Intermittent social isolation enhances social investigation but impairs social memory in adult male mice

Abstract

Social isolation profoundly impacts motivated behavior and neural plasticity. While the effects of acute and chronic social isolation have been extensively studied, the consequences of intermittent isolation during adulthood, particularly relevant to modern lifestyles, remain poorly understood. This study investigated the impact of intermittent social isolation (ISI) on social behavior and brain activation in adult male mice. Compared to group-housed controls, ISI males exhibited heightened social investigation and increased social interaction, reminiscent of craving-like behaviors. Intriguingly, this enhanced social investigation was accompanied by impaired social recognition memory in a three-chamber sociability test. Furthermore, ISI induced distinct patterns of neural activation in brain regions governing social processing, including the paraventricular nucleus of the hypothalamus, the intermediate part of lateral septum, the paraventricular nucleus of the thalamus, and the thalamic periventricular gray. Notably, ISI did not affect anxiety-like behaviors or spatial memory, emphasizing its specific impact on social domains. These findings demonstrate that ISI during adulthood selectively enhances social investigation while disrupting social memory in male mice, possibly mediated by distinct neural circuits. Understanding the neurobiological mechanisms underlying these effects may inform interventions for individuals experiencing social isolation, an increasingly prevalent phenomenon in modern society.