Glucocorticoid Receptor Overexpression in Forebrain: A Mouse Model of Increased Emotional Lability
The molecular mechanisms that control the range and stability of emotions are unknown, yet this knowledge is critical for understanding mood disorders, especially bipolar illness. Here, we show that the glucocorticoid receptor (GR) modulates these features of emotional responsiveness. We generated t...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2004-08, Vol.101 (32), p.11851-11856 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Wei, Qiang Lu, Xin-Yun Liu, Li Schafer, Gwen Shieh, Kun-Ruey Burke, Sharon Robinson, Terry E. Watson, Stanley J. Seasholtz, Andrey F. Akil, Huda McEwen, Bruce S. |
| description | The molecular mechanisms that control the range and stability of emotions are unknown, yet this knowledge is critical for understanding mood disorders, especially bipolar illness. Here, we show that the glucocorticoid receptor (GR) modulates these features of emotional responsiveness. We generated transgenic mice overexpressing GR specifically in forebrain. These mice display a significant increase in anxiety-like and depressant-like behaviors relative to wild type. Yet, they are also supersensitive to antidepressants and show enhanced sensitization to cocaine. Thus, mice overexpressing GR in forebrain have a consistently wider than normal range of reactivity in both positive and negative emotionality tests. This phenotype is associated, in specific brain regions, with increased expression of genes relevant to emotionality: corticotropin-releasing hormone, serotonin, norepinephrine and dopamine transporters, and 5-hydroxytryptamine1 Areceptor. Thus, GR overexpression in forebrain causes higher "emotional lability" secondary to a unique pattern of molecular regulation. This finding suggests that natural variations in GR gene expression can contribute to the fine-tuning of emotional stability or lability and may play a role in bipolar disorder. |
| doi_str_mv | 10.1073/pnas.0402208101 |
| format | Article |
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Here, we show that the glucocorticoid receptor (GR) modulates these features of emotional responsiveness. We generated transgenic mice overexpressing GR specifically in forebrain. These mice display a significant increase in anxiety-like and depressant-like behaviors relative to wild type. Yet, they are also supersensitive to antidepressants and show enhanced sensitization to cocaine. Thus, mice overexpressing GR in forebrain have a consistently wider than normal range of reactivity in both positive and negative emotionality tests. This phenotype is associated, in specific brain regions, with increased expression of genes relevant to emotionality: corticotropin-releasing hormone, serotonin, norepinephrine and dopamine transporters, and 5-hydroxytryptamine1 Areceptor. Thus, GR overexpression in forebrain causes higher "emotional lability" secondary to a unique pattern of molecular regulation. This finding suggests that natural variations in GR gene expression can contribute to the fine-tuning of emotional stability or lability and may play a role in bipolar disorder.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0402208101</identifier><identifier>PMID: 15280545</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Affective Symptoms - etiology ; Animals ; Antidepressants ; Antidepressive Agents - pharmacology ; Anxiety - etiology ; Biological Sciences ; Cocaine ; Cocaine - pharmacology ; Corticotropin-Releasing Hormone - genetics ; Depression - etiology ; Emotional expression ; Emotional stability ; Forebrain ; Gene expression ; Gene Expression Regulation - physiology ; Genotypes ; Intramuscular injections ; Membrane Transport Proteins - genetics ; Mental disorders ; Messenger RNA ; Mice ; Mice, Transgenic ; Models, Animal ; Mood Disorders - etiology ; Neurology ; Prosencephalon - chemistry ; Prosencephalon - physiopathology ; Receptor, Serotonin, 5-HT1A - genetics ; Receptors, Glucocorticoid - genetics ; Receptors, Glucocorticoid - physiology ; Sensitization ; Serotonin receptors</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2004-08, Vol.101 (32), p.11851-11856</ispartof><rights>Copyright 1993/2004 The National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Aug 10, 2004</rights><rights>Copyright © 2004, The National Academy of Sciences 2004</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c592t-79eed8e2d83dd1578fd5ee9291c217b1fb0c7ba70728c4d4d371ac80be01abef3</citedby><cites>FETCH-LOGICAL-c592t-79eed8e2d83dd1578fd5ee9291c217b1fb0c7ba70728c4d4d371ac80be01abef3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/101/32.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/3372979$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/3372979$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15280545$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wei, Qiang</creatorcontrib><creatorcontrib>Lu, Xin-Yun</creatorcontrib><creatorcontrib>Liu, Li</creatorcontrib><creatorcontrib>Schafer, Gwen</creatorcontrib><creatorcontrib>Shieh, Kun-Ruey</creatorcontrib><creatorcontrib>Burke, Sharon</creatorcontrib><creatorcontrib>Robinson, Terry E.</creatorcontrib><creatorcontrib>Watson, Stanley J.</creatorcontrib><creatorcontrib>Seasholtz, Andrey F.</creatorcontrib><creatorcontrib>Akil, Huda</creatorcontrib><creatorcontrib>McEwen, Bruce S.