Importance of early environment in the development of post-traumatic stress disorder-like behaviors

Imanaka, Akihiro; Morinobu, Shigeru; Toki, Shigeru; Yamawaki, Shigeto

doi:10.1016/j.bbr.2006.06.012

Cited by 154Posttraumatic Stress Disorder ResearchMemory and Neural MechanismsStress Responses and Cortisol

Importance of early environment in the development of post-traumatic stress disorder-like behaviors

Imanaka, Akihiro, Morinobu, Shigeru, Toki, Shigeru, Yamawaki, Shigeto·2006·Behavioural Brain Research

DOI 10.1016/j.bbr.2006.06.012

Open this paper in CoChat — free account

Abstract

A number of clinical studies in which early adversities were defined retrospectively, demonstrated that early adverse experiences increased the morbidity rate of post-traumatic stress disorder (PTSD) in later life. However, no prospective studies have yet been conducted to elucidate whether early adversity affects the risk or severity of PTSD. Thus, we examined whether early adversity would strengthen the severity of PTSD symptoms in later life by using neonatal isolation (NI) and single prolonged stress (SPS) as an animal model of PTSD. We measured anxiety-like behavior in the elevated plus maze (EPM), contextual freezing in the contextual fear (CF) test, and analgesia in the flinch-jump and hot-plate tests in four groups of adult rats (sham, NI, SPS, and NI+SPS). NI significantly enhanced the SPS-induced decrease in the percentage of open arm time and open arm entries in the EPM, enhanced the SPS-induced increase in contextual freezing, and strengthened SPS-induced analgesia, without any changes in locomotor activity in the open field locomotor test. In addition, we examined the effect of environmental enrichment (EE). Repeated exposure to EE ameliorated the NI-induced enhancement of contextual freezing, but not anxiety-like behavior or analgesia, in response to SPS. The results of the present study demonstrated that while early adversity strengthened PTSD-like symptoms, EE alleviated the enhanced contextual freezing by NI and SPS. These findings suggest that early adversity may worsen dysfunction of the amygdala and hippocampus in PTSD, and an early intervention may alleviate the early adversity-mediated enhancement of hippocampal dysfunction in PTSD.

Integrity signals

Registry

Crossref · 10.1016/j.bbr.2006.06.012

Cites

44 of 44 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

SPS rats exhibit stress-induced analgesia compared to Sham rats.
“Furthermore, we recently demonstrated that SPS rats exhibit enhanced contextual freezing, increased anxiety-like behavior in the elevated plus maze, and stress-induced analgesia compared to rats subjected to Sham treatment (Imanaka et al, 2006;Takahashi et al, 2006).”
From Effects of Single Prolonged Stress and D-Cycloserine on Contextual Fear Extinction and Hippocampal NMDA Receptor Expression in a Rat Model of PTSD (2008) · cites this paper as Imanaka et al, 2006
SPS rats exhibit enhanced contextual freezing compared to Sham rats.
“Furthermore, we recently demonstrated that SPS rats exhibit enhanced contextual freezing, increased anxiety-like behavior in the elevated plus maze, and stress-induced analgesia compared to rats subjected to Sham treatment (Imanaka et al, 2006;Takahashi et al, 2006).”
From Effects of Single Prolonged Stress and D-Cycloserine on Contextual Fear Extinction and Hippocampal NMDA Receptor Expression in a Rat Model of PTSD (2008) · cites this paper as Imanaka et al, 2006
SPS rats exhibit increased anxiety-like behavior in the elevated plus maze compared to Sham rats.
“Furthermore, we recently demonstrated that SPS rats exhibit enhanced contextual freezing, increased anxiety-like behavior in the elevated plus maze, and stress-induced analgesia compared to rats subjected to Sham treatment (Imanaka et al, 2006;Takahashi et al, 2006).”
From Effects of Single Prolonged Stress and D-Cycloserine on Contextual Fear Extinction and Hippocampal NMDA Receptor Expression in a Rat Model of PTSD (2008) · cites this paper as Imanaka et al, 2006

