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

• Published in: Neuroscience letters 2017-08, Vol.656, p.131-137
• Main Authors: da Silva Leal, Vanessa Marques, Bonassoli, Vivian Taciany, Soares, Lígia Mendes, Milani, Humberto, de Oliveira, Rúbia M. Weffort
• Format: Article
• Language: English
• Subjects: Animals; Antidepressant; Antidepressive Agents - administration & dosage; Antidepressive Agents - pharmacology; Behavior, Animal - drug effects; Depression - psychology; Dose-Response Relationship, Drug; Drug Tolerance; Fluoxetine - pharmacology; Forced swim test; Hippocampus - metabolism; Imines - administration & dosage; Imines - pharmacology; Indazoles - administration & dosage; Indazoles - pharmacology; Injections, Intraperitoneal; Male; Mice; Nitric oxide; Nitric Oxide Synthase Type I - antagonists & inhibitors; Nitric Oxide Synthase Type II - antagonists & inhibitors; Serotonin; Serotonin - deficiency; Serotonin - metabolism
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2017.07.035

•Repeated 7NI or 1400W administration results in antidepressant-like activity in mice.•nNOS and iNOS inhibitors effects were comparable to fluoxetine.•Antidepressant-like effect of 7NI was hippocampal serotonin-dependent. 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 1400W, 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 7days) 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 7days. 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.