Both mineralocorticoid and glucocorticoid receptors regulate emotional memory in mice

Corticosteroid hormones are thought to promote optimal behavioral adaptation under fearful conditions, primarily via glucocorticoid receptors (GRs). Here, we examined – using pharmacological and genetic approaches in mice – if mineralocorticoid receptors (MRs) also play a role in fearful memory formation. As expected, administration of the GR-antagonist RU38486 prior to training in a fear conditioning paradigm impaired contextual memory when tested 24 (but not when tested 3) h after training. Tone-cue memory was enhanced by RU38486 when tested at 4 (but not 25) h after training. Interestingly, pre (but not post)-training administration of MR antagonist spironolactone impaired contextual memory, both at 3 and 24 h after training. Similar effects were also found in forebrain-specific MR knockout mice. Spironolactone also impaired tone-cue memory, but only at 4 h after training. These results reveal that – in addition to GRs – MRs also play a critical role in establishing fear memories, particularly in the early phase of memory formation.

Research highlights► Mineralocorticoid (MR) in addition to glucocorticoid receptors (GR) play an important role in fear conditioning. ► The two receptor types affect different aspects of fear conditioning. ► MR is particularly important in the early phase of fear conditioning, involving appraisal and strategic decisions. ► GR seems more important in later phases, involving consolidation processes.