Abstract
RationaleWorking 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.ObjectiveThe 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.MethodsWe 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).ResultsWhile 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.ConclusionsOur results suggest that noradrenergic stimulation through yohimbine does not affect (non-spatial) working memory in healthy human participants.
Highlights
Working memory is a core cognitive function that is essential for goal-directed behavior
One-hundred and thirty right-handed, healthy individuals participated in this experiment after criteria for participation had baseline session of an adaptive n-back task in which they were requested to indicate for each number presented on the computer screen whether the number was different from the number that had been displayed n positions before
Yohimbine was associated with significant increases in systolic and diastolic blood pressure, which are often considered to be indirect measures of noradrenergic arousal (Goldberg et al 1983; Swann et al 2005)
Summary
Working memory is a core cognitive function that is essential for goal-directed behavior. At a neural level, working memory relies heavily on the dorsolateral prefrontal cortex (Barbey et al 2013; Cohen et al 1997; D'Esposito and Postle 1999). This brain area is known to be regulated by catecholamines in general and noradrenaline in particular (Arnsten 2011; Robbins 2000). The most compelling evidence for an association between noradrenaline and working memory comes from animal studies. Evidence from non-human primates suggested further differential effects of alpha-2(A) adrenergic and alpha-1 adrenergic receptors in the impact of noradrenaline
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
