Effects of noradrenergic blockade on emotional working memory and its neural underpinnings: A randomized, double-blind, placebo-controlled trial.

The neurotransmitter noradrenaline (NA) has been previously associated with brain-wide regulatory functions for various cognitive as well as affective processes. Clonidine, an adrenoceptor agonist, predominantly stimulates α2-receptors, reducing NA release. However, the specific effects of clonidine, as well as NA's general impact on neural mechanisms underlying cognitive and affective processing remain incompletely understood. 74 healthy men were included in a double-blind, randomized, parallel-group functional magnetic resonance imaging (fMRI) study with two treatment conditions: single-dose clonidine (0.15 mg) and placebo. The fMRI procedure comprised a 2-back working memory (WM) task with positive, negative and neutral words used as stimuli. No behavioral effects of clonidine on WM performance for emotional or neutral words were observed. Clonidine primarily attenuated neural activation in response to emotional compared to neutral stimuli in the ventromedial prefrontal cortex (vmPFC). In the placebo condition, emotional activation of the vmPFC was negatively correlated with emotional WM accuracy, implying involvement of this region in emotional resource allocation during cognitive processing. Interestingly, no effects of clonidine on valence-specific (positive vs. negative condition) or general WM-related neural activation were found. Our results thus indicate that clonidine modulates neural mechanisms specifically associated with the processing of emotional information and emotional reactivity, suggesting a distinct role for NA in affective functions.