Advertisement

Defining Valid Chronic Stress Models for Depression With Female Rodents

      Abstract

      Women are twice as likely to experience depression than men, yet until recently, preclinical studies in rodents have focused almost exclusively on males. As interest in sex differences and sex-specific mechanisms of stress susceptibility increases, chronic stress models for inducing depression-relevant behavioral and physiological changes in male rodents are being applied to females, and several new models have emerged to include both males and females, yet not all models have been systematically validated in females. An increasing number of researchers seek to include female rodents in their experimental designs, asking the question “what is the ideal chronic stress model for depression in females?” We review criteria for assessing female model validity in light of key research questions and the fundamental distinction between studying sex differences and studying both sexes. In overviewing current models, we explore challenges inherent to establishing an ideal female chronic stress model, with particular emphasis on the need for standardization and adoption of validated behavioral tests sensitive to stress effects in females. Taken together, these considerations will empower female chronic stress models to provide a better understanding of stress susceptibility and allow the development of efficient sex-specific treatments.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Malhi G.S.
        • Mann J.J.
        Depression.
        Lancet. 2018; 392: 2299-2312
        • Whiteford H.A.
        • Degenhardt L.
        • Rehm J.
        • Baxter A.J.
        • Ferrari A.J.
        • Erskine H.E.
        • et al.
        Global burden of disease attributable to mental and substance use disorders: Findings from the Global Burden of Disease Study 2010.
        Lancet. 2013; 382: 1575-1586
        • Kuehner C.
        Gender differences in unipolar depression: An update of epidemiological findings and possible explanations.
        Acta Psychiatr Scand. 2003; 108: 163-174
        • Seedat S.
        • Scott K.M.
        • Angermeyer M.C.
        • Berglund P.
        • Bromet E.J.
        • Brugha T.S.
        • et al.
        Cross-national associations between gender and mental disorders in the World Health Organization World Mental Health Surveys.
        Arch Gen Psychiatry. 2009; 66: 785-795
        • Marcus S.M.
        • Kerber K.B.
        • Rush A.J.
        • Wisniewski S.R.
        • Nierenberg A.
        • Balasubramani G.K.
        • et al.
        Sex differences in depression symptoms in treatment-seeking adults: Confirmatory analyses from the Sequenced Treatment Alternatives to Relieve Depression study.
        Compr Psychiatry. 2008; 49: 238-246
        • Silverstein B.
        • Edwards T.
        • Gamma A.
        • Ajdacic-Gross V.
        • Rossler W.
        • Angst J.
        The role played by depression associated with somatic symptomatology in accounting for the gender difference in the prevalence of depression.
        Soc Psychiatry Psychiatr Epidemiol. 2013; 48: 257-263
        • Blanco C.
        • Vesga-López O.
        • Stewart J.W.
        • Liu S.M.
        • Grant B.F.
        • Hasin D.S.
        Epidemiology of major depression with atypical features: Results from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC).
        J Clin Psychiatry. 2012; 73: 224-232
        • Khan A.
        • Brodhead A.E.
        • Schwartz K.A.
        • Kolts R.L.
        • Brown W.A.
        Sex differences in antidepressant response in recent antidepressant clinical trials.
        J Clin Psychopharmacol. 2005; 25: 318-324
        • Kornstein S.G.
        • Schatzberg A.F.
        • Thase M.E.
        • Yonkers K.A.
        • McCullough J.P.
        • Keitner G.I.
        • et al.
        Gender differences in treatment response to sertraline versus imipramine in chronic depression.
        Am J Psychiatry. 2000; 157: 1445-1452
        • Beery A.K.
        • Zucker I.
        Sex bias in neuroscience and biomedical research.
        Neurosci Biobehav Rev. 2011; 35: 565-572
        • Palanza P.
        • Parmigiani S.
        How does sex matter? Behavior, stress and animal models of neurobehavioral disorders.
        Neurosci Biobehav Rev. 2017; 76: 134-143
        • Shansky R.M.
        Are hormones a “female problem” for animal research?.
        Science. 2019; 364: 825-826
        • Prendergast B.J.
        • Onishi K.G.
