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Early, postnatal experience alters hypothalamic corticotropin-releasing factor (CRF) mRNA, median eminence CRF content and stress-induced release in adult rats
Abstract
Rat pups 2-14 days of age were exposed daily to handling (15 min of separation from mother and home cage), maternal separation (MS; 180 min of comparable separation), or were left entirely undisturbed (non-handled; NH). As adults, MS rats showed increased hypothalamic corticotropin-releasing factor (CRF) mRNA levels compared with NH rats, while CRF mRNA levels in H rats were significantly lower than either MS or NH animals. Hypothalamic CRF content under basal conditions followed exactly the same pattern. A 20-min period of restraint stress produced significant CRF depletion in all groups, although the percentage of depletion was significantly lower in H animals compared with either MS or NH animals. Restraint stress produced significantly higher increases in plasma corticosterone in MS and NH animals than in H animals. These data reflect the importance of early environmental factors in regulating the development of the hypothalamic CRF system and the responsiveness of the hypothalamic-pituitary-adrenal axis to stress.
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“Short periods of maternal separation, however, can elicit higher rates of licking and grooming from rat mothers, which appears to blunt rises in these HPA products (Plotsky and Meaney, 1993).”
From Quality of maternal and paternal care predicts later stress reactivity in the cooperatively-breeding marmoset (Callithrix geoffroyi) (2013) · cites this paper as Plotsky and Meaney, 1993
In the citing paper
“Repeated and prolonged maternal separation in rodent pups results in exaggerated SNS and HPA-axis responses to stress during adolescence and adulthood (Kalinichev et al., 2002; Plotsky and Meaney, 1993).”
From Developmental psychoneuroendocrine and psychoneuroimmune pathways from childhood adversity to disease (2017) · cites this paper as Plotsky and Meaney, 1993
In the citing paper
“Environmental conditions that increased the frequency of pup LG in the rat are associated with decreased paraventricular CRF expression.66,110-113”
From Early life adversity and the epigenetic programming of hypothalamic-pituitary-adrenal function (2014) · cites this paper as [111]
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Self-citationClinical Importance of Pain and Stress in Preterm Neonates
Anand, K. J. S. (1997) · Neonatology · doi:10.1159/000013953 · Cited by 427
McLaughlin, K. A., Sheridan, M. A., Tibu, F., Fox, N. A., Zeanah, C. H., & Nelson, C. A. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1423363112 · Cited by 426
Maternal separation as a model of brain-gut axis dysfunction
O’Mahony, S. M., Hyland, N. P., Dinan, T. G., & Cryan, J. F. (2011) · Psychopharmacology · doi:10.1007/s00213-010-2010-9 · Cited by 415
“On the other hand, brief MS (usually ≤15 min) appears to lead to a decrease in anxiety-like behaviours, decreased HPA axis tone and responsiveness to stress (Levine 2005; Plotsky and Meaney 1993; Plotsky et al. 2005) in adulthood.”
BackgroundEpigenetics across the human lifespan
Kanherkar, R. R., Bhatia-Dey, N., & Csoka, A. B. (2014) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2014.00049 · Cited by 407
Pryce, C. R., Rüedi‐Bettschen, D., Dettling, A. C., Weston, A. A., Russig, H., Ferger, B., & Feldon, J. (2005) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2005.03.011 · Cited by 430
Ivy, A. S., Brunson, K. L., Sandman, C., & Baram, T. Z. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.04.019 · Cited by 407
Heim, C., & Nemeroff, C. B. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00224-3 · Cited by 502
Early life stress confers lifelong stress susceptibility in mice via ventral tegmental area OTX2
Peña, C. J., Kronman, H. G., Walker, D. M., Cates, H. M., Bagot, R. C., Purushothaman, I., Issler, O., Loh, Y.-H. E., Leong, T., Kiraly, D. D., et al. (2017) · Science · doi:10.1126/science.aan4491 · Cited by 394
GRUNAU, R. E., Holsti, L., Haley, D. W., Oberlander, T. F., Weinberg, J., Solimano, A. J., Whitfield, M. F., Fitzgerald, C., & Yu, W. K. (2004) · Pain · doi:10.1016/j.pain.2004.10.020 · Cited by 390
“…to stressors in ELGA preterm infants at 8 months who had the most exposure to painful procedures since birth are consistent with those found in animal models of maternal separation stress, which reported sensitization of the HPA axis to subsequent stressors (e.g. Plotsky and Meaney, 1993).”
MethodLUPIEN, S. J., Juster, R., Raymond, C., & Marin, M. (2018) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2018.02.001 · Cited by 445
Stress and the Microbiota–Gut–Brain Axis in Visceral Pain: Relevance to Irritable Bowel Syndrome
Moloney, R. D., Johnson, A. C., O’Mahony, S. M., Dinan, T. G., Meerveld, B. G., & Cryan, J. F. (2015) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12490 · Cited by 412
Immune and neuroendocrine mechanisms of stress vulnerability and resilience
Ménard, C., Pfau, M. L., Hodes, G. E., & Russo, S. J. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.90 · Cited by 374
Neonatal maternal separation reduces hippocampal mossy fiber density in adult Long Evans rats
Huot, R. L., Plotsky, P. M., Lenox, R. H., & McNamara, R. K. (2002) · Brain Research · doi:10.1016/s0006-8993(02)02985-2 · Cited by 392
Self-citationChampagne, F. A., & Meaney, M. J. (2007) · Behavioral Neuroscience · doi:10.1037/0735-7044.121.6.1353 · Cited by 381
“…found to exert long-term consequences for maternal behavior (Boccia & Pedersen, 2001; Fleming et al., 2002; Ladd et al., 2000; Liu et al., 2000; Plotsky & Meaney, 1993; Pryce, Bettschen, & Feldon, 2001), with females showing deficits in maternal LG toward their own offspring (Fleming et al.,…”
BackgroundSelf-citationFrancis, D. D., Caldji, C., Champagne, F., Plotsky, P. M., & Meaney, M. J. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00237-1 · Cited by 380
Self-citation
Metadata
- Authors
- Plotsky, P. M., & Meaney, M. J.
- Affiliations
- Salk Institute for Biological Studies (US)
- Douglas Mental Health University Institute (CA)
- Corresponding author
- Meaney, Michael J.
- ORCID
- Meaney, Michael J.
- Venue
- Molecular Brain Research
- Publisher
- Elsevier BV
- Published
- 1993-05
- Volume
- 18
- Issue
- 3
- Pages
- 195-200
- ISSN
- 0169-328X (ISSN-L)
- OpenAlex
- W1984427714
- Cited by
- 1,638
- References
- 34
- Citations by year
- 2026: 26 · 2025: 12 · 2024: 18 · 2023: 21 · 2022: 32 · 2021: 36 · 2020: 40 · 2019: 40 · 2018: 49 · 2017: 47 · 2016: 61 · 2015: 49 · 2014: 83 · 2013: 65 · 2012: 75
- FWCI
- 7.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01mh045216-05)
- National Institute of Mental Health (MH45216)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- corticotropin-releasing factor, hypothalamus, maternal separation, early life stress, handling, restraint stress, hypothalamic-pituitary-adrenal axis, corticosterone, median eminence, stress responsiveness, developmental programming
- MeSH terms
- Actins, Aging, Animals, Animals, Newborn, Corticosterone, Corticotropin-Releasing Hormone, Female, Handling, Psychological, Hypothalamus, Maternal Behavior, Median Eminence, Reference Values, Restraint, Physical, RNA, Messenger, Social Isolation, Stress, Psychological, Blotting, Northern, Rats
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