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Can I Get a Witness? Using Vicarious Defeat Stress to Study Mood-Related Illnesses in Traditionally Understudied Populations

Published:February 18, 2020DOI:https://doi.org/10.1016/j.biopsych.2020.02.004

      Abstract

      The chronic social defeat stress model has been instrumental in shaping our understanding of neurobiology relevant to affect-related illnesses, including major depressive disorder. However, the classic chronic social defeat stress procedure is limited by its exclusive application to adult male rodents. We have recently developed a novel vicarious social defeat stress procedure wherein one mouse witnesses the physical defeat bout of a conspecific from the safety of an adjacent compartment. This witness mouse develops a similar behavioral phenotype to that of the mouse that physically experiences social defeat stress, modeling multiple aspects of major depressive disorder. Importantly, this new procedure allows researchers to perform vicarious social defeat stress in males or females and in juvenile mice, which typically are excluded from classic social defeat experiments. Here we discuss several recent advances made using this procedure and how its application provides a new preclinical approach to study the neurobiology of psychological stress-induced phenotypes.

      Keywords

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      References

        • Rehm J.
        • Shield K.D.
        Global burden of disease and the impact of mental and addictive disorders.
        Curr Psychiatry Rep. 2019; 21: 10
        • World Health Organization
        Depression and Other Common Mental Disorders: Global Health Estimates.
        WHO, Geneva, Switzerland2017
        • Gonda X.
        • Petschner P.
        • Eszlari N.
        • Baksa D.
        • Edes A.
        • Antal P.
        • et al.
        Genetic variants in major depressive disorder: From pathophysiology to therapy.
        Pharmacol Ther. 2019; 194: 22-43
        • McIntosh A.M.
        • Sullivan P.F.
        • Lewis C.M.
        Uncovering the genetic architecture of major depression.
        Neuron. 2019; 102: 91-103
        • Hodes G.E.
        • Epperson C.N.
        Sex differences in vulnerability and resilience to stress across the life span.
        Biol Psychiatry. 2019; 86: 421-432
        • Sharma S.
        • Powers A.
        • Bradley B.
        • Ressler K.J.
        Gene × environment determinants of stress- and anxiety-related disorders.
        Annu Rev Psychol. 2016; 67: 239-261
        • Pena C.J.
        • Nestler E.J.
        Progress in epigenetics of depression.
        Prog Mol Biol Transl Sci. 2018; 157: 41-66
        • Robinson E.S.J.
        Translational new approaches for investigating mood disorders in rodents and what they may reveal about the underlying neurobiology of major depressive disorder.
        Philos Trans R Soc Lond B Biol Sci. 2018; 373
        • Soderlund J.
        • Lindskog M.
        Relevance of rodent models of depression in clinical practice: Can we overcome the obstacles in translational neuropsychiatry?.
        Int J Neuropsychopharmacol. 2018; 21: 668-676
        • 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
        • 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
        • Robison A.J.
        • Vialou V.
        • Sun H.S.
        • Labonte B.
        • Golden S.A.
        • Dias C.
        • et al.
        Fluoxetine epigenetically alters the CaMKIIalpha promoter in nucleus accumbens to regulate DeltaFosB binding and antidepressant effects.
        Neuropsychopharmacology. 2014; 39: 1178-1186
        • 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
        • Tsankova N.M.
        • Berton O.
        • Renthal W.
        • Kumar A.
        • Neve R.L.
        • Nestler E.J.
        Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action.
        Nat Neurosci. 2006; 9: 519-525
        • Fitzgerald P.J.
        Forbearance for fluoxetine: Do monoaminergic antidepressants require a number of years to reach maximum therapeutic effect in humans?.
        Int J Neurosci. 2014; 124: 467-473
        • Donahue R.J.
        • Muschamp J.W.
        • Russo S.J.
        • Nestler E.J.
        • Carlezon Jr., W.A.
        Effects of striatal DeltaFosB overexpression and ketamine on social defeat stress-induced anhedonia in mice.
        Biol Psychiatry. 2014; 76: 550-558
        • Dong C.
        • Zhang J.C.
        • Yao W.
        • Ren Q.
        • Ma M.
        • Yang C.
        • et al.
        Rapid and sustained antidepressant action of the mGlu2/3 receptor antagonist MGS0039 in the social defeat stress model: Comparison with ketamine.
