Reproducible induction of depressive-like behavior in C57BL/6J mice exposed to chronic social defeat stress with a modified sensory contact protocol

Aims: C57BL/6J mice are well-known to exhibit resilience to chronic social defeat stress (CSDS) for induction of depressive-like behavior. Establishment of protocols for reproducible induction of depressive-like behavior in C57BL/6J mice would be useful to elucidate the underlying molecular mechanisms using target gene-knock-in and -out mice whose background is generally C57BL/6J. Here, we developed a modified CSDS protocol for reproducible induction of depressive-like behavior in C57BL/6J mice, and compared the profile of their gut microbiota with that with the standard CSDS protocol.

Main methods: To prevent acclimation of defeated C57BL/6J mice to aggressive ICR mice, the sensory contact following a daily 10 min-defeat episode was performed by housing an individual defeated mouse in a cage set next to a cage for the aggressor one.

Key findings: The number of attacks by ICR mice on C57BL/6J ones was significantly increased with the modified CSDS protocol, and the susceptible mice exhibited greater hippocampal inflammation and an increased immobility time in the forced swim test, compared in the case of the standard CSDS protocol, and the reproducibility was confirmed in another set of experiments. Both the standard and modified CSDS protocols changed the diversity and relative composition of gut microbiota in the susceptible mice, but there was no apparent difference in them between the standard and modified CSDS-susceptible mice.

Significance: We established a CSDS protocol for reproducible induction of depressive-like behavior in C57BL/6J mice, and the features of the gut microbiota were similar in the susceptible mice with and without the depressive-like behavior.