Individual differences in stress coping are linked to working memory performance in male and female F344 rats

Executive dysfunction and altered stress reactivity are core features of many neuropsychiatric disorders, contributing substantially to global disability and frequently exhibiting sex-specific prevalence and symptom profiles. Understanding how stress responses normally relate to executive function, and whether these relationships differ by sex, is critical for identifying mechanisms of vulnerability and resilience. Although sex differences in stress and cognition have been reported, preclinical findings remain mixed, and few studies assess behavioral coping, endocrine responses, and working memory performance within the same subjects. In this study, we used F344 rats to examine how individual differences in behavioral and hormonal responses to acute stress relate to working memory, assessed using an operant delayed match-to-sample task. Males and females differed in stress reactivity: females exhibited greater immobility across “pre-test” and “test” sessions of the forced swim test (FST) and a more rapid decline in corticosterone (CORT) following restraint, suggesting sex-specific patterns of behavioral and physiological regulation. Despite these differences, working memory accuracy did not differ by sex, although females completed fewer trials and responded more slowly than males. Estrous cycle did not influence cognitive or non-mnemonic performance. Crucially, individual variation in FST immobility, rather than sex or CORT dynamics, was the strongest predictor of working memory accuracy. These findings bridge observed sex differences in stress reactivity with the absence of sex differences in cognition, revealing a trait-level relationship that generalizes across sexes. By jointly considering sex and individual behavioral traits, this work supports approaches to identify biologically meaningful cognitive phenotypes in preclinical models.