</creatorcontrib><title>Glucocorticoid Receptor Overexpression in Forebrain: A Mouse Model of Increased Emotional Lability</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>The molecular mechanisms that control the range and stability of emotions are unknown, yet this knowledge is critical for understanding mood disorders, especially bipolar illness. Here, we show that the glucocorticoid receptor (GR) modulates these features of emotional responsiveness. We generated transgenic mice overexpressing GR specifically in forebrain. These mice display a significant increase in anxiety-like and depressant-like behaviors relative to wild type. Yet, they are also supersensitive to antidepressants and show enhanced sensitization to cocaine. Thus, mice overexpressing GR in forebrain have a consistently wider than normal range of reactivity in both positive and negative emotionality tests. This phenotype is associated, in specific brain regions, with increased expression of genes relevant to emotionality: corticotropin-releasing hormone, serotonin, norepinephrine and dopamine transporters, and 5-hydroxytryptamine1 Areceptor. Thus, GR overexpression in forebrain causes higher "emotional lability" secondary to a unique pattern of molecular regulation. This finding suggests that natural variations in GR gene expression can contribute to the fine-tuning of emotional stability or lability and may play a role in bipolar disorder.</description><subject>Affective Symptoms - etiology</subject><subject>Animals</subject><subject>Antidepressants</subject><subject>Antidepressive Agents - pharmacology</subject><subject>Anxiety - etiology</subject><subject>Biological Sciences</subject><subject>Cocaine</subject><subject>Cocaine - pharmacology</subject><subject>Corticotropin-Releasing Hormone - genetics</subject><subject>Depression - etiology</subject><subject>Emotional expression</subject><subject>Emotional stability</subject><subject>Forebrain</subject><subject>Gene expression</subject><subject>Gene Expression Regulation - physiology</subject><subject>Genotypes</subject><subject>Intramuscular injections</subject><subject>Membrane Transport Proteins - genetics</subject><subject>Mental disorders</subject><subject>Messenger RNA</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Models, Animal</subject><subject>Mood Disorders - etiology</subject><subject>Neurology</subject><subject>Prosencephalon - chemistry</subject><subject>Prosencephalon - physiopathology</subject><subject>Receptor, Serotonin, 5-HT1A - genetics</subject><subject>Receptors, Glucocorticoid - genetics</subject><subject>Receptors, Glucocorticoid - physiology</subject><subject>Sensitization</subject><subject>Serotonin receptors</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFksFrFDEUxgdR7Fo9exEJHgQP076XmdkkBQ-ltLWwUhA9h0zyRrPMTsZkprT_vVl26aqXXpJDft8j3_e9oniLcIIgqtNxMOkEauAcJAI-KxYICstlreB5sQDgopQ1r4-KVymtAUA1El4WR9hwCU3dLIr2up9tsCFO3gbv2DeyNE4hsts7inQ_RkrJh4H5gV2FSG00fjhj5-xrmBPl01HPQsduBhvJJHLschOmLDA9W5nW9356eF286Eyf6M3-Pi5-XF1-v_hSrm6vby7OV6VtFJ9KoYicJO5k5Rw2QnauIVJcoeUoWuxasKI1AgSXtna1qwQaK6ElQNNSVx0Xn3dzx7ndkLM0TNH0eox-Y-KDDsbrf18G_0v_DHe6QYRllfUf9_oYfs-UJr3xyVLfm4GyW71cCpUDVU-CKGStBMoMfvgPXIc55myS5oDZWQ3baac7yMaQUqTu8ccIeluy3pasDyVnxfu_jR74fasZ-LQHtsrDONQV14iyQd3NfT_R_ZRZ9gSbkXc7ZJ3yZjwyVSW4ynH8AfwjxrQ</recordid><startdate>20040810</startdate><enddate>20040810</enddate><creator>Wei, Qiang</creator><creator>Lu, Xin-Yun</creator><creator>Liu, Li</creator><creator>Schafer, Gwen</creator><creator>Shieh, Kun-Ruey</creator><creator>Burke, Sharon</creator><creator>Robinson, Terry E.</creator><creator>Watson, Stanley J.</creator><creator>Seasholtz, Andrey F.</creator><creator>Akil, Huda</creator><creator>McEwen, Bruce S.</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20040810</creationdate><title>Glucocorticoid Receptor Overexpression in Forebrain: A Mouse Model of Increased Emotional Lability</title><author>Wei, Qiang ; 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Here, we show that the glucocorticoid receptor (GR) modulates these features of emotional responsiveness. We generated transgenic mice overexpressing GR specifically in forebrain. These mice display a significant increase in anxiety-like and depressant-like behaviors relative to wild type. Yet, they are also supersensitive to antidepressants and show enhanced sensitization to cocaine. Thus, mice overexpressing GR in forebrain have a consistently wider than normal range of reactivity in both positive and negative emotionality tests. This phenotype is associated, in specific brain regions, with increased expression of genes relevant to emotionality: corticotropin-releasing hormone, serotonin, norepinephrine and dopamine transporters, and 5-hydroxytryptamine1 Areceptor. Thus, GR overexpression in forebrain causes higher "emotional lability" secondary to a unique pattern of molecular regulation. This finding suggests that natural variations in GR gene expression can contribute to the fine-tuning of emotional stability or lability and may play a role in bipolar disorder.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>15280545</pmid><doi>10.1073/pnas.0402208101</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Affective Symptoms - etiology Animals Antidepressants Antidepressive Agents - pharmacology Anxiety - etiology Biological Sciences Cocaine Cocaine - pharmacology Corticotropin-Releasing Hormone - genetics Depression - etiology Emotional expression Emotional stability Forebrain Gene expression Gene Expression Regulation - physiology Genotypes Intramuscular injections Membrane Transport Proteins - genetics Mental disorders Messenger RNA Mice Mice, Transgenic Models, Animal Mood Disorders - etiology Neurology Prosencephalon - chemistry Prosencephalon - physiopathology Receptor, Serotonin, 5-HT1A - genetics Receptors, Glucocorticoid - genetics Receptors, Glucocorticoid - physiology Sensitization Serotonin receptors |
| title | Glucocorticoid Receptor Overexpression in Forebrain: A Mouse Model of Increased Emotional Lability |
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