mPFC-VTA通路在控制罗马高回避和低回避大鼠冲动行为和风险决策中的不同作用

IF 4.5 2区 医学 Q1 CLINICAL NEUROLOGY
Ginna Urueña-Méndez, Chloé Arrondeau, Florian Marchessaux, Raphaël Goutaudier, Nathalie Ginovart
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引用次数: 0

摘要

背景:冲动行为和风险相关决策(RDM)与包括药物滥用在内的各种精神疾病有关。然而,尽管内侧前额叶皮层(mPFC)直接投射到 VTA,但 mPFC 到 VTA 通路在控制冲动行为和 RDM 方面的具体作用仍有待探索:方法:我们使用[18F]-氟脱氧葡萄糖正电子发射断层扫描评估了罗马高回避大鼠(RHA)和低回避大鼠(RLA)的大脑代谢活动,这两种大鼠在冲动行为和RDM方面表现出先天性差异。值得注意的是,我们使用了基于病毒的双重解离化学遗传学策略,首次分离出了 mPFC 到 VTA 通路在控制这些行为中的作用。我们选择性地激活了RHA大鼠的mPFC-VTA通路,抑制了RLA大鼠的mPFC-VTA通路,评估了其对大鼠赌博任务中冲动行为和RDM的影响:结果表明,与基线时的RLA大鼠相比,RHA大鼠表现出更高的冲动行为、更低的最优决策能力和更低的皮质活动。化学基因激活 mPFC 至 VTA 通路可减少 RHA 大鼠的冲动行为,而化学基因抑制则对 RLA 大鼠产生相反的效果。然而,这些操作并不影响冲动性行为障碍。因此,通过以表型依赖的方式特异性地靶向 mPFC 到 VTA 通路,我们恢复了冲动行为的先天模式,但没有恢复 RDM:我们的研究结果表明,mPFC-VTA通路在冲动行为和RDM中扮演着不同的角色,突出了其作为研究冲动相关疾病靶点的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Dissociable Roles of the mPFC-to-VTA Pathway in the Control of Impulsive Action and Risk-Related Decision-Making in Roman High- and Low-Avoidance Rats.

Background: Impulsive action and risk-related decision-making (RDM) are associated with various psychiatric disorders, including drug abuse. Both behavioral traits have also been linked to reduced frontocortical activity and alterations in dopamine function in the ventral tegmental area (VTA). However, despite direct projections from the medial prefrontal cortex (mPFC) to the VTA, the specific role of the mPFC-to-VTA pathway in controlling impulsive action and RDM remains unexplored.

Methods: We used positron emission tomography with [18F]-fluorodeoxyglucose to evaluate brain metabolic activity in Roman high- (RHA) and low-avoidance (RLA) rats, which exhibit innate differences in impulsive action and RDM. Notably, we used a viral-based double dissociation chemogenetic strategy to isolate, for the first time to our knowledge, the role of the mPFC-to-VTA pathway in controlling these behaviors. We selectively activated the mPFC-to-VTA pathway in RHA rats and inhibited it in RLA rats, assessing the effects on impulsive action and RDM in the rat gambling task.

Results: Our results showed that RHA rats displayed higher impulsive action, less optimal decision-making, and lower cortical activity than RLA rats at baseline. Chemogenetic activation of the mPFC-to-VTA pathway reduced impulsive action in RHA rats, whereas chemogenetic inhibition had the opposite effect in RLA rats. However, these manipulations did not affect RDM. Thus, by specifically targeting the mPFC-to-VTA pathway in a phenotype-dependent way, we reverted innate patterns of impulsive action but not RDM.

Conclusion: Our findings suggest a dissociable role of the mPFC-to-VTA pathway in impulsive action and RDM, highlighting its potential as a target for investigating impulsivity-related disorders.

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来源期刊
CiteScore
8.40
自引率
2.10%
发文量
230
审稿时长
4-8 weeks
期刊介绍: The central focus of the journal is on research that advances understanding of existing and new neuropsychopharmacological agents including their mode of action and clinical application or provides insights into the biological basis of psychiatric disorders and thereby advances their pharmacological treatment. Such research may derive from the full spectrum of biological and psychological fields of inquiry encompassing classical and novel techniques in neuropsychopharmacology as well as strategies such as neuroimaging, genetics, psychoneuroendocrinology and neuropsychology.
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