Hierarchy in the home cage affects behaviour and gene expression in group-housed C57BL/6 male mice

Yasuyuki Horii,Michiko T Yasuda,Kayoko Shimoi,Yuki Matsumoto,Kazuto Yoshimi,Tsuyoshi Koide,Akira Tanave,Hiroyuki Sakakibara,Aki Takahashi,Hiromichi Nagayama,Tatsuhiro Nagasawa

doi:10.1038/s41598-017-07233-5

Abstract

Group-housed male mice exhibit aggressive behaviour towards their cage mates and form a social hierarchy. Here, we describe how social hierarchy in standard group-housed conditions affects behaviour and gene expression in male mice. Four male C57BL/6 mice were kept in each cage used in the study, and the social hierarchy was determined from observation of video recordings of aggressive behaviour. After formation of a social hierarchy, the behaviour and hippocampal gene expression were analysed in the mice. Higher anxiety- and depression-like behaviours and elevated gene expression of hypothalamic corticotropin-releasing hormone and hippocampal serotonin receptor subtypes were observed in subordinate mice compared with those of dominant mice. These differences were alleviated by orally administering fluoxetine, which is an antidepressant of the selective serotonin reuptake inhibitor class. We concluded that hierarchy in the home cage affects behaviour and gene expression in male mice, resulting in anxiety- and depression-like behaviours being regulated differently in dominant and subordinate mice.

Highlights

Mice are useful model animals for studying a wide range of human diseases, including psychological disorders
Aggressive behaviour in males caged together largely depends on the genetic background of the mouse strain used, but agonistic behaviour between males in a cage has been observed in a wide range of mouse strains
Brain-derived neurotrophic factor (BDNF), which is related to neural cell functions, including adult neurogenesis, is expressed more highly in the hippocampi of dominant males than in the hippocampi of subordinate males[19]

Summary

Introduction

Mice are useful model animals for studying a wide range of human diseases, including psychological disorders. This was the case even when genetically identical mice from an inbred strain were kept under the same environmental conditions in behavioural experiments[5] It is recommended in many animal care and ethical guidelines that mice should be kept under group housing to decrease the stress caused by social isolation[5, 6]. Brain-derived neurotrophic factor (BDNF), which is related to neural cell functions, including adult neurogenesis, is expressed more highly in the hippocampi of dominant males than in the hippocampi of subordinate males[19] These previous findings suggest that agonistic interactions between male mice alter neurological function in individuals kept under social conditions. The main objective of the present study was to determine whether the behaviours and other phenotypes of male mice housed together were affected by agonistic interactions between the mice that occurred to establish and maintain a social hierarchy that naturally occurs in mice in group housing

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Conclusion