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.
Bibliographical note© 2013 Cold Spring Harbor Laboratory Press
Baker-andresen, D., Law, C., Li, X., & Bredy, T. W. (2013). Activation of BDNF signaling prevents the return of fear in female mice. Learning & Memory , 20, 237-240. https://doi.org/10.1101/lm.029520.112