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Sex differences in fear memory and extinction of mice with forebrain‐specific disruption of the mineralocorticoid receptor
Author(s) -
ter Horst J. P.,
Carobrez A. P.,
van der Mark M. H.,
de Kloet E. R.,
Oitzl M. S.
Publication year - 2012
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2012.08237.x
Subject(s) - extinction (optical mineralogy) , forebrain , fear conditioning , psychology , context (archaeology) , freezing behavior , neuroscience , anxiety , fear processing in the brain , developmental psychology , amygdala , biology , central nervous system , psychiatry , paleontology
Previous studies showed that the mineralocorticoid receptor (MR) is needed for behavioral flexibility in a fear conditioning paradigm. Female mice with forebrain‐specific deletion of the MR gene (MR CaMKCre ) were unable to show extinction of contextual fear, and could not discriminate between cue and context fear unlike control mice. In the present study, male and female (MR CaMKCre ) mice and control littermates were used to study sex‐specific fear conditioning, memory performance and extinction. The fear conditioning paradigm assessed both context‐ and cue‐related fear within one experimental procedure. We observed that at the end of the conditioning all mice acquired the fear‐motivated response. During the first minutes of the memory test, both male and female MR CaMKCre mice remembered and feared the context more than the control mice. Furthermore, female MR CaMKCre mice were not able to extinguish this memory even on the second day of memory testing. The female mutants also could not discriminate between cue (more freezing) and context periods (less freezing). In contrast, male MR CaMKCre mice and the controls showed extinction and were capable to discriminate, although the MR CaMKCre mice needed more time before they started extinction. These findings further support the relevance of MR for behavioral flexibility and extinction of fear‐motivated behavior. In conclusion, the loss of MR in the forebrain results in large differences in emotional and cognitive behaviors between female and male mice, which suggests a role of this receptor in the female prevalence of stress‐ and anxiety‐regulated disorders.