The effects of estradiol replacement therapy on novel-object recognition and extinction of conditioned fear memory in ovariectomized rats

Abstract

Objective To investigate the effects of estradiol replacement therapy on novel-object recognition and extinction of conditioned fear memory in ovariectomized (OVX) rats. Methods Sixty sexually mature (>90 days) female SD rats weighing 250g-300g were used as subjects. The rats were randomly divided into 7 groups as following: OVX with low dose of estradiol replacement (OVX+ LD, 0.1mg·kg-1), medium dose (OVX+ MD, 0.3mg·kg-1) and high dose (OVX+ HD, 0.9mg·kg-1), estradiol replacement with medium dose at 2 weeks after OVX (MD+ 2W) and 4 weeks after OVX (MD+ 4W), OVX group and Sham group (SH). According to the different dose and time schedules, each group was administrated estradiol or vehicle via subcutaneous injection on the dorsal side of the rat. Estradiol maintained for one month after the surgery, and then the novel-object recognition and extinction of conditioned fear memory were tested. Results (1) The rats after OVX (5.83±4.5)s showed access-dependent impairments on novel-object recognition ((5.83±4.5)s vs(27.14±6.6)s, P 0.05). Moreover, group MD(27.86±2.6)s had a significant difference compared with group OVX (P<0.05). (2)The conditioned fear memory of rats after OVX (21.67±2.0)% showed significantly lower than group SH(56.81±4.6)% (P<0.01). Chronic administration with estradiol enhanced acquisition of context fear, respectively(P<0.01), but except group HD and group MD+ 4W. The group HD(18.43±1.1)% was negatively enhanced and the group MD+ 4W(25.25±2.5)% was no difference compared with group OVX. (3) On extinction of conditioned fear memory, the OVX rats produced significantly less freezing by fear context(F=3.337, P<0.01), and estradiol treatment (except group MD+ 4W)also facilitated the extinction of conditioned fear memory, respectively(P<0.01). Conclusion These results demonstrate that estradiol may have a beneficial effect on the cognition function, and the improving effect is better when estradiol replacement is given at once depriving of sex hormone. Key words: Estradiol; Sex difference; Fear inhibition; Learning and memory