神经元型一氧化氮合酶对氟西汀抗抑郁样作用的影响

Effects of neuronal nitric oxide synthase on antidepressant-like effect of fluoxetine

目的:探讨神经元型一氧化氮合酶(nNOS)与氟西汀抗抑郁样作用之间的关系。方法:以强迫游泳和悬尾实验的不动时间为指标评价药物的抗抑郁样作用。ICR小鼠接受氟西汀治疗或氟西汀治疗前予L-精氨酸/D-精氨酸预处理,观察给药后小鼠不动时间的改变;nNOS敲除鼠和野生型背景鼠均接受氟西汀治疗,观察给药后小鼠不动时间的改变。结果:在ICR小鼠,氟西汀显著缩短小鼠不动时间,产生抗抑郁样作用,L-精氨酸能有效拮抗氟西汀的这一作用,而D-精氨酸不能拮抗氟西汀的作用。氟西汀缩短野生型小鼠的强迫游泳不动时间,产生显著的抗抑郁样作用,而氟西汀治疗nNOS敲除小鼠没有改变强迫游泳不动时间,未产生抗抑郁样作用。结论:nNOS分子介导了氟西汀的抗抑郁样作用。

Objective：To explore the relationship between neuronal nitrie oxide synthase（nNOS） molecule and antidepressant-like effects of fluoxetine.Methods：The antidepressant activity was assessed in forced swimming test（FST） and tail suspension test（TST） behavioral paradigm.Total immobility time was registered during the period of 5 or 6 min.ICR mice were treated with fluoxetine or pretreated with L-arginine / D-arginine,and wildtype（WT） mice and mice lacking nNOS gene[knock-out（KO）]were treated with fluoxetine,and then the immobility time in the FST and TST was analyzed.Results：In ICR mice,the immobility time in the FST and TST as reduced by fluoxetine treatment,and the antidepressant-like effect of fluoxetine in the FST and TST was prevented by the pretreatment with L-arginine,but not D-arginine.In WT mice,administrations of fluoxetine caused antidepressant-like effect in the FST,whereas in KO mice fluoxetine was ineffective.Conclusion：nNOS molecule is required by antidepressant-like effect of fluoxetine.