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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Mathieu, G., Denis, S., Lavialle, M., & Vancassel, S. (2008) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2008.05.003 · Cited by 62
Effect of Neonatal Handling and Sex on Basal and Chronic Stress-Induced Corticosterone and Leptin Secretion
Panagiotaropoulos, T. I., Papaioannou, A., Pondiki, S., Prokopiou, A., Stylianopoulou, F., & Gerozissis, K. (2004) · Neuroendocrinology · doi:10.1159/000076633 · Cited by 57
Enduring Neurobehavioral Effects of Early Life Trauma Mediated Through Learning and Corticosterone Suppression
Moriceau, S. (2009) · Frontiers in Behavioral Neuroscience · doi:10.3389/neuro.08.022.2009 · Cited by 58
“…the release of endogenous CRH in central nucleus of the amygdala in both infant and adult rats, while early life stress only alters CRH in infancy (Plotsky and Meaney, 1993; Makino et al., 1994; Hatalski et al., 1998; Avishai-Eliner et al., 2001; Fenoglio et al., 2004; Korosi and Baram, 2008;…”
Early maternal separation impacts cognitive flexibility at the age of first independence in mice
Thomas, A. W., Caporale, N., Wu, C., & Wilbrecht, L. (2015) · Developmental Cognitive Neuroscience · doi:10.1016/j.dcn.2015.09.005 · Cited by 57
“, 2008) or employed more invasive separation paradigms which remove pups from their mother during the early postnatal period (Plotsky and Meaney, 1993; Francis et al., 2002).”
Long maternal separation accelerates behavioural sensitization to ethanol in female, but not in male mice
Kawakami, S. E., Quadros, I. M., Takahashi, S., & Suchecki, D. (2007) · Behavioural Brain Research · doi:10.1016/j.bbr.2007.06.023 · Cited by 60
Effects of a Non-peptide CRF Antagonist (DMP696) on the Behavioral and Endocrine Sequelae of Maternal Separation
Maciag, C. M. (2002) · Neuropsychopharmacology · doi:10.1016/s0893-133x(01)00398-0 · Cited by 57
Early neonatal experience of Long-Evans rats results in long-lasting changes in morphine tolerance and dependence
Kalinichev, M., Easterling, K. W., & Holtzman, S. G. (2001) · Psychopharmacology · doi:10.1007/s002130100806 · Cited by 56
Unpredictable chronic stress in juvenile or adult rats has opposite effects, respectively, promoting and impairing resilience
Ricon, T., Toth, E., Leshem, M., Braun, K., & Richter-Levin, G. (2012) · Stress · doi:10.3109/10253890.2011.572207 · Cited by 55
Enhanced Glucocorticoid Feedback Inhibition of Hypothalamo-Pituitary-Adrenal Responses to Stress in Adult Rats Neonatally Treated with Dexamethasone
Kamphuis, P. J. G. H., Bakker, J. M., Broekhoven, M. H., Kunne, C., Croiset, G., Lentjes, E. G. W. M., Tilders, F. J. H., van Bel, F., & Wiegant, V. M. (2002) · Neuroendocrinology · doi:10.1159/000064526 · Cited by 56
Maternal deprivation induces depressive-like behaviours only in female rats
Mourlon, V., Baudin, A., Blanc, O., Lauber, A. H., Giros, B., Naudon, L., & Daugé, V. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.05.017 · Cited by 60
Programming of Stress-Sensitive Neurons and Circuits by Early-Life Experiences
Bolton, J. L., Short, A. K., Simeone, K. A., Daglian, J. M., & Baram, T. Z. (2019) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2019.00030 · Cited by 58
“In the PVN, a major change induced by augmented, predictable maternal care was decreased CRH expression by P9, prior to the GR change (Plotsky and Meaney, 1993; Liu et al., 1997; Fenoglio et al., 2004, 2005).”
Background
Growth Retardation Is Associated with Changes in the Stress Response System and Behavior in School-Aged Jamaican Children
Fernald, L. C. H., & Grantham‐McGregor, S. (2002) · Journal of Nutrition · doi:10.1093/jn/132.12.3674 · Cited by 55
Glucocorticoids and serotonin alter glucocorticoid receptor (GR) but not mineralocorticoid receptor (MR) mRNA levels in fetal mouse hippocampal neurons, in vitro
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A mechanistic look at the effects of adversity early in life on cardiovascular disease risk during adulthood
Loria, A. S., Ho, D. H., & Pollock, J. S. (2014) · Acta Physiologica · doi:10.1111/apha.12189 · Cited by 53
“Exaggerated behavioral and cardiovascular stress-related response (Enthoven et al. 2008b, Plotsky and Meaney, 1993, Renard et al. 2007).”
Background
Neonatal Maternal Separation Alters the Capacity of Adult Neural Precursor Cells to Differentiate into Neurons Via Methylation of Retinoic Acid Receptor Gene Promoter
Boku, S., Toda, H., Nakagawa, S., Kato, A., Inoue, T., Koyama, T., Hiroi, N., & Kusumi, I. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.07.008 · Cited by 56
“Meaney MJ (2001): Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations.”
MethodInfluential
Increased cortisol awakening response and afternoon/evening cortisol output in healthy young adults with low early life parental care
Engert, V., Efanov, S. I., Dedovic, K., Dagher, A., & Pruessner, J. C. (2010) · Psychopharmacology · doi:10.1007/s00213-010-1918-4 · Cited by 58
“…negative feedback sensitivity to glucocorticoids, increased hypothalamic corticotropin-releasing factor mRNA expression, and consequently increased adrenocorticotropic hormone (ACTH) and cortisol stress responsivity (Ladd et al. 2004; Liu et al. 1997; Plotsky and Meaney 1993; Plotsky et al. 2005).”
