Fluoxetine and environmental enrichment similarly reverse chronic social stress-related depression- and anxiety-like behavior, but have differential effects on amygdala gene expression
The adverse effects of stress on brain and behavior have long been known and well-studied, with abundant evidence linking stress to, among other things, mood and anxiety disorders. Likewise, many have investigated potential treatments for stress-related mood and anxiety phenotypes and demonstrated g...
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doaj-a3b8625a03fc42d7a03b1b549afa54c62021-09-17T04:36:32ZengElsevierNeurobiology of Stress2352-28952021-11-0115100392Fluoxetine and environmental enrichment similarly reverse chronic social stress-related depression- and anxiety-like behavior, but have differential effects on amygdala gene expressionZachary A. Cordner0Isaiah Marshall-Thomas1Gretha J. Boersma2Richard S. Lee3James B. Potash4Kellie L.K. Tamashiro5Department of Psychiatry & Behavioral Sciences, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 618, Baltimore, MD, 21205, USADepartment of Psychiatry & Behavioral Sciences, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 618, Baltimore, MD, 21205, USADepartment of Psychiatry & Behavioral Sciences, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 618, Baltimore, MD, 21205, USADepartment of Psychiatry & Behavioral Sciences, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 618, Baltimore, MD, 21205, USADepartment of Psychiatry & Behavioral Sciences, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 618, Baltimore, MD, 21205, USADepartment of Psychiatry & Behavioral Sciences, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 618, Baltimore, MD, 21205, USA; Cellular & Molecular Medicine Program, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 618, Baltimore, MD, 21205, USA; Corresponding author. Department of Psychiatry & Behavioral Sciences Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 618, Baltimore, MD, 21205, USA.The adverse effects of stress on brain and behavior have long been known and well-studied, with abundant evidence linking stress to, among other things, mood and anxiety disorders. Likewise, many have investigated potential treatments for stress-related mood and anxiety phenotypes and demonstrated good response to standard antidepressant medications like selective serotonin reuptake inhibitors (SSRIs), as well as environmental manipulations like exercise or enrichment. However, the extent to which stress and various treatments act on overlapping pathways in the brain is less well understood. Here, we used a widely studied social defeat stress paradigm to induce a robust depression- and anxiety-like phenotype and chronic corticosterone elevation that persisted for at least 4 weeks in wild type male mice. When mice were treated with either the SSRI fluoxetine or an enriched environment, both led to similar behavioral recovery from social defeat. We then focused on the amygdala and assessed the effects of social defeat, fluoxetine, and enrichment on 168 genes broadly related to synaptic plasticity or oxidative stress. We found 24 differentially expressed genes in response to social defeat stress. Interestingly, fluoxetine led to broad normalization of the stress-induced expression pattern while enrichment led to expression changes in a separate set of genes. Together, this study provides additional insight into the chronic effects of social defeat stress on behavior and gene expression in the amygdala. The findings also suggest that, for a subset of genes assessed, fluoxetine and environmental enrichment have strikingly divergent effects on expression in the amygdala, despite leading to similar behavioral outcomes.http://www.sciencedirect.com/science/article/pii/S2352289521001004StressGene expressionAmygdalaFluoxetineEnvironmental enrichmentAffective disorders |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zachary A. Cordner Isaiah Marshall-Thomas Gretha J. Boersma Richard S. Lee James B. Potash Kellie L.K. Tamashiro |
spellingShingle |
Zachary A. Cordner Isaiah Marshall-Thomas Gretha J. Boersma Richard S. Lee James B. Potash Kellie L.K. Tamashiro Fluoxetine and environmental enrichment similarly reverse chronic social stress-related depression- and anxiety-like behavior, but have differential effects on amygdala gene expression Neurobiology of Stress Stress Gene expression Amygdala Fluoxetine Environmental enrichment Affective disorders |
author_facet |
Zachary A. Cordner Isaiah Marshall-Thomas Gretha J. Boersma Richard S. Lee James B. Potash Kellie L.K. Tamashiro |
author_sort |
Zachary A. Cordner |
title |
Fluoxetine and environmental enrichment similarly reverse chronic social stress-related depression- and anxiety-like behavior, but have differential effects on amygdala gene expression |
title_short |
Fluoxetine and environmental enrichment similarly reverse chronic social stress-related depression- and anxiety-like behavior, but have differential effects on amygdala gene expression |
title_full |
Fluoxetine and environmental enrichment similarly reverse chronic social stress-related depression- and anxiety-like behavior, but have differential effects on amygdala gene expression |
title_fullStr |
Fluoxetine and environmental enrichment similarly reverse chronic social stress-related depression- and anxiety-like behavior, but have differential effects on amygdala gene expression |
title_full_unstemmed |
Fluoxetine and environmental enrichment similarly reverse chronic social stress-related depression- and anxiety-like behavior, but have differential effects on amygdala gene expression |
title_sort |
fluoxetine and environmental enrichment similarly reverse chronic social stress-related depression- and anxiety-like behavior, but have differential effects on amygdala gene expression |
publisher |
Elsevier |
series |
Neurobiology of Stress |
issn |
2352-2895 |
publishDate |
2021-11-01 |
description |
The adverse effects of stress on brain and behavior have long been known and well-studied, with abundant evidence linking stress to, among other things, mood and anxiety disorders. Likewise, many have investigated potential treatments for stress-related mood and anxiety phenotypes and demonstrated good response to standard antidepressant medications like selective serotonin reuptake inhibitors (SSRIs), as well as environmental manipulations like exercise or enrichment. However, the extent to which stress and various treatments act on overlapping pathways in the brain is less well understood. Here, we used a widely studied social defeat stress paradigm to induce a robust depression- and anxiety-like phenotype and chronic corticosterone elevation that persisted for at least 4 weeks in wild type male mice. When mice were treated with either the SSRI fluoxetine or an enriched environment, both led to similar behavioral recovery from social defeat. We then focused on the amygdala and assessed the effects of social defeat, fluoxetine, and enrichment on 168 genes broadly related to synaptic plasticity or oxidative stress. We found 24 differentially expressed genes in response to social defeat stress. Interestingly, fluoxetine led to broad normalization of the stress-induced expression pattern while enrichment led to expression changes in a separate set of genes. Together, this study provides additional insight into the chronic effects of social defeat stress on behavior and gene expression in the amygdala. The findings also suggest that, for a subset of genes assessed, fluoxetine and environmental enrichment have strikingly divergent effects on expression in the amygdala, despite leading to similar behavioral outcomes. |
topic |
Stress Gene expression Amygdala Fluoxetine Environmental enrichment Affective disorders |
url |
http://www.sciencedirect.com/science/article/pii/S2352289521001004 |
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