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

• Chronic social defeat stress lead to behavioural changes.
• Susceptible and unsusceptible mice showed different behavioural responses.
• CREB phosphorylation may play important roles.

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.