Behavioral insights from mouse models of forebrain- and amygdala-specific glucocorticoid receptor genetic disruption
Open accessAbstract
Genetic modulation of glucocorticoid receptor (GR) function in the brain using transgenic and gene knockout mice has yielded important insights into many aspects of GR effects on behavior and neuroendocrine responses, but significant limitations regarding interpretation of region-specific and temporal requirements remain. Here, we summarize the behavioral phenotype associated with two knockout mouse models to define the role of GRs specifically within the forebrain and amygdala. We report that forebrain-specific GR knockout mice exhibit impaired negative feedback regulation of the hypothalamic-pituitary-adrenal (HPA) axis and increased despair- and anxiety-like behaviors. In addition, mice with a disruption of GR specifically within the central nucleus of the amygdala (CeA) are deficient in conditioned fear behavior. Overall, these models serve as beneficial tools to better understand the biology of GR signaling in the normal stress response and in mood disorders.
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The central amygdala nucleus (CEA) is rich in stress hormones and their receptors and contributes to processing of stress signals.
“The CEA is rich in stress hormones and their receptors,98, 99, 100, 101 and contributes to processing of stress signals.102, 103, 104”
From Preferential loss of dorsal-hippocampus synapses underlies memory impairments provoked by short, multimodal stress (2014) · cites this paper as [102]
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Brain corticosteroid receptor balance in health and disease
de Kloet, E. R., Vreugdenhil, E., Oitzl, M. S., & Joëls, M. (1998) · Endocrine Reviews · doi:10.1210/edrv.19.3.0331 · Cited by 2,614 · see citing works
The Corticosteroid Receptor Hypothesis of Depression
Holsboer, F. (2000) · Neuropsychopharmacology · doi:10.1016/s0893-133x(00)00159-7 · Cited by 2,181 · see citing works
Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety
Tronche, F., Kellendonk, C., Kretz, O., Gass, P., Anlag, K., Orban, P. C., Bock, R., Klein, R., & Schütz, G. (1999) · Nature Genetics · doi:10.1038/12703 · Cited by 1,841 · see citing works
Steroid hormone receptors: Many Actors in search of a plot
Beato, M., Herrlich, P. A., & Schütz, G. (1995) · Cell · doi:10.1016/0092-8674(95)90201-5 · Cited by 1,806 · see citing works
Subregion- and Cell Type–Restricted Gene Knockout in Mouse Brain
Tsien, J. Z., Chen, D. F., Gerber, D., Tom, C., Mercer, E. H., Anderson, D. J., Mayford, M., Kandel, E. R., & Tonegawa, S. (1996) · Cell · doi:10.1016/s0092-8674(00)81826-7 · Cited by 1,280 · see citing works
Cole, T. J., Blendy, J. A., Monaghan, A. P., Krieglstein, K., Schmid, W., Aguzzi, A., Fantuzzi, G., Hummler, E., Unsicker, K., & Schütz, G. (1995) · Genes & Development · doi:10.1101/gad.9.13.1608 · Cited by 946 · see citing works
Boyle, M. P., Brewer, J. A., Funatsu, M., Wozniak, D. F., Tsien, J. Z., Izumi, Y., & Muglia, L. J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0406458102 · Cited by 378 · see citing works
Self-citationImpaired type II glucocorticoid-receptor function in mice bearing antisense RNA transgene
Pépin, M.-C., Pothier, F., & Barden, N. (1992) · Nature · doi:10.1038/355725a0 · Cited by 319 · see citing works
Depression, Stress and the Adrenal axis
(2003) · Journal of Neuroendocrinology · doi:10.1046/j.1365-2826.2003.01058.x · Cited by 242 · see citing works
Montkowski, A., Barden, N., Wotjak, C. T., Stec, I. S. M., Ganster, J., Meaney, M. J., Engelmann, M., Reul, J. M. H. M., Landgraf, R., & Holsboer, F. (1995) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.1995.tb00724.x · Cited by 174 · see citing works
Boyle, M. P., Kolber, B. J., Vogt, S. K., Wozniak, D. F., & Muglia, L. J. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.2173-05.2006 · Cited by 172 · see citing works
