Cited by 512Stress Responses and CortisolNeuroendocrine regulation and behaviorMemory and Neural Mechanisms

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Effect of social isolation on stress-related behavioural and neuroendocrine state in the rat

Weiss, Isabelle C, Pryce, Christopher R, Jongen-Rêlo, Ana L, Nanz-Bahr, Nina I, Feldon, Joram·2004·Behavioural Brain Research

DOI 10.1016/j.bbr.2003.10.015

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Abstract

The present study investigated the effects of post-weaning social isolation (SI) on behavioural and neuroendocrine reactivity to stress of male and female rats. Innate aspects of fear and anxiety were assessed in the open field and elevated plus maze tests. Spontaneous startle reflex and conditioned fear response were further investigated. The neuroendocrine response of isolates was examined by measuring basal and stress release of ACTH and corticosterone and by evaluating the mRNA expression of mineralocorticoid (MR) and glucocorticoid (GR) receptors using in situ hybridization. Locomotor activity in the open field was not modified by chronic SI. In males, but not females, SI produced an anxiogenic profile in the elevated plus maze. Male isolates showed a trend towards increased startle reflex amplitude relative to socially-reared controls. Moreover, SI in males produced alterations of the HPA axis functioning as reflected by higher basal levels of ACTH, and enhanced release of ACTH and corticosterone following stress. In contrast, startle response or HPA axis functioning were not altered in female isolates. Social isolates from both genders showed reduced contextual fear-conditioning. Finally, the mRNA expression of MR and GR was not modified by SI. The results of the present study suggest that chronic SI increases emotional reactivity to stress and produces a hyperfunction of the HPA axis in adult rats, particularly in males.