        • Zucker I.
        Female mice liberated for inclusion in neuroscience and biomedical research.
        Neurosci Biobehav Rev. 2014; 40: 1-5
        • Machida T.
        • Yonezawa Y.
        • Noumura T.
        Age-associated changes in plasma testosterone levels in male mice and their relation to social dominance or subordinance.
        Horm Behav. 1981; 15: 238-245
        • Sayegh J.F.
        • Kobor G.
        • Lajtha A.
        • Vadasz C.
        Effects of social isolation and the time of day on testosterone levels in plasma of C57BL/6By and BALB/cBy mice.
        Steroids. 1990; 55: 79-82
        • Lucas L.A.
        • Eleftheriou B.E.
        Circadian variation in concentrations of testosterone in the plasma of male mice: A difference between BALB/cBy and C57BL/6By inbred strains.
        J Endocrinol. 1980; 87: 37-46
        • Miller L.R.
        • Marks C.
        • Becker J.B.
        • Hurn P.D.
        • Chen W.J.
        • Woodruff T.
        • et al.
        Considering sex as a biological variable in preclinical research.
        FASEB J. 2017; 31: 29-34
        • LeGates T.A.
        • Kvarta M.D.
        • Thompson S.M.
        Sex differences in antidepressant efficacy.
        Neuropsychopharmacology. 2019; 44: 140-154
        • Czéh B.
        • Fuchs E.
        • Wiborg O.
        • Simon M.
        Animal models of major depression and their clinical implications.
        Prog Neuropsychopharmacol Biol Psychiatry. 2016; 64: 293-310
        • Yan H.C.
        • Cao X.
        • Das M.
        • Zhu X.H.
        • Gao T.M.
        Behavioral animal models of depression.
        Neurosci Bull. 2010; 26: 327-337
        • Belzung C.
        • Lemoine M.
        Criteria of validity for animal models of psychiatric disorders: Focus on anxiety disorders and depression.
        Biol Mood Anxiety Disord. 2011; 1: 9
        • Gururajan A.
        • Reif A.
        • Cryan J.F.
        • Slattery D.A.
        The future of rodent models in depression research.
        Nat Rev Neurosci. 2019; 20: 686-701
        • Dadomo H.
        • Gioiosa L.
        • Cigalotti J.
        • Ceresini G.
        • Parmigiani S.
        • Palanza P.
        What is stressful for females? Differential effects of unpredictable environmental or social stress in CD1 female mice.
        Horm Behav. 2018; 98: 22-32
        • Kokras N.
        • Dalla C.
        Sex differences in animal models of psychiatric disorders.
        Br J Pharmacol. 2014; 171: 4595-4619
        • Zimmerberg B.
        • Farley M.J.
        Sex differences in anxiety behavior in rats: Role of gonadal hormones.
        Physiol Behav. 1993; 54: 1119-1124
        • An X.L.
        • Zou J.X.
        • Wu R.Y.
        • Yang Y.
        • Tai F.D.
        • Zeng S.Y.
        • et al.
        Strain and sex differences in anxiety-like and social behaviors in C57BL/6J and BALB/cJ mice.
        Exp Anim. 2011; 60: 111-123
        • Roman E.
        • Arborelius L.
        Male but not female Wistar rats show increased anxiety-like behaviour in response to bright light in the defensive withdrawal test.
        Behav Brain Res. 2009; 202: 303-307
        • Imhof J.T.
        • Coelho Z.M.
        • Schmitt M.L.
        • Morato G.S.
        • Carobrez A.P.
        Influence of gender and age on performance of rats in the elevated plus maze apparatus.
        Behav Brain Res. 1993; 56: 177-180
        • Rodgers R.J.
        • Cole J.C.
        Influence of social isolation, gender, strain, and prior novelty on plus-maze behaviour in mice.
        Physiol Behav. 1993; 54: 729-736
        • Bogdanova O.V.
        • Kanekar S.
        • D’Anci K.E.
        • Renshaw P.F.
        Factors influencing behavior in the forced swim test.
        Physiol Behav. 2013; 118: 227-239
        • Campbell T.
        • Lin S.
