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

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.