P.2.035 - Studying social withdrawal in group housed mice using semi-natural conditions

Abstract

Background Currently, neuropsychiatric disorders are separated by convention based clustering of qualitative symptoms, not underlying aetiology. This methodology might be sufficient for general clinical management, but it disregards neurobiology. A better understanding of the neurobiology and the application of this knowledge will lead to enhanced treatment efficacy and would provide patients with improved understanding of their condition. A first step in linking nosology to neuroscience is showing how neuropsychiatric symptoms can be measured by quantitative biological parameters and, how these quantitative biological parameters are shaped by neurobiological processes. For example, Schizophrenia, Alzheimer’s disease, Major Depressive disorder and autism spectrum disorder have one overlapping symptom, social withdrawal [1]. This suggests that neurobiological mechanisms might overlap. Thus, scrutinizing the characteristics of this behavioural deficit could elucidate mechanisms relevant for multiple neuropsychiatric disorders. Animal studies are essential in this endeavour, as behaviour and the underlying mechanisms can be examined in more detail. However, efforts are needed to establish the definition and assessment tools for social withdrawal that is relevant beyond the diagnostic boundaries. In earlier studies, the focus has primarily been on scrutinizing social withdrawal in a dyadic interaction, in which a single animals can engage in social behaviour with a single other (e.g., [2]). This, however, does not allow for the natural behavioural potential, such as the natural burrowing behaviour of these animals. Studying social behaviour in a semi-natural environment would allow for a translational setting in which the full range of behaviours can be explored. This study proposes the visible burrow system (VBS) for this purpose. This system consists of an open arena and a burrow with separate nests, from which the latter is exposed to constant darkness. Mimicking the natural setting, this system allows rodents to display natural behaviours and withdraw into one of the nests. Aim This study aims to explore the full behavioural range of the BTBR mouse, a mouse line showing aberrant social behaviours, in a semi-natural VBS environment to study social withdrawal. Furthermore we aim to connect this to GABA, which has been shown to play a key role in social behaviour [3]. Method In assessing the full range of behavioural deficits accompanying social withdrawal, BTBR and C57BL/6J reference mice are placed in the VBS. Colonies of 8 mice (6 males and 2 females) are exposed to the VBS for five consecutive days after which animals are sacrificed and brains are extracted for GABA measurement by mean of HPLC. Statistical analyses is performed by means of ANOVA (longitudinal) and Student’s T-test (week means), comparing BTBR with C57Bl/6j mice (α=0.05). Results/Conclusion In accordance with previous data [4], BTBR mice showed a significant decrease in social behaviours and an increase in non-social behaviour. This coincided with a reduction of GABA in both the prefrontal cortex and the amygdala. Taken together, these data suggests the VBS as a tool for studying translation behavioural characteristics regarding social withdrawal and its neurochemical correlates.