The effects of reboxetine on emotional processing in healthy volunteers: an fMRI study

Abstract

Recent neuropsychological studies in healthy volunteers suggest that antidepressants enhance the processing of positive emotional information. However, the neural substrates underpinning these changes have not been fully elucidated. The current study, therefore, used functional magnetic resonance imaging (fMRI) to map brain systems activated during successful categorization and subsequent recognition of self-referent positive and negative personality characteristics in healthy volunteers following short-term (7 days) repeated administration of the selective noradrenergic reuptake inhibitor reboxetine. Twenty-four healthy volunteers were randomly assigned to 7-day double-blind intervention with reboxetine or placebo. On day 7, neural responses during the categorization and subsequent recognition of positive and negative characteristics were assessed using fMRI. Questionnaires monitoring mood, hostility and anxiety were given before and during this intervention. During categorization, reboxetine was associated with greater activation to positive words, relative to negative words, in left precuneus and right inferior frontal gyrus. By contrast, at subsequent recognition reboxetine was associated with reduced response to positive words, relative to negative words, in left precuneus, anterior cingulate and medial frontal gyrus. These changes in the neural processing of positive and negative words occurred in the absence of significant differences in ratings of mood and anxiety. Such adaptations in the neural processing of emotional information support the hypothesis that antidepressants have early effects on emotional processing in a manner which would be expected to reverse negative biases in depression.

Serotonergic and Noradrenergic Modulation of Emotion Processing by Single Dose Antidepressants

“…Further studies administered (es)citalopram (Kumar et al, 2008;Rose et al, 2006) and reboxetine (Norbury et al, 2008 for 3 or 7 days, which may be at the very beginning of an antidepressive effect (Katz et al, 2004), and at which time regulatory effects are to be supposed.…”

A neurocognitive model for understanding treatment action in depression

“…Seven days of reboxetine reduced the reaction time to classify positive self-referent words, and both reboxetine and citalopram increased later recall of positive versus negative words [22]. At the neural level, 7 days of reboxetine increased activity to positive relative to negative words in the inferior frontal gyrus and precuneus during categorization, while decreasing activity in medial frontal gyrus and precuneus during correct recognition of positive words [47]. Increased activity to positive words during categorization may reflect heightened attentional processing of these words.…”

Modeling a Negative Response Bias in the Human Amygdala by Noradrenergic–Glucocorticoid Interactions

“…RBX is a highly selective inhibitor of presynaptic NE reuptake, thus increasing the availability of NE in the synaptic cleft (Kent, 2000;Scates and Doraiswamy, 2000). A 4 mg single oral dose of RBX was administered in analogy to previous studies investigating noradrenergic effects on emotion and cognition (Papps et al, 2002;Hurlemann et al, 2005;Norbury et al, 2008). A 30 mg single oral dose of hydrocortisone was administered to elevate CORT activity to levels ranging between moderate (20 mg) and extreme (40 mg) acute stress (Abercrombie et al, 2003).…”