Maternal separation induced resilience to depression and spatial memory deficit despite intensifying hippocampal inflammatory responses to chronic social defeat stress in young adult male rats.

Early life adversity has been suggested to affect neuroendocrine responses to subsequent stressors and accordingly vulnerability for behavioral disorders. This is the first work to study the effects of maternal separation (MS) stress on the co-occurrence of depression and cognitive impairments along with hippocampal inflammatory response under chronic social defeat stress (CSDS) in young adult male rats. During the first two postnatal weeks, the male pups were either exposed to MS or left undisturbed with their mothers (Std). Subsequently, starting on postnatal day 50, the animals of each group were either left undisturbed in the standard group housing (Con) or underwent CSDS for three weeks. Totally, there were four groups (n = 10/group), namely Std-Con, Ms-Con, Std-CSDS, and MS-CSDS. Pup retrieval test was performed on daily basis from PND1 to PND14. During the last week of the CSDS exposure, in the light phase, the behavioral tests and the retro-orbital blood sampling were performed to assess basal plasma corticosterone levels. Afterwards, the hippocampus of the animals was removed to measure the interleukin 1β (IL-1β) content. Exposure to CSDS increased the plasma corticosterone levels and induced social avoidance along with memory deficit. Maternal separation intensified hippocampal IL-1β contents as well as the plasma corticosterone levels in response to CSDS. Meanwhile, it facilitated the spatial learning and potentiated resilience to social avoidance and memory deficit. In conclusion, although maternal separation increased the basal plasma corticosterone levels, it could facilitate the learning process and induce resilience to the onset of depression and memory deficit in response to CSDS, probably through the compensatory increase in maternal care and the induction of mild hippocampal inflammatory response.