Both mineralocorticoid and glucocorticoid receptors regulate emotional memory in mice

• Published in: Neurobiology of learning and memory 2010-11, Vol.94 (4), p.530-537
• Main Authors: Zhou, Ming, Bakker, Eveline H.M., Velzing, Els H., Berger, Stefan, Oitzl, Melly, Joëls, Marian, Krugers, Harm J.
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animal cognition; Animals; Association Learning - drug effects; Association Learning - physiology; Avoidance Learning - drug effects; Avoidance Learning - physiology; Behavioral psychophysiology; Biological and medical sciences; Emotions; Fear - physiology; Fear conditioning; Fundamental and applied biological sciences. Psychology; Gene Knockdown Techniques; Glucocorticoid receptor; Hormone Antagonists - pharmacology; Male; Memory - drug effects; Memory - physiology; Mice; Mice, Inbred C57BL; Mifepristone - pharmacology; Mineralocorticoid receptor; Mineralogy; Prosencephalon - physiology; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Receptors, Glucocorticoid - antagonists & inhibitors; Receptors, Glucocorticoid - physiology; Receptors, Mineralocorticoid - drug effects; Receptors, Mineralocorticoid - genetics; Receptors, Mineralocorticoid - physiology; Rodents; Spironolactone - pharmacology; Steroids; Time Factors
• ISSN: 1074-7427; 1095-9564
• DOI: 10.1016/j.nlm.2010.09.005

► 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. 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.