在恐惧灭绝过程中存在的高卵巢荷尔蒙减少了恐惧复发,通过尼格罗斯特里亚特多巴胺通路减少了恐惧复发
Alyssa A Hohorst1,2, Margaret K Tanner1, Rebecca Han1,3
1Department of Psychology, University of Colorado Denver, Denver, CO, USA.
Biology of sex differences
|June 1, 2025
概括
在恐惧灭绝期间,卵巢激素通过激活 substantia nigra-dorsolateral striatum 多巴胺通路来减少复发. 这一途径是减少两性恐惧复发的潜在目标.
科学领域:
- 神经科学是一个神经科学.
- 行为神经科学 行为神经科学
- 内分泌学 在内分泌学.
背景情况:
- 卵巢激素升高会增强恐惧灭绝记忆,减少复发,但机制尚不清楚.
- 高水平的卵巢激素与多巴胺 (DA) 传输的增加相关,这对恐惧灭绝至关重要.
- 在男性中,黑色物质 (SN) 在恐惧灭绝期间的DA神经元刺激减少了复发,这种效应被背侧条纹体 (DLS) 的DA D1受体激活剂模仿.
研究的目的:
- 调查SN-DLS途径在雌性周期调节的恐惧灭绝和复发中的作用.
- 确定性和卵巢激素水平如何影响恐惧复发及其潜在的神经生物学机制.
主要方法:
- 使用雄性和雌性Long-Evans老鼠研究性别和激素对恐惧灭绝和复发的影响.
- 在SN DA神经元中使用免疫组织化学量化恐惧灭绝诱导的cFos.
- 使用化学遗传学来评估SN-DLS途径在激素调节的恐惧复发中的必要性和充分性.
- 使用快速扫描循环电压测量来测量DLS中的DA释放,并验证化学遗传疗效.
主要成果:
- 高激素阶段 (孕期/孕期) 的雌性老鼠比低激素阶段 (孕期/孕期) 的雄性或雌性更少出现恐惧复发.
- 女性的高激素水平与SN DA神经元中的cFos增加和DLS中的DA释放有关.
- 雌激醇模仿了这些效应;在灭绝期间抑制SN-DLS通路恢复了高激素女性的恐惧更新,而刺激减少了男性的更新.
结论:
- 在恐惧灭绝期间的卵巢激素通过SN-DLS多巴胺通路减少随后的恐惧复发.
- SN-DLS DA路径代表了一种新的治疗点,用于减少两性恐惧复发.
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