恐惧灭绝是多巴胺和L-DOPA在腹中介前额叶皮层中的拯救作用
Simone B Sartori1, Thomas M V Keil1, Kai K Kummer2
1Department of Pharmacology and Toxicology, Institute of Pharmacy and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, Austria.
Translational psychiatry
|January 8, 2024
概括
在下肢皮层 (IL) 中增加多巴胺可以恢复小鼠的恐惧灭绝. 这表明多巴胺在治疗焦虑和创伤障碍方面发挥着关键作用.
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
- 药理学 药理学是指药理学的学科.
背景情况:
- 腹中前额叶皮层 (vmPFC),或动物的下边皮层 (IL),与恐惧灭绝有关.
- 假设多巴胺 (DA) 前体L-DOPA有助于恐惧灭绝,但这需要直接测试.
- 一个有损恐惧灭绝 (129S1/SvImJ菌株;S1) 的小鼠模型被用来调查这个假设.
研究的目的:
- 调查多巴胺在恐惧灭绝期间在IL中的作用.
- 测试L-DOPA通过IL的影响促进恐惧灭绝的假设.
- 探索潜在的神经机制受损的恐惧灭绝和多巴胺的影响.
主要方法:
- 在体内微透析以监测S1小鼠在恐惧灭绝和L-DOPA管理期间在IL中的细胞外DA.
- 系统性L-DOPA的管理和DA的直接微输入IL.
- 在mPFC中的IL神经元的ex vivo多电极阵列记录和直接早期基因和DA受体信号标记的量化.
主要成果:
- 系统性L-DOPA增加了ILDA水平,并促进了S1小鼠的短期灭绝学习和保留.
- 直接向IL注入DA微输注导致长期的恐惧灭绝,独立于上腺体受体.
- 与有能力的C57BL/6J小鼠相比,S1小鼠显示DA引起的mPFC网络反应减少,部分原因是D1受体激活.
结论:
- 在IL中局部多巴胺的增加足以拯救受损的恐惧灭绝,这表明IL多巴胺的关键作用.
- 系统性L-DOPA的暂时效应表明在达到有效ILDA水平或在其他大脑区域的相反作用方面存在潜在的限制.
- 这些发现提供了关于DA和L-DOPA在恐惧灭绝中的神经基础的见解,并表明对焦虑和创伤障碍的治疗潜力.
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