Depletion of 5 hydroxy-triptamine (5-HT) affects the antidepressant-like effect of neuronal nitric oxide synthase inhibitor in mice

Clinical and experimental evidence indicates that nitric oxide (NO) is involved in the genesis of depression as well as in antidepressant drug effects. Inhibitors of nitric oxide synthases (NOS) exert antidepressant-like effect in several animal models, but also interfere with the locomotor activity. The involvement of different isoforms of NOS in the antidepressant-like effects is not clearly established. The objective of this study was to investigate the effects of acute or repeated administration of selective inhibitors of neuronal NOS (nNOS) and induced NOS (iNOS), 7 nitroindazole (7NI) and 1400 W, respectively, in mice subjected to open field (OF) and forced swim test (FST). We also investigated if the antidepressant-like effect of nNOS inhibitor, 7NI, was dependent on hippocampal serotonin. The results demonstrated that single or repeated (3 and 7 days) administration of 7NI resulted in antidepressant-like effects in mice, evidenced by a significant decrease in immobility time in the FST. However, antidepressant-like effects of the iNOS inhibitor, 1400W, were only identified after repeated administration for 3 or 7 days. The effects of both inhibitors were comparable to those obtained with the classical antidepressant fluoxetine. It was also demonstrated that the effect of 7NI was dependent of hippocampal serotonin. We concluded that inhibition of nNOS and iNOS result in antidepressant-like effects, and that these effects hold up after repeated administration.