        • DeVries C.
        • Lambert K.
        Coping strategies in male and female rats exposed to multiple stressors.
        Physiol Behav. 2003; 78: 495-504
        • Dalla C.
        • Antoniou K.
        • Drossopoulou G.
        • Xagoraris M.
        • Kokras N.
        • Sfikakis A.
        • Papadopoulou-Daifoti Z.
        Chronic mild stress impact: Are females more vulnerable?.
        Neuroscience. 2005; 135: 703-714
        • Dalla C.
        • Antoniou K.
        • Kokras N.
        • Drossopoulou G.
        • Papathanasiou G.
        • Bekris S.
        • et al.
        Sex differences in the effects of two stress paradigms on dopaminergic neurotransmission.
        Physiol Behav. 2008; 93: 595-605
        • Konkle A.T.
        • Baker S.L.
        • Kentner A.C.
        • Barbagallo L.S.
        • Merali Z.
        • Bielajew C.
        Evaluation of the effects of chronic mild stressors on hedonic and physiological responses: Sex and strain compared.
        Brain Res. 2003; 992: 227-238
        • Mateus-Pinheiro A.
        • Patrício P.
        • Alves N.D.
        • Machado-Santos A.R.
        • Morais M.
        • Bessa J.M.
        • et al.
        The Sweet Drive Test: Refining phenotypic characterization of anhedonic behavior in rodents.
        Front Behav Neurosci. 2014; 8: 74
        • Shansky R.M.
        Sex differences in PTSD resilience and susceptibility: Challenges for animal models of fear learning.
        Neurobiol Stress. 2015; 1: 60-65
        • Duque-Wilckens N.
        • Torres L.Y.
        • Yokoyama S.
        • Minie V.A.
        • Tran A.M.
        • Petkova S.P.
        • et al.
        Extrahypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance.
        Proc Natl Acad Sci U S A. 2020; 117: 26406-26413
        • Newman E.L.
        • Covington 3rd, H.E.
        • Suh J.
        • Bicakci M.B.
        • Ressler K.J.
        • DeBold J.F.
        • Miczek K.A.
        Fighting females: Neural and behavioral consequences of social defeat stress in female mice.
        Biol Psychiatry. 2019; 86: 657-668
        • Antoniuk S.
        • Bijata M.
        • Ponimaskin E.
        • Wlodarczyk J.
        Chronic unpredictable mild stress for modeling depression in rodents: Meta-analysis of model reliability.
        Neurosci Biobehav Rev. 2019; 99: 101-116
        • Matthews K.
        • Forbes N.
        • Reid I.C.
        Sucrose consumption as an hedonic measure following chronic unpredictable mild stress.
        Physiol Behav. 1995; 57: 241-248
        • Liu M.Y.
        • Yin C.Y.
        • Zhu L.J.
        • Zhu X.H.
        • Xu C.
        • Luo C.X.
        • et al.
        Sucrose preference test for measurement of stress-induced anhedonia in mice.
        Nat Protoc. 2018; 13: 1686-1698
        • Franceschelli A.
        • Herchick S.
        • Thelen C.
        • Papadopoulou-Daifoti Z.
        • Pitychoutis P.M.
        Sex differences in the chronic mild stress model of depression.
        Behav Pharmacol. 2014; 25: 372-383
        • Vollmayr B.
        • Gass P.
        Learned helplessness: Unique features and translational value of a cognitive depression model.
        Cell Tissue Res. 2013; 354: 171-178
        • Maier S.F.
        • Seligman M.E.P.
        Learned helplessness at fifty: Insights from neuroscience.
        Psychol Rev. 2016; 123: 349-367
        • Seligman M.E.
        • Beagley G.
        Learned helplessness in the rat.
        J Comp Physiol Psychol. 1975; 88: 534-541
        • Chourbaji S.
        • Zacher C.
        • Sanchis-Segura C.
        • Dormann C.
        • Vollmayr B.
        • Gass P.
        Learned helplessness: Validity and reliability of depressive-like states in mice.
        Brain Res Brain Res Protoc. 2005; 16: 70-78
        • Kott J.M.
        • Mooney-Leber S.M.
