Behavioral and molecular alterations in mice resulting from chronic treatment with dexamethasone: Relevance to depression
Neuroscience. 2015-02-01; 286: 141-150
DOI: 10.1016/j.neuroscience.2014.11.035
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Chronic stress, the administration of glucocorticoids and the prolonged
activation of glucocorticoid receptors (GRs) are reported to induce affective
changes in humans and rodents that resemble a depressive state. However, data
concerning the behavioral and molecular effects of the selective activation of
specific GRs are limited, and the conclusions derived remain debatable. In this
study, our goal was to investigate the behavioral and molecular changes following
the prolonged activation of GRs in mice via exposure to the specific agonist
dexamethasone (DEX). C57BL/6J mice were injected daily with DEX (4 mg/kg, i.p.)
or saline, and the behavior of the animals was assessed in the following
paradigms: the forced swimming test (FST), the light-dark box test, the saccharin
preference test and activity boxes. The mRNA expression levels of the
corticosteroid receptors mineralocorticoid (MR, Nr3c2) and glucocorticoid (GR,
Nr3c1), selected stress dependent genes and glial markers were analyzed in the
prefrontal cortex, hippocampus and striatum. DEX-treated mice exhibited a variety
of depression-like behaviors: increased time of immobility in the FST, a reduced
preference for saccharin consumption and increased anxiety-like behavior.
Behavioral alterations were accompanied by a decrease in the mRNA expression of
GR and the increased expression of Fkbp5 and Sgk1 in the prefrontal cortex,
hippocampus and striatum of DEX-treated mice. Furthermore, our results indicate a
decrease in the mRNA expression of glutamate aspartate transporter (GLAST,
Slc1a3), an astroglial cell marker, in the hippocampus and prefrontal cortex.
These results demonstrate that the prolonged activation of GR receptors induced a
depression-like state in mice, activated stress-related genes and induced a
decrease in the mRNA expression of GLAST, an astroglial marker, in the prefrontal
cortex and hippocampus. Together, the results reported here challenge several
hypotheses concerning the role of GRs in the development of behavioral and
molecular alterations relevant to stress-related disorders, such as depression,
under the same experimental conditions.
Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.
DOI: 10.1016/j.neuroscience.2014.11.035
PMID: 25433240 [Indexed for MEDLINE]