Sensitized corticosterone responses do not mediate the enhanced fear memories in chronically stressed rats.
Sensitized corticosterone responses do not mediate the enhanced fear memories in chronically stressed rats.
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敏化的皮质酮反应不会介导长期应激大鼠的恐惧记忆增强。
DOI：
10.1016/j.bbr.2020.112480
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发表时间：
2020
影响因子：
2.7
通讯作者：
Johnson,JohnD
中科院分区：
文献类型：
--
作者：
Kulp,AdamC;Lowden,BrettM;Chaudhari,Sachi;Ridley,CassidyA;Krzoska,JamesC;Barnard,DavidF;Mehta,DevanshiM;Johnson,JohnD
应激事件发生后，下丘脑-垂体-肾上腺轴调节应激激素皮质醇（啮齿类动物的皮质酮; CORT）的释放。升高的CORT与糖皮质激素受体结合以介导生理反应，包括促进记忆形成。我们实验室以前的工作表明，暴露于慢性应激的雄性大鼠表现出增强的背景恐惧记忆和敏感的CORT反应，随后的压力暴露，然而，这是未知的雌性大鼠。本实验测试了慢性应激是否会增强雌性大鼠的恐惧记忆形成，以及慢性应激大鼠的致敏CORT反应是否有助于其增强的恐惧记忆。研究首先检查了雄性和雌性大鼠对情境恐惧条件反射的CORT反应，并检查了慢性应激是否增强了24小时后情境恐惧记忆的形成。然后，研究使用CORT合成抑制剂甲吡酮来研究阻断血浆CORT是否会消除慢性应激诱导的背景恐惧记忆增强。结果表明，雌性大鼠比雄性大鼠有更大的CORT反应，慢性应激敏感的CORT反应的恐惧条件反射在两种性别。然而，雌性大鼠在慢性应激后并没有表现出增强的背景恐惧记忆。慢性应激的雄性大鼠表现出更大的记忆获得和更大的上下文恐惧记忆24小时后，恐惧条件反射。甲吡酮抑制所有大鼠的背景恐惧记忆，但不能消除慢性应激大鼠的冻结行为的增强。总的来说，这些研究表明，慢性应激大鼠的致敏CORT反应可能不是慢性应激促进记忆形成的机制。
Following a stressful event, the hypothalamus-pituitary-adrenal axis mediates the release of the stress hormone cortisol (corticosterone in rodents; CORT). Elevated CORT binds to glucocorticoid receptors to mediate physiological responses including facilitating memory formation. Previous work from our laboratory demonstrated that male rats exposed to chronic stress demonstrate enhanced contextual fear memories and sensitized CORT responses to subsequent stress exposure; however, this is unknown in female rats. The experiments here tested whether chronic stress enhances fear memory formation in female rats and whether the sensitized CORT response in chronic stress rats contributes to their enhanced fear memory. Studies first examined CORT responses to contextual fear conditioning in male and female rats and examined whether chronic stress enhanced the formation of contextual fear memories 24 h later. Studies then used metyrapone, a CORT synthesis inhibitor, to investigate whether blockade of plasma CORT would eliminate the chronic stress-induced enhancement in contextual fear memory. Results show that female rats have greater CORT responses than males, and chronic stress sensitizes the CORT response to fear conditioning in both sexes. However, female rats do not show enhanced contextual fear memory following chronic stress. Chronically stressed male rats show greater memory acquisition and show greater contextual fear memory 24 h later following fear conditioning. Metyrapone dampens contextual fear memory in all rats but does not eliminate the enhancement in freezing behavior in chronic stress rats. Collectively, these studies indicate sensitized CORT responses in chronically stressed rats is likely not the mechanism by which chronic stress facilitates memory formation.