Neonatal handling of Amazon parrots alters the stress response and immune function
Collette, J. C., Millam, J. R., Klasing, K. C., & Wakenell, P. S. (2000) · Applied Animal Behaviour Science · doi:10.1016/s0168-1591(99)00098-2 · Cited by 55
Maternal separation affects cocaine-induced locomotion and response to novelty in adolescent, but not in adult rats
Marin, M. T., & Planeta, C. S. (2004) · Brain Research · doi:10.1016/j.brainres.2004.04.003 · Cited by 55
Effects of neonatal handling and maternal separation on rough‐and‐tumble play in the rat
Arnold, J. L., & Siviy, S. M. (2002) · Developmental Psychobiology · doi:10.1002/dev.10069 · Cited by 54
Catecholamines, Stress, and Disease
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Corticotropin-Releasing Factor Testing Reveals a Dose-Dependent Difference in Methadone Maintained Vs Control Subjects
Schluger, J. H., Bart, G. B., Green, M., Ho, A., & Kreek, M. J. (2003) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300156 · Cited by 55
Perinatal exposure to bisphenol A at the intersection of stress, anxiety, and depression
Wiersielis, K., Samuels, B. A., & Roepke, T. A. (2020) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2020.106884 · Cited by 57
“For instance, during early postnatal periods, maternal separation stress is enough to induce long-term changes in CRF system dysregulation in the adult (Plotsky and Meaney, 1993).”
Background
How might stress contribute to increased risk for schizophrenia in children with chromosome 22q11.2 deletion syndrome?
Beaton, E. A., & Simon, T. J. (2010) · Journal of Neurodevelopmental Disorders · doi:10.1007/s11689-010-9069-9 · Cited by 57
“Velo-cardio-facial syndrome (VCFS)”
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The Role of Stress, Trauma, and PTSD in the Etiology and Treatment of Eating Disorders, Addictions, and Substance Use Disorders
Brewerton, T. D., & Brady, K. T. (2014) · Springer eBooks · doi:10.1007/978-3-642-45378-6_17 · Cited by 56
Periodic postpartum separation from the offspring results in long-lasting changes in anxiety-related behaviors and sensitivity to morphine in Long-Evans mother rats
Kalinichev, M., Easterling, K. W., & Holtzman, S. G. (2000) · Psychopharmacology · doi:10.1007/s002130000556 · Cited by 54
Effects of maternal separation on behavioural sensitization produced by repeated cocaine administration in adulthood
Li, Y., Robinson, T. E., & Bhatnagar, S. (2003) · Brain Research · doi:10.1016/s0006-8993(02)03752-6 · Cited by 54
Sustained hyperphagia in adolescent rats that experienced neonatal maternal separation
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Neonatal handling reduces the number of cells in the locus coeruleus of rats.
Lucion, A. B., Pereira, F. M., Duarte, E. C. W., Sanvitto, G. L., & Anselmo-Franci, J. A. (2003) · Behavioral Neuroscience · doi:10.1037/0735-7044.117.5.894 · Cited by 52
Synaptic rewiring of stress-sensitive neurons by early-life experience: A mechanism for resilience?
Singh-Taylor, A., Kőrösi, A., Molet, J., Gunn, B. G., & Baram, T. Z. (2014) · Neurobiology of Stress · doi:10.1016/j.ynstr.2014.10.007 · Cited by 56
Predation threat exerts specific effects on rat maternal behaviour and anxiety-related behaviour of male and female offspring
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“For example, although daily maternal separation (MS; 3–6 h) produces adult offspring that display higher HPA activity and heightened fearfulness [27,40–42], these effects appear to be due to differences in the imposed temporal distribution of the care, as opposed to a loss of maternal care per se [43].”
Early life adversity and adult social behavior: focus on arginine vasopressin and oxytocin as potential mediators
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Biology and the Future of Psychoanalysis: A New Intellectual Framework for Psychiatry Revisited
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Early and later life stress alter brain activity and sleep in rats
Mrdalj, J., Pallesen, S., Milde, A. M., Jellestad, F. K., Murison, R., Ursin, R., Bjorvatn, B., & Grønli, J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0069923 · Cited by 51
“Hence, these results add significant findings to the literature of neuronal changes after long maternal separation and low maternal care [21–30,39].”
BackgroundResult
Neonatal handling and the maternal odor preference in rat pups: Involvement of monoamines and cyclic AMP response element-binding protein pathway in the olfactory bulb
Raineki, C., de Souza, M. A., Szawka, R. E., Lutz, M. L., de Vasconcellos, L. F. T., Sanvitto, G. L., Izquierdo, I., Bevilaqua, L. R., Cammarota, M., & Lucion, A. B. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.12.012 · Cited by 51
Effects of early life trauma are dependent on genetic predisposition: a rat study
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“These may lead to persistent behavioural, endocrine, and neurochemical changes [5-8].”
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Perinatal development and adult blood pressure
Ashton, N. (2000) · Brazilian Journal of Medical and Biological Research · doi:10.1590/s0100-879x2000000700002 · Cited by 51
Early-life stress and antidepressant treatment involve synaptic signaling and Erk kinases in a gene-environment model of depression
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Neonatal handling induces anovulatory estrous cycles in rats
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Stresses on Female Mice Impair Oocyte Developmental Potential:Effects of Stress Severity and Duration on Oocytes at the Growing Follicle Stage
Gao, Y., Chen, F., Kong, Q.-Q., Ning, S.-F., Yuan, H.-J., Lian, H.-Y., Luo, M.-J., & Tan, J.-H. (2016) · Reproductive Sciences · doi:10.1177/1933719116630416 · Cited by 57

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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