School of Psychology, University of New South Wales, Sydney, Australia.
School of Psychology, University of New South Wales, Sydney, Australia.
Horm Behav. 2018 Jan;97:67-74. doi: 10.1016/j.yhbeh.2017.10.009. Epub 2017 Nov 8.
Administering estradiol to females during periods of low endogenous estradiol enhances their ability to extinguish fear, the laboratory basis of exposure therapy for anxiety disorders. It has therefore been proposed that estradiol could be a useful adjunct to enhance exposure therapy outcomes. The present study aimed to clarify the boundary conditions under which estradiol could be used for this purpose, by assessing whether the impact of estradiol, administered systemically prior to extinction training, differs depending on dose and estrous phase in adult female rats. Results demonstrated that in rats extinguished during metestrus (naturally low estradiol), a low dose of estradiol reduced freezing during extinction training and augmented extinction recall the following day, whereas a high dose of estradiol had no effect on either extinction training or recall. In rats extinguished during proestrus (naturally high estradiol), a high dose of estradiol impaired extinction recall, whereas a low dose of estradiol had no effect, or impairing effects, on extinction recall in different experiments. A subsequent analysis revealed that estradiol-treated proestrus rats that exhibited impaired extinction recall had significantly higher pre-treatment serum estradiol levels than those that exhibited good extinction recall. Together, these results indicate that systemically administered estradiol interacts with endogenous estradiol to produce an inverted U shaped dose effect on fear extinction, where low and high estradiol levels lead to poor extinction recall, and moderate estradiol levels lead to good extinction recall. These results highlight potential limitations to the use of estradiol as an adjunct to exposure therapy in clinical settings.
在内源性雌二醇水平较低的时期向女性施用雌二醇会增强她们消除恐惧的能力，这是焦虑障碍暴露疗法的实验室基础。因此，有人提出雌二醇可以作为增强暴露疗法效果的有用辅助手段。本研究旨在通过评估在成年雌性大鼠中，在消退训练前系统性给予雌二醇的剂量和发情周期阶段是否会影响其效果，来阐明可以将雌二醇用于此目的的边界条件。结果表明，在发情间期（自然低雌二醇）消退的大鼠中，低剂量的雌二醇可减少消退训练期间的冻结，增强次日的消退记忆，而高剂量的雌二醇对消退训练或记忆均无影响。在发情前期（自然高雌二醇）消退的大鼠中，高剂量的雌二醇会损害消退记忆，而低剂量的雌二醇在不同实验中对消退记忆无影响或产生损害作用。随后的分析表明，表现出消退记忆受损的雌二醇处理发情前期大鼠的治疗前血清雌二醇水平明显高于表现出良好消退记忆的大鼠。总之，这些结果表明，系统性给予的雌二醇与内源性雌二醇相互作用，对恐惧消退产生了倒 U 形剂量效应，其中低和高雌二醇水平会导致消退记忆不良，而适度的雌二醇水平会导致良好的消退记忆。这些结果突出了在临床环境中使用雌二醇作为暴露疗法辅助手段的潜在局限性。
