Original articles
LI Fengan, QIN Yu, SHI Tianyao, ZHOU Wenxia
Objective To investigate the protective effects and underlying mechanisms of Liuwei Dihuang Glucoside （LW-AFC） against fear sensitization induced by traumatic stress. Methods Mice were divided into naive, control, stressed and LW-AFC administration groups. The LW-AFC treated group received LW-AFC （1.6 g/kg daily） via oral gavage for two weeks following exposure to traumatic stress. The non-associative memory dependent fear sensitization responses in mice subjected to trauma were investigated, including behavior in novel environments, social interaction, and observational fear tests. Z-score normalization method was employed to integrate and assess multiple behavioral variables such as travel distance, freezing time, and corner time, and comprehensively examined fear sensitization behaviors across the groups. Additionally, serum concentrations of adrenocorticotropic hormone, corticosterone, aldosterone, renin, angiotensin Ⅱ, and aldosterone were measured using ELISA. Results Compared to the control group, stressed mice exhibited significantly reduced travel distance （P< 0.0001） and increased freezing time （P< 0.0001） in the new context test. Integrated Z-scores indicated a significant increase in fear behavior among stressed mice during the new context test （P< 0.0001）. In the social interaction test, stressed mice demonstrated significantly reduced travel distance （P< 0.0001）, increased freezing time （P< 0.0001）, increased corner time （P< 0.05）, and higher integrated Z-scores （P< 0.0001）. In the observational fear test, stressed mice showed significantly reduced travel distance （P< 0.05）, increased freezing time （P< 0.001）, increased corner time （P< 0.05）, and higher integrated Z-scores （P< 0.0001）. Compared to the stressed group, mice in the LW-AFC treated group displayed trends toward improvement in travel distance, freezing time, corner time, and integrated Z-scores in the new context tests, albeit without statistical significance. In the social interaction test, the LW-AFC treated group exhibited a significant reduction in freezing time （P< 0.05） and integrated Z-scores （P< 0.05）. In the observational fear test, the LW-AFC treated group showed a significant reduction in freezing time （P< 0.05） and integrated Z-scores （P< 0.01）. Compared to the naive group, control and stressed groups exhibited an increased trend in renin and aldosterone levels after the fear sensitization test. Although there were no significant differences between stressed and control groups, renin and aldosterone levels significantly increased between stressed and naive groups （P< 0.05, P< 0.05）. Following LW-AFC treatment, serum renin levels showed no significant change, while aldosterone levels significantly decreased （P< 0.05）. Conclusion Stressed mice exhibited significant fear sensitization behavior in new context, social interaction, and observational fear tests, possibly associated with partial activation of the renin-angiotensin-aldosterone system （RAAS） system. LW-AFC treatment significantly mitigated fear sensitization behavior of stressed mice in social interaction and observational fear test, potentially due to its regulatory effects on the RAAS system in mice subjected to traumatic stress.
