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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Main Authors: Zachary A. Cordner, Isaiah Marshall-Thomas, Gretha J. Boersma, Richard S. Lee, James B. Potash, Kellie L.K. Tamashiro
Format: Article
Language:English
Published: Elsevier 2021-11-01
Series:Neurobiology of Stress
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2352289521001004
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spelling 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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