Brain-derived neurotrophic factor signaling mitigates the impact of acute social stress

NEUROPHARMACOLOGY

卷:148

Article

Rosenhauer, Anna M.¹  Beach, Linda Q.¹  Jeffress, Elizabeth C.¹  Thompson, Brittany M.¹  McCann, Katharine E.¹  Partrick, Katherine A.¹  Diaz, Bryan¹  Norvelle, Alisa¹  Choi, Dennis C.¹  Huhman, Kim L.¹ 

[1] Georgia State Univ, Ctr Behav Neurosci, Neurosci Inst, Atlanta, GA 30303 USA

关键词: Social avoidance;    Conditioned defeat;    TrkB;    Social defeat;    Basolateral amygdala;    Nucleus accumbens;   

DOI  :  10.1016/j.neuropharm.2018.12.016

来源: Elsevier

【 摘 要 】

Brain-derived neurotrophic factor (BDNF) is known to promote fear learning as well as avoidant behavioral responses to chronic social defeat stress, but, conversely, this peptide can also have antidepressant effects and can reduce depressant-like symptoms such as social avoidance. The purpose of this study was to use a variety of approaches to determine whether BDNF acting on tropomyosin receptor kinase B (TrkB) promotes or prevents avoidant phenotypes in hamsters and mice that have experienced acute social defeat stress. We utilized systemic and brain region-dependent manipulation of BDNF signaling before or immediately following social defeat stress in Syrian hamsters, TrkB(F616A) knock-in mice, and C57BI/6J mice and measured the subsequent behavioral response to a novel opponent. Systemic TrkB receptor agonists reduced, and TrkB receptor antagonists enhanced, behavioral responses to social defeat in hamsters and mice. In the neural circuit that we have shown mediates defeat-induced behavioral responses, BDNF in the basolateral amygdala, but not the nucleus accumbens, also reduced social avoidant phenotypes. Conversely, knockdown in the basolateral amygdala of TrkB signaling in TrkB(F616A) mice enhanced defeat-induced social avoidance. These data demonstrate that systemic administration of BDNF-TrkB drugs at the time of social defeat alters the behavioral response to the defeat stressor. These drugs appear to act, at least in part, in the basolateral amygdala and not the nucleus accumbens. These findings were generalizable to two rodent species with very different social structures and, within mice, to a variety of strains providing converging evidence that BDNF-TrkB signaling reduces anxiety- and depression-like symptoms following short-term social stress.

【 授权许可】

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