Human cognitive flexibility depends on dopamine D2 receptor signaling
Human cognitive flexibility depends on dopamine D2 receptor signaling
复制标题
人类认知灵活性取决于多巴胺 D2 受体信号传导
作者：
Mieke van Holstein;E. Aarts;M. E. van der Schaaf;Dirk E. M. Geurts;R. Verkes;B. Franke;M. V. van Schouwenburg;R. Cools
越来越多的证据表明，多巴胺的认知效应取决于被激活的多巴胺受体的亚型。特别是，最近对动物的研究以及目前的理论研究表明，认知灵活性取决于多巴胺D2受体信号。然而，有没有类似的mechanisms在human.ObjectivesWe的目的是证明，最佳多巴胺D2受体信号是至关重要的人类cognitive flexibility.MethodsTo为此，药理学预处理设计。这使我们能够调查是否与D2受体拮抗剂舒必利预处理的多巴胺受体激动剂溴隐亭对任务集转换的影响被废除。为了解释个体（遗传）多巴胺基线水平的差异，我们利用了多巴胺转运蛋白基因DAT 1 3′-非翻译区的一个常见的可变数目串联重复序列（VNTR）多态性。结果与安慰剂相比，溴隐亭改善了认知灵活性，但仅在遗传决定的低多巴胺水平受试者中（n = 27）。溴隐亭对认知灵活性的这种有益作用被阻断预处理与选择性多巴胺D2受体拮抗剂舒必利（n = 14）conclusionsThese结果提供了强有力的证据支持的假设，人类认知灵活性牵连多巴胺D2受体信号。
RationaleAccumulating evidence indicates that the cognitive effects of dopamine depend on the subtype of dopamine receptor that is activated. In particular, recent work with animals as well as current theorizing has suggested that cognitive flexibility depends on dopamine D2 receptor signaling. However, there is no evidence for similar mechanisms in humans.ObjectivesWe aim to demonstrate that optimal dopamine D2 receptor signaling is critical for human cognitive flexibility.MethodsTo this end, a pharmacological pretreatment design was employed. This enabled us to investigate whether effects of the dopamine receptor agonist bromocriptine on task-set switching were abolished by pretreatment with the D2 receptor antagonist sulpiride. To account for individual (genetic) differences in baseline levels of dopamine, we made use of a common variable number of tandem repeat (VNTR) polymorphism in the 3′-untranslated region of the dopamine transporter gene, DAT1.ResultsBromocriptine improved cognitive flexibility relative to placebo, but only in subjects with genetically determined low levels of dopamine (n = 27). This beneficial effect of bromocriptine on cognitive flexibility was blocked by pretreatment with the selective dopamine D2 receptor antagonist sulpiride (n = 14).ConclusionsThese results provide strong evidence in favor of the hypothesis that human cognitive flexibility implicates dopamine D2 receptor signaling.
DOI：
--
发表时间：
2005-05
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
--
作者：
C. V. van Dyck;R. Malison;L. Jacobsen;J. Seibyl;J. Staley;M. Laruelle;R. Baldwin;R. Innis;J. Gelernter
通讯作者：
C. V. van Dyck;R. Malison;L. Jacobsen;J. Seibyl;J. Staley;M. Laruelle;R. Baldwin;R. Innis;J. Gelernter
成年年龄对工作记忆结构和操作能力的影响。
影响因子：
3.7
作者：
Salthouse,TA;Babcock,RL;Shaw,RJ
通讯作者：
Shaw,RJ