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.