        • Shoubah F.A.
        • Brummelte S.
        Effectiveness of different corticosterone administration methods to elevate corticosterone serum levels, induce depressive-like behavior, and affect neurogenesis levels in female rats.
        Neuroscience. 2016; 312: 201-214
        • Kokras N.
        • Krokida S.
        • Varoudaki T.Z.
        • Dalla C.
        Do corticosterone levels predict female depressive-like behavior in rodents?.
        J Neurosci Res. 2021; 99: 324-331
        • Chiba S.
        • Numakawa T.
        • Ninomiya M.
        • Richards M.C.
        • Wakabayashi C.
        • Kunugi H.
        Chronic restraint stress causes anxiety- and depression-like behaviors, downregulates glucocorticoid receptor expression, and attenuates glutamate release induced by brain-derived neurotrophic factor in the prefrontal cortex.
        Prog Neuropsychopharmacol Biol Psychiatry. 2012; 39: 112-119
        • Luo Y.W.
        • Xu Y.
        • Cao W.Y.
        • Zhong X.L.
        • Duan J.
        • Wang X.Q.
        • et al.
        Insulin-like growth factor 2 mitigates depressive behavior in a rat model of chronic stress.
        Neuropharmacology. 2015; 89: 318-324
        • Zain M.A.
        • Pandy V.
        • Majeed A.B.A.
        • Wong W.F.
        • Mohamed Z.
        Chronic restraint stress impairs sociability but not social recognition and spatial memory in C57BL/6J mice.
        Exp Anim. 2019; 68: 113-124
        • Zhu S.
        • Shi R.
        • Wang J.
        • Wang J.F.
        • Li X.M.
        Unpredictable chronic mild stress not chronic restraint stress induces depressive behaviours in mice.
        Neuroreport. 2014; 25: 1151-1155
        • Toth I.
        • Neumann I.D.
        Animal models of social avoidance and social fear.
        Cell Tissue Res. 2013; 354: 107-118
        • Willner P.
        The chronic mild stress (CMS) model of depression: History, evaluation and usage.
        Neurobiol Stress. 2017; 6: 78-93
        • Mutlu O.
        • Gumuslu E.
        • Ulak G.
        • Celikyurt I.K.
        • Kokturk S.
        • Kır H.M.
        • et al.
        Effects of fluoxetine, tianeptine and olanzapine on unpredictable chronic mild stress-induced depression-like behavior in mice.
        Life Sci. 2012; 91: 1252-1262
        • Willner P.
        • Towell A.
        • Sampson D.
        • Sophokleous S.
        • Muscat R.
        Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant.
        Psychopharmacology (Berl). 1987; 93: 358-364
        • Willner P.
        Chronic mild stress (CMS) revisited: Consistency and behavioural-neurobiological concordance in the effects of CMS.
        Neuropsychobiology. 2005; 52: 90-110
        • Abelaira H.M.
        • Réus G.Z.
        • Quevedo J.
        Animal models as tools to study the pathophysiology of depression.
        Braz J Psychiatry. 2013; 35: S112-S120
        • Ma L.
        • Xu Y.
        • Wang G.
        • Li R.
        What do we know about sex differences in depression: A review of animal models and potential mechanisms.
        Prog Neuropsychopharmacol Biol Psychiatry. 2019; 89: 48-56
        • Lu Y.
        • Ho C.S.
        • Liu X.
        • Chua A.N.
        • Wang W.
        • McIntyre R.S.
        • Ho R.C.
        Chronic administration of fluoxetine and pro-inflammatory cytokine change in a rat model of depression.
        PLoS One. 2017; 12e0186700
        • Filho C.B.
        • Jesse C.R.
        • Donato F.
        • Giacomeli R.
        • Del Fabbro L.
        • da Silva Antunes M.
        • et al.
        Chronic unpredictable mild stress decreases BDNF and NGF levels and Na(+),K(+)-ATPase activity in the hippocampus and prefrontal cortex of mice: Antidepressant effect of chrysin.
        Neuroscience. 2015; 289: 367-380
        • Borrow A.P.
        • Bales N.J.