Self-citationKolber, B. J., Roberts, M. S., Howell, M. P., Wozniak, D. F., Sands, M. S., & Muglia, L. J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0803216105 · Cited by 169 · see citing works
Self-citationGlucocorticoids and depression
Steckler, T., Holsboer, F., & Reul, J. M. H. M. (1999) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1053/beem.1999.0046 · Cited by 160 · see citing works
T-cell glucocorticoid receptor is required to suppress COX-2-mediated lethal immune activation
Brewer, J. A., Khor, B., Vogt, S. K., Muglia, L. M., Fujiwara, H., Haegele, K. E., Sleckman, B. P., & Muglia, L. J. (2003) · Nature Medicine · doi:10.1038/nm895 · Cited by 149 · see citing works
Self-citationKolber, B. J., Wieczorek, L., & Muglia, L. J. (2008) · Stress · doi:10.1080/10253890701821081 · Cited by 106 · see citing works
Self-citationBarden, N., Stec, I. S. M., Montkowski, A., Holsboer, F., & Reul, J. M. H. M. (2008) · Neuroendocrinology · doi:10.1159/000127240 · Cited by 94 · see citing works
Pitts, M. W., Todorovic, C., Blank, T., & Takahashi, L. K. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.0740-09.2009 · Cited by 90 · see citing works
Reul, J. M. H. M., Bilang‐Bleuel, A., Droste, S. K., Linthorst, A. C. E., Holsboer, F., & Gesing, A. (2000) · Zeitschrift für Rheumatologie · doi:10.1007/s003930070013 · Cited by 21 · see citing works
Corticosteroid Receptor Transgenic Mice
Urani, A., & Gass, P. (2003) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1286.037 · Cited by 21 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Glucocorticoid receptor signaling in health and disease
Kadmiel, M., & Cidlowski, J. A. (2013) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2013.07.003 · Cited by 849 · see citing works
Singh, M. (2014) · Frontiers in Psychology · doi:10.3389/fpsyg.2014.00925 · Cited by 337 · see citing works
Myers, B., McKlveen, J. M., & Herman, J. P. (2014) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2013.12.003 · Cited by 318 · see citing works
Metabolic disturbances connecting obesity and depression
Hryhorczuk, C., Sharma, S., & Fulton, S. E. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00177 · Cited by 322 · see citing works
de Kloet, E. R., Meijer, O. C., Nicola, A. F. D., Rijk, R. H. D., & Joëls, M. (2018) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2018.02.003 · Cited by 279 · see citing works
Suri, D., & Vaidya, V. A. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.08.065 · Cited by 253 · see citing works
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de Kloet, E. R. (2014) · Endocrinology · doi:10.1210/en.2014-1048 · Cited by 205 · see citing works
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Aguilera, G., & Liu, Y. (2012) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2011.08.002 · Cited by 198 · see citing works
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Xiong, F., & Zhang, L. (2013) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2012.11.002 · Cited by 177 · see citing works
Short, A. K., Yeshurun, S., Powell, R., Perreau, V. M., Fox, A., Kim, J. H., Pang, T. Y., & Hannan, A. J. (2017) · Translational Psychiatry · doi:10.1038/tp.2017.82 · Cited by 166 · see citing works
Schroeder, F. A., Lewis, M. C., Fass, D. M., Wagner, F. F., Zhang, Y.-L., Hennig, K. M., Gale, J., Zhao, W.-N., Reis, S., Barker, D. D., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0071323 · Cited by 146 · see citing works
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de Kloet, E. R., de Kloet, S. F., de Kloet, C. S., & de Kloet, A. D. (2018) · Journal of Neuroendocrinology · doi:10.1111/jne.12675 · Cited by 120 · see citing works
Maras, P. M., Molet, J., Chen, Y., Rice, C., Ji, S. G., Solodkin, A., & Baram, T. Z. (2014) · Molecular Psychiatry · doi:10.1038/mp.2014.12 · Cited by 118 · see citing works
Mellor, C. L., Steinmetz, F. P., & Cronin, M. (2015) · Critical Reviews in Toxicology · doi:10.3109/10408444.2015.1089471 · Cited by 114 · see citing works
Loss of hypothalamic corticotropin-releasing hormone markedly reduces anxiety behaviors in mice
