Social defeat stress induces a depression-like phenotype in adolescent male c57BL/6 mice
Open accessAbstract
Abstract Exposure to stress is highly correlated with the emergence of mood-related illnesses. Because major depressive disorder often emerges in adolescence, we assessed the effects of social defeat stress on responses to depressive-like behaviors in juvenile mice. To do this, postnatal day (PD) 35 male c57BL/6 mice were exposed to 10 days of social defeat stress (PD35-44), while control mice were handled daily. Twenty-four hours after the last episode of defeat (PD45), separate groups of mice were tested in the social interaction, forced swimming, sucrose preference, and elevated plus-maze behavioral assays (n = 7-12 per group). Also, we examined body weight gain across days of social defeat and levels of blood serum corticosterone 40 min after the last episode of defeat stress. Our data indicates that defeated mice exhibited a depressive-like phenotype as inferred from increased social avoidance, increased immobility in the forced swim test, and reduced sucrose preference (a measure of anhedonia), when compared to non-defeated controls. Defeated mice also displayed an anxiogenic-like phenotype when tested on the elevated plus-maze. Lastly, stressed mice displayed lower body weight gain, along with increased blood serum corticosterone levels, when compared to non-stressed controls. Overall, we show that in adolescent male c57BL/6 mice, social defeat stress induces a depression- and anxiety-like phenotype 24 h after the last episode of stress. These data suggest that the social defeat paradigm may be used to examine the etiology of stress-induced mood-related disorders during adolescence.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Chronic social stress, particularly cSDS, is one of the most potent environmental risk factors precipitating depressive symptoms, as shown in human epidemiological data and animal models.
“Chronic social stress, particularly paradigms like chronic social defeat stress (cSDS), stands out as one of the most potent environmental risk factors precipitating depressive symptoms, as demonstrated in both human epidemiological data and well - established animal models of depression [4–6].”
From A nucleus accumbens-projecting prefrontal cortex circuit underlies chronic social stress-induced depression-like behaviors (2026) · cites this paper as [4]
The Introduction describes social defeat as a robust animal model of stress-induced mood disorders, and the Conclusions report that 10 days of defeat induced depression- and anxiety-like symptoms in adolescent male mice. The paper does not present human epidemiological evidence that chronic social stress is among the most potent environmental risk factors for depression; its epidemiological discussion concerns the age at which depression first occurs. The supplied passages have section labels but no page numbers. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
No citation lists for this paper
No citation lists for this paper yet — checked again daily.
References 55 · Cited by 269
Research works printed but not linked: 48
- APA 2000 Diagnostic and Statistical Manual of Mental Disorders DSM-IV Edition Washington, DC American Psychiatric Association
- Axelson DA Birmaher B 2001 Relation between anxiety and depressive disorders in childhood and adolescence Depress Anxiety 14 67 78 11668659
- Backström T Winberg S 2013 Central corticotropin releasing factor and social stress Front Neurosci 7 117 10.3389/fnins.2013.00117 23847465 PMC3705187 · DOI
- Berton O McClung CA Dileone RJ Krishnan V Renthal W Russo SJ Graham D 2006 Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress Science 311 864 8 16469931
- Beuke CJ Fischer R McDowall J 2003 Anxiety and depression: why and how to measure their separate effects Clin Psychol Rev 23 831 48 14529700
- Burke KC Burke JD Jr Regier DA Rae DS 1990 Age at onset of selected mental disorders in five community populations Arch Gen Psychiatry 47 511 18 2350203
- Buwalda B Stubbendorff C Zickert N Koolhaas JM 2013 Adolescent social stress does not necessarily lead to a compromised adaptive capacity during adulthood: a study on the consequences of social stress in rats Neuroscience 249 258 70 23305766
- Buwalda B de Boer SF Schmidt ED Felszeghy K Nyakas C Sgoifo A Van der Vegt BJ 1999 Long-lasting deficient dexamethasone suppression of hypothalamic-pituitary-adrenocortical activation following peripheral CRF challenge in socially defeated rats J Neuroendocrinol 11 513 20 10444308