        • Stover S.A.
        • Handa R.J.
        Chronic variable stress induces sex-specific alterations in social behavior and neuropeptide expression in the mouse.
        Endocrinology. 2018; 159: 2803-2814
        • Liu J.
        • Dietz K.
        • Hodes G.E.
        • Russo S.J.
        • Casaccia P.
        Widespread transcriptional alternations in oligodendrocytes in the adult mouse brain following chronic stress.
        Dev Neurobiol. 2018; 78: 152-162
        • Johnson A.
        • Rainville J.R.
        • Rivero-Ballon G.N.
        • Dhimitri K.
        • Hodes G.E.
        Testing the limits of sex differences using variable stress.
        Neuroscience. 2021; 454: 72-84
        • Labonté B.
        • Engmann O.
        • Purushothaman I.
        • Menard C.
        • Wang J.
        • Tan C.
        • et al.
        Sex-specific transcriptional signatures in human depression.
        Nat Med. 2017; 23: 1102-1111
        • LaPlant Q.
        • Chakravarty S.
        • Vialou V.
        • Mukherjee S.
        • Koo J.W.
        • Kalahasti G.
        • et al.
        Role of nuclear factor kappaB in Ovarian Hormone-Mediated Stress Hypersensitivity in Female Mice.
        Biol Psychiatry. 2009; 65: 874-880
        • Hodes G.E.
        • Pfau M.L.
        • Purushothaman I.
        • Ahn H.F.
        • Golden S.A.
        • Christoffel D.J.
        • et al.
        Sex differences in nucleus accumbens transcriptome profiles associated with susceptibility versus resilience to subchronic variable stress.
        J Neurosci. 2015; 35: 16362-16376
        • Pfau M.L.
        • Purushothaman I.
        • Feng J.
        • Golden S.A.
        • Aleyasin H.
        • Lorsch Z.S.
        • et al.
        Integrative analysis of sex-specific microRNA networks following stress in mouse nucleus accumbens.
        Front Mol Neurosci. 2016; 9: 144
        • Brancato A.
        • Bregman D.
        • Ahn H.F.
        • Pfau M.L.
        • Menard C.
        • Cannizzaro C.
        • et al.
        Sub-chronic variable stress induces sex-specific effects on glutamatergic synapses in the nucleus accumbens.
        Neuroscience. 2017; 350: 180-189
        • Zhang S.
        • Zhang H.
        • Ku S.M.
        • Juarez B.
        • Morel C.
        • Tzavaras N.
        • et al.
        Sex differences in the neuroadaptations of reward-related circuits in response to subchronic variable stress.
        Neuroscience. 2018; 376: 108-116
        • Williams E.S.
        • Manning C.E.
        • Eagle A.L.
        • Swift-Gallant A.
        • Duque-Wilckens N.
        • Chinnusamy S.
        • et al.
        Androgen-dependent excitability of mouse ventral hippocampal afferents to nucleus accumbens underlies sex-specific susceptibility to stress.
        Biol Psychiatry. 2020; 87: 492-501
        • Muir J.
        • Tse Y.C.
        • Iyer E.S.
        • Biris J.
        • Cvetkovska V.
        • Lopez J.
        • Bagot R.C.
        Ventral hippocampal afferents to nucleus accumbens encode both latent vulnerability and stress-induced susceptibility.
        Biol Psychiatry. 2020; 88: 843-854
        • Kuehner C.
        Why is depression more common among women than among men?.
        Lancet Psychiatry. 2017; 4: 146-158
        • Zaletel I.
        • Filipović D.
        • Puškaš N.
        Hippocampal BDNF in physiological conditions and social isolation.
        Rev Neurosci. 2017; 28: 675-692
        • Palanza P.
        • Gioiosa L.
        • Parmigiani S.
        Social stress in mice: Gender differences and effects of estrous cycle and social dominance.
        Physiol Behav. 2001; 73: 411-420
        • Singewald G.M.
        • Nguyen N.K.
        • Neumann I.D.
        • Singewald N.
        • Reber S.O.
        Effect of chronic psychosocial stress-induced by subordinate colony (CSC) housing on brain neuronal activity patterns in mice.
