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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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BackgroundA comprehensive approach to modeling maternal immune activation in rodents
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Yu, P., An, S.-C., Tai, F., Wang, J., Wu, R., & Wang, B. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.09.012 · Cited by 34
Siviy, S. M., & Harrison, K. A. (2008) · Journal of comparative psychology · doi:10.1037/0735-7036.122.1.1 · Cited by 35
“…activation of the HPA axis is markedly attenuated in handled rats (Meaney, Aitken, Bodnoff, Iny, & Sapolsky, 1985; Meaney et al., 1991; Plotsky & Meaney, 1993) and this is believed to be due to enhanced negative feedback resulting from increased expression of glucocorticoid receptors…”
BackgroundTrombini, M., Hulshof, H. J., Graiani, G., Carnevali, L., Meerlo, P., Quaini, F., & Sgoifo, A. (2011) · Stress · doi:10.3109/10253890.2011.639414 · Cited by 32
Kodama, Y., Kikusui, T., Takeuchi, Y., & Mori, Y. (2008) · Developmental Psychobiology · doi:10.1002/dev.20289 · Cited by 32
Neonatal stress and litter composition alter sucrose intake in both rat dam and offspring
Michaels, C. C., & Holtzman, S. G. (2006) · Physiology & Behavior · doi:10.1016/j.physbeh.2006.08.015 · Cited by 32
Social interaction attenuates stress responses following chronic stress in maternally separated rats
Babygirija, R., Yoshimoto, S., Gribovskaja‐Rupp, I., Bülbül, M., Ludwig, K., & Takahashi, T. (2012) · Brain Research · doi:10.1016/j.brainres.2012.06.007 · Cited by 32
Stress Hormones, Genotype, and Brain Organization Implications for Aggressiona
de Kloet, E. R., Korte, S. M., Rots, N. Y., & Kruk, M. R. (1996) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1996.tb32520.x · Cited by 32
Neuron stem cell NLRP6 sustains hippocampal neurogenesis to resist stress-induced depression
Tang, C., Wang, Q., Shen, J., Wang, C., Ding, H., Wen, S., Yang, F., Jiao, R., Wu, X., Li, J., et al. (2023) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2023.03.010 · Cited by 31
Pautassi, R. M., Nizhnikov, M. E., Fabio, M. C., & Spear, N. E. (2011) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2011.11.005 · Cited by 31
“Most of these results have been gathered through the maternal separation (MS) paradigm (Plotsky & Meaney, 1993), in which animals experience daily episodes of maternal separation for varying periods of time (usually 180 or 360 min each day) during the first weeks of life.”
BackgroundTodkar, A., Granholm, L., Aljumah, M., Nilsson, K. W., Comasco, E., & Nylander, I. (2016) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2015.00090 · Cited by 31
McCormick, G. L., Robbins, T. R., Cavigelli, S. A., & Langkilde, T. L. (2016) · Hormones and Behavior · doi:10.1016/j.yhbeh.2016.11.010 · Cited by 31
Early life stress increases vulnerability to the sequelae of pediatric mild traumatic brain injury
Díaz-Chávez, A., Lajud, N., Roque, A., B, J. P. C. A., Meléndez‐Herrera, E., Valdez-Alarcón, J. J., Bondi, C. O., & Kline, A. E. (2020) · Experimental Neurology · doi:10.1016/j.expneurol.2020.113318 · Cited by 31
“The most common rodent model to study the effects of ELS is maternal separation for 180 min per day (MS180) (Plotsky and Meaney, 1993; Wigger and Neumann, 1999; Lajud et al., 2012; Ruiz et al., 2018).”
BackgroundLajud, N., Roque, A., B, J. P. C. A., Bondi, C. O., & Kline, A. E. (2020) · Journal of Neurotrauma · doi:10.1089/neu.2020.7354 · Cited by 31
“sponse after each separation episode even during the stress hyporesponsive period, and affects brain development.(18,27,38,40,41)”
BackgroundEffects of Genes and Stress on the Neurobiology of Depression
Mann, J. J., & Currier, D. (2006) · International review of neurobiology · doi:10.1016/s0074-7742(06)73005-7 · Cited by 32
The Contributions of Early Experience to Biological Development and Sensitivity to Context
Bush, N. R., & Boyce, W. T. (2014) · Springer eBooks · doi:10.1007/978-1-4614-9608-3_15 · Cited by 33
Early behavioral effects of lead perinatal exposure in rat pups
Marco, M. D., Halpern, R., & Barros, H. M. T. (2005) · Toxicology · doi:10.1016/j.tox.2005.02.007 · Cited by 30
Petrullo, L. A., Mandalaywala, T. M., Parker, K. J., Dario Maestripieri, A., & Higham, J. P. (2016) · Hormones and Behavior · doi:10.1016/j.yhbeh.2016.05.004 · Cited by 31
Viola, T. W., Wearick‐Silva, L. E., de Azeredo, L. A., Centeno‐Silva, A., Murphy, C. P., Marshall, P. R., Li, X., Singewald, N., Garcia, F. D., Bredy, T. W., et al. (2016) · Psychopharmacology · doi:10.1007/s00213-016-4373-z · Cited by 32
“The MS model of early life stress consists of exposing infant animals to daily episodes of maternal care deprivation during the first days of life (Plotsky and Meaney 1993).”
Greisen, M. H., Bolwig, T. G., Husum, H., Nedergaard, P., & Wörtwein, G. (2004) · Behavioural Brain Research · doi:10.1016/j.bbr.2004.09.018 · Cited by 31
Early social and physical deprivation leads to reduced social motivation in adulthood in Wistar rats
Mintz, M., Rüedi‐Bettschen, D., Feldon, J., & Pryce, C. R. (2004) · Behavioural Brain Research · doi:10.1016/j.bbr.2004.08.017 · Cited by 31
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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