- Charney DS Manji HK 2004 Life stress, genes, and depression: multiple pathways lead to increased risk and new opportunities for intervention Sci STKE 225 re5 10.1126/stke.2252004re5 15039492 · DOI
- Das-Munshi J Goldberg D Bebbington PE Bhugra DK Brugha TS Dewey ME Jenkins R 2008 Public health significance of mixed anxiety and depression: beyond current classification Br J Psychiatry 192 171 7 18310574
- Doremus-Fitzwater TL Varlinskaya EI Spear LP 2010 Motivational systems in adolescence: possible implications for age differences in substance abuse and other risk-taking behaviors Brain Cogn 72 114 23 19762139 PMC2814912
- Eiland L Romeo RD 2013 Stress and the developing adolescent brain Neuroscience 249 162 71 23123920 PMC3601560
- Eisch AJ Bolaños CA de Wit J Simonak RD Pudiak CM Barrot M Verhaagen J Nestler EJ 2003 Brain-derived neurotrophic factor in the ventral midbrain-nucleus accumbens pathway: a role in depression Biol Psychiatry 54 994 1005 14625141
- Findling RL McNamara NK Stansbrey RJ Feeny NC Young CM Peric FV Youngstrom EA 2006 The relevance of pharmacokinetic studies in designing efficacy trials in juvenile major depression J Child Adolesc Psychopharmacol 16 131 45 16553534
- Gladstone GL Parker GB Malhi GS 2006 Do bullied children become anxious and depressed adults?: a cross-sectional investigation of the correlates of bullying and anxious depression J Nerv Ment Dis 194 201 8 16534438
- Heinrichs SC Koob GF 2006 Application of experimental stressors in laboratory rodents Curr Protoc Neurosci Chapter 8 Unit 8 4 18428648
- Huang GB Zhao T Muna SS Bagalkot TR Jin HM Chae HJ Chung YC 2013 Effects of chronic social defeat stress on behaviour, endoplasmic reticulum proteins and choline acetyl-transferase in adolescent mice Int J Neuropsychopharmacol 16 1635 47 23442729
- Iñiguez SD Warren BL Bolaños-Guzmán CA 2010a Short- and long-term functional consequences of fluoxetine exposure during adolescence in male rats Biol Psychiatry 67 1057 66 20172503 PMC2868075
- Iñiguez SD Vialou V Warren BL Cao JL Alcantara LF Davis LC Manojlovic Z 2010b Extracellular signal-regulated kinase-2 within the ventral tegmental area regulates responses to stress J Neurosci 30 7652 63 20519540 PMC2895424
- Iñiguez SD Alcantara LF Warren BL Riggs LM Parise EM Vialou V Wright KN 2014 Fluoxetine exposure during adolescence alters responses to aversive stimuli in adulthood J Neurosci 34 1007 21 24431458 PMC3891944
- Jiang C Salton SR 2013 The role of neurotrophins in major depressive disorder Transl Neurosci 4 46 58 23691270 PMC3656715
- Kessler RC Avenevoli S Ries Merikangas K 2001 Mood disorders in children and adolescents: an epidemiologic perspective Biol Psychiatry 49 1002 14 11430842
- Krishnan V Nestler EJ 2008 The molecular neurobiology of depression Nature 455 894 902 18923511 PMC2721780
- Krishnan V Han MH Mazei-Robison M Iñiguez SD Ables JL Vialou V Berton O 2008 AKT signaling within the ventral tegmental area regulates cellular and behavioral responses to stressful stimuli Biol Psychiatry 64 691 700 18639865 PMC2742561
- Kudryavtseva NN Bakshtanovskaya IV Koryakina LA 1991 Social model of depression in mice of C57BL/6J strain Pharmacol Biochem Behav 38 315 20 2057501
- Kupfer DJ Frank E Phillips ML 2012 Major depressive disorder: new clinical, neurobiological, and treatment perspectives Lancet 379 1045 55 22189047 PMC3397431
- Laviola G Macri S Adriani W Morley Fletcher S 2002 Psychobiological determinants of risk behavior in adolescence Ann Ist Super Sanita 38 279 87 12645179
- Lewinsohn PM Hops H Roberts RE Seeley JR Andrews JA 1993 Adolescent psychophathology: I. Prevalence and incidence of depression and other DSM-III-R disorders in high school students J Abnorm Psychol 102 133 44 8436689
- Malkesman O Weller A 2009 Two different putative genetic animal models of childhood depression – a review Prog Neurobiol 88 153 69 19545781
- Miczek KA 1979 A new test for aggression in rats without aversive stimulation: differential effects of d-amphetamine and cocaine Psychopharmacology (Berl) 60 253 9 108702
- Montgomery KC 1955 The relation between fear induced by novel stimulation and exploratory behavior J Comp Physiol Psychol 48 254 60 13252152
- Niwa M Jaaro-Peled H Tankou S Seshadri S Hikida T Matsumoto Y Cascella NG 2013 Adolescent stress-induced epigenetic control of dopaminergic neurons via glucocorticoids Science 339 335 9 23329051 PMC3617477
