Social Downsizing Stress (SDS): A novel paradigm for studying social transitions in mice

Shrinking social networks and the transition to nuclear families represent significant structural changes in modern society. While traditional animal models have focused on total social isolation or defeat, the behavioral consequences of a dynamic reduction in group size remain poorly understood. We established a novel "Social Downsizing Stress (SDS)" model to investigate how a transition from high-density to low-density housing affects behavioral phenotypes and whether these effects are reversible through resocialization.

Mice were assigned to four groups: Stable-6 (S6), Stable-3 (S3), SDS (6-3 mice at 8 weeks), and Resocialization (ReSDS; 6-3 at 8 weeks, followed by 3-6 at 11 weeks). Behavioral batteries were conducted at 10 weeks (acute phase) and 13-14 weeks (chronic/recovery phase).

At 10 weeks, the SDS group exhibited a unique hyper-reactive phenotype distinct from the S3 group, characterized by significantly increased locomotor activity in the open field, increased entries in the light/dark transition test, and reduced social resting time. Both the S3 and SDS groups showed impaired spatial working memory in the Y-maze. By 13-14 weeks, resocialization (ReSDS) successfully restored social resting behavior and cognitive performance to control levels. However, SDS-induced hyperactivity in the open field persisted in both the SDS and ReSDS groups, regardless of the subsequent return to a higher-density environment. Furthermore, the ReSDS group exhibited significantly lower immobility in the tail suspension and forced swim tests compared to the S3 group.

Social downsizing induces a distinct behavioral phenotype that differs from chronic low-density housing. While social interaction and cognitive functions retain high plasticity, hyperactivity persisted throughout the tested period (up to 13-14 weeks) despite resocialization, suggesting a long-lasting, though not yet confirmed irreversible, consequence of losing social density. This model provides a new framework for investigating the enduring neurobehavioral impacts of shrinking social environments on mental health.