Effects of cholecalciferol on behavior and production of reactive oxygen species in female mice subjected to corticosterone-induced model of depression
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Major depressive disorder (or depression) is one of the most frequent psychiatric illnesses in the population, with chronic stress being one of the main etiological factors. Studies have shown that cholecalciferol supplementation can lead to attenuation of the depressive state; however, the biochemical mechanisms involved in the relationship between cholecalciferol and depression are not very well known. The objective of this study was to investigate the effects of the administration of cholecalciferol on behavioral parameters (tail suspension test (TST), open field test (OFT), splash test (ST)) and redox state (dichlorofluorescein (DCF)) in adult female Swiss mice subjected to a model of depression induced by chronic corticosterone treatment. Corticosterone (20 mg/kg, p.o.) was administered once a day for 21 days. For investigation of the antidepressant-like effect, cholecalciferol (100 IU/kg) or fluoxetine (10 mg/kg, positive control) was administered p.o. within the last 7 days of corticosterone administration. After the treatments, the behavioral tests and biochemical analyses in the hippocampus and prefrontal cortex of the rodent samples were performed. Animals submitted to repeated corticosterone administration showed a depressive-like behavior, evidenced by a significant increase in the immobility time in the TST, which was significantly reduced by the administration of cholecalciferol or fluoxetine. In addition, the groups treated with cholecalciferol and fluoxetine showed a significant decrease in the production of reactive oxygen species (ROS) in the hippocampus. These results show that cholecalciferol, similar to fluoxetine, has a potential antidepressant-like effect, which may be related to the lower ROS production.
KeywordsDepression Corticosterone Hippocampus Redox state ROS Vitamin D3
Reactive oxygen species
Nicotinamide adenine dinucleotide phosphate
Open field test
Forced swim test
Tail suspension test
Vitamin D receptor
Author contribution statement
MM and ALSR conceived and designed research. SVSS, PBR, VBN, and MM conducted experiments. SVSS, PBR, JDM, and MM analyzed data. SVSS, JDM, and MM wrote the manuscript. All authors read and approved the manuscript.
This study was financially supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) [grant numbers 150082/2018-5 and 310113/2017-2], and Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior (CAPES). ALSR is CNPq Research Fellow.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted (Ethics Committee CEUA PP00795).
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