        Stress. 2009; 12: 58-69
        • Wallace D.L.
        • Han M.H.
        • Graham D.L.
        • Green T.A.
        • Vialou V.
        • Iñiguez S.D.
        • et al.
        CREB regulation of nucleus accumbens excitability mediates social isolation-induced behavioral deficits.
        Nat Neurosci. 2009; 12: 200-209
        • Grippo A.J.
        • Cushing B.S.
        • Carter C.S.
        Depression-like behavior and stressor-induced neuroendocrine activation in female prairie voles exposed to chronic social isolation.
        Psychosom Med. 2007; 69: 149-157
        • Martin A.L.
        • Brown R.E.
        The lonely mouse: Verification of a separation-induced model of depression in female mice.
        Behav Brain Res. 2010; 207: 196-207
        • Liu N.
        • Wang Y.
        • An A.Y.
        • Banker C.
        • Qian Y.H.
        • O’Donnell J.M.
        Single housing-induced effects on cognitive impairment and depression-like behavior in male and female mice involve neuroplasticity-related signaling.
        Eur J Neurosci. 2020; 52: 2694-2704
        • Sarkar A.
        • Kabbaj M.
        Sex differences in effects of ketamine on behavior, spine density, and synaptic proteins in socially isolated rats.
        Biol Psychiatry. 2016; 80: 448-456
        • Herzog C.J.
        • Czéh B.
        • Corbach S.
        • Wuttke W.
        • Schulte-Herbrüggen O.
        • Hellweg R.
        • et al.
        Chronic social instability stress in female rats: A potential animal model for female depression.
        Neuroscience. 2009; 159: 982-992
        • Yohn C.N.
        • Ashamalla S.A.
        • Bokka L.
        • Gergues M.M.
        • Garino A.
        • Samuels B.A.
        Social instability is an effective chronic stress paradigm for both male and female mice.
        Neuropharmacology. 2019; 160: 107780
        • Goñi-Balentziaga O.
        • Perez-Tejada J.
        • Renteria-Dominguez A.
        • Lebeña A.
        • Labaka A.
        Social instability in female rodents as a model of stress related disorders: A systematic review.
        Physiol Behav. 2018; 196: 190-199
        • Haller J.
        • Fuchs E.
        • Halász J.
        • Makara G.B.
        Defeat is a major stressor in males while social instability is stressful mainly in females: Towards the development of a social stress model in female rats.
        Brain Res Bull. 1999; 50: 33-39
        • Sterlemann V.
        • Ganea K.
        • Liebl C.
        • Harbich D.
        • Alam S.
        • Holsboer F.
        • et al.
        Long-term behavioral and neuroendocrine alterations following chronic social stress in mice: Implications for stress-related disorders.
        Horm Behav. 2008; 53: 386-394
        • Schmidt M.V.
        • Scharf S.H.
        • Liebl C.
        • Harbich D.
        • Mayer B.
        • Holsboer F.
        • Müller M.B.
        A novel chronic social stress paradigm in female mice.
        Horm Behav. 2010; 57: 415-420
        • Baranyi J.
        • Bakos N.
        • Haller J.
        Social instability in female rats: The relationship between stress-related and anxiety-like consequences.
        Physiol Behav. 2005; 84: 511-518
        • Haller J.
        • Baranyi J.
        • Bakos N.
        • Halász J.
        Social instability in female rats: Effects on anxiety and buspirone efficacy.
        Psychopharmacology (Berl). 2004; 174: 197-202
        • Nowacka-Chmielewska M.M.
        • Kasprowska-Liśkiewicz D.
        • Barski J.J.
        • Obuchowicz E.
        • Małecki A.
        The behavioral and molecular evaluation of effects of social instability stress as a model of stress-related disorders in adult female rats.
        Stress. 2017; 20: 549-561
        • Planchez B.
        • Surget A.
        • Belzung C.
        Animal models of major depression: Drawbacks and challenges.
        J Neural Transm (Vienna). 2019; 126: 1383-1408
        • Krishnan V.
        • Han M.H.
        • Graham D.L.
        • Berton O.
        • Renthal W.
