神经元型一氧化氮合酶对氟西汀抗抑郁样作用的影响

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?

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

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.