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Dysfunctional nurturing behavior in rat dams with limited access to nesting material: A clinically relevant model for early-life stress
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Background Early-life emotional stress may be associated with affective and cognitive disorders later in life, yet satisfactory animal models for studying the underlying mechanisms are limited. Because maternal presence and behavior critically influence molecular and behavioral stress responses in offspring, we sought to create a model of dysfunctional, fragmented maternal nurturing behavior that would, in turn, provoke chronic early-life stress in the offspring. Methods Sprague-Dawley rat dams' nursing and nurturing behaviors were altered by limiting their ability to create satisfactory nests during postpartum days 2-9. Maternal behavior was observed throughout the diurnal cycle, and the frequency and duration of nurturing behaviors were scored. In addition, potential stress and anxiety of the dams were assessed using behavioral, molecular and hormonal measures. Results Both the quantity and the quality of dams' care of their pups were profoundly influenced by restriction of nesting materials in their cages: licking/grooming activities decreased and the frequency of leaving the pups increased, resulting in fragmented interactions between the dams and pups. The abnormal activity patterns of the dams were accompanied by increased anxiety-like behavior in the open field, but not in the elevated plus maze tests. Additionally, dams' plasma corticosterone levels and adrenal weights were augmented, suggesting chronic stress of these dams. By the end of the limited-nesting, stress-inducing period, hypothalamic corticotropin releasing hormone (CRH) mRNA expression was reduced in the limited-nesting dams, while arginine-vasopressin (AVP) mRNA levels were not significantly affected. Conclusion Limiting dams' ability to construct a nest for their pups leads to an abnormal repertoire of nurturing behaviors, possibly as a result of chronic stress and mild anxiety of the dams. Because the fragmented and aberrant maternal behavior provoked chronic stress in the pups, the limited-nesting paradigm provides a useful tool for studying the mechanisms and consequences of such early-life stress experience in the offspring.
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“Experimental models of early-life neglect demonstrate coordinated changes in stress-response and neurodevelopmental signaling following repeated maternal separation and reduced caregiving.”
From Epigenetic changes associated with multi-generational trauma: characterization, mechanisms, and therapeutics (2026) · cites this paper as [63]
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Metadata
- Authors
- Ivy, A. S., Brunson, K. L., Sandman, C., & Baram, T. Z.
- Affiliations
- University of California, Irvine (US)
- Corresponding author
- Baram, T.Z.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2008-06
- Volume
- 154
- Issue
- 3
- Pages
- 1132-1142
- ISSN
- 0306-4522 (ISSN-L)
- PMC
- PMC2517119
- OpenAlex
- W1998980503
- Cited by
- 407
- References
- 71
- Citations by year
- 2026: 29 · 2025: 21 · 2024: 29 · 2023: 17 · 2022: 30 · 2021: 31 · 2020: 26 · 2019: 37 · 2018: 28 · 2017: 32 · 2016: 29 · 2015: 26 · 2014: 24 · 2013: 20 · 2012: 8
- FWCI
- 2.95
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- National Institute of Mental Health (MH73136, R01MH073136)
- National Institute of Neurological Disorders and Stroke (R01NS028912, R01NS039307, NIH NS28912)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Keywords
- early life stress, nest building, maternal anxiety, corticosterone, vasopressin, chronic stress, anxiety-like behavior
- MeSH terms
- Animals, Arginine Vasopressin, Body Weight, Corticotropin-Releasing Hormone, Densitometry, Environment, Female, Hypothalamus, Maternal Behavior, Nesting Behavior, Paraventricular Hypothalamic Nucleus, RNA, Messenger, Stress, Psychological, Rats, Sprague-Dawley, In Situ Hybridization, Rats
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