        • Russo S.J.
        • et al.
        Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions.
        Cell. 2007; 131: 391-404
        • Hollis F.
        • Kabbaj M.
        Social defeat as an animal model for depression.
        ILAR J. 2014; 55: 221-232
        • Golden S.A.
        • Covington 3rd, H.E.
        • Berton O.
        • Russo S.J.
        A standardized protocol for repeated social defeat stress in mice.
        Nat Protoc. 2011; 6: 1183-1191
        • Berton O.
        • McClung C.A.
        • Dileone R.J.
        • Krishnan V.
        • Renthal W.
        • Russo S.J.
        • et al.
        Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress.
        Science. 2006; 311: 864-868
        • Donahue R.J.
        • Muschamp J.W.
        • Russo S.J.
        • Nestler E.J.
        • Carlezon Jr., W.A.
        Effects of striatal ΔFosB overexpression and ketamine on social defeat stress-induced anhedonia in mice.
        Biol Psychiatry. 2014; 76: 550-558
        • Vialou V.
        • Robison A.J.
        • Laplant Q.C.
        • Covington 3rd, H.E.
        • Dietz D.M.
        • Ohnishi Y.N.
        • et al.
        DeltaFosB in brain reward circuits mediates resilience to stress and antidepressant responses.
        Nat Neurosci. 2010; 13: 745-752
        • Harris A.Z.
        • Atsak P.
        • Bretton Z.H.
        • Holt E.S.
        • Alam R.
        • Morton M.P.
        • et al.
        A novel method for chronic social defeat stress in female mice.
        Neuropsychopharmacology. 2018; 43: 1276-1283
        • Takahashi A.
        • Chung J.R.
        • Zhang S.
        • Zhang H.
        • Grossman Y.
        • Aleyasin H.
        • et al.
        Establishment of a repeated social defeat stress model in female mice.
        Sci Rep. 2017; 7: 12838
        • Issler O.
        • van der Zee Y.Y.
        • Ramakrishnan A.
        • Wang J.
        • Tan C.
        • Loh Y.E.
        • et al.
        Sex-specific role for the long non-coding RNA LINC00473 in depression.
        Neuron. 2020; 106: 912-926.e5
        • Yohn C.N.
        • Dieterich A.
        • Bazer A.S.
        • Maita I.
        • Giedraitis M.
        • Samuels B.A.
        Chronic non-discriminatory social defeat is an effective chronic stress paradigm for both male and female mice.
        Neuropsychopharmacology. 2019; 44: 2220-2229
        • Solomon M.B.
        Evaluating social defeat as a model for psychopathology in adult female rodents.
        J Neurosci Res. 2017; 95: 763-776
        • Bourke C.H.
        • Neigh G.N.
        Exposure to repeated maternal aggression induces depressive-like behavior and increases startle in adult female rats.
        Behav Brain Res. 2012; 227: 270-275
        • Shimamoto A.
        • Debold J.F.
        • Holly E.N.
        • Miczek K.A.
        Blunted accumbal dopamine response to cocaine following chronic social stress in female rats: Exploring a link between depression and drug abuse.
        Psychopharmacol (Berl). 2011; 218: 271-279
        • Jacobson-Pick S.
        • Audet M.C.
        • McQuaid R.J.
        • Kalvapalle R.
        • Anisman H.
        Social agonistic distress in male and female mice: Changes of behavior and brain monoamine functioning in relation to acute and chronic challenges.
        PLoS One. 2013; 8e60133
        • Trainor B.C.
        • Pride M.C.
        • Villalon Landeros R.
        • Knoblauch N.W.
        • Takahashi E.Y.
        • Silva A.L.
        • Crean K.K.
        Sex differences in social interaction behavior following social defeat stress in the monogamous California mouse (Peromyscus californicus).
        PLoS One. 2011; 6e17405
        • Kingston R.C.
        • Smith M.
        • Lacey T.
        • Edwards M.
        • Best J.N.
        • Markham C.M.
        Voluntary exercise increases resilience to social defeat stress in Syrian hamsters.
        Physiol Behav. 2018; 188: 194-198
        • Steinman M.Q.
