Neurobiological Sequelae of Witnessing Stressful Events in Adult Mice

Background It is well known that exposure to severe stress increases the risk for developing mood disorders. However, most chronic stress models in rodents involve at least some form of physically experiencing traumatic events. Methods This study assessed the effects of a novel social stress paradig...

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Veröffentlicht in:Biological psychiatry (1969) 2013-01, Vol.73 (1), p.7-14
Hauptverfasser: Warren, Brandon L, Vialou, Vincent F, Iñiguez, Sergio D, Alcantara, Lyonna F, Wright, Katherine N, Feng, Jiang, Kennedy, Pamela J, LaPlant, Quincey, Shen, Li, Nestler, Eric J, Bolaños-Guzmán, Carlos A
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container_issue 1
container_start_page 7
container_title Biological psychiatry (1969)
container_volume 73
creator Warren, Brandon L
Vialou, Vincent F
Iñiguez, Sergio D
Alcantara, Lyonna F
Wright, Katherine N
Feng, Jiang
Kennedy, Pamela J
LaPlant, Quincey
Shen, Li
Nestler, Eric J
Bolaños-Guzmán, Carlos A
description Background It is well known that exposure to severe stress increases the risk for developing mood disorders. However, most chronic stress models in rodents involve at least some form of physically experiencing traumatic events. Methods This study assessed the effects of a novel social stress paradigm that is insulated from the effects of physical stress. Specifically, adult male C57BL/6J mice were exposed to either emotional (ES) or physical stress (PS) for 10 minutes per day for 10 days. The ES mice were exposed to the social defeat of a PS mouse by a larger, more aggressive CD-1 mouse from the safety of an adjacent compartment. Results Like PS mice, ES mice exhibited a range of depression- and anxiety-like behaviors both 24 hours and 1 month after the stress. Increased levels of serum corticosterone, part of the stress response, accompanied these behavioral deficits. Based on previous work that implicated gene expression changes in the ventral tegmental area (a key brain reward region) in the PS phenotype, we compared genome-wide mRNA expression patterns in this brain region of ES and PS mice using RNA-seq. We found significant overlap between these conditions, which suggests several potential gene targets for mediating the behavioral abnormalities observed. Conclusions These findings demonstrate that witnessing traumatic events is a potent stress in adult male mice capable of inducing long-lasting neurobiological perturbations.
doi_str_mv 10.1016/j.biopsych.2012.06.006
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However, most chronic stress models in rodents involve at least some form of physically experiencing traumatic events. Methods This study assessed the effects of a novel social stress paradigm that is insulated from the effects of physical stress. Specifically, adult male C57BL/6J mice were exposed to either emotional (ES) or physical stress (PS) for 10 minutes per day for 10 days. The ES mice were exposed to the social defeat of a PS mouse by a larger, more aggressive CD-1 mouse from the safety of an adjacent compartment. Results Like PS mice, ES mice exhibited a range of depression- and anxiety-like behaviors both 24 hours and 1 month after the stress. Increased levels of serum corticosterone, part of the stress response, accompanied these behavioral deficits. Based on previous work that implicated gene expression changes in the ventral tegmental area (a key brain reward region) in the PS phenotype, we compared genome-wide mRNA expression patterns in this brain region of ES and PS mice using RNA-seq. We found significant overlap between these conditions, which suggests several potential gene targets for mediating the behavioral abnormalities observed. Conclusions These findings demonstrate that witnessing traumatic events is a potent stress in adult male mice capable of inducing long-lasting neurobiological perturbations.</description><identifier>ISSN: 0006-3223</identifier><identifier>EISSN: 1873-2402</identifier><identifier>DOI: 10.1016/j.biopsych.2012.06.006</identifier><identifier>PMID: 22795644</identifier><identifier>CODEN: BIPCBF</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Adult and adolescent clinical studies ; Animals ; Anxiety - drug therapy ; Anxiety - metabolism ; Anxiety disorders. 