青春期多巴胺转运器阻塞会增加成人多巴胺功能,冲动性和攻击性
Deepika Suri1,2, Giulia Zanni1,2, Darshini Mahadevia1,2
1Department of Psychiatry, Columbia University, New York, NY, 10032, USA.
Molecular psychiatry
|August 2, 2023
概括
在敏感时期 (P32-41) 青少年的多巴胺转运器阻塞通过改变多巴胺神经元活动增加了成年人的攻击性和冲动性. 这项研究提供了关于神经精神疾病发育起源的见解.
科学领域:
- 神经科学是一个神经科学.
- 发育生物学 发展生物学
- 行为科学 行为科学
背景情况:
- 敏感的发育期对于神经电路的形成至关重要,但也使人容易受到干扰.
- 多巴胺系统对青少年行为至关重要,并且表现出高度的可塑性,使其易受持久变化的影响.
- 了解超越感官发育的多巴胺敏感期对于理解神经精神疾病病因至关重要.
研究的目的:
- 为了获得有关青春期特定多巴胺敏感时期及其对成人行为影响的机制性洞察力.
- 在这个敏感的窗口中识别多巴胺转运器 (DAT) 阻塞的神经相关物和行为后果.
- 研究特定多巴胺基通路在调解观察到的行为变化中的作用.
主要方法:
- 在特定的产后几天 (P32-41) 中使用了具有多巴胺转运器 (DAT) 阻塞的小鼠模型.
- 评估成人行为,包括攻击性,冲动性,认知,工作记忆和动机.
- 采用体外和体外电生理学来测量多巴胺激应神经元发射.
- 使用光遗传学来选择性地激活腹膜区域 (VTA) 和黑质部分紧 (SNc) 多巴胺神经元.
主要成果:
- 青少年DAT阻塞 (P32-41) 显著增加了成年人的攻击性和冲动性.
- 这种阻塞导致多巴胺激应神经元的发射增加,被确定为神经相关物.
- 冲动性,但不是认知,工作记忆或动机,在成年后受到影响.
- VTA多巴胺神经元的光遗传激活模仿了在DAT阻塞后观察到的冲动性增加.
结论:
- 青春期代表了对多巴胺敏感的关键时期,其中DAT阻塞可以诱导长期的行为变化,特别是增加了侵略性和冲动性.
- 改变多巴氨基神经元活动,特别是在VTA,是这些行为缺陷的基础.
- 这些发现为侵略性和冲动性的发育起源提供了关键的见解,可能为相关神经精神疾病的诊断和治疗策略提供信息.
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