Epigenetic programming by maternal behavior
Weaver, I. C. G., Cervoni, N., Champagne, F. A., D'Alessio, A. C., Sharma, S., Seckl, J. R., Dymov, S., Szyf, M., & Meaney, M. J. (2004) · Nature Neuroscience · doi:10.1038/nn1276 · Cited by 6,177 · see citing works
Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning.
Phillips, R. G., & LeDoux, J. E. (1992) · Behavioral Neuroscience · doi:10.1037/0735-7044.106.2.274 · Cited by 3,292 · see citing works
Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning.
Phillips, R. G., & LeDoux, J. E. (1992) · Behavioral Neuroscience · doi:10.1037//0735-7044.106.2.274 · Cited by 3,262 · see citing works
Maternal Care, Hippocampal Glucocorticoid Receptors, and Hypothalamic-Pituitary-Adrenal Responses to Stress
Liu, D., Diorio, J., Tannenbaum, B., Caldji, C., Francis, D., Freedman, A., Sharma, S., Pearson, D., Plotsky, P. M., & Meaney, M. J. (1997) · Science · doi:10.1126/science.277.5332.1659 · Cited by 3,170 · see citing works
Early, postnatal experience alters hypothalamic corticotropin-releasing factor (CRF) mRNA, median eminence CRF content and stress-induced release in adult rats
Plotsky, P. M., & Meaney, M. J. (1993) · Molecular Brain Research · doi:10.1016/0169-328x(93)90189-v · Cited by 1,638 · see citing works
Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat
Caldji, C., Tannenbaum, B., Sharma, S., Francis, D., Plotsky, P. M., & Meaney, M. J. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.9.5335 · Cited by 1,437 · see citing works
Effects of inescapable shock upon subsequent escape and avoidance responding.
Overmier, J. B., & Seligman, M. E. P. (1967) · Journal of Comparative and Physiological Psychology · doi:10.1037/h0024166 · Cited by 1,200 · see citing works
Posttraumatic stress disorder in abused and neglected children grown up
Widom, C. S. (1999) · American Journal of Psychiatry · doi:10.1176/ajp.156.8.1223 · Cited by 945 · see citing works
Clinical Characteristics of Women With a History of Childhood Abuse: Unhealed Wounds
McCauley, J. (1997) · JAMA · doi:10.1001/jama.1997.03540410040028 · Cited by 904 · see citing works
Early Environmental Regulation of Forebrain Glucocorticoid Receptor Gene Expression: Implications for Adrenocortical Responses to Stress; pp. 49–60
Meaney, M. J., Diorio, J., Francis, D., Widdowson, J., LaPlante, P., Caldji, C., Sharma, S., Seckl, J. R., & Plotsky, P. M. (2010) · Developmental Neuroscience · doi:10.1159/000111395 · Cited by 878 · see citing works
Environmental Enrichment Reverses the Effects of Maternal Separation on Stress Reactivity
Francis, D. D., Diorio, J., Plotsky, P. M., & Meaney, M. J. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-18-07840.2002 · Cited by 663 · see citing works
Do early‐life events permanently alter behavioral and hormonal responses to stressors?
Anisman, H., Zaharia, M. D., Meaney, M. J., & Merali, Z. (1998) · International Journal of Developmental Neuroscience · doi:10.1016/s0736-5748(98)00025-2 · Cited by 654 · see citing works
Effects of environmental enrichment on gene expression in the brain
Rampon, C., Jiang, C. H., Dong, H., Tang, Y., Lockhart, D. J., Schultz, P. G., Tsien, J. Z., & Hu, Y. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.23.12880 · Cited by 614 · see citing works
The Effects of Early Rearing Environment on the Development of GABAA and Central Benzodiazepine Receptor Levels and Novelty-Induced Fearfulness in the Rat
Caldji, C. (2000) · Neuropsychopharmacology · doi:10.1016/s0893-133x(99)00110-4 · Cited by 606 · see citing works
Stress-restress: Effects on ACTH and fast feedback
Liberzon, I., Krstov, M., & Young, E. A. (1997) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(97)00044-9 · Cited by 556 · see citing works
Stimulation of cAMP response element (CRE)-mediated transcription during contextual learning
