No evidence for enhanced extinction memory consolidation through noradrenergic reuptake inhibition—delayed memory test and reinstatement in human fMRI

Abstract

One promising approach in the current ambition to maximise treatment benefit for anxiety disorders is the pharmacological enhancement of cognitive-behavioural treatment efficacy, which can be experimentally modelled by pharmacological enhancement of extinction learning/consolidation. Noradrenaline (NA) is involved in memory consolidation, and NAergic innervations are found in brain areas implicated in fear conditioning and extinction. Thus, to enhance extinction memory consolidation through boosted NAergic signalling, we administered 4mg reboxetine (RBX) immediately after extinction learning (day2, 24h after conditioning on day1) in a randomised, placebo (PLC)-controlled design. At a delayed memory test (day8), we probed cued and contextual fear and extinction memories before and after a reinstatement manipulation. After reinstatement, we find significantly enhanced amygdala and posterior hippocampus activation in the RBX group, areas implicated in fear memory expression, while the PLC group exhibited enhanced activation in areas associated with extinction memory expression (vmPFC, anterior hippocampus). No group differences were found in skin conductance responses. Thus, our data do not support our hypothesis that enhancement of NA signalling may facilitate extinction memory consolidation and provide preliminary evidence that this might rather enhance fear memories on a neural but not physiological (skin conductance responses) level.