Experiential contributions to social dominance in a rat model of fragile-X syndrome.

K Saxena,P Kind,S Chatterji,R G M Morris,J Webster,A Hallas-Potts,R Mackenzie,D Thomson,P A Spooner

doi:10.1098/rspb.2018.0294

Abstract

Social withdrawal is one phenotypic feature of the monogenic neurodevelopmental disorder fragile-X. Using a ‘knockout' rat model of fragile-X, we examined whether deletion of the Fmr1 gene that causes this condition would affect the ability to form and express a social hierarchy as measured in a tube test. Male fragile-X ‘knockout' rats living together could successfully form a social dominance hierarchy, but were significantly subordinate to wild-type animals in mixed group cages. Over 10 days of repeated testing, the fragile-X mutant rats gradually showed greater variance and instability of rank during their tube-test encounters. This affected the outcome of future encounters with stranger animals from other cages, with the initial phenotype of wild-type dominance lost to a more complex picture that reflected, regardless of genotype, the prior experience of winning or losing. Our findings offer a novel insight into the complex dynamics of social interactions between laboratory living groups of fragile-X and wild-type rats. Even though this is a monogenic condition, experience has an impact upon future interactions with other animals. Gene/environment interactions should therefore be considered in the development of therapeutics.

Highlights

The aim of this study was to investigate whether deletion of the fragile-X mental retardation protein (FMRP) would impact the expression of a social hierarchy in group-living laboratory rats
Previous studies of social dominance in animal models of autism-spectrum disorders have focused on mice due to the relative ease of making deletions of murine genes by homologous recombination [12,26]
We sought to examine whether deletion of FMRP would have an impact on (a) the ability to form and express a social hierarchy as measured in a tube test, (b) social dominance behaviour when animals are confronted by another rat living in the same cage and (c) social dominance when confronted by a stranger rat from another cage

Summary

Introduction

The aim of this study was to investigate whether deletion of the fragile-X mental retardation protein (FMRP) would impact the expression of a social hierarchy in group-living laboratory rats. During a single day of habituation, all animals in a cage were placed singly in the apparatus and allowed to run freely in the tube between the holding boxes for 30 min. The entrance barriers were lifted and the rats introduced into the tube, whereupon they generally moved to the centre Once both rats touched the central barrier, it was raised to allow the dominance test rspb.royalsocietypublishing.org Proc. The tube test was initially used to establish within-cage dominance hierarchies (figure 1b, phase I). In the case of equal points, the ranking was decided based on the outcome of the specific competition between the two equal scoring individuals, with the winner ranked higher This test of position in the hierarchy was repeated 10 times across successive sessions. All the plots are represented as mean + s.e.m

Results

Findings

Discussion