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.