        • Trainor B.C.
        Sex differences in the effects of social defeat on brain and behavior in the California mouse: Insights from a monogamous rodent.
        Semin Cell Dev Biol. 2017; 61: 92-98
        • Greenberg G.D.
        • Laman-Maharg A.
        • Campi K.L.
        • Voigt H.
        • Orr V.N.
        • Schaal L.
        • Trainor B.C.
        Sex differences in stress-induced social withdrawal: Role of brain derived neurotrophic factor in the bed nucleus of the stria terminalis.
        Front Behav Neurosci. 2014; 7: 223
        • Logan R.W.
        Adapting social defeat stress for female mice using species-typical interfemale aggression.
        Biol Psychiatry. 2019; 86: e31-e32
        • Sial O.K.
        • Warren B.L.
        • Alcantara L.F.
        • Parise E.M.
        • Bolaños-Guzmán C.A.
        Vicarious social defeat stress: Bridging the gap between physical and emotional stress.
        J Neurosci Methods. 2016; 258: 94-103
        • Warren B.L.
        • Vialou V.F.
        • Iñiguez S.D.
        • Alcantara L.F.
        • Wright K.N.
        • Feng J.
        • et al.
        Neurobiological sequelae of witnessing stressful events in adult mice.
        Biol Psychiatry. 2013; 73: 7-14
        • Patki G.
        • Salvi A.
        • Liu H.
        • Salim S.
        Witnessing traumatic events and post-traumatic stress disorder: Insights from an animal model.
        Neurosci Lett. 2015; 600: 28-32
        • Nakatake Y.
        • Furuie H.
        • Yamada M.
        • Kuniishi H.
        • Ukezono M.
        • Yoshizawa K.
        • Yamada M.
        The effects of emotional stress are not identical to those of physical stress in mouse model of social defeat stress.
        Neurosci Res. 2020; 158: 56-63
        • Patki G.
        • Solanki N.
        • Salim S.
        Witnessing traumatic events causes severe behavioral impairments in rats.
        Int J Neuropsychopharmacol. 2014; 17: 2017-2029
        • Iñiguez S.D.
        • Flores-Ramirez F.J.
        • Riggs L.M.
        • Alipio J.B.
        • Garcia-Carachure I.
        • Hernandez M.A.
        • et al.
        Vicarious social defeat stress induces depression-related outcomes in female mice.
        Biol Psychiatry. 2018; 83: 9-17
        • Finnell J.E.
        • Muniz B.L.
        • Padi A.R.
        • Lombard C.M.
        • Moffitt C.M.
        • Wood C.S.
        • et al.
        Essential role of ovarian hormones in susceptibility to the consequences of witnessing social defeat in female rats.
        Biol Psychiatry. 2018; 84: 372-382
        • Gaskill B.N.
        • Karas A.Z.
        • Garner J.P.
        • Pritchett-Corning K.R.
        Nest building as an indicator of health and welfare in laboratory mice.
        J Vis Exp. 2013; 82: 51012
        • Neely C.L.C.
        • Pedemonte K.A.
        • Boggs K.N.
        • Flinn J.M.
        Nest building behavior as an early indicator of behavioral deficits in mice.
        J Vis Exp. 2019; 152
        • Carrier N.
        • Kabbaj M.
        Sex differences in the antidepressant-like effects of ketamine.
        Neuropharmacology. 2013; 70: 27-34
        • Dalla C.
        • Edgecomb C.
        • Whetstone A.S.
        • Shors T.J.
        Females do not express learned helplessness like males do.
        Neuropsychopharmacology. 2008; 33: 1559-1569
        • Caldarone B.J.
        • George T.P.
        • Zachariou V.
        • Picciotto M.R.
        Gender differences in learned helplessness behavior are influenced by genetic background.
        Pharmacol Biochem Behav. 2000; 66: 811-817
        • Ngoupaye G.T.
        • Yassi F.B.
        • Bahane D.A.N.
        • Bum E.N.
        Combined corticosterone treatment and chronic restraint stress lead to depression associated with early cognitive deficits in mice.
        Metab Brain Dis. 2018; 33: 421-431