Impey, S., Smith, D. M., Obrietan, K. H., Donahue, R. J., Wade, C. B., & Storm, D. R. (1998) · Nature Neuroscience · doi:10.1038/2830 · Cited by 520 · see citing works
Effects of early adverse experiences on brain structure and function: clinical implications
Kaufman, J., Plotsky, P. M., Nemeroff, C. B., & Charney, D. S. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(00)00998-7 · Cited by 508 · see citing works
Influence of Neonatal Rearing Conditions on Stress‐Induced Adrenocorticotropin Responses and Norepinepherine Release in the Hypothalamic Paraventricular Nucleus
Liu, Caldji, Sharma, Plotsky, & Meaney (2000) · Journal of Neuroendocrinology · doi:10.1046/j.1365-2826.2000.00422.x · Cited by 451 · see citing works
The role of corticotropin-releasing factor–norepinephrine systems in mediating the effects of early experience on the development of behavioral and endocrine responses to stress
Francis, D. D., Caldji, C., Champagne, F., Plotsky, P. M., & Meaney, M. J. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00237-1 · Cited by 380 · see citing works
Early Sexual Abuse and Clinical Depression in Adult Life
Bifulco, A., Brown, G. W., & Adler, Z. (1991) · British Journal of Psychiatry · doi:10.1192/bjp.159.1.115 · Cited by 335 · see citing works
Differential Regulation of Hippocampal Glucocorticoid Receptors mRNA and Fast Feedback: Relevance to Post‐Traumatic Stress Disorder
Liberzon, López, Flagel, Vázquez, & Young (1999) · Journal of Neuroendocrinology · doi:10.1046/j.1365-2826.1999.00288.x · Cited by 308 · see citing works
Naloxone-Reversible Analgesic Response to Combat-Related Stimuli in Posttraumatic Stress Disorder: A Pilot Study
Pitman, R. K. (1990) · Archives of General Psychiatry · doi:10.1001/archpsyc.1990.01810180041007 · Cited by 296 · see citing works
Posttraumatic stress disorder following political imprisonment: the role of mental defeat, alienation, and perceived permanent change
Ehlers, A., Maercker, A., & Boos, A. (2000) · Journal of Abnormal Psychology · doi:10.1037/0021-843x.109.1.45 · Cited by 274 · see citing works
Predicting response to exposure treatment in PTSD: The role of mental defeat and alienation
Ehlers, A., Clark, D. M., Dunmore, E., Jaycox, L. H., Meadows, E. A., & Foa, E. B. (1998) · Journal of Traumatic Stress · doi:10.1023/a:1024448511504 · Cited by 250 · see citing works
Auditory Thalamus, Dorsal Hippocampus, Basolateral Amygdala, and Perirhinal Cortex Role in the Consolidation of Conditioned Freezing to Context and to Acoustic Conditioned Stimulus in the Rat
Sacchetti, B., Lorenzini, C. A., Baldi, E., Tassoni, G., & Bucherelli, C. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-21-09570.1999 · Cited by 243 · see citing works
Exposure to juvenile stress exacerbates the behavioural consequences of exposure to stress in the adult rat
Avital, A., & Richter‐Levin, G. (2005) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145704004808 · Cited by 219 · see citing works
Topiramate attenuates exaggerated acoustic startle in an animal model of PTSD
Khan, S., & Liberzon, I. (2004) · Psychopharmacology · doi:10.1007/s00213-003-1634-4 · Cited by 192 · see citing works
Differential role of the medial and lateral prefrontal cortices in fear and anxiety.
Lacroix, L. P., Spinelli, S., Heidbreder, C. A., & Feldon, J. (2000) · Behavioral Neuroscience · doi:10.1037//0735-7044.114.6.1119 · Cited by 185 · see citing works
Dentate gyrus-selective colchicine lesion and disruption of performance in spatial tasks: Difficulties in ?place strategy? because of a lack of flexibility in the use of environmental cues?
Xavier, G. F., Oliveira-Filho, F. J. B., & Santos, A. M. G. (1999) · Hippocampus · doi:10.1002/(sici)1098-1063(1999)9:6 · Cited by 175 · see citing works
Relationship between objective and subjective sleep measures in depressed patients and healthy controls