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However, most chronic stress models in rodents involve at least some form of physically experiencing traumatic events. Methods This study assessed the effects of a novel social stress paradigm that is insulated from the effects of physical stress. Specifically, adult male C57BL/6J mice were exposed to either emotional (ES) or physical stress (PS) for 10 minutes per day for 10 days. The ES mice were exposed to the social defeat of a PS mouse by a larger, more aggressive CD-1 mouse from the safety of an adjacent compartment. Results Like PS mice, ES mice exhibited a range of depression- and anxiety-like behaviors both 24 hours and 1 month after the stress. Increased levels of serum corticosterone, part of the stress response, accompanied these behavioral deficits. Based on previous work that implicated gene expression changes in the ventral tegmental area (a key brain reward region) in the PS phenotype, we compared genome-wide mRNA expression patterns in this brain region of ES and PS mice using RNA-seq. We found significant overlap between these conditions, which suggests several potential gene targets for mediating the behavioral abnormalities observed. Conclusions These findings demonstrate that witnessing traumatic events is a potent stress in adult male mice capable of inducing long-lasting neurobiological perturbations.</description><subject>Adult and adolescent clinical studies</subject><subject>Animals</subject><subject>Anxiety - drug therapy</subject><subject>Anxiety - metabolism</subject><subject>Anxiety disorders. 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Psychiatry</subject><subject>RNA-seq</subject><subject>Social Behavior</subject><subject>social defeat</subject><subject>Stress, Physiological - drug effects</subject><subject>Stress, Psychological - drug therapy</subject><subject>Stress, Psychological - genetics</subject><subject>Stress, Psychological - metabolism</subject><subject>Stress, Psychological - psychology</subject><subject>ventral tegmental area</subject><subject>Ventral Tegmental Area - metabolism</subject><issn>0006-3223</issn><issn>1873-2402</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUk1v1DAUjBCIbgt_ocoFiUvCsx3byaWiqrYUqcBhQRwtx3neesnGi52stP8eR7stHxdO_po3bzzzsuySQEmAiHebsnV-Fw_moaRAaAmiBBDPsgWpJStoBfR5toB0VTBK2Vl2HuMmHSWl5GV2RqlsuKiqRbb8jFPwiav3a2d0n6_w54S9xtzb_LsbB4zRDet8NYa0s1OfL_c4jDF3Q37dTf2Yf3IGX2UvrO4jvj6tF9m32-XXm7vi_suHjzfX94UR0IxFLbhtbS1qxiUHTTsLPOmVrGtawQlDKbHiFRIjRSda0nC0lGkgVgC2yNlFdnXk3U3tFjuTlATdq11wWx0Oymun_n4Z3INa-71iVVNzCYng7Ykg-PTPOKqtiwb7Xg_op6gIZRIaILxOUHGEmuBjDGif2hBQcwZqox4zUHMGCoRKhqfCyz9FPpU9mp4Ab04AHZPlNujBuPgbJ4kE2swK3h9xmCzdOwwqGoeDwc4FNKPqvPu_lqt_KEzvhjnoH3jAuPFTGFJgiqiYatRqnph5YAgF4Ixz9guv3r3N</recordid><startdate>20130101</startdate><enddate>20130101</enddate><creator>Warren, Brandon L</creator><creator>Vialou, Vincent F</creator><creator>Iñiguez, Sergio D</creator><creator>Alcantara, Lyonna F</creator><creator>Wright, Katherine N</creator><creator>Feng, Jiang</creator><creator>Kennedy, Pamela J</creator><creator>LaPlant, Quincey</creator><creator>Shen, Li</creator><creator>Nestler, Eric J</creator><creator>Bolaños-Guzmán, Carlos A</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20130101</creationdate><title>Neurobiological Sequelae of Witnessing Stressful Events in Adult Mice</title><author>Warren, Brandon L ; Vialou, Vincent F ; Iñiguez, Sergio D ; Alcantara, Lyonna F ; Wright, Katherine N ; Feng, Jiang ; Kennedy, Pamela J ; LaPlant, Quincey ; Shen, Li ; Nestler, Eric J ; Bolaños-Guzmán, Carlos A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c609t-865fbf86835750a2df0518773d9b6513e77e454e1c76d6b195ef23a01f60ebe53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult and adolescent clinical studies</topic><topic>Animals</topic><topic>Anxiety - drug therapy</topic><topic>Anxiety - metabolism</topic><topic>Anxiety disorders. Neuroses</topic><topic>Behavior, Animal - drug effects</topic><topic>Biological and medical sciences</topic><topic>Corticosterone - metabolism</topic><topic>Depression</topic><topic>Depression - drug therapy</topic><topic>Depression - metabolism</topic><topic>Disease Models, Animal</topic><topic>emotional stress</topic><topic>Fluoxetine - pharmacology</topic><topic>Fluoxetine - therapeutic use</topic><topic>Gene Expression Profiling</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Inbred ICR</topic><topic>Mood disorders</topic><topic>Photic Stimulation</topic><topic>Post-traumatic stress disorder</topic><topic>posttraumatic stress disorder</topic><topic>Psychiatry</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopathology. Psychiatry</topic><topic>RNA-seq</topic><topic>Social Behavior</topic><topic>social defeat</topic><topic>Stress, Physiological - drug effects</topic><topic>Stress, Psychological - drug therapy</topic><topic>Stress, Psychological - genetics</topic><topic>Stress, Psychological - metabolism</topic><topic>Stress, Psychological - psychology</topic><topic>ventral tegmental area</topic><topic>Ventral Tegmental Area - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Warren, Brandon L</creatorcontrib><creatorcontrib>Vialou, Vincent F</creatorcontrib><creatorcontrib>Iñiguez, Sergio D</creatorcontrib><creatorcontrib>Alcantara, Lyonna F</creatorcontrib><creatorcontrib>Wright, Katherine N</creatorcontrib><creatorcontrib>Feng, Jiang</creatorcontrib><creatorcontrib>Kennedy, Pamela J</creatorcontrib><creatorcontrib>LaPlant, Quincey</creatorcontrib><creatorcontrib>Shen, Li</creatorcontrib><creatorcontrib>Nestler, Eric J</creatorcontrib><creatorcontrib>Bolaños-Guzmán, Carlos A</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biological psychiatry (1969)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Warren, Brandon L</au><au>Vialou, Vincent F</au><au>Iñiguez, Sergio D</au><au>Alcantara, Lyonna F</au><au>Wright, Katherine N</au><au>Feng, Jiang</au><au>Kennedy, Pamela J</au><au>LaPlant, Quincey</au><au>Shen, Li</au><au>Nestler, Eric J</au><au>Bolaños-Guzmán, Carlos A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neurobiological Sequelae of Witnessing Stressful Events in Adult Mice</atitle><jtitle>Biological psychiatry (1969)</jtitle><addtitle>Biol Psychiatry</addtitle><date>2013-01-01</date><risdate>2013</risdate><volume>73</volume><issue>1</issue><spage>7</spage><epage>14</epage><pages>7-14</pages><issn>0006-3223</issn><eissn>1873-2402</eissn><coden>BIPCBF</coden><abstract>Background It is well known that exposure to severe stress increases the risk for developing mood disorders. 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Based on previous work that implicated gene expression changes in the ventral tegmental area (a key brain reward region) in the PS phenotype, we compared genome-wide mRNA expression patterns in this brain region of ES and PS mice using RNA-seq. We found significant overlap between these conditions, which suggests several potential gene targets for mediating the behavioral abnormalities observed. Conclusions These findings demonstrate that witnessing traumatic events is a potent stress in adult male mice capable of inducing long-lasting neurobiological perturbations.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>22795644</pmid><doi>10.1016/j.biopsych.2012.06.006</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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subjects Adult and adolescent clinical studies
Animals
Anxiety - drug therapy
Anxiety - metabolism
Anxiety disorders. Neuroses
Behavior, Animal - drug effects
Biological and medical sciences
Corticosterone - metabolism
Depression
Depression - drug therapy
Depression - metabolism
Disease Models, Animal
emotional stress
Fluoxetine - pharmacology
Fluoxetine - therapeutic use
Gene Expression Profiling
Male
Medical sciences
Mice
Mice, Inbred C57BL
Mice, Inbred ICR
Mood disorders
Photic Stimulation
Post-traumatic stress disorder
posttraumatic stress disorder
Psychiatry
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
RNA-seq
Social Behavior
social defeat
Stress, Physiological - drug effects
Stress, Psychological - drug therapy
Stress, Psychological - genetics
Stress, Psychological - metabolism
Stress, Psychological - psychology
ventral tegmental area
Ventral Tegmental Area - metabolism
title Neurobiological Sequelae of Witnessing Stressful Events in Adult Mice
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