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Long-lasting changes in stress-induced corticosterone response and anxiety-like behaviors as a consequence of neonatal maternal separation in Long–Evans rats
Abstract
Early neonatal environmental factors appear to have powerful and long-lasting influences on an organism's physiology and behavior. Long-Evans male rats separated from their dam for 3 h daily over the first 2 weeks of life (maternally separated, MS rats) when tested as adults exhibit exaggerated behavioral and neuroendocrine responses to stress compared to 15-min separated (handled, H) animals. The purpose of this study was to compare male and female adult rats that were MS, H or were undisturbed (nonhandled, NH) as neonates in anxiety-like behaviors, in the elevated plus-maze, and in response to startle-inducing auditory stimuli. We confirmed that MS males oversecrete corticosterone (CORT; 2.5-5 times) in response to mild handling stress. MS males and females were less likely to explore open arms of the plus-maze. MS males exhibited 35% higher startle amplitudes compared to controls. Furthermore, MS males were more likely to emit ultrasonic vocalizations in response to startle than were H controls. However, MS and control females did not differ in auditory startle response or in startle-induced ultrasonic vocalizations. Therefore, experiencing maternal separation results in a long-lasting increase in anxiety-like behaviors that occurs in a sex-dependent manner.
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“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 Kalinichev et al., 2002
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Metadata
- Authors
- Kalinichev, M., Easterling, K. W., Plotsky, P. M., & Holtzman, S. G.
- Affiliations
- Emory University (US)
- Corresponding author
- Kalinichev, Mikhail
- ORCID
- Kalinichev, Mikhail
- Venue
- Pharmacology Biochemistry and Behavior
- Publisher
- Elsevier BV
- Published
- 2002-08
- Volume
- 73
- Issue
- 1
- Pages
- 131-140
- ISSN
- 0091-3057 (ISSN-L)
- OpenAlex
- W2055408622
- Cited by
- 484
- References
- 56
- Citations by year
- 2026: 9 · 2025: 3 · 2024: 12 · 2023: 16 · 2022: 18 · 2021: 18 · 2020: 19 · 2019: 23 · 2018: 20 · 2017: 15 · 2016: 20 · 2015: 17 · 2014: 40 · 2013: 30 · 2012: 27
- FWCI
- 6.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacology Biochemistry and Behavior (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Drug Abuse (K05-DA00008, DA11384, K05DA000008, R21DA011384)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- neonatal maternal separation, anxiety-like behavior, corticosterone, stress response, sex differences, ultrasonic vocalizations, startle response, elevated plus maze, Long-Evans rats, early life experience, handling stress
- MeSH terms
- Acoustic Stimulation, Animals, Animals, Newborn, Anxiety, Corticosterone, Female, Male, Maternal Deprivation, Pregnancy, Stress, Physiological, Time, Vocalization, Animal, Rats, Long-Evans, Rats
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