EARLY-LIFE STRESS IMPAIRS AVERSIVE MEMORY EXTINCTION AND ELEVATES OXIDATIVE STRESS IN THE DORSAL HIPPOCAMPUS OF ADULT MALE AND FEMALE RATS

We investigated how maternal separation (MS) modulates the late effects of acute restraint stress in adulthood on aversive memories extinction and oxidative stress in the dorsal hippocampus (dHP) of male and female rats. To analyze the late effect on extinction memory, 10 days after 2-hour restraint stress, all rats underwent contextual aversive conditioning (footshock, 0.5 mA/1s) followed by an extinction protocol (6 re-exposures). Additionally, oxidative stress markers and antioxidant enzyme activities were analyzed in the dHP 1, 10, or 17 days after restraint stress (24 hours/10 days post-restraint or 24 hours post-extinction). Following conditioning-induced aversive memory acquisition, all animals displayed elevated freezing, which progressively declined in control animals. Freezing remained high in both male and female rats subjected to MS, consistent with previous observations in restraint-stressed males. These findings suggest that these stressors significantly impaired fear extinction, although no synergistic effect was observed when they were combined. Biochemical analyses demonstrated that lipid peroxidation and protein carbonylation in the dHP were generally exacerbated by stress. Notably, animals subjected to restraint or the combination of MS and restraint exhibited the most enduring cellular damage. Antioxidant responses were sex-dependent: reduced SOD and increased CAT in males and increased SOD in females 24 h post-restraint; sustained enzyme activity at 10 days, mainly in restrained animals; and increased activity at 17 days only under combined MS and restraint. Collectively, these findings demonstrate the long-term impact of early-life stress on memory and redox homeostasis in dHP of stressed and non-stressed animals in adulthood.