Chronic stress beginning in adolescence decreases spatial memory following an acute inflammatory challenge in adulthood.

Prolonged stress beginning in adolescence can contribute to the dysregulation of the neuroendocrine system in adulthood. As the neuroendocrine and neuroimmune systems participate in bi-directional regulatory control, adolescent stress can prime the neuroimmune system to future inflammatory insults. Previous work from our group demonstrates that stress exaggerates the hippocampal response to inflammation, which can lead to deficits in learning and memory. In the current study, we sought to interrogate the interaction between an acute peripheral challenge of lipopolysaccharide (LPS) in male and female Wistar rats with a history of stress beginning in adolescence (CAS). Males from the CAS group were more vulnerable to the peripheral effects of LPS compared to non-stressed males including porphyrin staining and ruffled fur. In contrast, LPS generated similar peripheral effects in females regardless of adolescent stress history. Learning and memory were differentially impacted by LPS as a function of stress history and effects manifested differently when stratified by sex. Males with a history of adolescent stress exhibited deficits in initial learning. Females from the CAS group performed similar to controls during acquisition but exhibited a slight impairment during reversal learning. Males and females with a history of stress displayed memory impairment during the probe assessments as compared to their same-sex control group. We conclude that while stress beginning in adolescence enhanced the vulnerability of learning and memory to an inflammatory challenge, the phenotype of this effect manifested differently in males and females. These data demonstrate a sustained impact of adolescent stress on the neuroimmune system which is sufficient to influence cognitive performance in both sexes.