“Isolation stress” revisited: isolation-rearing effects depend on animal care methods
Abstract
Early reports of enhanced behavioral reactivity in isolation-reared rats attributed this syndrome to "isolation stress." In the studies reported here, this "isolation stress syndrome" was reliably obtained in adult rats reared from weaning in individual hanging metal cages. Such isolates showed behavioral and adrenocortical symptoms of profound fear during open-field testing, unlike group-housed controls or littermate isolates reared singly in plastic cages. Animals in hanging metal cages are never touched by human caretakers, whereas rats reared in plastic cages are picked up and put in clean cages twice weekly. Handling hanging-cage isolates twice weekly to model the handling associated with cage changes completely protected against this syndrome. Further, there was no hormonal, neurochemical or anatomical evidence of chronic stress even in hanging-cage isolates. Littermates housed in social groupings (three rats per plastic cage) also froze and defecated in the open field at rates comparable to hanging-cage isolates if they were the first animals to be tested from their social group cage. It is probable that odor cues from familiar cagemates in the open field protected socially reared animals tested subsequently from the same cage from this syndrome. It is concluded that isolates are not chronically stressed, and that rearing effects are the result of a complex interaction between prior handling, social experience and test conditions.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Social isolation after weaning increases HPA axis sensitivity, particularly in males, and leads to an anxiety-like profile.
“As with maternal separation, post-weaning social isolation results in enhanced sensitivity of the HPA axis, especially in male rats (Holson et al., 1991; Viveros et al., 1988; Weiss et al., 2004), as well as an overall anxiogenic phenotype.”
From The effects of early life stress on reward processing (2018) · cites this paper as Holson et al., 1991
Cites
PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENT
Lowry, O. H., Rosebrough, N., Farr, A. L., & Randall, R. (1951) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)52451-6 · Cited by 315,771 · see citing works
II. New evidence for a locus coeruleus-norepinephrine connection with anxiety
Redmond, D. E., & Huang, Y. H. (1979) · Life Sciences · doi:10.1016/0024-3205(79)90087-0 · Cited by 662 · see citing works
Two independent behavioral dimensions in open-field performance.
Whimbey, A. E., & Denenberg, V. H. (1967) · Journal of Comparative and Physiological Psychology · doi:10.1037/h0024620 · Cited by 431 · see citing works
A critical period for social isolation in the rat
Einon, D. F., & Morgan, M. J. (1977) · Developmental Psychobiology · doi:10.1002/dev.420100205 · Cited by 342 · see citing works
Response to stress of mesocortico-frontal dopaminergic neurones in rats after long-term isolation
Blanc, G., Hervé, D., Simon, H., Lisoprawski, A., Glowinski, J., & Tassin, J. (1980) · Nature · doi:10.1038/284265a0 · Cited by 298 · see citing works
Sahakian, B. J., Robbins, T. W., Morgan, M. J., & Iversen, S. D. (1975) · Brain Research · doi:10.1016/0006-8993(75)90975-0 · Cited by 278 · see citing works
Levitsky, D. A., & Barnes, R. H. (1972) · Science · doi:10.1126/science.176.4030.68 · Cited by 246 · see citing works
Gentsch, C., Lichtsteiner, M., & Feer, H. (1981) · Physiology & Behavior · doi:10.1016/0031-9384(81)90320-6 · Cited by 233 · see citing works
Brief periods of socialization and later behavior in the rat
Einon, D. F., Morgan, M. J., & Kibbler, C. C. (1978) · Developmental Psychobiology · doi:10.1002/dev.420110305 · Cited by 232 · see citing works
Long-Term Isolation Stress in Rats
Hatch, A., Wiberg, G., Balázs, T., & Grice, H. C. (1963) · Science · doi:10.1126/science.142.3591.507 · Cited by 228 · see citing works
Neurobiological mechanisms in human anxiety evidence supporting central noradrenergic hyperactivity
Charney, D. S., & Redmond, D. E. (1983) · Neuropharmacology · doi:10.1016/0028-3908(83)90122-3 · Cited by 184 · see citing works
Stress adaptation and adrenal activity in isolated and crowded rats
Gamallo, A., Villanua, A., Trancho, G. J., & Fraile, A. (1986) · Physiology & Behavior · doi:10.1016/0031-9384(86)90006-5 · Cited by 169 · see citing works
Claustre, Y., Rivy, J.-P., Dennis, T., & Scatton, B. (1986) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)24841-8 · Cited by 165 · see citing works
The effects of social restriction on the behavior of rhesus monkeys: I. Free social behavior.
