摘要
目的用Z-score归一化法整合观察性恐惧习得(OFL)模型小鼠的多项行为指标,探讨小鼠OFL的性别差异。方法①将雌性和雄性C57BL/6J小鼠分别分为对照组和模型组。在OFL训练阶段,令小鼠目睹同类小鼠遭受足底电击(模型组)或不遭受足底电击(对照组)以建立OFL模型,24 h后进行观察性恐惧回忆测试。分别记录训练阶段和24 h后恐惧回忆阶段雌、雄小鼠的僵住行为、旷场回避行为和社会交互行为,比较各行为的性别差异。应用Z-score归一化整合3种行为参数,以综合情绪Z值比较小鼠OFL反应的性别差异。②雌性小鼠行双侧卵巢切除术制备去势小鼠,检测OFL实验中3种恐惧行为,以综合情绪Z值比较去势模型组、假手术模型组与各自对照组以及假手术模型组与去势模型组之间的差异。结果①在训练阶段,雌、雄模型组小鼠的僵住时间和旷场回避时间均较同性别对照组显著增加(P<0.05),雌性模型组的社会交互次数较同性别对照组显著降低(P<0.01),但雌、雄模型组之间的僵住行为、旷场回避行为和社会交互行为均无显著差异。24 h后恐惧回忆阶段,雄性模型组的僵住时间较同性别对照组仍显著升高(P<0.01),雌性模型组与同性别对照组之间已无明显差异,雌、雄模型组的旷场回避和社会交互行为与同性别对照组相比均无显著差异,但与雌性模型组相比,雄性模型组的僵住时间显著增加(P<0.01)、旷场回避无差异、社会交互次数显著降低(P<0.01);根据整合后的综合情绪Z值,雌、雄模型组在训练阶段的恐惧情绪反应较同性别对照组强烈(P<0.01),雌雄之间无明显差异;在24 h后恐惧回忆阶段,雄性模型组的恐惧情绪反应仍较同性别对照组强烈(P<0.05),且明显强于雌性模型组(P<0.01)。②去势雌性模型组小鼠在训练阶段较去势对照组恐惧情绪反应明显增强(P<0.05),但与假手术模型组之间无差异;在24 h后恐惧回忆阶段,去势模型组恐惧情绪反应仍强于去势对照组,较假手术模型组也显著增强(P<0.01)。结论在OFL中,雌雄小鼠均能通过目睹同类遭受痛苦而获得恐惧,基于多种行为指标整合后的综合情绪Z值证明,雄鼠习得性恐惧比雌鼠更强。通过双侧卵巢切除消除雌激素的影响后,去势雌鼠的OFL反应与雄鼠相似。
OBJECTIVE To integrate multiple behavioral parameters of mice undergoing observational fear learning(OFL)and to explore the gender differences in OFL among mice.METHODS①Female and male C57BL/6J mice were divided into the control group and model group respectively.In the OFL training stage,mice were allowed to witness the partner suffering from plantar electric shock(model group)or not(control group)to establish an OFL model.After 24 hours,the observational fear retrieval test was conducted.The freezing behavior,avoidance behavior and social interaction behavior of these mice were recorded in the training stage and observational fear retrieval stage respectively,before gender differences in each behavior were studied.Three behavioral parameters were normalized and integrated by Z-value,and the gender differences in observational fear response in mice was revealed via the comprehensive emotional Z-value.②Female mice underwent bilateral ovariectomy to prepare ovariectomized mice before three fear behaviors in OFL were detected.The differences between the ovariectomized model,sham-operated model group and their respective control groups,and between the shamoperated model group and ovariectomized model group were studied via the comprehensive emotional Z-value.RESULTS①During the training stage of OFL,the freezing time and corner zone time in female and male model groups increased significantly compared with their respective control groups(P<0.05),while the interaction zone entries of the female model group was significantly decreased compared with the control group(P<0.01),but there was no significant gender difference in freezing,open field avoidance or social interaction behaviors between female and male model groups.After 24 hours,the freezing time in the male model group remained significantly longer than that of the control group(P<0.01),but there was no significant difference between the female model group and the female control group.There was no significant difference in the open field avoidance and social interaction behaviors between the female model group and the male model group,but the freezing time in the male model group was significantly longer than that of the female model group(P<0.01).There was no significant difference in the open field avoidance between the male model group and the female model group,but the interaction zone entries of the male model group was significantly decreased compared with the female model group(P<0.01).According to the integrated comprehensive emotional Z-value,the fear response of the female and male model mice in the training stage was obviously stronger than that of their respective control mice(P<0.01),but there was no significant difference between male and female mice.After 24 hours,the fear response of the male model group remained significantly higher than that of the control group(P<0.05)and the female model group(P<0.01)in the 24 h fear retrieval stage.②In the training stage,the fear response of the ovariectomized model group was significantly stronger than that of the ovariectomized control group(P<0.05),but there was no difference between the ovariectomized model group and the sham-operated model group.In the 24 h fear retrieval stage,the fear response of the ovariectomized model group remained stronger than that of the ovariectomized control group and the sham-operated model group(P<0.01).CONCLUSION In OFL,both male and female mice can acquire fear by witnessing the suffering of their partners.The comprehensive emotional Z-value based on the integration of the three behavioral indicators proves that the observational fear learning of male mice is more lasting than that of female mice.After elimination of the influence of estrogen through bilateral ovariectomy,the observational fear learning response of ovariectomized female mice is similar to that of male mice.
作者
付圆
石天尧
周文霞
FU Yuan;SHI Tianyao;ZHOU Wenxia(Nanjing University of Chinese Medicine,Nanjing 210023,China;State Key Laboratory of Toxicology and Medical Countermeasures,Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Beijing 100850,China)
出处
《中国药理学与毒理学杂志》
CAS
北大核心
2023年第10期733-743,共11页
Chinese Journal of Pharmacology and Toxicology
基金
国家自然科学基金(81801342)
北京市自然科学基金(7154229)。
作者简介
付圆,硕士研究生,主要从事神经药理学研究,E-mail:847717358@qq.com;石天尧,博士,副研究员,主要从事神经精神药理学研究;周文霞,博士,研究员,主要从事中药和神经免疫药理学研究;通讯作者:周文霞,E-mail:zhouwx@bmi.ac.cn;通讯作者:石天尧,E-mail:tianyao_shi@163.com。