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The Evidence for Altered BDNF Expression in the Brain of Rats Reared or Housed in Social Isolation: A Systematic Review
Murínová, J., Hlaváčová, N., Chmelová, M., & Riečanský, I. (2017) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2017.00101 · Cited by 110
“First, there is little evidence for a chronic increase in basal GC levels in socially isolated rats (Weiss et al., 2004; Serra et al., 2005; Fone and Porkess, 2008; Cacioppo et al., 2015).”
Background
Post-weaning chronic social isolation produces profound behavioral dysregulation with decreases in prefrontal cortex synaptic-associated protein expression in female rats
Hermes, G., Li, N., Duman, C., & Duman, R. (2011) · Physiology & Behavior · doi:10.1016/j.physbeh.2010.12.019 · Cited by 111
“Other psychopathological disturbances associated with social isolation include hoarding [3] and anxiety [4].”
Background
Social isolation impairs the prefrontal-nucleus accumbens circuit subserving social recognition in mice
Park, G., Ryu, C., Kim, S., Jeong, S. J., Koo, J. W., Lee, Y., & Kim, S. J. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109104 · Cited by 109
Synergistic and additive actions of a psychosocial stressor and endotoxin challenge: Circulating and brain cytokines, plasma corticosterone and behavioral changes in mice
Gibb, J., Hayley, S. P., Gandhi, R., Poulter, M. O., & Anisman, H. (2008) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2007.12.001 · Cited by 111
“It appears, as well, that although prolonged isolation might not affect basal corticosterone levels and immune functioning, it may engender higher levels of emotional reactivity and a hyperactive HPA response to subsequent psychosocial stressors (Bartolomucci et al., 2003; Weiss et al., 2004).”
Early Adolescence as a Critical Window During Which Social Stress Distinctly Alters Behavior and Brain Norepinephrine Activity
Bingham, B. C., McFadden, K., Zhang, X., Bhatnagar, S., Beck, S. G., & Valentino, R. J. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2010.229 · Cited by 112
“Although social isolation can be a stressor, particularly in EA rats (Weiss et al., 2004; Leussis and Andersen, 2008), it is unlikely to have contributed to the effects seen in the present study for several reasons.”
Three different coping styles in police dogs exposed to a short-term challenge
Horváth, Z., Igyártó, B. Z., Magyar, A., & Miklósi, Á. (2007) · Hormones and Behavior · doi:10.1016/j.yhbeh.2007.08.001 · Cited by 110
“The strategy applied to cope with stressors is influenced not only by personality factors but also by learning and rearing (Benus et al., 1991; Capitanio andMason, 2000; Hall et al., 1997;Weiss et al., 2004).”
Hippocampal BDNF in physiological conditions and social isolation
Zaletel, I. V., Filipović, D., & Puškaš, N. (2017) · Reviews in the Neurosciences · doi:10.1515/revneuro-2016-0072 · Cited by 110
“While most studies reported no effect of social isolation on the basal CORT levels (Weiss et al., 2004; Lukkes et al., 2009; Williams et al., 2009; Toth et al., 2011), others demonstrated either increased (Gamallo et al., 1986; Chida et al., 2005; Perelló et al., 2006) or reduced basal CORT…”
Background
Sex differences in the outcome of juvenile social isolation on HPA axis function in rats
Pisu, M. G., Garau, A., Boero, G., Biggio, F., Pibiri, V., Dore, R., Locci, V., Paci, E., Porcu, P., & Serra, M. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.02.009 · Cited by 112
The effects of social isolation on neuropeptide Y levels, exploratory and anxiety-related behaviors in rats
Thorsell, A., Slawecki, C. J., Khoury, A. E., Mathé, A. A., & Ehlers, C. L. (2006) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2005.12.005 · Cited by 111
Social isolation alters behavior, the gut-immune-brain axis, and neurochemical circuits in male and female prairie voles
Donovan, M., Mackey, C. S., Platt, G. N., Rounds, J., Brown, A. N., Trickey, D. J., Liu, Y., Jones, K. M., & Wang, Z. (2020) · Neurobiology of Stress · doi:10.1016/j.ynstr.2020.100278 · Cited by 85
“Further, social isolation can have a differential impact on males and females, and such sex differences can also be tied to differences in inflammatory activation (Hermes et al., 2006; Weiss et al., 2004).”
Stress before Puberty Exerts a Sex- and Age-Related Impact on Auditory and Contextual Fear Conditioning in the Rat
Toledo‐Rodriguez, M., & Sandi, C. (2007) · Neural Plasticity · doi:10.1155/2007/71203 · Cited by 109
“This finding is consistent with, and extends, works using different models of early life stress, such as social isolation given from weeks 3 to 13 [38] or separation from the mother for one hour per day from postnatal days 2 to 9 [39].”
BackgroundResult
Chronic Cold Stress Alters Prefrontal Cortical Modulation of Amygdala Neuronal Activity in Rats
Correll, C. M., Rosenkranz, J. A., & Grace, A. A. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.04.009 · Cited by 106
