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多巴胺 D₂ 受体对人类反应抑制和错误意识的调节作用。

Dopamine D₂ receptor modulation of human response inhibition and error awareness.

机构信息

The University of Queensland, Queensland, Australia.

出版信息

J Cogn Neurosci. 2013 Apr;25(4):649-56. doi: 10.1162/jocn_a_00327. Epub 2012 Nov 19.

DOI:10.1162/jocn_a_00327
PMID:23163418
Abstract

Response inhibition, comprising action cancellation and action restraint, and error awareness are executive functions of considerable clinical relevance to neuropsychiatric disorders. Nevertheless, our understanding of their underlying catecholamine mechanisms, particularly regarding dopamine, is limited. Here, we used the dopamine D2 agonist cabergoline to study its ability to improve inhibitory control and modulate awareness of performance errors. A randomized, double-blind, placebo-controlled, crossover design with a single dose of cabergoline (1.25 mg) and placebo (dextrose) was employed in 25 healthy participants. They each performed the stop-signal task, a well-validated measure of action cancellation, and the Error Awareness Task, a go/no-go measure of action restraint and error awareness, under each drug condition. Cabergoline was able to selectively reduce stop-signal RT, compared with placebo, indicative of enhanced action cancellation (p < .05). This enhancement occurred without concomitant changes in overall response speed or RT variability and was not seen for errors of commission on the Error Awareness Task. Awareness of performance errors on the go/no-go task was, however, significantly improved by cabergoline compared with placebo (p < .05). Our results contribute to growing evidence for the dopaminergic control of distinct aspects of human executive ability, namely, action cancellation and error awareness. The findings may aid the development of new, or the repurposing of existing, pharmacotherapy that targets the cognitive dysfunction of psychiatric and neurological disorders. They also provide further evidence that specific cognitive paradigms have correspondingly specific neurochemical bases.

摘要

反应抑制包括动作取消和动作抑制以及错误意识,是与神经精神障碍具有重要临床相关性的执行功能。然而,我们对其潜在儿茶酚胺机制的理解,特别是关于多巴胺的理解是有限的。在这里,我们使用多巴胺 D2 激动剂卡麦角林来研究其改善抑制控制和调节对表现错误的意识的能力。采用随机、双盲、安慰剂对照、交叉设计,对 25 名健康参与者进行单次剂量卡麦角林(1.25mg)和安慰剂(葡萄糖)的处理。他们每个人都在每种药物条件下进行停止信号任务,这是一种用于衡量动作取消的良好验证的措施,以及错误意识任务,这是一种用于衡量动作抑制和错误意识的 Go/No-Go 措施。与安慰剂相比,卡麦角林能够选择性地降低停止信号 RT,表明动作取消得到增强(p<0.05)。这种增强发生在整体反应速度或 RT 变异性没有变化的情况下,在错误意识任务的错误发生率上没有出现。然而,与安慰剂相比,卡麦角林显著提高了对表现错误的意识(p<0.05)。我们的结果为越来越多的证据表明多巴胺能控制人类执行能力的不同方面做出了贡献,即动作取消和错误意识。这些发现可能有助于开发新的或重新利用现有的针对精神和神经障碍的认知功能障碍的药物治疗方法。它们还提供了进一步的证据表明,特定的认知范式具有相应的特定神经化学基础。

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