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Repeated treatment with nitric oxide synthase inhibitor attenuates learned helplessness development in rats and increases hippocampal BDNF expression

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Stanquini, Laura Alves [1, 2] ; Biojone, Caroline [1, 2] ; Guimaraes, Francisco Silveira [3, 2] ; Joca, Samia Regiane [3, 1]
Número total de Autores: 4
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Lab Pharmacol, Dept Chem & Phys, Sch Pharmaceut Sci Ribeirao Preto FCFRP, Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Dept Pharmacol, Sch Med Ribeirao Preto FMRP, Ribeirao Preto, SP - Brazil
[3] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, Sao Paulo, SP - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: ACTA NEUROPSYCHIATRICA; v. 30, n. 3, p. 127-136, JUN 2018.
Citações Web of Science: 3

Background: Nitric oxide synthase (NOS) inhibitors induce antidepressant-like effects in animal models sensitive to acute drug treatment such as the forced swimming test. However, it is not yet clear if repeated treatment with these drugs is required to induce antidepressant-like effects in preclinical models. Objective: The aim of this study was to test the effect induced by acute or repeated (7 days) treatment with 7-nitroindazole (7-NI), a preferential inhibitor of neuronal NOS, in rats submitted to the learned helplessness (LH) model. In addition, we aimed at investigating if 7-NI treatment would increase brain-derived neurotrophic factor (BDNF) protein levels in the hippocampus, similarly to the effect of prototype antidepressants. Methods: Animals were submitted to a pre-test (PT) session with inescapable footshocks or habituation (no shocks) to the experimental shuttle box. Six days later they were exposed to a test with escapable footshocks. Independent groups received acute (a single injection after PT or before test) or repeated (once a day for 7 days) treatment with vehicle or 7-NI (30 mg/kg). Results: Repeated, but not acute, treatment with 7-NI attenuated LH development. The effect was similar to repeated imipramine treatment. Moreover, in an independent experimental group, only repeated treatment with 7-NI and imipramine increased BDNF protein levels in the hippocampus. Conclusion: The results suggest the nitrergic system could be a target for the treatment of depressive-like conditions. They also indicate that, similar to the positive control imipramine, the antidepressant-like effects of NOS inhibition could involve an increase in hippocampal BDNF levels. (AU)

Processo FAPESP: 12/17626-7 - Mecanismos celulares e moleculares envolvidos no papel de neurotransmissores atípicos em transtornos neuropsiquiátricos
Beneficiário:Francisco Silveira Guimaraes
Linha de fomento: Auxílio à Pesquisa - Temático