Zhang, R., Asai, M., Mahoney, C. E., Joachim, M., Shen, Y., Gunner, G., & Majzoub, J. A. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.136 · Cited by 97 · see citing works
Hartmann, J., Dedic, N., Pöhlmann, M. L., Häusl, A. S., Karst, H., Engelhardt, C., Westerholz, S., Wagner, K. V., Labermaier, C., Hoeijmakers, L., et al. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.87 · Cited by 74 · see citing works
Caldwell, K. E., Labrecque, M. T., Solomon, B. R., Ali, A.-M. S., & Allan, A. M. (2014) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2014.11.006 · Cited by 60 · see citing works
Laryea, G. N., Muglia, L. M., Arnett, M. G., & Muglia, L. J. (2014) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2014.09.002 · Cited by 53 · see citing works
Self-citationUvnäs‐Moberg, K., Groß, M. M., Calleja‐Agius, J., & Turner, J. D. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1272270 · Cited by 53 · see citing works
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Evans, A. N., Liu, Y., MacGregor, R., Huang, V., & Aguilera, G. (2013) · Molecular Endocrinology · doi:10.1210/me.2013-1095 · Cited by 50 · see citing works
Malikowska‐Racia, N., & Sałat, K. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.02.001 · Cited by 46 · see citing works
Chourbaji, S., Hoyer, C., Richter, S. H., Brandwein, C., Pfeiffer, N., Vogt, M. A., Vollmayr, B., & Gass, P. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019218 · Cited by 40 · see citing works
Di, T., Zhang, S., Hong, J., Zhang, T., & Chen, L. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00287 · Cited by 38 · see citing works
Schmidt, M., Lax, E., Zhou, R., Cheishvili, D., Ruder, A. M., Ludiro, A., Lapert, F., Macedo da Cruz, A., Sandrini, P., Calzoni, T., et al. (2019) · Translational Psychiatry · doi:10.1038/s41398-018-0348-7 · Cited by 37 · see citing works
Glucocorticoid receptor number predicts increase in amygdala activity after severe stress
Geuze, E., van Wingen, G. A., van Zuiden, M., Rademaker, A. R., Vermetten, E. H. G. J. M., Kavelaars, A., Fernández, G., & Heijnen, C. J. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.03.017 · Cited by 35 · see citing works
Effects of environmental manipulations in genetically targeted animal models of affective disorders
Renoir, T., Pang, T. Y., & Hannan, A. J. (2012) · Neurobiology of Disease · doi:10.1016/j.nbd.2012.04.003 · Cited by 31 · see citing works
El-Hage, W., Phillips, M. L., Radua, J., Gohier, B., Zelaya, F. O., Collier, D. A., & Surguladze, S. A. (2013) · Molecular Psychiatry · doi:10.1038/mp.2011.145 · Cited by 24 · see citing works
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Vinson, G. P., & Brennan, C. H. (2013) · Endocrine Connections · doi:10.1530/ec-13-0028 · Cited by 23 · see citing works
Wiktorowska, L., Bilecki, W., Tertil, M., Kudla, L., Szumiec, Ł., Maćkowiak, M., & Przewłocki, R. (2021) · Behavioural Brain Research · doi:10.1016/j.bbr.2020.113095 · Cited by 22 · see citing works
Hay, C. W., Shanley, L. J., Davidson, S., Cowie, P., Lear, M., McGuffin, P., Riedel, G., McEwan, I. J., & MacKenzie, A. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.04.017 · Cited by 15 · see citing works
Taylor, M. A., & Kokiko‐Cochran, O. N. (2024) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2024.1351685 · Cited by 15 · see citing works
Numakawa, T., Odaka, H., Adachi, N., Chiba, S., Ooshima, Y., Matsuno, H., Nakajima, S., Yoshimura, A., Fumimoto, K., Hirai, Y., et al. (2018) · Neurochemistry International · doi:10.1016/j.neuint.2018.06.009 · Cited by 12 · see citing works
Stress Adaptation and the Hypothalamic‐Pituitary‐Adrenal Axis
Aguilera, G. (2016) · Wiley eBooks · doi:10.1002/9781118760369.ch17 · Cited by 8 · see citing works
Unteroberdörster, M., Herring, A., Bendix, I., Lückemann, L., Petschulat, J., Sure, U., Keyvani, K., Hetze, S., Schedlowski, M., & Hadamitzky, M. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108424 · Cited by 8 · see citing works
Oyola, M. G., Malysz, A. M., Mani, S. K., & Handa, R. J. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-802114-9.00013-5 · Cited by 7 · see citing works
