Drug-induced stimulation and suppression of action monitoring in healthy volunteers
Drug-induced stimulation and suppression of action monitoring in healthy volunteers
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DOI：
10.1007/s00213-004-1915-6
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发表时间：
2004-12-01
影响因子：
3.4
通讯作者：
Sabbe, BGC
中科院分区：
文献类型：
--
作者：
de Bruijn, ERA;Hulstijn, W;Sabbe, BGC
原理：通过测量误差相关负性（ERN），对动作监测进行了广泛的研究。ERN是在错误反应后立即引发的事件相关电位（ERP），被认为起源于前扣带皮层（ACC）。虽然前扣带在大脑中起着核心作用，但只有少数研究直接调查了药物对动作监测的影响。最近的一项理论认为，中脑多巴胺系统将错误信号传递给前扣带皮层，并在那里产生神经神经网络。方法：采用Eriksen Flankers任务对12名健康志愿者进行erp和行为测量。在4个测试日的每一天，在双盲、四向交叉设计中口服兴奋剂d -安非他明、镇静剂劳拉西泮、抗抑郁药米氮平或安慰剂。结果：多巴胺间接激动剂安非他明可使神经神经网络振幅明显增大，但不影响反应时间。劳拉西泮和米氮平均表现出反应减慢，但只有劳拉西泮导致ERN振幅降低。结论：给药安非他明导致刺激的动作监测，反映在增加的ERN振幅。这一结果为多巴胺能参与动作监测提供了证据，并且与神经精神疾病中发现的ERN振幅差异一致，也表明多巴胺能参与。劳拉西泮和米氮平的不同作用可能是由这两种镇静类型的神经生物学特性引起的。给予劳拉西泮后，动作监测受到抑制，因为gaba能通路直接抑制ACC功能，而米氮平的组胺能通路不直接支配ACC。
Rationale: Action monitoring has been studied extensively by means of measuring the error-related negativity (ERN). The ERN is an event-related potential (ERP) elicited immediately after an erroneous response and is thought to originate in the anterior cingulate cortex (ACC). Although the ACC has a central role in the brain, only a few studies have been performed to investigate directly the effects of drugs on action monitoring. A recent theory argues that the mesencephalic dopamine system carries an error signal to the ACC, where it generates the ERN. Methods: ERPs and behavioral measurements were obtained from 12 healthy volunteers performing an Eriksen Flankers task. On each of the 4 test days, the stimulant D-amphetamine, the sedative lorazepam, the antidepressant mirtazapine, or a placebo was orally administered in a double-blind, four-way crossover design. Results: The indirect dopamine agonist amphetamine led to a strong enlargement of ERN amplitudes without affecting reaction times. Lorazepam and mirtazapine both showed slowing of responses, but only lorazepam led to reduced ERN amplitudes. Conclusions: Administration of amphetamine leads to stimulated action monitoring, reflected in increased ERN amplitudes. This result provides evidence for dopaminergic involvement in action monitoring and is in line with differences in ERN amplitude found in neuropsychiatric disorders also suggesting dopaminergic involvement. The different effects for lorazepam and mirtazapine are probably caused by the neurobiological characteristics of these two types of sedation. Action monitoring is suppressed after administration of lorazepam, because the GABAergic pathways directly inhibit ACC functioning, whereas the histaminergic pathways of mirtazapine do not innervate the ACC directly.