Isolation rearing induces social and emotional function abnormalities and alters glutamate and neurodevelopment-related gene expression in rats
Zhao, X., Sun, L., Jia, H., Meng, Q., Wu, S., Li, N., & He, S. (2009) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2009.06.016 · Cited by 105
“He). l rights reserved. reported are inconsistent, if not contradictory (Fone et al., 1996;Weiss et al., 2004; Wongwitdecha and Marsden, 1996).”
Cognition in the field: comparison of reversal learning performance in captive and wild passerines
Cauchoix, M., Hermer, E., Chaine, A. S., & Morand‐Ferron, J. (2017) · Scientific Reports · doi:10.1038/s41598-017-13179-5 · Cited by 112
Early deprivation under specific conditions leads to reduced interest in reward in adulthood in Wistar rats
Rüedi-Bettschen, D., Pedersen, E.-M., Feldon, J., & Pryce, C. R. (2005) · Behavioural Brain Research · doi:10.1016/j.bbr.2004.06.001 · Cited by 97
Rehabilitation of research chimpanzees: Stress and coping after long-term isolation
Reimers, M., Schwarzenberger, F., & Preuschoft, S. (2007) · Hormones and Behavior · doi:10.1016/j.yhbeh.2006.12.011 · Cited by 98
“that is characterized by anxiety, inactivity and neophobia, as well as chronically increased cortisol values (Seligman, 1974; Weiss et al., 2004).”
BackgroundInfluential
Differential effects of social isolation in adolescent and adult mice on behavior and cortical gene expression
Lander, S. S., Linder-Shacham, D., & Gaisler‐Salomon, I. (2016) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.09.005 · Cited by 102
The enduring effects of an adolescent social stressor on synaptic density, part II: Poststress reversal of synaptic loss in the cortex by adinazolam and MK‐801
Leussis, M. P., Lawson, K., Stone, K., & Andersen, S. L. (2008) · Synapse · doi:10.1002/syn.20483 · Cited by 95
“In this sense, it differs from the more strenuous stressor of social isolation that spans across weeks of adolescent development and affects the prefrontal cortex (Hall, 1998; Weiss et al., 2004).”
Neurobiological effects of neonatal maternal separation and post-weaning environmental enrichment.
Vivinetto, A. L., Suárez, M. M., & Rivarola, M. A. (2013) · Behavioural Brain Research · doi:10.1016/j.bbr.2012.11.014 · Cited by 103
Pair Housing of Dairy Calves and Age at Pairing: Effects on Weaning Stress, Health, Production and Social Networks
Bolt, S. L., Boyland, N. K., Mlynski, D. T., James, R., & Croft, D. P. (2017) · PLoS ONE · doi:10.1371/journal.pone.0166926 · Cited by 94
Long-term social isolation exacerbates the impairment of spatial working memory in APP/PS1 transgenic mice
Huang, H.-J., Liang, K., Ke, H.-C., Chang, Y.-Y., & Hsieh‐Li, H. M. (2010) · Brain Research · doi:10.1016/j.brainres.2010.11.043 · Cited by 94
Gender and sex hormones in multiple sclerosis pathology and therapy
Nicot, A. B. (2009) · Frontiers in bioscience · doi:10.2741/3543 · Cited by 95
“HPA responses are generally greater in males subjected to a psychological stressor compared to females (50, 51), but inversely when other stressors such as opioid antagonist naloxone (an inducer of ACTH) or”
Background
Post-weaning social isolation alters anxiety-related behavior and neurochemical gene expression in the brain of male prairie voles
Pan, Y., Liu, Y., Young, K. A., Zhang, Z., & Wang, Z. (2009) · Neuroscience Letters · doi:10.1016/j.neulet.2009.02.064 · Cited by 93
“Therefore, post-weaning social isolation is stressful, and this stress may alter neuroendocrine systems that modulate behavior in male prairie voles, as in other rodent species [3,21,47].”
Isolation Housing Exacerbates Alzheimer's Disease-Like Pathophysiology in Aged APP/PS1 Mice
Huang, H., Wang, L., Cao, M., Marshall, C., Gao, J., Xiao, N., Hu, G., & Xiao, M. (2015) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyu116 · Cited by 94
“Previous studies have reported that rearing juvenile or adult rodents in SI environments elicits a variety of behavioral abnormalities, such as increased aggres-siveness, anxiety, and hyperactivity (Weiss et al., 2004; Koike et al., 2009; Lukkes et al., 2009; Ouchi et al., 2013).”
Convergence of genetic and environmental factors on parvalbumin-positive interneurons in schizophrenia
Jiang, Z., Cowell, R. M., & Nakazawa, K. (2013) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2013.00116 · Cited by 91
“…that chronic early life social isolation is associated with higher basal levels of glucocorticoids and increased HPA response to acute stressors (Weiss et al., 2004; Chida et al., 2005; Perelló et al., 2006; Ruscio et al., 2007; Williams et al., 2009; Weintraub et al., 2010; Toth et al., 2011).”
Background
Chronic social isolation decreases glutamate and glutamine levels and induces oxidative stress in the rat hippocampus
Shao, Y., Yan, G., Xuan, Y., Peng, H., Huang, Q., Wu, R., & Xu, H. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.01.005 · Cited by 90
