Activation of the mPFC-NAc Pathway Reduces Motor Impulsivity but Does Not Affect Risk-Related Decision-Making in Innately High-Impulsive Male Rats

IF 2.9 3区 医学 Q2 NEUROSCIENCES
Chloé Arrondeau, Ginna Urueña-Méndez, Florian Marchessaux, Raphaël Goutaudier, Nathalie Ginovart
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Abstract

Attention-deficit/hyperactivity disorder (ADHD) and substance use disorders (SUD) are characterized by exacerbated motor and risk-related impulsivities, which are associated with decreased cortical activity. In rodents, the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) have been separately implicated in impulsive behaviors, but studies on the specific role of the mPFC-NAc pathway in these behaviors are limited. Here, we investigated whether heightened impulsive behaviors are associated with reduced mPFC activity in rodents and determined the involvement of the mPFC-NAc pathway in motor and risk-related impulsivities. We used the Roman High- (RHA) and Low-Avoidance (RLA) rat lines, which display divergent phenotypes in impulsivity. To investigate alterations in cortical activity in relation to impulsivity, regional brain glucose metabolism was measured using positron emission tomography and [18F]-fluorodeoxyglucose ([18F]FDG). Using chemogenetics, the activity of the mPFC-NAc pathway was either selectively activated in high-impulsive RHA rats or inhibited in low-impulsive RLA rats, and the effects of these manipulations on motor and risk-related impulsivity were concurrently assessed using the rat gambling task. We showed that basal [18F]FDG uptake was lower in the mPFC and NAc of RHA compared to RLA rats. Activation of the mPFC-NAc pathway in RHA rats reduced motor impulsivity, without affecting risk-related decision-making. Conversely, inhibition of the mPFC-NAc pathway had no effect in RLA rats. Our results suggest that the mPFC-NAc pathway controls motor impulsivity, but has limited involvement in risk-related decision-making in our current model. Our findings suggest that reducing fronto-striatal activity may help attenuate motor impulsivity in patients with impulse control dysregulation.

Abstract Image

激活 mPFC-NAc 通路可降低天生高冲动性雄性大鼠的运动冲动性,但不会影响其与风险相关的决策。
注意力缺陷/多动障碍(ADHD)和药物使用障碍(SUD)的特征是运动冲动和与风险相关的冲动加剧,这与大脑皮层活动减少有关。在啮齿类动物中,内侧前额叶皮层(mPFC)和伏隔核(NAc)分别与冲动行为有牵连,但有关 mPFC-NAc 通路在这些行为中的具体作用的研究却很有限。在这里,我们研究了啮齿类动物冲动行为的增强是否与 mPFC 活性的降低有关,并确定了 mPFC-NAc 通路在运动冲动和风险相关冲动中的参与程度。我们使用了Roman High-(RHA)和Low-Avoidance(RLA)大鼠品系,它们在冲动性方面表现出不同的表型。为了研究与冲动有关的大脑皮层活动的改变,我们使用正电子发射断层扫描和[18F]-氟脱氧葡萄糖([18F]FDG)测量了区域脑葡萄糖代谢。利用化学遗传学方法,选择性地激活高冲动型 RHA 大鼠或抑制低冲动型 RLA 大鼠的 mPFC-NAc 通路活性,并同时使用大鼠赌博任务评估这些操作对运动冲动和风险相关冲动的影响。我们发现,与 RLA 大鼠相比,RHA 大鼠 mPFC 和 NAc 的基础[18F]FDG 摄取较低。激活RHA大鼠的mPFC-NAc通路可减少运动冲动,但不会影响与风险相关的决策。相反,抑制 mPFC-NAc 通路对 RLA 大鼠没有影响。我们的研究结果表明,在我们目前的模型中,mPFC-NAc通路控制着运动冲动,但对风险相关决策的影响有限。我们的研究结果表明,减少前额纹状体的活动可能有助于减轻冲动控制失调患者的运动冲动。
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来源期刊
Journal of Neuroscience Research
Journal of Neuroscience Research 医学-神经科学
CiteScore
9.50
自引率
2.40%
发文量
145
审稿时长
1 months
期刊介绍: The Journal of Neuroscience Research (JNR) publishes novel research results that will advance our understanding of the development, function and pathophysiology of the nervous system, using molecular, cellular, systems, and translational approaches. JNR covers both basic research and clinical aspects of neurology, neuropathology, psychiatry or psychology. The journal focuses on uncovering the intricacies of brain structure and function. Research published in JNR covers all species from invertebrates to humans, and the reports inform the readers about the function and organization of the nervous system, with emphasis on how disease modifies the function and organization.
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