新型5-HT1A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

目的 研究兼有5-HT_1A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5 mg/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（0.625～2.5 mg/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〔0.625～1.25 mg/（kg·d），1～4 d〕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。

Antidepressant-like effect of a novel compound YL-0919,a dual 5-HT1A agonist and serotonin reuptake inhibitor

Objective To evaluate the antidepressant-like effect on animal models of a novel compound YL-0919，a dual 5-HT_1A 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.