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An organoselenium compound improves behavioral, endocrinal and neurochemical changes induced by corticosterone in mice

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Abstract

Rationale

3-(4-Fluorophenylselenyl)-2,5-diphenylselenophene (F-DPS) is a promising organoselenium compound that shows antidepressant-like properties related to interaction with the serotonergic system.

Objectives

In this study, a mouse model of anxiety/depressant-like behavior induced by long-term corticosterone treatment was used to evaluate behavioral, endocrinal, and neurochemical changes in mice and their possible modulation of F-DPS treatment.

Methods

Swiss mice were subjected to 4 weeks of corticosterone administration (20 μg/ml in drinking water) and a new therapeutic approach with F-DPS (0.1 mg/kg/day, intragastric route, during 1 week) was employed to modulate changes induced by corticosterone exposure.

Results

Treatment with corticosterone caused a significant depressant-like behavior in the forced swimming test and tail suspension test, which was accompanied by anxiety-like condition in the light–dark test and novelty suppressed-feeding; similarly to the classical antidepressant drug paroxetine, F-DPS treatment was effective in reversing these behavioral changes. Further, F-DPS normalized serum levels of corticosterone and adrenocorticotropic hormone, which were increased after corticosterone exposure. Corticosterone also significantly inhibited glutamate uptake in the prefrontal cortex of mice, whereas glutamate release was not modified. Besides normalizing glutamate uptake in the corticosterone-exposed mice, F-DPS promoted an inhibition of 5-HT uptake in the prefrontal cortex and hippocampus. In addition, hippocampal monoamine oxidase-A activity was also inhibited by F-DPS treatment.

Conclusions

These findings suggest a modulation of both serotonergic and glutamatergic systems by F-DPS after a long-term corticosterone exposure in mice, which may be involved in the antidepressant- and anxiolytic-like actions of this organoselenium compound.

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Acknowledgments

The financial support by UFSM, CAPES, FAPERGS/CNPq (PRONEX) research grant # 10/0005-1, and FAPERGS #10/0711-6 is gratefully acknowledged. BMG, CFB, and CWN are recipients of CNPq fellowships. The experiments comply with the current Brazilian laws on the Protection of Animals.

Conflict of interest

The authors declare no conflicts of interest in the present study.

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Authors and Affiliations

  1. Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil

    Bibiana Mozzaquatro Gai, Cristiani Folharini Bortolatto, Suélen Osório Heck, André Luiz Stein, Marta Maria Medeiros Frescura Duarte, Gilson Zeni & Cristina Wayne Nogueira

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  1. Bibiana Mozzaquatro Gai
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  2. Cristiani Folharini Bortolatto
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  3. Suélen Osório Heck
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  4. André Luiz Stein
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  5. Marta Maria Medeiros Frescura Duarte
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  6. Gilson Zeni
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  7. Cristina Wayne Nogueira
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Correspondence to Cristina Wayne Nogueira.

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Gai, B.M., Bortolatto, C.F., Heck, S.O. et al. An organoselenium compound improves behavioral, endocrinal and neurochemical changes induced by corticosterone in mice. Psychopharmacology 231, 2119–2130 (2014). https://doi.org/10.1007/s00213-013-3361-9

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  • DOI: https://doi.org/10.1007/s00213-013-3361-9

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