Department of Cognitive Psychology, University of Hamburg, 20146, Hamburg, Germany.
Department of Psychiatry, University Clinic Hamburg-Eppendorf, Hamburg, Germany.
Psychopharmacology (Berl). 2020 Oct;237(10):3033-3046. doi: 10.1007/s00213-020-05590-0. Epub 2020 Jun 25.
Working memory depends on prefrontal cortex functioning, which is particularly sensitive to levels of noradrenaline. Studies in non-human primates have shown that modest levels of noradrenaline improve working memory, and that higher levels of noradrenaline impair working memory performance. However, research in humans provided inconsistent findings concerning noradrenergic effects on working memory.
The present study aimed at assessing dose-dependent effects of yohimbine, an alpha-2 adrenoceptor antagonist, on working memory performance in healthy humans. We further aimed to explore a potential interactive effect between noradrenergic arousal and lack of control over aversive events on working memory performance.
We used a double-blind, fully crossed, placebo-controlled, between-subject design. Participants (N = 121) performed an adaptive n-back task before and after oral administration of either a placebo, 20 mg, or 40 mg yohimbine and a manipulation of controllability, during which participants could either learn to avoid electric shocks (controllability groups), had no instrumental control over shock administration (uncontrollability groups), or did not receive any shocks (no-shock control group).
While no significant results of noradrenergic stimulation through yohimbine were obtained using conventional frequentist analyses, additional Bayesian analyses provided strong evidence for the absence of an association between pharmacological treatment and working memory performance. We further observed no effect of controllability and no interaction between noradrenergic stimulation and the manipulation of controllability.
Our results suggest that noradrenergic stimulation through yohimbine does not affect (non-spatial) working memory in healthy human participants.
工作记忆依赖于前额叶皮层的功能，而前额叶皮层对去甲肾上腺素的水平特别敏感。非人类灵长类动物的研究表明，适度的去甲肾上腺素水平可以改善工作记忆，而较高的去甲肾上腺素水平会损害工作记忆表现。然而，人类的研究结果对去甲肾上腺素对工作记忆的影响提供了不一致的发现。
本研究旨在评估育亨宾，一种α-2 肾上腺素受体拮抗剂，对健康人类工作记忆表现的剂量依赖性影响。我们还旨在探索去甲肾上腺素兴奋与对厌恶事件缺乏控制之间的潜在相互作用对工作记忆表现的影响。
我们使用了双盲、完全交叉、安慰剂对照、被试间设计。参与者（N=121）在口服安慰剂、20 毫克或 40 毫克育亨宾前后进行了自适应 n 回任务，以及操纵可控性，在此期间，参与者可以学习避免电击（可控性组）、对电击的实施没有工具性控制（不可控性组）或不接受任何电击（无电击对照组）。
虽然通过育亨宾进行的去甲肾上腺素刺激的常规频率分析没有得到显著结果，但额外的贝叶斯分析提供了强有力的证据，表明药物治疗与工作记忆表现之间不存在关联。我们还观察到可控性没有影响，去甲肾上腺素刺激与可控性操纵之间也没有相互作用。
我们的结果表明，育亨宾通过去甲肾上腺素刺激不会影响健康人类参与者的（非空间）工作记忆。
