Sex Differences and the Impact of Gonadal Hormones on Fear Memory: the Roles of Testosterone in Fear-Potentiated Startle

• Main Authors: Chia-Wen Tsai, 蔡佳妏
• Other Authors: Lung Yu
• Format: Others
• Language: en_US
• Online Access: http://ndltd.ncl.edu.tw/handle/84530750785501341938

碩士 === 國立成功大學 === 行為醫學研究所 === 97 === An obvious sexual difference in anxiety disorders has been documented with a prevalence of 2 fold higher in women than it in men. Such sexual difference implies the roles of sex hormones in modulating the differential susceptibility to stress in two sexes. Although the sex-dependent prevalence rate has been consistently reported greater in women than in men, the specific roles of sex hormones on fear memory formation and extinction remained scarcely explored in animal models. This study was undertaken to examine the sexual differences in fear memory and the roles of testosterone in central anatomical substrates in mediating such sex differences by utilizing fear potentiated startle (FPS) paradigm in a rat model. Male and female rats were first accustomed to the constraint chamber in the dark and their startle responses were recorded then for the sporadic tone presentation (95dB). Our fear conditioning protocol consisted of an episode of 10-trial light-foot shock pairings. Three consecutive days (30 trials/day) of light alone presentation served as one bout of the extinction protocol. A total of two bouts of extinction protocol were used. Bilateral gonadectomy, systemic estradiol and testosterone supplement, and intra-accumbal injection of gonadal hormones were used in appropriate groups. We found that female rats exhibited greater fear potentiated startle responses in the acquisition test and lesser degree of extinction after the second bout of the extinction protocol as compared to male rats. We further demonstrated that ovariectomized rats displayed similar fear potentiated startle acquisition and extinction as the intact female rats, while orchidectomized rats displayed greater degree of fear-potentiated startle responses and more resistant to the extinction protocol as compared to the intact male rats. Finally, intra-accumbal testosterone infusion was found to effectively reverse such sensitized potentiated startle responses and resistance to extinction. We conclude that testosterone may play a pivotal role in determining the sexual differences of fear memory acquisition and forgetting process.