        Int J Neuropsychopharmacol. 2017; 20: 228-236
        • Bagot R.C.
        • Cates H.M.
        • Purushothaman I.
        • Vialou V.
        • Heller E.A.
        • Yieh L.
        • et al.
        Ketamine and imipramine reverse transcriptional signatures of susceptibility and induce resilience-specific gene expression profiles.
        Biol Psychiatry. 2017; 81: 285-295
        • Friedman A.K.
        • Juarez B.
        • Ku S.M.
        • Zhang H.
        • Calizo R.C.
        • Walsh J.J.
        • et al.
        KCNQ channel openers reverse depressive symptoms via an active resilience mechanism.
        Nat Commun. 2016; 7: 11671
        • Friedman A.K.
        • Walsh J.J.
        • Juarez B.
        • Ku S.M.
        • Chaudhury D.
        • Wang J.
        • et al.
        Enhancing depression mechanisms in midbrain dopamine neurons achieves homeostatic resilience.
        Science. 2014; 344: 313-319
        • Cathomas F.
        • Murrough J.W.
        • Nestler E.J.
        • Han M.H.
        • Russo S.J.
        Neurobiology of resilience: Interface between mind and body.
        Biol Psychiatry. 2019; 86: 410-420
        • Kessler R.C.
        • Berglund P.
        • Demler O.
        • Jin R.
        • Merikangas K.R.
        • Walter E.E.
        Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication.
        Arch Gen Psychiatry. 2005; 62: 593-602
        • Auerbach R.P.
        • Mortier P.
        • Bruffaerts R.
        • Alonso J.
        • Benjet C.
        • Cuijpers P.
        • et al.
        WHO World Mental Health Surveys International College Student Project: Prevalence and distribution of mental disorders.
        J Abnorm Psychol. 2018; 127: 623-638
        • Kessler R.C.
        • Sampson N.A.
        • Berglund P.
        • Gruber M.J.
        • Al-Hamzawi A.
        • Andrade L.
        • et al.
        Anxious and non-anxious major depressive disorder in the World Health Organization World Mental Health Surveys.
        Epidemiol Psychiatr Sci. 2015; 24: 210-226
        • LeGates T.A.
        • Kvarta M.D.
        • Thompson S.M.
        Sex differences in antidepressant efficacy.
        Neuropsychopharmacology. 2019; 44: 140-154
        • 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
        • Laman-Maharg A.
        • Trainor B.C.
        Stress, sex, and motivated behaviors.
        J Neurosci Res. 2017; 95: 83-92
        • Bodden D.H.M.
        • Stikkelbroek Y.
        • Dirksen C.D.
        Societal burden of adolescent depression, an overview and cost-of-illness study.
        J Affect Disord. 2018; 241: 256-262
        • Johnson D.
        • Dupuis G.
        • Piche J.
        • Clayborne Z.
        • Colman I.
        Adult mental health outcomes of adolescent depression: A systematic review.
        Depress Anxiety. 2018; 35: 700-716
        • Vibhakar V.
        • Allen L.R.
        • Gee B.
        • Meiser-Stedman R.
        A systematic review and meta-analysis on the prevalence of depression in children and adolescents after exposure to trauma.
        J Affect Disord. 2019; 255: 77-89
        • 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
        • Sial O.K.
        • Warren B.L.
        • Alcantara L.F.
        • Parise E.M.
        • Bolaños-Guzman C.A.
        Vicarious social defeat stress: Bridging the gap between physical and emotional stress.
        J Neurosci Methods. 2016; 258: 94-103
        • 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
        • Miao Z.
        • Mao F.
        • Liang J.
        • Szyf M.
        • Wang Y.
        • Sun Z.S.
        Anxiety-related behaviours associated with microRNA-206-3p and BDNF Expression in pregnant female mice following psychological social stress.
        Mol Neurobiol. 2018; 55: 1097-1111
        • Nakatake Y.
        • Furuie H.
        • Yamada M.
        • Kuniishi H.
        • Ukezono M.
        • Yoshizawa K.
        • Mitsuhiko Y.
        The effects of emotional stress are not identical to those of physical stress in mouse model of social defeat stress.
        Neurosci Res. 2019; ([published online ahead of print October 16])
        • Hodes G.E.
        • Pfau M.L.
        • Leboeuf M.
        • Golden S.A.
        • Christoffel D.J.
        • Bregman D.
        • et al.
        Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress.
        Proc Natl Acad Sci U S A. 2014; 111: 16136-16141
        • Russo S.J.
        • Murrough J.W.
        • Han M.H.
        • Charney D.S.
        • Nestler E.J.
        Neurobiology of resilience.
        Nat Neurosci. 2012; 15: 1475-1484
        • Rutter M.
        Resilience as a dynamic concept.
        Dev Psychopathol. 2012; 24: 335-344
        • Avgustinovich D.F.
        • Kovalenko I.L.
        • Kudryavtseva N.N.
        A model of anxious depression: Persistence of behavioral pathology.
        Neurosci Behav Physiol. 2005; 35: 917-924
        • 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
        • Cao J.L.
        • Covington 3rd, H.E.
        • Friedman A.K.
        • Wilkinson M.B.
        • Walsh J.J.
        • Cooper D.C.
        • et al.
        Mesolimbic dopamine neurons in the brain reward circuit mediate susceptibility to social defeat and antidepressant action.
        J Neurosci. 2010; 30: 16453-16458
        • Jianhua F.
        • Wei W.
        • Xiaomei L.
        • Shao-Hui W.
        Chronic social defeat stress leads to changes of behaviour and memory-associated proteins of young mice.
        Behav Brain Res. 2017; 316: 136-144
        • Porsolt R.D.
        • Bertin A.
        • Jalfre M.
        Behavioral despair in mice: A primary screening test for antidepressants.
        Arch Int Pharmacodyn Ther. 1977; 229: 327-336
        • Porsolt R.D.
        • Le Pichon M.
        • Jalfre M.
        Depression: A new animal model sensitive to antidepressant treatments.
        Nature. 1977; 266: 730-732
        • Der-Avakian A.
        • Mazei-Robison M.S.
        • Kesby J.P.
        • Nestler E.J.
        • Markou A.
        Enduring deficits in brain reward function after chronic social defeat in rats: Susceptibility, resilience, and antidepressant response.
        Biol Psychiatry. 2014; 76: 542-549
        • Keeney A.J.
        • Hogg S.
        Behavioural consequences of repeated social defeat in the mouse: Preliminary evaluation of a potential animal model of depression.
        Behav Pharmacol. 1999; 10: 753-764
        • Razzoli M.
        • Carboni L.
        • Andreoli M.
        • Ballottari A.
        • Arban R.
        Different susceptibility to social defeat stress of BalbC and C57BL6/J mice.
        Behav Brain Res. 2011; 216: 100-108
        • Razzoli M.
        • Carboni L.
        • Andreoli M.
        • Michielin F.
        • Ballottari A.
        • Arban R.
        Strain-specific outcomes of repeated social defeat and chronic fluoxetine treatment in the mouse.
        Pharmacol Biochem Behav. 2011; 97: 566-576
        • Kochi C.
        • Liu H.
        • Zaidi S.
        • Atrooz F.
        • Dantoin P.
        • Salim S.
        Prior treadmill exercise promotes resilience to vicarious trauma in rats.
        Prog Neuropsychopharmacol Biol Psychiatry. 2017; 77: 216-221
        • Montgomery K.C.
        • Monkman J.A.
        The relation between fear and exploratory behavior.
        J Comp Physiol Psychol. 1955; 48: 132-136
        • Duque A.
        • Vinader-Caerols C.
        • Monleon S.
        Indomethacin counteracts the effects of chronic social defeat stress on emotional but not recognition memory in mice.
        PLoS One. 2017; 12e0173182
        • Wilkinson M.B.
        • Dias C.
        • Magida J.
        • Mazei-Robison M.
        • Lobo M.
        • Kennedy P.
        • et al.
        A novel role of the WNT-dishevelled-GSK3beta signaling cascade in the mouse nucleus accumbens in a social defeat model of depression.
        J Neurosci. 2011; 31: 9084-9092
        • Veeraiah P.
        • Noronha J.M.
        • Maitra S.
        • Bagga P.
        • Khandelwal N.
        • Chakravarty S.
        • et al.
        Dysfunctional glutamatergic and gamma-aminobutyric acidergic activities in prefrontal cortex of mice in social defeat model of depression.
        Biol Psychiatry. 2014; 76: 231-238
        • Hollis F.
        • Duclot F.
        • Gunjan A.
        • Kabbaj M.
        Individual differences in the effect of social defeat on anhedonia and histone acetylation in the rat hippocampus.
