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行为解码揭示皮质内大麻素潜能在THC-THC损伤期间

Anthony English^1,2, David Marcus^3,2, Khushi Yadav³

¹Department of Pharmacology, University of Washington School of Medicine, Seattle, WA, 98195, USA.

bioRxiv : the preprint server for biology

|October 3, 2025

概括

德尔塔-9-四大麻 (THC) 通过改变中部前额叶皮质 (mPFC) 中的大脑活动来破坏小鼠的自然行为. 这会导致通过GABAergic活性和内分泌素释放的变化导致运动障碍.

科学领域:

神经科学是一个神经科学.
行为科学行为科学
药理学药理学是指药理学的学科.

背景情况:

德尔塔-9-四大麻 (THC) 影响自然行为的确切机制尚未完全理解.
研究THC诱导的行为变化的神经支柱对于理解其影响至关重要.

研究的目的:

为了阐明THC如何损害小鼠的自然行为.
为了确定涉及THC诱导的运动缺陷的特定神经回路和分子通路.

主要方法:

开发一个视频监控的行为平台,利用机器学习分类器来分析鼠标的自然行为.
将THC注入中部前额叶皮层 (mPFC) 并评估其对行走动力学的影响.
测量mPFC的GABAergic活性和刺激/抑制 (E/I) 平衡.
闭环光遗传刺激mPFCGABAergic神经元以调查运动障碍.
测量内分泌素 (eCB) 释放和CB1受体 (CB1R) 活性.

主要成果:

将THC输入到mPFC中破坏了行走动力学,表明有损.
在步行开始前,THC增加了mPFC的GABAergic活性,改变了E/I平衡.
模仿THC效应的光遗传刺激加剧了运动障碍.
THC诱导了mPFC eCB释放的暂时增强,与运动和CB1R介导的突触抑制有关.

结论:

通过eCB释放的动态变化,THC通过激发来改变mPFC E/I平衡.
这些由THC诱导的神经化学变化直接导致行为障碍.

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