Inflammatory Factors Predicted the Resilient Phenotype in Social Defeat-induced Depression of Male Mouse

Neuroscience. 2023 May 21:519:38-46. doi: 10.1016/j.neuroscience.2023.02.022. Epub 2023 Mar 8.


An absence of reward in chronic stress may impair the reward circuit in the brain, resulting in major depressive disorder (MDD). In a part of chronically stressed individuals, MDD is not present, i.e., there is resilience, implying endogenous anti-depressive mechanisms in the brain. We studied social defeat model mice and analyzed the mRNA maps of the hippocampus from a control group and social defeat (SD)-susceptible and SD-resilient mice using high-throughput sequencing techniques. It was found that the immune response was associated with depression. Existing studies have proven that microglia play an important role in the brain immune response, and their activation level increases after chronic social defeat stress (CSDS). In our study, minocycline inhibited the activation of microglia, thereby improving the depressive state of CSDS mice. In addition, minocycline combined with fluoxetine enhanced the efficacy of fluoxetine. Thus, our results propose the most probable mechanism underlying different responses to CSDS and indicate the potential of a combination of anti-inflammatory drugs and antidepressants in treating refractory depression.

Keywords: CSDS; depression; hippocampus; inflammatory factors; microglia.

MeSH terms

  • Animals
  • Depressive Disorder, Major* / drug therapy
  • Fluoxetine / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Minocycline / pharmacology
  • Phenotype
  • Social Behavior
  • Social Defeat*
  • Stress, Psychological / drug therapy


  • Fluoxetine
  • Minocycline