Impact of social isolation and enriched environment during adolescence on voluntary ethanol intake and anxiety in C57BL/6J mice
Lopez, M. F., & Laber, K. (2014) · Physiology & Behavior · doi:10.1016/j.physbeh.2014.11.012 · Cited by 87
“This chronic stress situation has long-lasting effects on various behavioral and neural functions (Lapiz et al. 2003; Weiss et al. 2004).”
The mGluR2/3 agonist LY379268 reverses post-weaning social isolation-induced recognition memory deficits in the rat
Jones, C. A., Brown, A. M., Auer, D. P., & Fone, K. C. F. (2010) · Psychopharmacology · doi:10.1007/s00213-010-1931-7 · Cited by 86
“In similar studies, no difference (Fulford and Marsden 1998a, b) or reductions (Fulford and Marsden 2007; Weiss et al. 2004) in freezing behaviour have been identified between group- and isolation-reared animals, indicative of impaired conditioned learning, as reported herein.”
The impact of social isolation on HPA axis function, anxiety-like behaviors, and ethanol drinking
Butler, T. R., Ariwodola, O. J., & Weiner, J. L. (2014) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2013.00102 · Cited by 85
“Previous studies measuring plasma CORT in GH/SI rats have shown no difference between groups (Weiss et al., 2004; Colaianna et al., 2013), greater CORT levels in SI rats (Serra et al., 2005) or greater CORT levels in GH rats (Raz, 2013), though these studies vary in methodology and use of different…”
Result
Models of Neurodevelopmental Abnormalities in Schizophrenia
Powell, S. B. (2010) · Current topics in behavioral neurosciences · doi:10.1007/7854_2010_57 · Cited by 87
“…rats and mice show increased anxiety-like behavior (Da Silva et al. 1996; Wright et al. 1991), deficits in fear learning (Voikar et al. 2005; Weiss et al. 2004), impaired recognition memory (e.g., novel object recognition; Bianchi et al. 2006; McLean et al. 2010; Voikar et al. 2005),…”
Background
Social stress and escalated drug self-administration in mice I. Alcohol and corticosterone
Norman, K. J., Seiden, J. A., Klickstein, J. A., Han, X., Hwa, L. S., DeBold, J. F., & Miczek, K. A. (2014) · Psychopharmacology · doi:10.1007/s00213-014-3733-9 · Cited by 92
“Different types of stress, such as chronic subordination in a social colony, social isolation, and episodic social defeat stress alter plasma corticosterone levels in rodents (Raab et al. 1986; Tornatzky and Miczek 1993; Uschold-Schmidt et al. 2012; Weiss et al. 2004).”
Testosterone and social isolation influence adult neurogenesis in the dentate gyrus of male rats
Spritzer, M. D., Ibler, E., Inglis, W., & Curtis, M. G. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.08.034 · Cited by 83
“Social isolation is stressful for rats, inducing an increase in the stress hormone corticosterone (Ruis et al., 1999; Weiss et al., 2004).”
Background
Schizophrenia and Depression Co-Morbidity: What We have Learned from Animal Models
Samsom, J., & Wong, A. H. C. (2015) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2015.00013 · Cited by 88
Social environment regulates corticotropin releasing factor, corticosterone and vasopressin in juvenile prairie voles
Ruscio, M. G., Sweeny, T., Hazelton, J., Suppatkul, P., & Sue Carter, C. (2007) · Hormones and Behavior · doi:10.1016/j.yhbeh.2006.08.004 · Cited by 81
“Results from previous studies measuring basal CORT levels following isolation in rodents are mixed, showing increases (Gamallo et al., 1986; Hatch et al., 1965), decreases (Viveros et al., 1988; Sanchez et al., 1998) or no change (Holson et al., 1991; Morinan and Leonard, 1980; Weiss et al., 2004 ).”
A single exposure to social isolation in domestic piglets activates behavioural arousal, neuroendocrine stress hormones, and stress-related gene expression in the brain
Kanitz, E., Puppe, B., Tuchscherer, M., Heberer, M., Viergutz, T., & Tuchscherer, A. (2009) · Physiology & Behavior · doi:10.1016/j.physbeh.2009.05.007 · Cited by 81
Effects of stressors in adolescence on learning and memory in rodent models
Green, M. R., & McCormick, C. M. (2013) · Hormones and Behavior · doi:10.1016/j.yhbeh.2012.09.012 · Cited by 86
“The evidence that social deprivation increases basal tone and stress responsiveness of the HPA axis is mixed (Lukkes et al., 2009a; Scaccianoce et al., 2006; Serra et al., 2005;Weiss et al., 2004).”
BackgroundInfluential
Isolation rearing and hyperlocomotion are associated with reduced immediate early gene expression levels in the medial prefrontal cortex
Levine, J. B., Youngs, R. M., MacDonald, M. L., Chu, M. S., Leeder, A., Francois Berthiaume, B., & Konradi, C. L. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2006.11.063 · Cited by 81
Post-weaning isolation promotes food intake and body weight gain in rats that experienced neonatal maternal separation
Ryu, V., Yoo, S. B., Kang, D. W., Lee, J.-H., & Jahng, J. W. (2009) · Brain Research · doi:10.1016/j.brainres.2009.08.006 · Cited by 83

