The DOI matches its Crossref record; 93 of the 94 references it cites were found in a registry or an index.
Long-term adaptations in glucocorticoid receptor and mineralocorticoid receptor mrna and negative feedback on the hypothalamo-pituitary-adrenal axis following neonatal maternal separation
Abstract
Background Maternally separated rats exhibit exaggerated hypothalamic-pituitary-adrenal responses to an acute stressor but normal diurnal trough functioning. We hypothesized that maternally separated rats experience adequate proactive glucocorticoid negative feedback but deficient "reactive" negative feedback, contributing to prolonged hypothalamic-pituitary-adrenal stress responses.Methods We measured plasma adrenocorticotropic hormone and corticosterone concentrations following an acute stressor or 6 to 8 hours after dexamethasone administration in adult rats previously exposed to daily handling-maternal separation for 15 minutes (HMS15) or 180 minutes (HMS180) during postnatal days 2 to 14. We also examined regional mineralocorticoid receptor and glucocorticoid receptor messenger RNA density in these two groups.Results HMS180 rats appeared to escape dexamethasone suppression of plasma adrenocorticotropic hormone and corticosterone faster than their HMS15 counterparts (p <.01). In situ hybridization analysis revealed increased hippocampal mineralocorticoid receptor messenger RNA density (p <.05) with decreased cortical (p <.05) and hippocampal (p <.05) glucocorticoid receptor messenger RNA density in HMS180 versus HMS15 animals.Conclusions These results are consistent with the hypothesis that in rats exposed to moderate neonatal handling-maternal separation, enhanced proactive feedback maintains the hypothalamic-pituitary-adrenal axis during the diurnal trough, while decreased reactive feedback contributes to prolonged responsiveness of the hypothalamic-pituitary-adrenal axis following an acute stressor.
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“Childhood adversity may both up-regulate HPA stress responses (122) and reduce serotonin neuron firing (108) in parallel (123), the former amplifying neuroinflammation (124) and the latter dampening neurotrophic factors (125).”
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Metadata
- Authors
- Ladd, C. O., Huot, R. L., Thrivikraman, K. V., Nemeroff, C. B., & Plotsky, P. M.
- Affiliations
- Emory University (US)
- Corresponding author
- Plotsky, Paul M
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2004-02
- Volume
- 55
- Issue
- 4
- Pages
- 367-375
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2140973156
- Cited by
- 368
- References
- 94
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 6 · 2023: 7 · 2022: 6 · 2021: 7 · 2020: 22 · 2019: 12 · 2018: 22 · 2017: 18 · 2016: 17 · 2015: 25 · 2014: 21 · 2013: 18 · 2012: 20
- FWCI
- 8.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5f30mh012163-02)
- National Institute of Mental Health (P50MH058922, MH58922, MH12163, MH-50113, R01MH050113)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Keywords
- neonatal maternal separation, hypothalamic-pituitary-adrenal axis, glucocorticoid receptor, mineralocorticoid receptor, negative feedback, ACTH, corticosterone, dexamethasone suppression, acute stress response, hippocampus, cortex, diurnal cycle
- MeSH terms
- Adaptation, Physiological, Adrenocorticotropic Hormone, Animals, Animals, Newborn, Corticosterone, Densitometry, Dexamethasone, Female, Glucocorticoids, Hippocampus, Hypothalamo-Hypophyseal System, Male, Maternal Deprivation, Pituitary-Adrenal System, Pregnancy, Radioimmunoassay, Receptors, Glucocorticoid, RNA, Messenger, Time Factors, In Situ Hybridization, Receptors, Mineralocorticoid, Rats, Long-Evans, Feedback, Physiological, Rats
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