Coping with stress produces differential systemic and brain corticosterone patterns in female rats

Coping factors, such as perceived or actual behavioral control over some aspect of an adverse event, are associated with resilience and are often argued to help optimize or even dampen glucocorticoid responses to stressors. Interestingly, when coping responses (i.e., stressor controllability) are experimentally manipulated in animals, controllable and uncontrollable stressors produce identical peripheral glucocorticoid responses despite eliciting markedly different behavioral outcomes. However, these studies have been conducted exclusively in male rats. In the present study, we investigated corticosterone (CORT) levels in female rats using the same controllability parameters that have been shown to produce differences in behavioral outcomes. Replicating previous studies, both controllable [escapable shock (ES)] and uncontrollable [inescapable shock (IS)] stress produced equivalent elevations in CORT levels in male rats. In contrast, in female rats, IS produced a greater increase in CORT levels than ES. We further assessed in the same animals whether initial controllability alters the CORT response to a future challenge. In male rats, but not female rats, prior IS (Time 1) sensitized the CORT response to subsequent IS (Time 2), an effect blocked by prior ES. Finally, in a separate cohort, the female controllability difference in the acute plasma CORT response was not observed in medial prefrontal cortex or striatal regions. Prefrontal expression of 11β-hydroxysteroid dehydrogenase type 1, an enzyme that regulates local concentrations of CORT, was increased in female rats exposed to ES relative to those exposed to IS. These results support the growing evidence that stress-induced differences in peripheral CORT are not necessarily reflected in brain structures that support behavioral outcomes, potentially due to regulatory mechanisms at the local tissue level.