Introduction Stress-related disorders such as major depression and anxiety disorder are disproportionately prevalent in women. However, the biological mechanism of the sex difference in the prevalence rate remains unclear. Fear conditioning and extinction paradigm is a widely used model in researching the biological basis of clinical anxiety related disorders. We have reported that female mice required longer fear extinction sessions to inhibit the spontaneous recovery than male mice, while recent or remote fear memory did not differ between males and females (Matsuda et al., 35th and 36th Annual Meeting of JNS). To understand molecular mechanisms behind the sex differences in fear extinction, we measured phosphorylation of extracellular signal-regulated kinase (ERK) 2 in the dorsal hippocampus and the medial prefrontal cortex following fear extinction sessions using western blotting.
Results & Discussion In males, phosphorylation of ERK2/ total ERK2 in the medial prefrontal cortex transiently increased after fear extinction. Moreover, phosphorylation of ERK2/ total ERK2 in the dorsal hippocampus increased after the extinction sessions that prevented the remote spontaneous recovery. In contrast, fear extinction did not increase phosphorylation of ERK2/ total ERK2 in both regions of females. These results suggest that phosphorylation of ERK may be involved in the sex differences in fear extinction.