CONTEXT-DEPENDENT EFFECTS OF SOCIAL RE‑EXPOSURE ON ISOLATION‑INDUCED AGGRESSION AND MCC NEURONAL MORPHOLOGY

Social isolation (SI) produces behavioral impairments, including heightened territorial aggression accompanied by structural alterations in pyramidal neurons of the midcingulate cortex (MCC), a cortical region implicated in regulating aggression. In this study, we examined whether repeated, social exposure could reduce SI‑induced aggression. For this purpose, adult Swiss mice were isolated for six weeks before assessing baseline aggression using the Resident-Intruder test. Subsequently, two experiments were conducted to evaluate the effects of repeated social exposure. In both, isolated mice were assigned either to an exposure group, receiving daily interactions with a conspecific stimulus mouse, or to a control group. In Experiment 1, interactions occurred in the resident’s home cage, whereas in Experiment 2, exposures took place in the intruder’s cage. Aggression was reassessed on Day 8 in both experiments and again on Day 16 in Experiment 2. At the end of behavioral testing, the Golgi-Cox technique was used to analyze morphological changes in MCC pyramidal neurons. Our results showed that social re-exposure within the resident’s cage increased aggression. In contrast, exposure in the intruder’s cage led to a progressive reduction in aggression, suggesting that social contact in a non‑territorial setting can attenuate SI‑induced aggression. These behavioral improvements were accompanied by enhanced MCC pyramidal neurons structure, including increased dendrites number in experiment 2 and higher dendritic spine density in both protocols. Overall, these findings demonstrate that social re-exposure context determines whether social contact exacerbates or alleviates SI‑induced aggression and its associated neural alterations.