POST-WEANING SOCIAL ISOLATION ALTERS ADDICTION-LIKE BEHAVIORS AND SYNAPTIC PLASTICITY IN THE NUCLEUS ACCUMBENS AND PREFRONTAL CORTEX: ROLE OF SEX AND NEUROIMMUNE SIGNALING

Abstract

Social isolation during adolescence can have long lasting negative effects in both humans and animal models. In mice, post-weaning social isolation leads to increased addiction-like behaviors in adulthood. However, little is known about how post-weaning social isolation alters the brain. Stress during development can lead to persistent restructuring of neurons. Changes in dendritic spines can be long-lasting and have been theorized to play an important role in the maintenance of cocaine craving. We found that post-weaning isolation led to a persistent increase in spine density in adulthood within both the core and shell regions of the nucleus accumbens in male mice, but not female mice. In contrast, in the infralimbic cortex, post-weaning social isolation led to an increase in spine density only in female mice. This study highlights the long-lasting, sex-specific effects of post-weaning isolation. Microglia have been shown to assist in both the formation and elimination of dendritic spines, and are activated following exposure to stress and cocaine. Therefore, we hypothesized that microglia may be involved in the restructuring of dendritic spines during post-weaning isolation, and contribute to addiction-like behavior in adulthood. We examined whether inhibiting microglia with minocycline during the first three weeks of post-weaning isolation altered the impact of isolation in cocaine seeking. Isolated animals that received minocycline showed increased cocaine seeking in adulthood compared to group housed mice and isolated mice that received saline. Minocycline and isolation also caused sex-specific alterations in spine density. The findings of these studies provide insight into the mechanisms by which social isolation during adolescence increases vulnerability to addiction later in life.