Social defeat affects inflammatory signaling and exploratory behavior in mice in a sex-dependent manner

Abstract

Aim: Psychosocial stress negatively affects both physical and mental health; and stress-related psychiatric disorders are more common in women. Interestingly, preclinical studies have predominately investigated the effects of psychosocial stress on male mice. These studies suggest that adverse effects of psychosocial stress are due in part to the disruption of inflammatory signaling; however, the extent to which these findings translate to females remains unclear, particularly in the context of female-mediated aggression. Methods: We investigated the effects of acute (2 h) and repeated social defeat (RSD; 2 h/day × 6 days) on proinflammatory cytokine/chemokine expression in male and female C57BL/6J mice: importantly, the CD-1 aggressor mice were the same sex as the subject mice. Results: The effects on these inflammatory factors were dependent on the duration of social defeat, sex, and tissue. A single bout of social defeat reduced brain IL-1β levels in females only, whereas liver IL-1β and CXCL10 levels increased only in males. RSD decreased brain IL-1β levels in males only; while liver IL-1β and CCL2 levels decreased only in females. RSD led to increased exploratory activity in females; behavioral changes were not