The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Glucocorticoid receptor overexpression in forebrain: A mouse model of increased emotional lability
Open accessAbstract
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-hydroxytryptamine 1A receptor. 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.
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Cites
Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants
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Self-citationDNA binding of the glucocorticoid receptor is not essential for survival
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de Kloet, E. R., Joëls, M., & Holsboer, F. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1683 · Cited by 4,621
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Mechanisms of stress in the brain
McEwen, B. S., Bowles, N. P., Gray, J. D., Hill, M. N., Hunter, R. G., Karatsoreos, I. N., & Nasca, C. (2015) · Nature Neuroscience · doi:10.1038/nn.4086 · Cited by 1,386
Neurobiological and Systemic Effects of Chronic Stress
McEwen, B. S. (2017) · Chronic Stress · doi:10.1177/2470547017692328 · Cited by 1,059
“Genetically induced overexpression of GR in forebrain leads to increased ability of moodrelated behaviors and yet also confers greater responsiveness to antidepressant drugs.(30) Genetically induced underexpression of GR has the opposite effect.”
Background
Metadata
- Authors
- Wei, Q., Lu, X.-Y., Liu, L., Schafer, G., Shieh, K.-R., Burke, S., Robinson, T. E., Watson, S. J., Seasholtz, A. F., & Akil, H.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2004-07-27
- Volume
- 101
- Issue
- 32
- Pages
- 11851-11856
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2163663276
- Cited by
- 248
- References
- 9
- FWCI
- 6.37
- Type
- journal article
- Language
- en
- Open access
- green
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- Wei, Q., Lu, X.-Y., Liu, L., Schafer, G., Shieh, K.-R., Burke, S., Robinson, T. E., Watson, S. J., Seasholtz, A. F., & Akil, H. (2004). Glucocorticoid receptor overexpression in forebrain: A mouse model of increased emotional lability. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0402208101
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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