Mason, W. A. (1960) · Journal of Comparative and Physiological Psychology · doi:10.1037/h0045216 · Cited by 165 · see citing works
Hatch, A., Wiberg, G., Zawidzka, Z., Cann, M. C., Airth, J. M., & Grice, H. C. (1965) · Toxicology and Applied Pharmacology · doi:10.1016/0041-008x(65)90132-8 · Cited by 158 · see citing works
The interpretation of physiological correlates of differential housing in laboratory rats
Brain, P. F., & Benton, D. (1979) · Life Sciences · doi:10.1016/0024-3205(79)90119-x · Cited by 156 · see citing works
Ader, R. (1965) · Journal of Comparative and Physiological Psychology · doi:10.1037/h0022313 · Cited by 130 · see citing works
Gentsch, C., Lichtsteiner, M., Frischknecht, H. R., Feer, H., & Siegfried, B. (1988) · Physiology & Behavior · doi:10.1016/0031-9384(88)90091-1 · Cited by 128 · see citing works
Garzón, J., & Rı́o, J. D. (1981) · European Journal of Pharmacology · doi:10.1016/0014-2999(81)90047-9 · Cited by 108 · see citing works
Incentive motivation and behavioral inhibition in socially-isolated rats
Morgan, M. J. (1975) · Physiology & Behavior · doi:10.1016/0031-9384(75)90205-x · Cited by 103 · see citing works
Einon, D. F., Humphreys, A. P., Chivers, S. M., Field, S., & Naylor, V. (1981) · Developmental Psychobiology · doi:10.1002/dev.420140407 · Cited by 87 · see citing works
Einon, D. F., & Morgan, M. K. (1978) · Quarterly Journal of Experimental Psychology · doi:10.1080/14640747808400663 · Cited by 87 · see citing works
Gentsch, C., Lichtsteiner, M., Kräuchi, K., & Feer, H. (1982) · Behavioural Brain Research · doi:10.1016/0166-4328(82)90163-2 · Cited by 84 · see citing works
EFFECTS OF ENVIRONMENTAL COMPLEXITY ON CONSTITUENTS OF BRAIN AND LIVER*
Geller, E., Yuwiler, A., & Zolman, J. F. (1965) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1965.tb11938.x · Cited by 84 · see citing works
Antidepressants selectively antagonize the hyperactivity induced in rats by long-term isolation
Garzón, J., Fuentes, J., & Rı́o, J. D. (1979) · European Journal of Pharmacology · doi:10.1016/0014-2999(79)90293-0 · Cited by 82 · see citing works
Stern, J. A., Winokur, G., Eisenstein, A. B., Taylor, R., & Sly, M. (1960) · Journal of Psychosomatic Research · doi:10.1016/0022-3999(60)90010-6 · Cited by 77 · see citing works
Smith, H. V. (1972) · Journal of Comparative and Physiological Psychology · doi:10.1037/h0032841 · Cited by 75 · see citing works
Social isolation at weaning: Some effects on two measures of activity
Syme, L. A. (1973) · Animal Learning & Behavior · doi:10.3758/bf03199065 · Cited by 73 · see citing works
The development of intersession habituation and emergence in socially reared and isolated rats
Einon, D. F., Morgan, M. J., & Sahakian, B. J. (1975) · Developmental Psychobiology · doi:10.1002/dev.420080613 · Cited by 72 · see citing works
Gender and early environmental influences on activity, overresponsiveness, and exploration
Joseph, R., & Gallagher, R. E. (1980) · Developmental Psychobiology · doi:10.1002/dev.420130512 · Cited by 71 · see citing works
Weinstock, M., Speiser, Z., & Ashkenazi, R. (1978) · Psychopharmacology · doi:10.1007/bf00431851 · Cited by 68 · see citing works
Incentive motivation and behavioral inhibition in socially-isolated rats
Morgan, M. J., & Einon, D. F. (1975) · Physiology & Behavior · doi:10.1016/0031-9384(75)90250-4 · Cited by 67 · see citing works
Segal, D. S., Knapp, S., Kuczenski, R. T., & Mandell, A. J. (1973) · Behavioral Biology · doi:10.1016/s0091-6773(73)80005-7 · Cited by 60 · see citing works
Ader, R., & Friedman, S. B. (1964) · Psychological Reports · doi:10.2466/pr0.1964.15.2.535 · Cited by 52 · see citing works
Effects of early experience on social behaviour.