Armitage, R., Trivedi, M. H., Hoffmann, R. F., & Rush, A. J. (1997) · Depression and Anxiety · doi:10.1002/(sici)1520-6394(1997)5:2 · Cited by 169 · see citing works
Differential role of the medial and lateral prefrontal cortices in fear and anxiety.
Lacroix, L. P., Spinelli, S., Heidbreder, C. A., et al. (2000) · Behavioral Neuroscience · doi:10.1037/0735-7044.114.6.1119 · Cited by 167 · see citing works
Childhood adversity and vulnerability to mood and anxiety disorders.
Young, E. A., Abelson, J. L., Curtis, G. C., & Nesse, R. M. (1997) · PubMed · Cited by 143 · see citing works
Effects of early-life stress on behavior and neurosteroid levels in the rat hypothalamus and entorhinal cortex
Avital, A., Ram, E., Maayan, R., Weizman, A., & Richter‐Levin, G. (2005) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2005.09.015 · Cited by 85 · see citing works
Stress during adolescence alters behavioral sensitization to amphetamine
Kabbaj, M., Isgor, C., Watson, S. J., & Akil, H. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00188-4 · Cited by 76 · see citing works
A selective increase in phosphorylation of cyclic AMP response element-binding protein in hippocampal CA1 region of male, but not female, rats following contextual fear and passive avoidance conditioning
Kudo, K., Qiao, C.-X., Kanba, S., & Arita, J. (2004) · Brain Research · doi:10.1016/j.brainres.2004.08.007 · Cited by 68 · see citing works
The experience of mental death: The core feature of complex posttraumatic stress disorder
Ebert, A., & Dyck, M. J. (2004) · Clinical Psychology Review · doi:10.1016/j.cpr.2004.06.002 · Cited by 65 · see citing works
GABAergic and glutamatergic modulation of exploratory behavior in the dorsomedial hypothalamus
Jardim, M. C., & Guimarães, F. S. (2001) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(01)00560-3 · Cited by 46 · see citing works
Postnatally induced differences in adult pain sensitivity depend on genetics, gender and specific experiences: reversal of maternal deprivation effects by additional postnatal tactile stimulation or chronic imipramine treatment
Stephan, M., Helfritz, F., Pabst, R., & von Hörsten, S. (2002) · Behavioural Brain Research · doi:10.1016/s0166-4328(01)00468-5 · Cited by 44 · see citing works
The anxiolytic-like effect of nicotine undergoes rapid tolerance in a model of contextual fear conditioning in rats
Szyndler, J., Sienkiewicz‐Jarosz, H., Maciejak, P., Siemiątkowski, M., Rokicki, D., Członkowska, A., & Płaźnik, A. (2001) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(01)00548-2 · Cited by 42 · see citing works
Differential contribution of some cortical sites to the formation of memory traces supporting fear conditioning
Sacchetti, B., Baldi, E., Lorenzini, C. A., & Bucherelli, C. (2002) · Experimental Brain Research · doi:10.1007/s00221-002-1165-y · Cited by 42 · see citing works
PTSD : brain mechanisms and clinical implications
加藤, 進., 河田, 光., & Pitman, R. K. (2006) · Springer eBooks · Cited by 38 · see citing works
Psychiatric progress
Telner, J. I., & Singhal, R. L. (1984) · Journal of Psychiatric Research · doi:10.1016/0022-3956(84)90011-6 · Cited by 37 · see citing works
Temporary inactivation of the rostral perirhinal cortex induces an anxiolytic-like effect on the elevated plus-maze and on the yohimbine-enhanced startle response
Schulz-Klaus, B., Fendt, M., & Schnitzler, H. (2005) · Behavioural Brain Research · doi:10.1016/j.bbr.2005.04.022 · Cited by 16 · see citing works
Stress Vulnerability Induced by Neonatal Isolation and the Disturbance Between the Phosphorylation and Dephosphorylation of CREB
Morinobu, S., Tsuji, S., Takahashi, M., Russell, D., Takahashi, J., Tanaka, K., Fujimaki, K., Yamawaki, S., Endoh, S., & Endoh, M. (2006) · Springer eBooks · doi:10.1007/4-431-29567-4_4 · Cited by 2 · see citing works
Self-citation

