Activation of BDNF signaling prevents the return of fear in female mice
- Psychiatric Epigenomics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia
Abstract
There are significant sex differences in vulnerability to develop fear-related anxiety disorders. Females exhibit twice the rate of post-traumatic stress disorder (PTSD) as males and sex differences have been observed in fear extinction learning in both humans and rodents, with a failure to inhibit fear emerging as a precipitating factor in the development of PTSD. Here we report that female mice are resistant to fear extinction, and exhibit increased DNA methylation of Bdnf exon IV and a concomitant decrease in mRNA expression within the medial prefrontal cortex. Activation of BDNF signaling by the trkB agonist 7,8-dihydroxyflavone blocks the return of fear in female mice after extinction training, and thus represents a novel approach to treating fear-related anxiety disorders that are characterized by a resistance to extinction and increased propensity for renewal.
Footnotes
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↵1 Corresponding author
E-mail: t.bredy{at}uq.edu.au
- Received November 7, 2012.
- Accepted February 12, 2013.
- © 2013 Cold Spring Harbor Laboratory Press