Neurobiological and Behavioral Characterization of Adult Male and Female Mice in Prolonged Social Isolation

As social animals, our health depends in part on interactions with other human beings. Yet millions suffer from chronic social isolation, including those in nursing/assisted living facilities and people experiencing chronic loneliness. Perhaps the most egregious form of chronic isolation is seen in criminal justice system, where approximately 80,000 people are housed, on any one day, in solitary confinement. In this study, we developed a model of isolation that starts in adulthood. Mice (C57BL/6J) were born and raised in an enriched environment until 4 months of age and then either maintained in that environment or moved to social isolation for 1 or 3 months. We then examined neuronal structure, catecholamine and brain derived neurotrophic factor (BDNF) levels, and CNS-mediated behaviors, comparing social isolation to enriched environment controls. We found there were significant changes in neuronal volume, dendritic length, neuronal complexity, and spine density that were dependent on brain region, sex, and duration of the isolation. Isolation altered dopamine in the striatum and serotonin levels in the forebrain in a sex-dependent manner, and also reduced levels of BDNF in the motor cortex and hippocampus of male but not female mice. To determine if SI altered a behavior, we tested mice in the open-field (general activity), the resident intruder paradigm (aggression), the tail suspension test (depression), and the Barnes maze (spatial memory). Adult male mice isolated for 1 month exhibited increased locomotor activity, aggression, and enhanced aspects of spatial memory, most of which remained after 3 months of isolation. After 3 months of isolation, mice also exhibited depressive behaviors. Similar (but not exact) results were seen in female mice, with the exception that the females did not show increased aggression. These studies show that isolation enforced in adulthood has significant impact on brain structure, neurochemistry, and behavior ### Competing Interest Statement The authors have declared no competing interest.