Repeated social defeat stress impairs attentional set shifting irrespective of social avoidance and increases female preference associated with heightened anxiety

Shu Higashida,Shuh Narumiya,Midori Nagai,Satoshi Yawata,Kazuki Nakayama,Hirotaka Nagai,Shiho Kitaoka,Ryota Shinohara,Tomoyuki Furuyashiki,Yukio Ago,Takatoshi Hikida,Masayuki Taniguchi

doi:10.1038/s41598-018-28803-1

Abstract

Repeated social defeat stress (R-SDS) induces multiple behavioral changes in mice. However, the relationships between these behavioral changes were not fully understood. In the first experiment, to examine how the social avoidance is related to R-SDS-impaired behavioral flexibility, 10-week-old male C57BL/6N mice received R-SDS followed by the social interaction test and the attentional set shifting task. R-SDS impaired attentional set shifting irrespective of the development of social avoidance. In the second experiment, to examine whether R-SDS affects sexual preference and how this behavioral change is related to the social avoidance and R-SDS-heightened anxiety, another group of 10-week-old male C57BL/6N mice were subjected to R-SDS followed by the social interaction test, the female encounter test and the elevated plus maze test. The anxiety was heightened in the defeated mice without social avoidance, but not in those which showed social avoidance. Furthermore, female preference was increased specifically in the defeated mice which showed heightened anxiety, but was not related to the level of social avoidance. Together, these results showed that attentional set shifting is more sensitive to R-SDS than social interaction, and that female preference is affected by R-SDS in association with heightened anxiety rather than the social avoidance.

Highlights

Repeated environmental stress induces behavioral changes, such as depression and heightened anxiety as well as impaired cognitive performance, in various animal species, and predisposes to mental illnesses in humans
We examined the effects of Repeated social defeat stress (R-SDS) on attentional set shifting and female preference, and compared these effects with other R-SDS-induced behavioral changes
We examined the effects of R-SDS on attentional set shifting and sexual preference in addition to social interaction and anxiety and their relationships

Summary

Introduction

Repeated environmental stress induces behavioral changes, such as depression and heightened anxiety as well as impaired cognitive performance, in various animal species, and predisposes to mental illnesses in humans. Behavioral flexibility · Repeated social defeat stress · Social interaction test · Visual cue task · Response direction task Sexual preference and anxiety · Repeated social defeat stress · Social interaction test · Female encounter test · Elevated plus maze test Besides these behavioral changes, it has been shown that R-SDS as well as other types of repeated stress impairs behavioral flexibility as measured by attentional set shifting[8]. It has been shown that R-SDS as well as other types of repeated stress impairs behavioral flexibility as measured by attentional set shifting[8] It remains to be examined how the social avoidance is related to R-SDS-impaired behavioral flexibility. We found that R-SDS heightened anxiety as measured by the EPM test in the defeated mice which did not develop social avoidance and that R-SDS increased female preference in a subpopulation of defeated mice which showed heightened anxiety

Methods

Results

Conclusion