Role of Prefrontal Cortex Glucocorticoid Receptors in Stress and Emotion
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Background Stress-related disorders (e.g., depression) are associated with hypothalamic-pituitary-adrenocortical axis dysregulation and prefrontal cortex (PFC) dysfunction, suggesting a functional link between aberrant prefrontal corticosteroid signaling and mood regulation.Methods We used a virally mediated knockdown strategy (short hairpin RNA targeting the glucocorticoid receptor [GR]) to attenuate PFC GR signaling in the rat PFC. Adult male rats received bilateral microinjections of vector control or short hairpin RNA targeting the GR into the prelimbic (n = 44) or infralimbic (n = 52) cortices. Half of the animals from each injection group underwent chronic variable stress, and all were subjected to novel restraint. The first 2 days of chronic variable stress were used to assess depression- and anxiety-like behavior in the forced swim test and open field.Results The GR knockdown confined to the infralimbic PFC caused acute stress hyper-responsiveness, sensitization of stress responses after chronic variable stress, and induced depression-like behavior (increased immobility in the forced swim test). Knockdown of GR in the neighboring prelimbic PFC increased hypothalamic-pituitary-adrenocortical axis responses to acute stress and caused hyperlocomotion in the open field, but did not affect stress sensitization or helplessness behavior.Conclusions The data indicate a marked functional heterogeneity of glucocorticoid action in the PFC and highlight a prominent role for the infralimbic GR in appropriate stress adaptation, emotional control, and mood regulation.
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GR knockdown in IL induces compromised stress adaptation and depression-like behavior, while GR knockdown in PL increases HPA axis responses to acute stress but does not affect stress sensitization or helplessness behavior.
“Glucocorticoid receptor (GR) knockdown in IL induces compromised stress adaptation and depression-like behavior, while GR knockdown in PL increases HPA axis responses to acute stress but does not affect stress sensitization or helplessness behavior 93”
From Mechanisms of synaptic transmission dysregulation in the prefrontal cortex: pathophysiological implications (2022) · cites this paper as [93]
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- Authors
- McKlveen, J. M., Myers, B., Flak, J. N., Bundzikova, J., Solomon, M. B., Seroogy, K. B., & Herman, J. P.
- Affiliations
- University of Cincinnati (US)
- Corresponding author
- Herman, James P.
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2013-11
- Volume
- 74
- Issue
- 9
- Pages
- 672-679
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC3797253
- OpenAlex
- W2030184709
- Cited by
- 237
- References
- 42
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 13 · 2023: 24 · 2022: 18 · 2021: 22 · 2020: 23 · 2019: 17 · 2018: 25 · 2017: 14 · 2016: 23 · 2015: 17 · 2014: 15 · 2013: 5
- FWCI
- 9.07
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR000077)
- National Institute of Mental Health (R01MH049698, MH069860, R01MH069860, F31MH097430, MH049698, MH097430)
- National Institute of Neurological Disorders and Stroke (NS007453, NS058830, P50NS058830, T32NS007453)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- prefrontal cortex, glucocorticoid receptor, stress, depression, anxiety, hypothalamic-pituitary-adrenal axis, chronic variable stress, stress sensitization, infralimbic cortex, prelimbic cortex, mood regulation, corticosteroid signaling, shRNA knockdown
- MeSH terms
- Adrenocorticotropic Hormone, Affect, Animals, Cells, Cultured, Corticosterone, Depression, Emotions, Hypothalamo-Hypophyseal System, Male, Microinjections, Motor Activity, Pituitary-Adrenal System, Receptors, Glucocorticoid, Stress, Psychological, Prefrontal Cortex, RNA, Small Interfering, Immobility Response, Tonic, Rats
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