Department of Chemistry and Bioscience, Faculty of Science, Kagoshima University, Kagoshima, Japan.
Department of Chemistry and Bioscience, Faculty of Science, Graduate School of Science and Engineering, Kagoshima University, Kagoshima, Japan.
PLoS One. 2018 May 15;13(5):e0197441. doi: 10.1371/journal.pone.0197441. eCollection 2018.
Several studies have reported regulatory effects of estrogens on fear conditioning in female rodents. However, these studies used different doses, durations, and/or administration methods, and reported inconsistent results. To clarify the effect of estrogen on fear conditioning, we investigated the effects of different doses and durations of estradiol administration on freezing behavior during contextual fear conditioning in ovariectomized (OVX) mice. In Experiment 1, OVX ICR mice received a single subcutaneous (s.c.) injection of either oil vehicle (control, 0.1 ml sesame oil) or varied doses (0.5 μg/0.1 ml, 5 μg/0.1 ml, or 50 μg/0.1 ml) of 17β-estradiol-3-benzoate (EB). Fear conditioning was conducted two days post-EB treatment, and the mice were tested for the learned fear response the following day. In Experiment 2, OVX female mice received an s.c. implantation of a Silastic capsule (I.D. 1.98 × 20.0 mm) containing either vehicle or varied doses (0.05 μg/0.1 ml, 0.5 μg/0.1 ml, 5 μg/0.1 ml, 50 μg/0.1 ml) of EB. Two weeks after implantation, fear conditioning was conducted. During the tests conducted 24 h after conditioning, the high dose EB group showed longer freezing times in both experiments, and lower locomotor activity compared to the control or lower dose groups. In Experiment 3, serum estradiol concentrations of the mice that were treated like those in Experiment 2, were measured; the serum levels of estradiol increased linearly according to the dose of EB administered. The results suggest that mice treated with a high dose of EB exhibit enhanced fear learning, regardless of treatment duration. As a woman's vulnerability to emotional disorders increases in the peripregnancy period, during which estrogen levels are high, the results from the high-dose EB groups may be important for understanding the hormonal mechanisms involved in these disorders.
一些研究报道了雌激素对雌性啮齿动物恐惧条件反射的调节作用。然而，这些研究使用了不同的剂量、持续时间和/或给药方法，报告的结果不一致。为了阐明雌激素对恐惧条件反射的影响，我们研究了不同剂量和持续时间的雌二醇给药对去卵巢（OVX）小鼠在情境恐惧条件反射期间的冻结行为的影响。在实验 1 中，OVX ICR 小鼠接受单次皮下（s.c.）注射油载体（对照，0.1 ml 芝麻油）或不同剂量（0.5 μg/0.1 ml、5 μg/0.1 ml 或 50 μg/0.1 ml）的 17β-雌二醇-3-苯甲酸酯（EB）。EB 处理后两天进行恐惧条件反射，第二天测试小鼠习得的恐惧反应。在实验 2 中，OVX 雌性小鼠接受皮下植入含有载体或不同剂量（0.05 μg/0.1 ml、0.5 μg/0.1 ml、5 μg/0.1 ml、50 μg/0.1 ml）的 EB 的硅酮胶囊（内径 1.98×20.0 mm）。植入后两周进行恐惧条件反射。在条件反射后 24 小时进行的测试中，高剂量 EB 组在两个实验中表现出更长的冻结时间，与对照组或低剂量组相比，运动活性更低。在实验 3 中，测量了像实验 2 中那样处理的小鼠的血清雌二醇浓度；血清雌二醇水平根据给予的 EB 剂量呈线性增加。结果表明，接受高剂量 EB 治疗的小鼠表现出增强的恐惧学习，无论治疗持续时间如何。由于女性在围孕期（雌激素水平较高）期间对情绪障碍的易感性增加，高剂量 EB 组的结果对于理解这些障碍涉及的激素机制可能很重要。
