Advertisement

Neurobiology of Chronic Social Defeat Stress: Role of Brain-Derived Neurotrophic Factor Signaling in the Nucleus Accumbens

  • Anita E. Autry
    Correspondence
    Address correspondence to Anita E. Autry, Ph.D., Molecular and Cellular Biology Department, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138-2020.
    Affiliations
    Molecular and Cellular Biology Department, Harvard University, Cambridge, Massachusetts
    Search for articles by this author
      Chronic stress is an important risk factor, not only for a number of psychiatric disorders—including depression, anxiety, and substance abuse—but also for a multitude of other diseases, such as heart disease, obesity, and diabetes. Given that the neural processes connected to the hypothalamic center kick-starting this response—for example, the corticotropin-releasing hormone neurons of the paraventricular nucleus of the hypothalamus—control the body’s stress response, discovering the neurobiology of chronic stress is key to understanding a myriad of human diseases. In this issue of Biological Psychiatry, Koo et al. present a comprehensive study examining the molecular mechanisms of chronic social defeat stress (CSDS), an animal model of chronic stress, in mesolimbic dopaminergic circuitry (
      • Koo J.W.
      • Labonte B.
      • Engmann O.
      • Calipari E.S.
      • Juarez B.
      • Lorsch Z.
      • et al.
      Essential role of mesolimbic brain-derived neurotrophic factor in chronic social stress–induced depressive behaviors.
      ). In this study, the authors show that brain-derived neurotrophic factor (BDNF) signaling (and not dopaminergic signaling), specifically onto D1-receptor expressing neurons in the nucleus accumbens (NAc) shell, mediates the behavioral effects of CSDS.
      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

        • Koo J.W.
        • Labonte B.
        • Engmann O.
        • Calipari E.S.
        • Juarez B.
        • Lorsch Z.
        • et al.
        Essential role of mesolimbic brain-derived neurotrophic factor in chronic social stress–induced depressive behaviors.
        Biol Psychiatry. 2016; 80: 469-478
        • Autry A.E.
        • Monteggia L.M.
        Brain-derived neurotrophic factor and neuropsychiatric disorders.
        Pharmacol Rev. 2012; 64: 238-258
        • 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
        • 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
        • 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
        • Calipari E.S.
        • Bagot R.C.
        • Purushothaman I.
        • Davidson T.J.
        • Yorgason J.T.
        • Pena C.J.
        • et al.
        In vivo imaging identifies temporal signature of D1 and D2 medium spiny neurons in cocaine reward.
        Proc Natl Acad Sci U S A. 2016; 113: 2726-2731
        • Lobo M.K.
        • Covington 3rd H.E.
        • Chaudhury D.
        • Friedman A.K.
        • Sun H.
        • Damez-Werno D.
        • et al.
        Cell type–specific loss of BDNF signaling mimics optogenetic control of cocaine reward.
        Science. 2010; 330: 385-390
        • Wall N.R.
        • De La Parra M.
        • Callaway E.M.
        • Kreitzer A.C.
        Differential innervation of direct- and indirect-pathway striatal projection neurons.
        Neuron. 2013; 79: 347-360

      Linked Article

      • Essential Role of Mesolimbic Brain-Derived Neurotrophic Factor in Chronic Social Stress–Induced Depressive Behaviors
        Biological PsychiatryVol. 80Issue 6
        • Preview
          Previous work has shown that chronic social defeat stress (CSDS) induces increased phasic firing of ventral tegmental area (VTA) dopamine (DA) neurons that project to the nucleus accumbens (NAc) selectively in mice that are susceptible to the deleterious effects of the stress. In addition, acute optogenetic phasic stimulation of these neurons promotes susceptibility in animals exposed to acute defeat stress. These findings are paradoxical, as increased DA signaling in NAc normally promotes motivation and reward, and the influence of chronic phasic VTA firing in the face of chronic stress is unknown.
        • Full-Text
        • PDF