        Horm Behav. 2011; 59: 331-337
        • Chang L.
        • Zhang K.
        • Pu Y.
        • Qu Y.
        • Wang S.M.
        • Xiong Z.
        • et al.
        Lack of dopamine D(1) receptors in the antidepressant actions of (R)-ketamine in a chronic social defeat stress model.
        Eur Arch Psychiatry Clin Neurosci. 2020; 270: 271-275
        • Carnevali L.
        • Mastorci F.
        • Graiani G.
        • Razzoli M.
        • Trombini M.
        • Pico-Alfonso M.A.
        • et al.
        Social defeat and isolation induce clear signs of a depression-like state, but modest cardiac alterations in wild-type rats.
        Physiol Behav. 2012; 106: 142-150
        • Iñiguez S.D.
        • Riggs L.M.
        • Nieto S.J.
        • Dayrit G.
        • Zamora N.N.
        • Shawhan K.L.
        • et al.
        Social defeat stress induces a depression-like phenotype in adolescent male c57BL/6 mice.
        Stress. 2014; 17: 247-255
        • Arena D.T.
        • Covington 3rd, H.E.
        • DeBold J.F.
        • Miczek K.A.
        Persistent increase of I.V. cocaine self-administration in a subgroup of C57BL/6J male mice after social defeat stress.
        Psychopharmacology (Berl). 2019; 236: 2027-2037
        • Bardo M.T.
        • Bevins R.A.
        Conditioned place preference: What does it add to our preclinical understanding of drug reward?.
        Psychopharmacology (Berl). 2000; 153: 31-43
        • Macedo G.C.
        • Morita G.M.
        • Domingues L.P.
        • Favoretto C.A.
        • Suchecki D.
        • Quadros I.M.H.
        Consequences of continuous social defeat stress on anxiety- and depressive-like behaviors and ethanol reward in mice.
        Horm Behav. 2018; 97: 154-161
        • Montagud-Romero S.
        • Aguilar M.A.
        • Maldonado C.
        • Manzanedo C.
        • Minarro J.
        • Rodriguez-Arias M.
        Acute social defeat stress increases the conditioned rewarding effects of cocaine in adult but not in adolescent mice.
        Pharmacol Biochem Behav. 2015; 135: 1-12
        • McLaughlin J.P.
        • Li S.
        • Valdez J.
        • Chavkin T.A.
        • Chavkin C.
        Social defeat stress-induced behavioral responses are mediated by the endogenous kappa opioid system.
        Neuropsychopharmacology. 2006; 31: 1241-1248
        • Stelly C.E.
        • Pomrenze M.B.
        • Cook J.B.
        • Morikawa H.
        Repeated social defeat stress enhances glutamatergic synaptic plasticity in the VTA and cocaine place conditioning.
        Elife. 2016; 5
        • Riad-Allen L.
        • van der Kooy D.
        Social defeat stress switches the neural system mediating benzodiazepine conditioned motivation.
        Behav Neurosci. 2013; 127: 515-523
        • Rodriguez-Arias M.
        • Navarrete F.
        • Blanco-Gandia M.C.
        • Arenas M.C.
        • Bartoll-Andres A.
        • Aguilar M.A.
        • et al.
        Social defeat in adolescent mice increases vulnerability to alcohol consumption.
        Addict Biol. 2016; 21: 87-97
        • Cooper S.E.
        • Kechner M.
        • Caraballo-Perez D.
        • Kaska S.
        • Robison A.J.
        • Mazei-Robison M.S.
        Comparison of chronic physical and emotional social defeat stress effects on mesocorticolimbic circuit activation and voluntary consumption of morphine.
        Sci Rep. 2017; 7: 8445
        • Yap J.J.
        • Miczek K.A.
        Social defeat stress, sensitization, and intravenous cocaine self-administration in mice.
        Psychopharmacology (Berl). 2007; 192: 261-273
        • Miczek K.A.
        • Yap J.J.
        • Covington 3rd, H.E.
        Social stress, therapeutics and drug abuse: Preclinical models of escalated and depressed intake.
        Pharmacol Ther. 2008; 120: 102-128
        • Kabbaj M.
        • Norton C.S.
        • Kollack-Walker S.
        • Watson S.J.
        • Robinson T.E.
        • Akil H.
        Social defeat alters the acquisition of cocaine self-administration in rats: Role of individual differences in cocaine-taking behavior.
        Psychopharmacology (Berl). 2001; 158: 382-387
        • Tidey J.W.
        • Miczek K.A.
        Social defeat stress selectively alters mesocorticolimbic dopamine release: An in vivo microdialysis study.
        Brain Res. 1996; 721: 140-149
        • Boyson C.O.
        • Holly E.N.
        • Shimamoto A.
        • Albrechet-Souza L.
        • Weiner L.A.
        • DeBold J.F.
        • et al.
        Social stress and CRF-dopamine interactions in the VTA: Role in long-term escalation of cocaine self-administration.
        J Neurosci. 2014; 34: 6659-6667
        • Covington 3rd, H.E.
        • Miczek K.A.
        Intense cocaine self-administration after episodic social defeat stress, but not after aggressive behavior: Dissociation from corticosterone activation.
        Psychopharmacology (Berl). 2005; 183: 331-340
        • Funk D.
        • Harding S.
        • Juzytsch W.
        • Le A.D.
        Effects of unconditioned and conditioned social defeat on alcohol self-administration and reinstatement of alcohol seeking in rats.
        Psychopharmacology (Berl). 2005; 183: 341-349
        • Manvich D.F.
        • Stowe T.A.
        • Godfrey J.R.
        • Weinshenker D.
        A method for psychosocial stress-induced reinstatement of cocaine seeking in rats.
        Biol Psychiatry. 2016; 79: 940-946
        • Fox M.E.
        • Lobo M.K.
        The molecular and cellular mechanisms of depression: A focus on reward circuitry.
        Mol Psychiatry. 2019; 24: 1798-1815
        • Altar C.A.
        • Cai N.
        • Bliven T.
        • Juhasz M.
        • Conner J.M.
        • Acheson A.L.
        • et al.
        Anterograde transport of brain-derived neurotrophic factor and its role in the brain.
        Nature. 1997; 389: 856-860
        • Miczek K.A.
        • Nikulina E.M.
        • Shimamoto A.
        • Covington 3rd, H.E.
        Escalated or suppressed cocaine reward, tegmental BDNF, and accumbal dopamine caused by episodic versus continuous social stress in rats.
        J Neurosci. 2011; 31: 9848-9857
        • Fanous S.
        • Terwilliger E.F.
        • Hammer Jr., R.P.
        • Nikulina E.M.
        Viral depletion of VTA BDNF in rats modulates social behavior, consequences of intermittent social defeat stress, and long-term weight regulation.
        Neurosci Lett. 2011; 502: 192-196
        • Christoffel D.J.
        • Golden S.A.
        • Dumitriu D.
        • Robison A.J.
        • Janssen W.G.
        • Ahn H.F.
        • et al.
        IkappaB kinase regulates social defeat stress-induced synaptic and behavioral plasticity.
        J Neurosci. 2011; 31: 314-321
        • Golden S.A.
        • Christoffel D.J.
        • Heshmati M.
        • Hodes G.E.
        • Magida J.
        • Davis K.
        • et al.
        Epigenetic regulation of RAC1 induces synaptic remodeling in stress disorders and depression.
        Nat Med. 2013; 19: 337-344
        • Khibnik L.A.
        • Beaumont M.
        • Doyle M.
        • Heshmati M.
        • Slesinger P.A.
        • Nestler E.J.
        • et al.
        Stress and cocaine trigger divergent and cell type-specific regulation of synaptic transmission at single spines in nucleus accumbens.
        Biol Psychiatry. 2016; 79: 898-905
        • Francis T.C.
        • Chandra R.
        • Friend D.M.
        • Finkel E.
        • Dayrit G.
        • Miranda J.
        • et al.
        Nucleus accumbens medium spiny neuron subtypes mediate depression-related outcomes to social defeat stress.
        Biol Psychiatry. 2015; 77: 212-222
        • Fox M.E.
        • Chandra R.
        • Menken M.S.
        • Larkin E.J.
        • Nam H.
        • Engeln M.
        • et al.
        Dendritic remodeling of D1 neurons by RhoA/Rho-kinase mediates depression-like behavior.
        Mol Psychiatry. 2020; 25: 1022-1034
        • Francis T.C.
        • Chandra R.
        • Gaynor A.
        • Konkalmatt P.
        • Metzbower S.R.
        • Evans B.
        • et al.
        Molecular basis of dendritic atrophy and activity in stress susceptibility.
        Mol Psychiatry. 2017; 22: 1512-1519
        • Francis T.C.
        • Gaynor A.
        • Chandra R.
        • Fox M.E.
        • Lobo M.K.
        The selective rhoa inhibitor rhosin promotes stress resiliency through enhancing D1-medium spiny neuron plasticity and reducing hyperexcitability.
        Biol Psychiatry. 2019; 85: 1001-1010
        • Chaudhury D.
        • Walsh J.J.
        • Friedman A.K.
        • Juarez B.
        • Ku S.M.
        • Koo J.W.
        • et al.
        Rapid regulation of depression-related behaviours by control of midbrain dopamine neurons.
        Nature. 2013; 493: 532-536
        • Walsh J.J.
        • Friedman A.K.
        • Sun H.
        • Heller E.A.
        • Ku S.M.
        • Juarez B.
        • et al.
        Stress and CRF gate neural activation of BDNF in the mesolimbic reward pathway.
        Nat Neurosci. 2014; 17: 27-29
        • Iñiguez S.D.
        • Vialou V.
        • Warren B.L.
        • Cao J.L.
        • Alcantara L.F.
        • Davis L.C.
        • et al.
        Extracellular signal-regulated kinase-2 within the ventral tegmental area regulates responses to stress.
        J Neurosci. 2010; 30: 7652-7663
        • Krishnan V.
        • Han M.H.
        • Mazei-Robison M.
        • Iñiguez S.D.
        • Ables J.L.
        • Vialou V.
        • et al.
        AKT signaling within the ventral tegmental area regulates cellular and behavioral responses to stressful stimuli.
        Biol Psychiatry. 2008; 64: 691-700
        • Iñiguez S.D.
        • Alcantara L.F.
        • Warren B.L.
        • Riggs L.M.
        • Parise E.M.
        • Vialou V.
        • et al.
        Fluoxetine exposure during adolescence alters responses to aversive stimuli in adulthood.
        J Neurosci. 2014; 34: 1007-1021
        • Warren B.L.
        • Sial O.K.
        • Alcantara L.F.
        • Greenwood M.A.
        • Brewer J.S.
        • Rozofsky J.P.
        • et al.
        Altered gene expression and spine density in nucleus accumbens of adolescent and adult male mice exposed to emotional and physical stress.
        Dev Neurosci. 2014; 36: 250-260
        • Finnell J.E.
        • Lombard C.M.
        • Padi A.R.
        • Moffitt C.M.
        • Wilson L.B.
        • Wood C.S.
        • et al.
        Physical versus psychological social stress in male rats reveals distinct cardiovascular, inflammatory and behavioral consequences.
        PLoS One. 2017; 12e0172868
        • Sawicki C.M.
        • Kim J.K.
        • Weber M.D.
        • Faw T.D.
        • McKim D.B.
        • Madalena K.M.
        • et al.
        Microglia promote increased pain behavior through enhanced inflammation in the spinal cord during repeated social defeat stress.
        J Neurosci. 2019; 39: 1139-1149
        • Pagliusi Jr., M.O.F.
        • Bonet I.J.M.
        • Dias E.V.
        • Vieira A.S.
        • Tambeli C.H.
        • Parada C.A.
        • Sartori C.R.
        Social defeat stress induces hyperalgesia and increases truncated BDNF isoforms in the nucleus accumbens regardless of the depressive-like behavior induction in mice.
        Eur J Neurosci. 2018; ([published online ahead of print June 9])
        • Rivat C.
        • Becker C.
        • Blugeot A.
        • Zeau B.
        • Mauborgne A.
        • Pohl M.
        • et al.
        Chronic stress induces transient spinal neuroinflammation, triggering sensory hypersensitivity and long-lasting anxiety-induced hyperalgesia.
        Pain. 2010; 150: 358-368
        • Li C.
        • Yang Y.
        • Liu S.
        • Fang H.
        • Zhang Y.
        • Furmanski O.
        • et al.
        Stress induces pain transition by potentiation of AMPA receptor phosphorylation.
        J Neurosci. 2014; 34: 13737-13746
        • Ueda H.
        • Neyama H.
        LPA1 receptor involvement in fibromyalgia-like pain induced by intermittent psychological stress, empathy.
        Neurobiol Pain. 2017; 1: 16-25
        • Huhman K.L.
        • Solomon M.B.
        • Janicki M.
        • Harmon A.C.
        • Lin S.M.
        • Israel J.E.
        • et al.
        Conditioned defeat in male and female Syrian hamsters.
        Horm Behav. 2003; 44: 293-299
        • Greenberg G.D.
        • Steinman M.Q.
        • Doig I.E.
        • Hao R.
        • Trainor B.C.
        Effects of social defeat on dopamine neurons in the ventral tegmental area in male and female California mice.
        Eur J Neurosci. 2015; 42: 3081-3094
        • Bowler C.M.
        • Cushing B.S.
        • Carter C.S.
        Social factors regulate female-female aggression and affiliation in prairie voles.
        Physiol Behav. 2002; 76: 559-566
        • Ophir A.G.
        • Crino O.L.
        • Wilkerson Q.C.
        • Wolff J.O.
        • Phelps S.M.
        Female-directed aggression predicts paternal behavior, but female prairie voles prefer affiliative males to paternal males.
        Brain Behav Evol. 2008; 71: 32-40
        • Scotti M.A.
        • Carlton E.D.
        • Demas G.E.
        • Grippo A.J.
        Social isolation disrupts innate immune responses in both male and female prairie voles and enhances agonistic behavior in female prairie voles (Microtus ochrogaster).
        Horm Behav. 2015; 70: 7-13
        • 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
        • Liu H.
        • Patki G.
        • Salvi A.
        • Kelly M.
        • Salim S.
        Behavioral effects of early life maternal trauma witness in rats.
        Prog Neuropsychopharmacol Biol Psychiatry. 2018; 81: 80-87
        • Lukkes J.L.
        • Meda S.
        • Thompson B.S.
        • Freund N.
        • Andersen S.L.
        Early life stress and later peer distress on depressive behavior in adolescent female rats: Effects of a novel intervention on GABA and D2 receptors.
        Behav Brain Res. 2017; 330: 37-45
        • Patki G.
        • Solanki N.
        • Salim S.
        Witnessing traumatic events causes severe behavioral impairments in rats.
        Int J Neuropsychopharmacol. 2014; 17: 2017-2029
        • Akinbo O.
        • Wardwell J.J.
        • Watanasriyakul W.T.
        • Normann M.C.
        • Cox M.
        • Ciosek S.
        • et al.
        Observing a sibling experience a stressor alters behavioral and endocrine stress reactivity in prairie voles. 2018; (Presented at the Annual Meeting of the Society for Neuroscience, November 8, 2018, San Diego, California)
        • Bruchey A.K.
        • Jones C.E.
        • Monfils M.H.
        Fear conditioning by-proxy: Social transmission of fear during memory retrieval.
        Behav Brain Res. 2010; 214: 80-84
        • Jeon D.
        • Kim S.
        • Chetana M.
        • Jo D.
        • Ruley H.E.
        • Lin S.Y.
        • et al.
        Observational fear learning involves affective pain system and Cav1.2 Ca2+ channels in ACC.
        Nat Neurosci. 2010; 13: 482-488
        • 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
        • Iñiguez S.D.
        • Aubry A.
        • Riggs L.M.
        • Alipio J.B.
        • Zanca R.M.
        • Flores-Ramirez F.J.
        • et al.
        Social defeat stress induces depression-like behavior and alters spine morphology in the hippocampus of adolescent male C57BL/6 mice.
        Neurobiol Stress. 2016; 5: 54-64
        • Li M.
        • Xu H.
        • Wang W.
        An improved model of physical and emotional social defeat: Different effects on social behavior and body weight of adolescent mice by interaction with social support.
        Front Psychiatry. 2018; 9: 688
        • Watt M.J.
        • Burke A.R.
        • Renner K.J.
        • Forster G.L.
        Adolescent male rats exposed to social defeat exhibit altered anxiety behavior and limbic monoamines as adults.
        Behav Neurosci. 2009; 123: 564-576
        • Kessler R.C.
        • Avenevoli S.
        • Ries Merikangas K.
        Mood disorders in children and adolescents: An epidemiologic perspective.
        Biol Psychiatry. 2001; 49: 1002-1014
        • McDonald R.
        • Jouriles E.N.
        • Ramisetty-Mikler S.
        • Caetano R.
        • Green C.E.
        Estimating the number of American children living in partner-violent families.
        J Fam Psychol. 2006; 20: 137-142