解郁丸抗抑郁作用机制的初步研究

目的 :初步探讨解郁丸抗抑郁作用机制。 方法 :采用高剂量阿朴吗啡导致体温下降试验,5-羟色胺酸(5-HTP)诱导甩头行为试验以及高效液相色谱-电化学检测法测定小鼠下丘脑、皮层、海马等脑内单胺类递质及其代谢产物含量。 结果 :解郁丸能显著拮抗高剂量阿朴吗啡所致小鼠体温下降;增加5-HTP诱导甩头行为。解郁丸单次和连续14 d给药,可提高下丘脑中去甲肾上腺素(NE)、多巴胺(DA)与DA的代谢产物3,4-二羟基苯乙二醇(DOPAC)的比值;也可使皮层中5-HT,NE,5-HT的代谢产物5-羟吲哚乙酸(5-HIAA),DOPAC含量升高,降低5-HT与5-HIAA及DA与DOPAC的比值;并可提高海马中5-HT与5-HIAA及DA与DOPAC的比值。解郁丸可使利血平化小鼠下丘脑中NE,5-HIAA,海马中5-HT,5-HIAA,DA与DOPAC的比值明显升高。 结论 :解郁丸抗抑郁作用机制可能与调节不同脑区的5-HT,NE等神经递质有关。单次和连续14 d给药可增加不同脑区5-HT,NE,DA的含量,连续14 d给药对利血平化所致不同脑区单胺类递质含量下降也有不同程度的翻转效应。

Preliminary Research on Mechanism of Antidepressant Effect of Jieyuwan

Objective: To study the antidepressant mechanism of Jieyuwan on animal models. Method: In order to elucidate the mechanism, the antidepressant effect of Jieyuwan was evaluated with antagonism of high dose of apomorphine and 5-HTP induced head-twitches in mice; the effects of Jieyuwan on the levels of monomine and its metabolites in normal and reserpinized-mice were also studied with HPLC-ECD methods. Result: Jieyuwan greatly decreased the range of hypothermia induced by apomorphine in mice; increased the times of 5-HTP induced head-twitches in mice. Acute administration of Jieyuwan could significantly enhance the levels of NE, DA concentration and the ratio of DA to DOPAC in the hypothalamus of mice . Also, an increase in 5-HT, NE, 5-HIAA, DOPAC concentration, a decrease in value of 5-HT/5-HIAA , DA/DOPAC in cortex; an increase in value of 5-HT/5-HIAA, DA/DOPAC in hippocampus have been observed. Chronic administration (two weeks) of Jieyuwan increased the levels of 5-HT, DOPAC concentration and the ratio of 5-HT to 5-HIAA in hypothalamus of mice. Meanwhile, an increase in NE, 5-HIAA, DOPAC, a decrease in value of 5-HT/5-HIAA, DA/DOPAC in cortex of mice; an increase in 5-HT, NE, DA, 5-HIAA concentration and value of DA/DOPAC in hippocampus were shown. Jieyuwan could enhance the levels of 5-HT, 5-HIAA concentration and value of DA/DOPAC in hippocampus and NE, 5-HIAA concentration in hypothalamus of reserpinized mice. Conclusion: The results indicate that Jieyuwan could enhance the levels of 5-HT, NE and DA in brains with the acute and chronic administration (two weeks). Jieyuwan could also reverse the NE, DA and 5-HT depletion induced by reserpine in brains of mice.