Flagged first, then by citations

Sorted by citations

Psychological stress in early life as a predisposing factor for the development of chronic pain: clinical and preclinical evidence and neurobiological mechanisms
Burke, N. N., Finn, D. P., McGuire, B. E., & Roche, M. (2017) · Journal of Neuroscience Research · doi:10.1002/jnr.23802 · Cited by 268 · see citing works
Effects of Single Prolonged Stress and D-Cycloserine on Contextual Fear Extinction and Hippocampal NMDA Receptor Expression in a Rat Model of PTSD
Yamamoto, S., Morinobu, S., Fuchikami, M., Kurata, A., Kozuru, T., & Yamawaki, S. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301605 · Cited by 224 · see citing works
Self-citation
Aversive life events enhance human freezing responses.
Hagenaars, M. A., Stins, J. F., & Roelofs, K. (2012) · Journal of Experimental Psychology General · doi:10.1037/a0024211 · Cited by 128 · see citing works
Cannabinoids and traumatic stress modulation of contextual fear extinction and GR expression in the amygdala–hippocampal–prefrontal circuit
Ganon-Elazar, E., & Akirav, I. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.01.014 · Cited by 98 · see citing works
A single prolonged stress paradigm produces enduring impairments in social bonding in monogamous prairie voles
Arai, A., Hirota, Y., Miyase, N., Miyata, S., Young, L. J., Osako, Y., Yuri, K., & Mitsui, S. (2016) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.08.022 · Cited by 21 · see citing works

Anxiety is correlated with running in adolescent female mice undergoing activity-based anorexia.
Wable, G. S., Min, J., Chen, Y.-W., & Aoki, C. J. (2015) · Behavioral Neuroscience · doi:10.1037/bne0000040 · Cited by 73 · see citing works
Inhibiting 5α-reductase in the amygdala attenuates antianxiety and antidepressive behavior of naturally receptive and hormone-primed ovariectomized rats
Walf, A. A., Sumida, K., & Frye, C. A. (2005) · Psychopharmacology · doi:10.1007/s00213-005-0100-x · Cited by 77 · see citing works
HFD-induced energy states-dependent bidirectional control of anxiety levels in mice
Sweeney, P. R., O’Hara, K., xu, Z., & Yang, Y. (2017) · International Journal of Obesity · doi:10.1038/ijo.2017.112 · Cited by 31 · see citing works
Commonly-used rodent tests of anxiety-like behavior lack predictive validity for human sex differences.
Börchers, S., Krieger, J.-P., Asker, M., Marić, I., & Skibicka, K. (2022) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2022.105733 · Cited by 47 · see citing works
Age, Sex and Anxiety Affect Locomotor Activity in Rats
Belviranlõ, M., & Okudan, N. (2012) · Cited by 2 · see citing works

Authors: Imanaka, A., Morinobu, S., Toki, S., & Yamawaki, S.
Affiliations: Hiroshima University (JP)
Corresponding author: Yamawaki, Shigeto
ORCID: Morinobu, Shigeru
Yamawaki, Shigeto
Venue: Behavioural Brain Research
Publisher: Elsevier BV
Published: 2006-10
Volume: 173
Issue: 1
Pages: 129-137
ISSN: 0166-4328 (ISSN-L)
DOI: 10.1016/j.bbr.2006.06.012
OpenAlex: W1978971276
Cited by: 154
References: 44
Citations by year: 2026: 3 · 2025: 9 · 2024: 6 · 2023: 9 · 2022: 5 · 2021: 9 · 2020: 6 · 2019: 8 · 2018: 3 · 2017: 14 · 2016: 5 · 2015: 8 · 2014: 16 · 2013: 10 · 2012: 9
FWCI: 7.74
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Behavioural Brain Research (publishedVersion)
PubMed (publishedVersion)
Funders: Ministry of Education, Culture, Sports, Science and Technology
Ministry of Health, Labour and Welfare
Topics: Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords: post-traumatic stress disorder, childhood adversity, neonatal isolation, single prolonged stress, environmental enrichment, anxiety-like behavior, contextual fear, analgesia, hippocampal dysfunction, amygdala, animal model of PTSD, early intervention
MeSH terms: Age Factors, Animals, Anxiety, Conditioning, Classical, Disease Models, Animal, Environment, Exploratory Behavior, Fear, Female, Male, Random Allocation, Social Isolation, Stress Disorders, Post-Traumatic, Stress, Psychological, Rats, Sprague-Dawley, Freezing Reaction, Cataleptic, Rats

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Importance of early environment in the development of post-traumatic stress disorder-like behaviors

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks