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目的探讨1,3,7,9-四甲基尿酸(theacrine,TC)的抗抑郁作用。方法采用悬尾实验、强迫游泳实验、自主活动实验、育亨宾(yohimbine)毒性实验、利血平(reserpine)实验以及5-羟色胺酸(5-HTP)诱导小鼠甩头行为等动物模型(各组剂量分别为3、10及30mg·kg-1,bid,连续7d灌胃给药)来评价TC的抗实验性抑郁效果及其可能的作用机制。结果与空白对照组相比,TC能明显缩短小鼠悬尾不动时间(P<0.01)及增加强迫游泳小鼠拨动转轮旋转次数(P<0.05),且对自主活动无影响。TC可一定程度上增强yohim-bine诱发实验动物死亡率,增强5-HTP导致的甩头行为(P<0.01)。此外,TC也具有明显地改善reserpine引起的小鼠体温下降(P<0.01),运动不能(P<0.05)和眼脸下垂(P<0.01)的作用。结论TC在多种抑郁模型上显示一定的药理活性,这些作用可能与影响单胺类神经递质有关。
Objective To investigate the antidepressant effects of 1,3,7,9-tetramethyluric acid (theacrine, TC). Methods Animal models such as tail suspension test, forced swimming test, spontaneous activity test, yohimbine toxicity test, reserpine test, and 5-hydroxytryptic acid (5-HTP) induced mouse shake behavior were used ( The doses of each group were 3, 10 and 30 mg·kg-1, bid, administered by gavage for 7 days continuously to evaluate the effect of TC on experimental antidepressant and its possible mechanism. Results Compared with the blank control group, TC significantly shortened the immobility time of mice (P<0.01) and increased the number of forced-swimming mice toggle the rotation (P<0.05), and had no effect on the autonomic activity. TC can increase yohim-bine-induced experimental animal mortality to a certain extent, and enhance 5-HTP-induced head shake behavior (P<0.01). In addition, TC also significantly improved reserpine-induced decline in body temperature in mice (P < 0.01), exercise inability (P <0.05) and eye-face drooping (P <0.01). Conclusion TC shows certain pharmacological activities in various depression models, and these effects may be related to the effects of monoamine neurotransmitters.