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Prolonged social isolation is associated with poor physical and mental health outcomes, findings observed in both humans, and rodent models of isolation. Humans, like mice, may engage in enhanced exploratory and social behaviour following isolation, which may protect against subsequent cognitive decline and psychological distress. Understanding how these effects may impact behaviour in older adults is particularly relevant, as this population is likely to experience periods of late-life social isolation. We report that late-life social isolation in female mice did not lead to robust depressive-like symptomology, altered social interaction behaviour, sensitivity to context fear acquisition and memory, or alterations in inflammatory cytokines (IL-6, IL-1β, Tnf-α) or microglial activation (Itgam) within the hippocampus. Rather, isolation increased hyperactivity and exploration behaviours. These findings have translational value as the first female mouse model of late-life social isolation, and provide evidence to inform the development of interventions aimed at promoting functional recovery following isolation in late-life. [ABSTRACT FROM AUTHOR]