Melzack, R., & Thompson, W. R. (1956) · Canadian Journal of Psychology/Revue Canadienne de Psychologie · doi:10.1037/h0083664 · Cited by 52 · see citing works
Hughes, R. N., & Syme, L. A. (1972) · Psychopharmacology · doi:10.1007/bf00429389 · Cited by 51 · see citing works
Evidence for dopamine autoreceptors in mesocortical dopamine neurons
Fadda, F., GESSA, G. L., Marcou, M., Mosca, E., & Rossetti, Z. L. (1984) · Brain Research · doi:10.1016/0006-8993(84)91453-7 · Cited by 49 · see citing works
Behavioral effects of isolation in the rat
Moyer, K. E., & Korn, J. H. (1965) · Psychonomic Science · doi:10.3758/bf03343255 · Cited by 48 · see citing works
Weinstock, M., & Speiser, Z. (1973) · Psychopharmacology · doi:10.1007/bf00422870 · Cited by 47 · see citing works
Holson, R. R. (1986) · Physiology & Behavior · doi:10.1016/0031-9384(86)90154-x · Cited by 44 · see citing works
Self-citationSocial Environment, Emotionality, and Alloxan Diabetes in the Rat
ALBERT, K., Ader, R., & Jacobs, H. L. (1963) · Psychosomatic Medicine · doi:10.1097/00006842-196301000-00007 · Cited by 44 · see citing works
Holson, R. R., Scallet, A. C., Ali, S. F., Sullivan, P. A., & Gough, B. (1988) · Physiology & Behavior · doi:10.1016/0031-9384(88)90286-7 · Cited by 43 · see citing works
Self-citationResponse to stimulus novelty and complexity as a function of rats' early rearing experiences.
Sackett, G. P. (1967) · Journal of Comparative and Physiological Psychology · doi:10.1037/h0024618 · Cited by 42 · see citing works
Exploration, distraction, and habituation in rats reared in isolation
File, S. E. (1978) · Developmental Psychobiology · doi:10.1002/dev.420110111 · Cited by 42 · see citing works
DYNAMIC TESTING AND MODELING OF ADRENOCORTICAL SECRETORY FUNCTION*
Urquhart, J., & Li, C. C. (1969) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1969.tb14012.x · Cited by 40 · see citing works
Some anatomical and physiological correlates of social isolation in the young rat
Morinan, A., & Leonard, B. E. (1980) · Physiology & Behavior · doi:10.1016/0031-9384(80)90265-6 · Cited by 40 · see citing works
Eating behavior: Social facilitation or social inhibition?
Shelley, H. P. (1965) · Psychonomic Science · doi:10.3758/bf03343264 · Cited by 40 · see citing works
ISOLATION STRESS IN MEDICAL AND MENTAL ILLNESS
Ziskind, E. (1958) · JAMA · doi:10.1001/jama.1958.03000110001001 · Cited by 35 · see citing works
Ali, S. F., Slikker, W., Newport, G. D., et al. (1986) · Acta Pharmacologica et Toxicologica · doi:10.1111/j.1600-0773.1986.tb00152.x · Cited by 34 · see citing works
Self-citationEffects of early social deprivation on emotionality in rats.
Koch, M. D., & Arnold, W. J. (1972) · Journal of Comparative and Physiological Psychology · doi:10.1037/h0032380 · Cited by 27 · see citing works
Early environmental influences on conditioned and unconditioned ingestional and locomotor behaviors
Domjan, M. P., Schorr, R., & Best, M. R. (1977) · Developmental Psychobiology · doi:10.1002/dev.420100603 · Cited by 20 · see citing works
Some effects of group size on behavior and physiology of the rat
Hahn, W. W. (1965) · Journal of Psychosomatic Research · doi:10.1016/0022-3999(65)90087-5 · Cited by 20 · see citing works
Einon, D. F., & Morgan, M. J. (1978) · Behavioral Biology · doi:10.1016/s0091-6773(78)92763-3 · Cited by 17 · see citing works
Methodology in long-term toxicity tests: A comparison of individual versus community housing
Wiberg, G., Airth, J. M., & Grice, H. C. (1966) · Food and Cosmetics Toxicology · doi:10.1016/s0015-6264(66)80375-9 · Cited by 15 · see citing works
Holson, R. R., Ali, S. F., & Scallet, A. C. (1988) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1988.tb42143.x · Cited by 14 · see citing works
Self-citationIsolation-induced general behavioral changes and brain monoamine levels in rat.
