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Brain Res Bull. 2018 Oct;143:97-105. doi: 10.1016/j.brainresbull.2018.10.005. Epub 2018 Oct 19.

Social defeat-induced Cingulate gyrus immediate-early gene expression and anxiolytic-like effect depend upon social rank.

Author information

1
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117600, Singapore; Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, 117456, Singapore; Singapore Institute for Neurotechnology (SINAPSE), 117456, Singapore.
2
Department of Molecular Biology, Ariel University, Ariel 4070000, Israel.
3
Department of Molecular Biology, Ariel University, Ariel 4070000, Israel. Electronic address: albertpi@ariel.ac.il.
4
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117600, Singapore; Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, 117456, Singapore; Singapore Institute for Neurotechnology (SINAPSE), 117456, Singapore. Electronic address: gavin_dawe@nuhs.edu.sg.

Abstract

Social hierarchy is considered to impart an adaptive advantage to the species by reducing long-term conflict between conspecifics. While social stratification is frequently established via stress-inducing stimuli, the subsequent integration of individuals into the hierarchy may attenuate anxiety. Presently, we hypothesized that repeated reinforcement of murine social hierarchy in the dominant-submissive relationship (DSR) food-competition test would engender divergent neuroplastic changes mediating both social and anxiety-like behavior among selectively-bred Dominant (Dom) and Submissive (Sub) mice. Two weeks of repeated respective social victory or defeat reduced serum corticosterone levels of both Dom and Sub mice, whereas socially-defeated Sub mice demonstrated markedly greater exploration of the open arms of the elevated plus maze (EPM). At the same time, social victory led to markedly greater expression of the immediate-early genes (IEGs) c-Jun and EGR-1 in the lateral septal nucleus (LSN) among Dom mice, in contrast with defeated Sub counterparts which demonstrated four-fold greater IEG expression in the cingulate gyrus (Cg). These findings point towards involvement of the Cg in the anxiety-like effect among Sub mice after repeated social defeat, and suggest stabilization of the social hierarchy to attenuate the stress-inducing nature of social interaction, particularly for subordinates. Further study of the potentially anxiolytic-like effects of Cg activity should shed light upon the functional significance of the Cg in social interaction, social hierarchical sorting and anxiety.

KEYWORDS:

Anxiety-like behavior; Cingulate gyrus (Cg); Dominant (Dom) and Submissive (Sub) mice; EGR-1; Lateral septal nucleus (LSN); c-Jun

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