Sex differences in biological mechanism of fear regulation

Abstract

Prevalence rate of some psychiatric disorders, including post-traumatic stress disorder, is higher in women than men. However, the biological mechanism of the sex differences remains unclear. To clear the biological mechanism of the sex differences, we have studied sex differences in neural circuits and molecular mechanism of fear memory and extinction. We found that female mice showed a resistance to fear extinction and a low stability of extinction memory when compared to male although acquisition and retrieval of fear memory did not differ between sexes. After fear extinction training, females showed lower neural activation in the CA3 region of the dorsal hippocampus (dHIP) and posterior basolateral amygdala than males. Females also showed low activation levels of extracellular signal-regulated kinase (ERK) 2, which is related to fear extinction, and high expression levels of immune-related genes in the dHIP when compared to males. Injection of immunosuppressant dexamethasone into the dHIP enhanced fear extinction in females. Thus, the resistance to fear extinction in females may be due to high activity of immune system in the dHIP. Additionally, we found some sex-specific drug or stress effects on fear memory or extinction. In this presentation, I will discuss sex differences in biological mechanism of fear regulation.