Cited by 1,638Stress Responses and CortisolNeuroendocrine regulation and behaviorNeuropeptides and Animal Physiology

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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

Plotsky, Paul M., Meaney, Michael J.·1993·Molecular Brain Research

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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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“‘MS rats’ display, in adulthood, abnormal anxiety-related behaviour, as well as an exaggerated endocrine response to an acute stressor (Biagini et al., 1998; Ladd et al., 1996, 2000, 2004; McIntosh et al., 1999; Plotsky and Meaney, 1993; Wigger and Neumann, 1999) and a pro-inflammatory phenotype (Clarke et al.”
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“Molecular changes reported in these recurrently separated rats have included decreased GR binding in both hippocampus and hypothalamus (Plotsky and Meaney, 1993), increased CRH levels in the ACe, LC, and parabrachial nucleus, accompanied by increased CRFR 1 mRNA expression levels in LC and the…”
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“…(for 1 min: Padoin, Cadore, Gomes, Barros, & Lucion, 2001; for 3 min: Denenberg & Karas, 1959; Levine et al., 1956; Weinberg, Smotherman, & Levine, 1978b; for 15 min: Fenoglio et al., 2005; Meaney, Aitken, Bodnoff, Iny, & Sapolsky, 1985; Plotsky & Meaney, 1993; Pryce, Bettschen, & Feldon, 2001).”
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“These animal models include the chronic mild stress (CMS) model (Willner et al. 1987), the Flinders sensitive line (FSL) of rats (Overstreet 1993), the “depressed” fawnhooded rat strain (Mathé et al. 1998) and early life trauma (Kalin and Carnes 1984; Plotsky and Meaney 1993; Ladd et al. 1996).”
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“In socially-deprived rodents, chronic experimenter handling attenuates anxiety-like behavior (Gentsch et al., 1988, Vinod et al., 2008, Haller et al., 2009) and induces stress-protective effects (Plotsky and Meaney, 1993, Krebs-Thomson et al., 2001).”
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“, 1999; Andersen and Teicher, 2004) and similar to others (Plotsky and Meaney, 1993).”
Early life adversity programs changes in central 5‐HT neuronal function in adulthood
Gartside, S. E., Johnson, D. A., Leitch, M. M., Troakes, C., & Ingram, C. D. (2003) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2003.02668.x · Cited by 90

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)
DOI: 10.1016/0169-328x(93)90189-v
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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Early, postnatal experience alters hypothalamic corticotropin-releasing factor (CRF) mRNA, median eminence CRF content and stress-induced release in adult rats

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