Nishikawa, T., Kajiwara, Y., Kono, Y., et al. (1974) · The Kurume Medical Journal · doi:10.2739/kurumemedj.21.117 · Cited by 14 · see citing works
Morley, B. J., & Worsham, E. (1978) · Physiological Psychology · doi:10.3758/bf03326698 · Cited by 13 · see citing works
Biochemical and Pharmacological Studies on an Animal Model of Hyperactivity States
Weinstock, M., Speiser, Z., & Ashkenazi, R. (1977) · Springer eBooks · doi:10.1007/978-1-4684-0778-5_11 · Cited by 11 · see citing works
The impact of biology on modern psychiatry
Roy, A. (1978) · Journal of Psychosomatic Research · doi:10.1016/0022-3999(78)90102-2 · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Fone, K. C. F., & Porkess, M. V. (2008) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2008.03.003 · Cited by 864 · see citing works
Effect of social isolation on stress-related behavioural and neuroendocrine state in the rat
Weiss, I. C., Pryce, C. R., Jongen-Rêlo, A. L., Nanz-Bahr, N. I., & Feldon, J. (2004) · Behavioural Brain Research · doi:10.1016/j.bbr.2003.10.015 · Cited by 512 · see citing works
Schrijver, N. C. A., Bahr, N. I., Weiss, I. C., & Würbel, H. (2002) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(02)00790-6 · Cited by 294 · see citing works
The effects of early life stress on reward processing
Novick, A. M., Levandowski, M. L., Laumann, L. E., Philip, N. S., Price, L. H., & Tyrka, A. R. (2018) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2018.02.002 · Cited by 192 · see citing works
“1 Neurobiology of Social Isolation: As with maternal separation, post-weaning social isolation results in enhanced sensitivity of the HPA axis, especially in male rats (Holson et al., 1991; Viveros et al., 1988; Weiss et al., 2004), as well as an overall anxiogenic phenotype.”
BackgroundFilipović, D., Todorović, N., Bernardi, R. E., & Gass, P. (2017) · Brain Structure and Function · doi:10.1007/s00429-016-1218-9 · Cited by 138 · see citing works
Ecological validity of social interaction tests in rats and mice
Kondrakiewicz, K., Kostecki, M., Szadzińska, W., & Knapska, E. (2019) · Genes, Brain and Behavior · doi:10.1111/gbb.12525 · Cited by 136 · see citing works
Social isolation in animal models of relevance to neuropsychiatric disorders
Kim, J. W., & Kirkpatrick, B. (1996) · Biological Psychiatry · doi:10.1016/0006-3223(95)00546-3 · Cited by 95 · see citing works
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 · see citing works
Schipper, L., Harvey, L., van der Beek, E. M., & van Dijk, G. (2018) · Obesity Reviews · doi:10.1111/obr.12663 · Cited by 67 · see citing works
- Authors
- Holson, R. R., Scallet, A. C., Ali, S. F., & Turner, B. B.
- Affiliations
- National Center for Toxicological Research (US)
- East Tennessee State University (US)
- Corresponding author
- Holson, R.R.
- ORCID
- Ali, S.F.
- Venue
- Physiology & Behavior
- Publisher
- Elsevier BV
- Published
- 1991-06
- Volume
- 49
- Issue
- 6
- Pages
- 1107-1118
- ISSN
- 0031-9384 (ISSN-L)
- OpenAlex
- W2025593500
- Cited by
- 166
- References
- 59
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 4 · 2022: 5 · 2021: 4 · 2020: 6 · 2019: 8 · 2018: 5 · 2017: 8 · 2016: 3 · 2015: 3 · 2014: 2 · 2013: 5 · 2012: 3
- FWCI
- 0.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Physiology & Behavior (publishedVersion)
- PubMed (publishedVersion)
- Digital Commons - East Tennessee State University (East Tennessee State University) (submittedVersion)
- Funders
- National Institutes of Health (1r01ns022158-01a1)
- National Institute of Neurological Disorders and Stroke (NS 22158)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Veterinary › Small Animals › Animal Behavior and Welfare Studies
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- rearing conditions, animal handling, fear behavior, freezing behavior, adrenocortical response, olfactory cues, social experience, chronic stress
- MeSH terms
- Animals, Arousal, Corticosterone, Dopamine, Fear, Female, Frontal Lobe, Handling, Psychological, Male, Rats, Inbred Strains, Receptors, Dopamine, Receptors, Glucocorticoid, Serotonin, Social Environment, Social Isolation, 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