Authors: Weiss, I. C., Pryce, C. R., Jongen-Rêlo, A. L., Nanz-Bahr, N. I., & Feldon, J.
Affiliations: ETH Zurich (CH)
Corresponding author: Feldon, Joram
ORCID: Pryce, Christopher R
Venue: Behavioural Brain Research
Publisher: Elsevier BV
Published: 2004-07
Volume: 152
Issue: 2
Pages: 279-295
ISSN: 0166-4328 (ISSN-L)
DOI: 10.1016/j.bbr.2003.10.015
OpenAlex: W2076236287
Cited by: 512
References: 76
Citations by year: 2026: 7 · 2025: 20 · 2024: 26 · 2023: 18 · 2022: 29 · 2021: 33 · 2020: 46 · 2019: 25 · 2018: 19 · 2017: 30 · 2016: 22 · 2015: 25 · 2014: 25 · 2013: 24 · 2012: 26
FWCI: 3.26
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Behavioural Brain Research (publishedVersion)
PubMed (publishedVersion)
Funders: Branco Weiss Fellowship – Society in Science
Eidgenössische Technische Hochschule Zürich
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: social isolation, post-weaning social isolation, stress reactivity, hypothalamic-pituitary-adrenal axis, ACTH, corticosterone, mineralocorticoid receptor, glucocorticoid receptor, anxiety, fear conditioning, startle response, sex differences, neuroendocrine response, rats
MeSH terms: Adrenocorticotropic Hormone, Analysis of Variance, Animals, Animals, Newborn, Behavior, Animal, Brain, Conditioning, Psychological, Corticosterone, Fear, Female, Glucocorticoids, Immunohistochemistry, Kidney, Male, Motor Activity, Neurosecretory Systems, Radioimmunoassay, Random Allocation, Reflex, Acoustic, Sex Factors, Social Isolation, Stress, Physiological, Weaning, Rats, Sprague-Dawley, In Situ Hybridization, Receptors, Mineralocorticoid, Maze Learning, Rats

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Effect of social isolation on stress-related behavioural and neuroendocrine state in the rat

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