title: Sex differences in fear extinction and involvements of extracellular signal-regulated kinase (ERK).
abstract: Stress-related disorders, such as post-traumatic stress disorder (PTSD) and panic disorders, are disproportionately prevalent in females. However, the biological mechanism underlying these sex differences in the prevalence rate remains unclear. In the present study, we examined sex differences in fear memory, fear extinction, and spontaneous recovery of fear. We investigated the presence of sex differences in recent and remote fear memory in mice using contextual fear conditioning, as well as sex differences in spontaneous recovery of fear memory using a consecutive fear extinction paradigm. We examined the number of fear extinction days required to prevent spontaneous recovery of fear in either sex. We investigated whether ovariectomy affected fear extinction and spontaneous recovery. We also measured the activation of extracellular signal-regulated kinase (ERK) 1 and 2 in the dorsal hippocampus and the medial prefrontal cortex following fear extinction sessions. In our results, we found no sex difference in recent or remote fear memory. However, females required more fear extinction sessions compared to males to prevent spontaneous recovery. Within-extinction freezing also differed between males and females. Moreover, females required more extinction sessions than males to increase ERK2 phosphorylation in the dorsal hippocampus. Our data suggest that contextual fear extinction was unstable in females compared to males and that such sex differences may be related to the ERK2 phosphorylation in the hippocampus.
authors.affiliation: Department of Ultrastructural Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan. Electronic address: matsutsuma@gmail.com.
authors.forename: Shingo
authors.initials: S
authors.lastname: Matsuda
authors.affiliation: Department of Cognitive Behavioral Physiology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670, Japan; Research Center for Child Mental Development, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Matsuzawa
authors.affiliation: Department of Cognitive Behavioral Physiology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ishii
authors.affiliation: Department of Cognitive Behavioral Physiology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670, Japan.
authors.forename: Haruna
authors.initials: H
authors.lastname: Tomizawa
authors.affiliation: Department of Cognitive Behavioral Physiology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Sutoh
authors.affiliation: Department of Cognitive Behavioral Physiology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670, Japan; Research Center for Child Mental Development, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D003213:Conditioning, Psychological; D005108:Extinction, Psychological / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005239:Fear / Q000502:physiology*; D005260:Female; D046352:Freezing Reaction, Cataleptic / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010052:Ovariectomy; D017397:Prefrontal Cortex / Q000378:metabolism; D012737:Sex Factors; D013997:Time Factors
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases
keywords: ERK; Fear conditioning; Fear extinction; Sex differences; Spontaneous recovery