Cited by 484Stress Responses and CortisolNeuroendocrine regulation and behaviorMemory and Neural Mechanisms

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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

Kalinichev, Mikhail, Easterling, Keith W, Plotsky, Paul M, Holtzman, Stephen G·2002·Pharmacology Biochemistry and Behavior

DOI 10.1016/s0091-3057(02)00781-5

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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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Huot, 1997, Alterations of maternal–infant interaction as a results of maternal separation in Long–Evans rats and its behavioral and neuroendocrine consequences, Psychoneuroendocrinology, 22, S173

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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)
DOI: 10.1016/s0091-3057(02)00781-5
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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Long-lasting changes in stress-induced corticosterone response and anxiety-like behaviors as a consequence of neonatal maternal separation in Long–Evans rats

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