卡帕阿片类受体通过减少释放和增加摄入来负面调节实时自发的多巴胺信号
Conner W Wallace1, Katherine M Holleran1, Clare Y Slinkard1
1Department of Translational Neuroscience, Wake Forest University School of Medicine, Winston-Salem, NC.
bioRxiv : the preprint server for biology
|February 19, 2024
概括
卡帕阿片类受体 (KOR) 系统通过减少DA释放和增强DA再吸收来抑制多巴胺 (DA) 信号传递. 这些影响,特别是对多巴胺波动的影响,在雄性小鼠中更为明显.
科学领域:
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
- 神经化学 神经化学
背景情况:
- 迪诺芬/卡帕阿片类受体 (KOR) 系统调节多巴胺 (DA) 神经传递.
- 众所周知,KOR激活可以降低细胞外DA,并增强DA转运器 (DAT) 功能.
研究的目的:
- 为了研究KOR激活对核突 (NAc) 中自发DA波动的实时影响.
- 为了确定KOR系统调节DA信号的性别差异.
主要方法:
- 在自由移动的雄性和雌性小鼠中使用dLight1.2遗传编码的DA传感器利用纤维光度学.
- 系统地使用KOR激动剂U50,488H (U50),使用或不使用KOR激动剂aticaprant (ATIC).
- 分析了自发的DA信号特征,包括振幅,宽度和频率.
主要成果:
- 通过U50激活KOR可以减少男性的DA信号幅度和宽度,以及女性的宽度.
- 幅度和宽度之间的相关性斜率增加表明,男女DA吸收率有所提高.
- U50降低了自发的DA信号频率,在男性中观察到更强烈的效应.
- 用aticaprant的预处理阻断了U50的作用,证实了KOR的调解.
结论:
- KORs在NAc核心中对自发的DA信号产生显著的抑制控制.
- KOR激活通过抑制DA释放,促进DAT介导吸收和降低信号频率来影响DA信号.
- 在KOR系统对DA信号传递的抑制作用的大小上存在性别依赖的差异.
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