Chronic social defeat stress leads to changes of behaviour and memory-associated proteins of young mice

Behav Brain Res. 2017 Jan 1;316:136-144. doi: 10.1016/j.bbr.2016.09.011. Epub 2016 Sep 5.


It is well known that social defeat stress can induce depressive behaviours and cognitive impairment. However, the molecular mechanism by which only a minority of stress-exposed individuals are affected is not clear. In this study, thirty 3-week-old male c57BL/6 mice were exposed to 30 days of social defeat stress, following which susceptible (socially avoidant) and unsusceptible (socially interactive) mice were identified using social investigation. Twenty-four hours after the last episode of defeat, separate groups of mice were tested in the sucrose preference, open field, elevated plus-maze and Morris water maze behavioural assays. Also, the levels of memory-associated proteins in the hippocampus were examined, including postsynaptic density 95 (PSD95), postsynaptic density 93 (PSD93), and Protein kinase A (PKA). The levels of PSD95, PSD93, and PKA were significantly lower in susceptible mice. We also found that the upstream regulatory factor of these proteins, phosphorylated Camp-Responsive Element-Binding Protein (CREB), was reduced after social defeat in the susceptible group only, while the level of histone deacetylase 6 (HDAC6) was significantly elevated. These data suggest that memory-associated proteins and phosphorylated CREB may play important roles in memory impairment and behavioural responses to chronic stress.

Keywords: Animal model; Anxiety; Creb; Depression; Social defeat stress; Spatial memory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CREB-Binding Protein / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Depression / etiology*
  • Disks Large Homolog 4 Protein / metabolism*
  • Dominance-Subordination*
  • Food Preferences
  • Gene Expression Regulation / physiology
  • Guanylate Kinases / metabolism*
  • Hippocampus / metabolism
  • Histone Deacetylase 6 / metabolism
  • Male
  • Maze Learning
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Stress, Psychological* / complications
  • Stress, Psychological* / metabolism
  • Stress, Psychological* / pathology
  • Sucrose


  • Disks Large Homolog 4 Protein
  • Dlg4 protein, mouse
  • Membrane Proteins
  • Sucrose
  • CREB-Binding Protein
  • Cyclic AMP-Dependent Protein Kinases
  • Dlgh2 protein, mouse
  • Guanylate Kinases
  • Histone Deacetylase 6