新型5-HT_(1A)受体激动和5-HT重摄取抑制双重活性化合物YL-0919抗抑郁作用的行为学评价

Antidepressant-like effect of a novel compound YL-0919, a dual 5-HT_(1A) agonist and serotonin reuptake inhibitor

目的研究兼有5-HT1A受体激动和5-HT重摄取抑制双重活性化合物YL-0919的抗抑郁作用。方法分别采用小鼠悬尾实验、小鼠强迫游泳实验、小鼠自发活动实验和大鼠获得性无助模型,观察不同剂量（0.625、1.25、2.5和5mg/kg）YL-0919的抗抑郁作用。结果在小鼠悬尾实验和小鼠强迫游泳实验中,单次灌胃给予YL-0919（0.625～2.5mg/kg）能够显著缩短小鼠悬尾不动时间和游泳不动时间;在小鼠自发活动实验中,YL-0919在上述剂量范围对自发活动无影响;在大鼠获得性无助模型上,灌胃给予YL-0919〔0.625～1.25mg/（kg·d）,1~4d〕能显著减少逃避失败次数。结论 YL-0919在小鼠和大鼠模型上具有明确的抗抑郁活性,并且在抗抑郁的有效剂量范围内无中枢兴奋和抑制作用,具有成为新型抗抑郁药物的研发潜力。

Objective To evaluate the antidepressant-like effect on animal models of a novel compound YL-0919, a dual 5-HT1A agonist and serotonin reuptake inhibitior. Methods Using the tail suspension test, the forced swimming test and the locomotor activity test in mice, and the learned helplessness test in rats,the antidepressant-like effect of YL-0919 （0.625,1.25,2.5 and 5.0 mg/kg） were evaluated. Results In the tail suspension test and the forced swimming test in mice, intragastric administration of YL-0919 （0.625-2.5 mg/kg） significantly decreased the immobility time. And in this dose range YL-0919 did not influence the locomotor activity in mice. In the learned helplessness test in rats,YL-0919 （0.625-1.25 mg/kg per day,once a day for 4 days ） significantly decreased the numbers of escape failure. Conclusion YL-0919 produced reliable antidepressive effect on the three animal models in the dose without stimulant or inhibitive effect on behaviors. And no excite or inhibition effect of YL-0919 on central nerve systems was observed. These results suggest that YL-0919 have the potential foreground as a novel antidepressant.