论文部分内容阅读
目的研究5-羟色胺1A受体(5-HT1A)部分激动和5-羟色胺(5-HT)重摄取抑制双靶标抗抑郁候选新药YL-0919的抗抑郁作用及对树突复杂性的影响。方法每天从10种刺激中随机选1~2种连续4周建立大鼠慢性应激抑郁模型,每天应激前1 h分别ig给予氟西汀10 mg·kg-1,YL-0919 0.625,1.25和2.5 mg·kg-1。应激结束后第2天行开场实验观察水平运动和垂直运动,第4天行蔗糖饮水实验检测蔗糖偏嗜度,第5天行新奇抑制摄食实验检测摄食潜伏期;第6天取脑,高尔基染色法观察海马齿状回锥体神经元树突长度、分支数以及树突棘密度。结果慢性应激模型组大鼠水平运动和垂直运动显著降低,蔗糖偏嗜度显著降低,新奇抑制摄食潜伏期时间显著延长(P<0.01)。给予YL-0919 2.5 mg·kg-1或氟西汀10 mg·kg-1可显著逆转上述抑郁样行为改变;高尔基染色结果显示,与应激模型组比较,YL-0919 1.25和2.5 mg·kg-1或氟西汀10 mg·kg-1组海马齿状回锥体细胞树突长度分别显著增加24.3%,64.7%和76.0%(P<0.01),分支数分别显著增加38.0%,118.2%和109.1%(P<0.01),YL-0919 2.5 mg·kg-1或氟西汀10mg·kg-1组树突棘密度分别显著增加20.5%和21.4%(P<0.05)。给予YL-0919可显著增强树突复杂性。结论 YL-0919的抗抑郁作用与保护海马齿状回锥体神经元树突结构可塑性,增强树突复杂性有关。
Objective To investigate the antidepressant effects of 5-hydroxytryptamine 1A receptor (5-HT1A) partial agonism and 5-hydroxytryptamine (5-HT) reuptake on the antidepressant effect of double-target antidepressant candidate drug YL-0919 and its effect on dendritic complexity. Methods Chronic stress depression model was established by randomly selecting one to two kinds of rats from 10 kinds of stimuli for four consecutive days every day. Fluoxetine 10 mg · kg -1, YL-0919 0.625, 1.25 And 2.5 mg · kg-1. On the second day after stress, horizontal motion and vertical motion were observed in open field experiment. Sucrose drinking water test was performed on the fourth day to detect sucrose partiality. On the fifth day, the novel feeding inhibition test was used to test the latent period of feeding. On the sixth day, brain and Golgi staining The dendrite length, branch number and dendritic spine density of hippocampal dentate gyrus neurons were observed. Results Chronic stress model rats significantly decreased horizontal motion and vertical motion, sucrose partial preference decreased significantly, novel inhibition of feeding latency significantly longer (P <0.01). YL-0919 2.5 mg · kg-1 or fluoxetine 10 mg · kg-1 significantly reversed the above-mentioned depression-like behaviors. The results of Golgi staining showed that compared with the stress model group, YL-0919 1.25 and 2.5 mg · kg 1 or fluoxetine 10 mg · kg -1 significantly increased the dendritic length of dentate gyrus cells by 24.3%, 64.7% and 76.0% (P <0.01), and the number of branches significantly increased by 38.0% and 118.2% respectively And 109.1% (P <0.01). The density of dendritic spines of YL-0919 2.5 mg · kg-1 or fluoxetine 10 mg · kg-1 increased significantly by 20.5% and 21.4% respectively (P <0.05). Administration of YL-0919 significantly enhanced dendritic complexity. Conclusion The antidepressant effect of YL-0919 is related to the dendritic plasticity and the dendritic complexity of protecting dentate gyrus neurons in hippocampus.