Renewal describes the recovery of an extinguished response if the contexts of extinction and recall differ, highlighting the context dependency of extinction. Studies demonstrated dopaminergic (DA) signalling to be important for context-related extinction learning with and without a fear component. In a previous study in humans, administration of the dopamine D2/D3 antagonist tiapride prior to extinction impaired extinction learning in a novel, but not a familiar context, without affecting renewal. In a further study, context processing during initial acquisition of associations was shown to be related to renewal. In this human fMRI study we investigated the potential role of DA signalling during this initial conditioning for the learning process and for renewal. While tiapride, administered prior to the start of learning, did not affect initial acquisition and renewal, extinction learning in a novel context was impaired, associated with reduced BOLD activation in vmPFC, left iFG and ACC – regions mediating response inhibition and selection from competing options using contextual information. Thus, different timepoints of administration of tiapride (before initial conditioning or extinction) had largely similar effects upon extinction and renewal. In addition, retrieval of previously acquired associations was impaired, pointing towards weaker association forming during acquisition.

Conceivably, effects of the DA blockade are associated with the challenge present in the respective task rather than the administration timepoint: the cognitive flexibility required for forming a new inhibitory association that includes a novel element clearly requires DA processing, while initial forming of associations, or of inhibitory associations without a new element, apparently rely less on the proper function of the DA system.

更新描述了如果灭绝和回忆的上下文不同，则消除响应的恢复，突出了灭绝的上下文依赖性。研究表明，多巴胺能 (DA) 信号对于有或没有恐惧成分的情境相关灭绝学习很重要。在先前的一项人类研究中，在灭绝之前施用多巴胺 D2/D3 拮抗剂 tiapride 会损害小说中的灭绝学习，但不是熟悉的背景，而不会影响更新。在进一步的研究中，最初获得关联期间的上下文处理被证明与更新有关。在这项人类功能磁共振成像研究中，我们研究了 DA 信号在学习过程和更新的初始调节过程中的潜在作用。虽然在开始学习之前服用 tiapride，不影响初始获取和更新，新环境中的灭绝学习受到损害，与 vmPFC、左侧 iFG 和 ACC 中的 BOLD 激活减少相关——区域介导反应抑制和使用上下文信息从竞争选项中进行选择。因此，tiapride 给药的不同时间点（在初始调节或消退之前）对消退和更新具有大致相似的影响。此外，对先前获得的关联的检索受到损害，表明在收购过程中形成的关联较弱。tiapride 给药的不同时间点（在初始调节或消退之前）对消退和更新具有大致相似的效果。此外，对先前获得的关联的检索受到损害，表明在收购过程中形成的关联较弱。tiapride 给药的不同时间点（在初始调节或消退之前）对消退和更新具有大致相似的效果。此外，对先前获得的关联的检索受到损害，表明在收购过程中形成的关联较弱。

可以想象，DA 阻断的效果与相应任务中存在的挑战相关，而不是与给药时间点相关：形成包含新元素的新抑制关联所需的认知灵活性显然需要 DA 处理，而初始形成关联，或没有新元素的抑制性关联，显然较少依赖于 DA 系统的适当功能。