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大鼠中由左旋多巴暴露导致的加速习惯性学习可被N-乙酰半胱氨酸阻止。

Accelerated habitual learning resulting from L-dopa exposure in rats is prevented by N-acetylcysteine.

作者信息

Gibson Anne S, Keefe Kristen A, Furlong Teri M

机构信息

Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT, USA; Interdepartmental Program in Neuroscience, University of Utah, Salt Lake City, UT, USA.

Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT, USA; Neuroscience Research Australia, 139 Barker Street, Randwick, NSW, Australia; School of Medical Sciences, University of New South Wales, Kensington, NSW, Australia.

出版信息

Pharmacol Biochem Behav. 2020 Nov;198:173033. doi: 10.1016/j.pbb.2020.173033. Epub 2020 Sep 2.

Abstract

Instrumental actions are initially goal-directed and driven by their associated outcome. However, with repeated experience habitual actions develop which are automated and efficient, as they are instead driven by antecedent stimuli. Dopamine is thought to facilitate the transition from goal-directed to habitual actions. This idea has been largely derived from evidence that psychostimulants accelerate the development of habitual actions. In the current study, we examined the impact of L-dopa (levodopa or L-dihydroxyphenylalanine), which also potentiates dopamine activity, on habitual learning. L-dopa was systemically administered prior to training rats to press a lever for a food outcome. When tested, L-dopa exposed animals were insensitive to changes in the value of the food outcome, and hence demonstrated accelerated habitual behavioral control compared to control animals that remained goal directed. We also showed that when N-acetylcysteine (NAC), an antioxidant and regulator of glutamate activity, was co-administered with L-dopa, it prevented the transition to habitual behavior; an effect demonstrated previously for cocaine. Therefore, this study establishes similarities between L-dopa and psychostimulants in both the development and prevention of habitual actions, and supports the notion that excess dopamine potentiates habitual learning. This finding extends the limited existing knowledge of the impact of L-dopa on learning and behavior, and has implications for neurological disorders where L-dopa is the primary treatment.

摘要

工具性动作最初是目标导向的,并由其相关结果驱动。然而,随着反复的经验,习惯性动作会发展起来,这些动作是自动且高效的,因为它们是由先前的刺激驱动的。多巴胺被认为有助于从目标导向动作向习惯性动作的转变。这个观点很大程度上源于精神兴奋剂加速习惯性动作发展的证据。在当前的研究中,我们研究了同样能增强多巴胺活性的左旋多巴(L - 多巴或L - 二羟基苯丙氨酸)对习惯性学习的影响。在训练大鼠按压杠杆以获取食物结果之前,对其进行左旋多巴的全身给药。在测试时,接受左旋多巴处理的动物对食物结果价值的变化不敏感,因此与仍保持目标导向的对照动物相比,表现出加速的习惯性行为控制。我们还表明,当抗氧化剂和谷氨酸活性调节剂N - 乙酰半胱氨酸(NAC)与左旋多巴共同给药时,它能阻止向习惯性行为的转变;这一效应先前在可卡因的研究中已得到证实。因此,本研究确立了左旋多巴与精神兴奋剂在习惯性动作的发展和预防方面的相似性,并支持了过量多巴胺增强习惯性学习的观点。这一发现扩展了关于左旋多巴对学习和行为影响的有限现有知识,并对以左旋多巴为主要治疗手段的神经系统疾病具有启示意义。

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