Impacts of Repeated Isolation and Dihydromyricetin on Anxiety, Cognition, and Social Behavior in Male and Female Mice: A Pilot Study

Abstract

In humans, positive social interactions and relationships are essential for maintaining good mental and physical health. Insufficiency of these interactions-i.e., social isolation–is associated with negative health outcomes, including anxiety and cognitive decline. To investigate the impacts of long-term, recurrent patterns of social isolation on behavior, we developed the repeated social isolation (RSI) model, where C57BL/6 mice were subjected to social isolation, social interaction, and re-isolation, followed by the administration of 2 mg/kg dihydromyricetin (DHM). DHM is a flavonoid known to ameliorate anxiety and cognitive impairment partly via γ-aminobutyric A receptors (GABAARs) and has the potential to counteract the negative effects of social isolation. In this pilot study, mice exposed to RSI exhibited increased anxiety-like behavior and decreased cognition, while DHM partially ameliorated these changes. In the social interaction test, male RSI mice had shorter latency to attack and less social interaction, while female RSI mice avoided conflict and interaction altogether. Compared to the 4-week social isolation model, DHM showed less significance in therapeutic efficacy, especially in anxious behaviors, potentially due to 1) small sample size and/or 2). Overall, RSI increased anxiety- like behavior, reduced cognition, and led to changes in social behavior, while DHM showed some therapeutic effects. Future studies will incorporate a larger sample size and investigate the cellular or molecular changes that may explain the findings in this study.