Zhang, J., Gao, L., Yang, G. L., & Kong, D. Z. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1369676 · Cited by 6 · see citing works
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Bult, C. J. (2012) · International review of neurobiology · doi:10.1016/b978-0-12-398323-7.00004-5 · Cited by 6 · see citing works
Wei, Q., Kumar, V., Moore, S. J., Li, F. R., Murphy, G. G., Watson, S. J., & Akil, H. (2023) · Neurobiology of Stress · doi:10.1016/j.ynstr.2023.100581 · Cited by 5 · see citing works
Firouzabadi, N., Nouraei, H., & Mandegary, A. (2018) · PubMed Central · doi:10.22086/gmj.v0i0.1181 · Cited by 4 · see citing works
Immunomodulatory and Anti-Inflammatory Properties of Glucocorticoids
Ayroldi, E., Migliorati, G., & Riccardi, C. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-820472-6.00052-9 · Cited by 2 · see citing works
Aguilera, G. (2015) · Interdisciplinary Information Sciences · doi:10.4036/iis.2015.b.13 · Cited by 2 · see citing works
A larval zebrafish model of glucocorticoid-serotonin interactions in behavioral stress reactivity
Griffiths, B. B. (2011) · California State University ScholarWorks (system-wide DSpace) · Cited by 1 · see citing works
An overview of behavioral neuroendocrinology: present, past and future
Wilkinson, M., & Brown, R. E. (2015) · Cambridge University Press eBooks · doi:10.1017/cbo9781139045803.016
Glucocorticoid Action in the Mediobasal Hypothalamus Regulates Glucose Production In Vivo
Beaulieu-Bayne, E. (2019) · ERA: Education and Research Archive (University of Alberta) · doi:10.7939/r3-eahb-a894
Sandi, C. (2014) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.718297966.793492714
Hypercortisolism and Behavioral Neuroscience
Vives, A. S., Webb, S. M., & Resmini, E. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819641-0.00093-1
Firouzabadi, N., Nouraei, H., & Mandegary, A. (2018) · Galen Medical Journal · doi:10.31661/gmj.v7i.1181
Kanczkowski, W., Sue, M., Wlodarczyk, A., & Chrousos, G. P. (2024) · Exploration of Endocrine and Metabolic Diseases · doi:10.37349/eemd.2024.00012 · Cited by 2 · see citing works
Variation in cocaine responses across genetically diverse mouse strains
Pollock, M., Abbas, A., Bui, H. M., Chung, J.-H., Dai, Y., DiCola, J., Goldberg, L., Hale, S., Joyce, C., Rubio, E., et al. (2026) · Psychopharmacology · doi:10.1007/s00213-026-07133-5
Models of depression for preclinical drug discovery and development: an update of the literature
Pavlidi, P., Kalampokis, D., Ioannidi, I., Skourti, K., Sotiropoulos, I., Antoniou, K., Dalla, C., & Kokras, N. (2026) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2026.2716135
Oxytocin as regulator of stress and inflammation in aging
Wright, K. D., Horta, M., Hayes, A., & Ebner, N. C. (2026) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2026.106924
- Authors
- Arnett, M. G., Kolber, B. J., Boyle, M. P., & Muglia, L. J.
- Affiliations
- Vanderbilt University (US)
- Washington University in St. Louis (US)
- Corresponding author
- Arnett, Melinda G.
- Venue
- Molecular and Cellular Endocrinology
- Publisher
- Elsevier BV
- Published
- 2011-04
- Volume
- 336
- Issue
- 1-2
- Pages
- 2-5
- ISSN
- 0303-7207 (ISSN-L)
- PMC
- PMC3172614
- OpenAlex
- W2047083143
- Cited by
- 53
- References
- 19
- Citations by year
- 2026: 3 · 2024: 4 · 2023: 1 · 2021: 3 · 2020: 1 · 2019: 3 · 2018: 6 · 2017: 2 · 2016: 3 · 2015: 4 · 2014: 7 · 2013: 6 · 2012: 6
- FWCI
- 2.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (NIH (MH079010))
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- glucocorticoid receptor, amygdala, central amygdala, hypothalamic-pituitary-adrenal axis, negative feedback regulation, anxiety-like behavior, despair-like behavior, fear conditioning, stress response, mood disorders, knockout mice
- MeSH terms
- Amygdala, Animals, Behavior, Animal, Organ Specificity, Receptors, Glucocorticoid, Gene Deletion, Models, Animal, Mice
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