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 24h after training. Similar effects were also found in forebrain-specific MR knockout mice. Spironolactone also impaired tone-cue memory, but only at 4h 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.
Zhou
Ming
M
Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Science Park, 1098 XH Amsterdam, The Netherlands. m.zhou@uva.nl
Bakker
Eveline H M
EH
Velzing
Els H
EH
Berger
Stefan
S
Oitzl
Melly
M
Joëls
Marian
M
Krugers
Harm J
HJ
D000704:Analysis of Variance; D000818:Animals; D001245:Association Learning / Q000187:drug effects / Q000502:physiology*; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D004644:Emotions; D005239:Fear / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015735:Mifepristone / Q000494:pharmacology; D016548:Prosencephalon / Q000502:physiology; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000502:physiology*; D018161:Receptors, Mineralocorticoid / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013148:Spironolactone / Q000494:pharmacology; D013997:Time Factors
D006727:Hormone Antagonists; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D015735:Mifepristone