- Papp M Willner P Muscat R 1991 An animal model of anhedonia: attenuation of sucrose consumption and place preference conditioning by chronic unpredictable mild stress Psychopharmacology (Berl) 104 255 9 1876670
- Parmigiani S Palanza P Rogers J Ferrari PF 1999 Selection, evolution of behavior and animal models in behavioral neuroscience Neurosci Biobehav Rev 23 957 69 10580310
- Paus T Keshavan M Giedd JN 2008 Why do many psychiatric disorders emerge during adolescence? Nat Rev Neurosci 9 947 57 19002191 PMC2762785
- Pellow S Chopin P File SE Briley M 1985 Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat J Neurosci Methods 14 149 67 2864480
- Porsolt RD Le Pichon M Jalfre M 1977 Depression: a new animal model sensitive to antidepressant treatments Nature 266 730 2 559941
- Richards JM Plate RC Ernst M 2012 Neural systems underlying motivated behavior in adolescence: implications for preventative medicine Prev Med 55 s7 16 22198622 PMC3480556
- Spear LP 2000 The adolescent brain and age-related behavioral manifestations Neurosci Biobehav Rev 24 417 63 10817843
- Stone EA Quartermain D 1997 Greater behavioral effects of stress in immature as compared to mature male mice Physiol Behav 63 143 5 9402627
- Tirelli E Laviola G Adriani W 2003 Ontogenesis of behavioral sensitization and conditioned place preference induced by psychos-timulants in laboratory rodents Neurosci Biobehav Rev 27 163 78 12732232
- Tsoory M Cohen H Richter-Levin G 2007 Juvenile stress induces a predisposition to either anxiety or depressive-like symptoms following stress in adulthood Eur Neuropsychopharmacol 17 245 56 16889944
- Ver Hoeve ES Kelly G Luz S Ghanshani S Bhatnagar S 2013 Short-term and long-term effects of repeated social defeat during adolescence or adulthood in female rats Neuroscience 249 63 73 23402852 PMC3743933
- Wals M Verhulst F 2005 Child and adolescent antecedents of adult mood disorders Curr Opin Psychiatry 18 15 19 16639178
- Warren BL Iñiguez SD Alcantara LF Wright KN Parise EM Weakley SK Bolaños-Guzmán CA 2011 Juvenile administration of concomitant methylphenidate and fluoxetine alters behavioral reactivity to reward- and mood-related stimuli and disrupts ventral tegmental area gene expression in adulthood J Neurosci 31 10347 58 21753012 PMC3139175
- Watt MJ Burke AR Renner KJ Forster GL 2009 Adolescent male rats exposed to social defeat exhibit altered anxiety behavior and limbic monoamines as adults Behav Neurosci 123 564 76 19485563 PMC2771678
- Willner P Towell A Sampson D Sophokleous S Muscat R 1987 Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant Psychopharmacology (Berl) 93 358 64 3124165
- Zito JM Tobi H de Jong-van den Berg LT Fegert JM Safer DJ Janhsen K Hansen DG 2006 Antidepressant prevalence for youths: a multi-national comparison Pharmacoepidemiol Drug Saf 15 793 8 16715536
- Authors
- Iñiguez, S. D., Riggs, L. M., Nieto, S. J., Dayrit, G., Zamora, N. N., Shawhan, K. L., Cruz, B., & Warren, B. L.
- Affiliations
- California State University, San Bernardino (US)
- National Institutes of Health (US)
- Corresponding author
- Iñiguez, Sergio D.
- Venue
- Stress
- Publisher
- Informa UK Limited
- Published
- 2014-04
- Volume
- 17
- Issue
- 3
- Pages
- 247-255
- ISSN
- 1025-3890 (ISSN-L)
- 1607-8888
- PMC
- PMC5534169
- OpenAlex
- W1979987032
- Cited by
- 269
- References
- 55
- Citations by year
- 2026: 11 · 2025: 18 · 2024: 27 · 2023: 34 · 2022: 29 · 2021: 32 · 2020: 22 · 2019: 27 · 2018: 21 · 2017: 19 · 2016: 15 · 2015: 11 · 2014: 2
- FWCI
- 7.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Stress (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Program for Education and Research in Biotechnology, California State University
- National Institute of Mental Health (T32MH093311)
- National Institute on Drug Abuse (R24DA033877)
- National Institute of General Medical Sciences (T34GM083883, SC2GM109811)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- social defeat stress, depression-like behavior, adolescent mice, anhedonia, anxiogenic-like behavior, social avoidance, corticosterone, weight gain, major depressive disorder, C57BL/6 mice
- MeSH terms
- Aging, Animals, Anxiety, Corticosterone, Depression, Depressive Disorder, Dietary Carbohydrates, Dominance-Subordination, Food Preferences, Interpersonal Relations, Male, Mice, Inbred C57BL, Phenotype, Sucrose, Swimming
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
