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

Published online by Cambridge University Press:  20 November 2017

Laura Alves Stanquini ,
Caroline Biojone ,
Francisco Silveira Guimarães  and
Sâmia Regiane Joca
Laura Alves Stanquini
Affiliation:
Laboratory of Pharmacology, Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo, Ribeirão Preto, SP, Brazil Department of Pharmacology, School of Medicine of Ribeirão Preto (FMRP), University of São Paulo, Ribeirão Preto, SP, Brazil
Caroline Biojone
Affiliation:
Laboratory of Pharmacology, Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo, Ribeirão Preto, SP, Brazil Department of Pharmacology, School of Medicine of Ribeirão Preto (FMRP), University of São Paulo, Ribeirão Preto, SP, Brazil
Francisco Silveira Guimarães
Affiliation:
Department of Pharmacology, School of Medicine of Ribeirão Preto (FMRP), University of São Paulo, Ribeirão Preto, SP, Brazil Center for Interdisciplinary Research on Applied Neurosciences (NAPNA) from University of São Paulo, SP, Brazil
Sâmia Regiane Joca*
Affiliation:
Laboratory of Pharmacology, Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo, Ribeirão Preto, SP, Brazil Center for Interdisciplinary Research on Applied Neurosciences (NAPNA) from University of São Paulo, SP, Brazil
*
Dr. Sâmia R. L. Joca, School of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo, Avenida do café s/n, 14040-903, Ribeirão Preto, SP, Brazil. Tel: +55 16 36024705; Fax: +55 16 36024880; E-mail: samia@usp.br
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Abstract

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.

Keywords

7-nitroindazoleantidepressantBDNFimipraminelearned helplessnessnitric oxide
Type
Original Article
Information
Acta Neuropsychiatrica , Volume 30 , Issue 3 , June 2018 , pp. 127 - 136
Copyright
© Scandinavian College of Neuropsychopharmacology 2017 

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