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目的:观察逍遥散的拆方药队(柴胡、当归、薄荷,简称柴当薄组)对CUMS抑郁模型小鼠行为学及5-HT1A/2A受体激动剂所引起的小鼠行为反应的影响,揭示该拆方药组的抗抑郁作用及5-HT/BDNF信号通路作用机制。方法:慢性不可预知温和应激+孤养6周制备CUMS小鼠抑郁模型,造模第3周逍遥散全方(30g/kg)、柴当薄组(16.43g/kg、21.90g/kg)、阿米替林(10mg/kg)开始灌胃给药,连续4周,以小鼠体重、自主活动量、糖水偏爱百分比、空间记忆探索能力等行为学指标评价抗抑郁作用。ELISA法测定模型小鼠血清BDNF、5-HT水平及海马部位5-HT含量,及采用8-OH-DPAT(5-HT1A受体激动剂)、DOI(5-HT2A受体激动剂)引起小鼠行为学变化实验,探讨作用机制。结果:与模型对照组比较,柴当薄组16.43g/kg、21.9g/kg剂量均显著提高CUMS模型小鼠的自主活动、糖水消耗量,明显缩短水迷宫测试中定位航行的潜伏期;柴当薄组16.43g/kg可显著增加空间探索实验时目标象限运动距离及有效区域进入次数。柴当薄组16.43g/kg、21.9g/kg显著增加模型小鼠血清BDNF、5-HT含量及海马部位5-HT水平,显著对抗DOI所致的小鼠甩头反应;柴当薄组21.9g/kg对8-OH-DPAT引起的小鼠5-HT样行为表现出明显的协同作用。结论:逍遥散功效拆方研究所获得的柴当薄药组对CUMS模型小鼠有良好的抗抑郁作用,并能协同8-OH-DPAT、拮抗DOI的作用,抗抑郁作用机制可能与激动5-HT1A受体、阻断5-HT2A受体从而影响5-HT/BDNF受体信号通路有关。
OBJECTIVE: To observe the effects of Xiaoyaosan’s prescription drug group (Bupleurum chinense, Angelicae sinensis, Peppermint, abbreviated as Chaidan thin group) on behavior and behavioral responses induced by 5-HT1A / 2A receptor agonist in CUMS depression model mice , To reveal the anti-depressive effect of the prescription group and the mechanism of 5-HT / BDNF signaling pathway. METHODS: CUMS mice model of depression was established by chronic unpredictable mild stress + solitary for 6 weeks. The rats in CUMS group (16.43g / kg, 21.90g / kg) , And amitriptyline (10 mg / kg) for 4 weeks. The antidepressant effects were evaluated by behavioral indexes such as body weight, voluntary activity, percentage of sweet and sour water, spatial memory exploring ability and so on. Serum levels of BDNF and 5-HT and 5-HT in the hippocampus of model mice were determined by ELISA. The effects of 8-OH-DPAT (5-HT1A receptor agonist) and DOI (5-HT2A receptor agonist) Rat behavior change experiments to explore the mechanism of action. Results: Compared with the model control group, the dosages of 16.43g / kg and 21.9g / kg in Chaidan thin group significantly increased autonomic activity and sugar consumption of CUMS mice and significantly shortened the latency of positioning navigation in water maze test. The thin group of 16.43g / kg can significantly increase the target quadrant movement distance and the effective area entry number in the space exploration experiment. Chai when the thin group 16.43g / kg, 21.9g / kg significantly increased serum BDNF, 5-HT content and 5-HT level in the hippocampus of mice, significantly against the DOI induced shatter reaction in mice; Chai thin group 21.9 g / kg showed a significant synergistic effect on 8-OH-DPAT-induced 5-HT-like behavior in mice. Conclusion: Xiaodan powder group had good antidepressant effect on CUMS model mice and could cooperate with 8-OH-DPAT to antagonize the effect of DOI. The mechanism of antidepressant may be related to the activation 5 -HT1A receptor, block the 5-HT2A receptor and thus affect the 5-HT / BDNF receptor signaling pathway.