mg · kg-1 gavage treatment, saline treatment group, gavage with saline, continuous treatment of 6 d, again CPP test after sacrifice, with the former material. The content of dopamine neurotransmitters was detected by high performance liquid chromatography. The expression of DAT and D2R was detected by Western blot. The results showed that compared with the saline treatment group, the time spent in the white box of Corydalis and L-THP high and medium dose groups was significantly reduced (P <0.01), meanwhile, the contents of dopamine in hippocampus and striatum were significantly (P <0.01 or P <0.05). DAT expression was up-regulated (P <0.01) and D2R expression was up-regulated (P <0.01). Learning and memory-related brain regions hippocampus and striatum are another neuroanatomical sites of spiritual dependence of corydalis and L-THP treatment, and its mechanism is related to the down-regulation of elevated DA neurotransmitters and the up-regulation of DAT and D2R expression. The pharmacodynamic effects of morphine CPP regress and the effects of DAT and D2R on learning and memory in the hippocampus, striatum, DAT and D2R in brain regions related to learning and memory, About 14 times the effect of L-THP monomer.