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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Inhibition of iNOS induces antidepressant-like effects in mice: Pharmacological and genetic evidence

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Montezuma, Karina [1] ; Biojone, Caroline [2] ; Lisboa, Sabrina F. [2] ; Cunha, Fernando Q. [2] ; Guimaraes, Francisco S. [2] ; Joca, Samia R. L. [1]
Total Authors: 6
[1] Univ Sao Paulo, Dept Chem & Phys, Sch Pharmaceut Sci Ribeirao Preto, BR-05508 Sao Paulo - Brazil
[2] Univ Sao Paulo, Dept Pharmacol, Sch Med Ribeirao Preto, BR-05508 Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Neuropharmacology; v. 62, n. 1, SI, p. 485-491, JAN 2012.
Web of Science Citations: 44

Recent evidence has suggested that systemic administration of non-selective NOS inhibitors induces antidepressant-like effects in animal models. However, the precise involvement of the different NOS isoforms (neuronal-nNOS and inducible-iNOS) in these effects has not been clearly defined yet. Considering that mediators of the inflammatory response, that are able to induce iNOS expression, can be increased by exposure to stress, the aim of the present study was to investigate iNOS involvement in stress-induced behavioral consequences in the forced swimming test (FST), an animal model sensitive to antidepressant drugs. Therefore, we investigated the effects induced by systemic injection of aminoguanidine (preferential iNOS inhibitor), 1400W (selective iNOS inhibitor) or n-propyl-L-arginine (NPA, selective nNOS inhibitor) in mice submitted to the FST. We also investigated the behavior of mice with genetic deletion of iNOS (knockout) submitted to the FST. Aminoguanidine significantly decreased the immobility time (IT) in the FST. 1400W but not NPA, when administered at equivalent doses considering the magnitude of their Ki values for iNOS and nNOS, respectively, reduced the IT, thus suggesting that aminoguanidine-induced effects would be due to selective iNOS inhibition. Similarly, iNOS KO presented decreased IT in the FST when compared to wild-type mice. These results are the first to show that selective inhibition of iNOS or its knockdown induces antidepressant-like effects, therefore suggesting that iNOS-mediated NO synthesis is involved in the modulation of stress-induced behavioral consequences. Moreover, they further support NO involvement in the neurobiology of depression. This article is part of a Special Issue entitled `Anxiety and Depression'. (C) 2011 Elsevier Ltd. All rights reserved. (AU)

FAPESP's process: 07/03685-3 - Typical and atypical neurotransmitters in neuropsychiatric disorders
Grantee:Francisco Silveira Guimaraes
Support type: Research Projects - Thematic Grants