Abstract
Cortisol and corticosterone (CORT) coordinate circadian events and manage the stress response by differential activation of two complementary brain receptor systems, i.e., the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR), which mediate rapid non-genomic and slow genomic actions. Several recent discoveries are highlighted from molecular fine-tuning of the MR/GR balance by FKBP5 to CORTs role in neural network regulation underlying stress adaptation in emotional, cognitive, and social domains of behavior. The data suggest that MR mediates CORT action on risk assessment, social interaction, and response selection, while GR activation promotes memory consolidation and behavioral adaptation; there are also sex differences in CORT action. New evidence suggests that targeting the MR/GR balance resets a dysregulated stress response system and promotes resilience.