title: No evidence for enhanced extinction memory consolidation through noradrenergic reuptake inhibition-delayed memory test and reinstatement in human fMRI.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  Thus, to enhance extinction memory consolidation through boosted NAergic signalling, we administered 4 mg reboxetine (RBX) immediately after extinction learning (day 2, 24 h after conditioning on day 1) in a randomised, placebo (PLC)-controlled design. At a delayed memory test (day 8), we probed cued and contextual fear and extinction memories before and after a reinstatement manipulation.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute for Systems Neuroscience, University Medical Center Hamburg-Eppendorf (UKE), Martinistrasse 52, 20246, Hamburg, Germany, t.lonsdorf@uke.de.
authors.forename: Tina B
authors.initials: TB
authors.lastname: Lonsdorf
authors.forename: Jan
authors.initials: J
authors.lastname: Haaker
authors.forename: Tahmine
authors.initials: T
authors.lastname: Fadai
authors.forename: Raffael
authors.initials: R
authors.lastname: Kalisch
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000328:Adult; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D001931:Brain Mapping; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D004597:Electroshock; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D005239:Fear / Q000187:drug effects / Q000502:physiology; D005712:Galvanic Skin Response / Q000187:drug effects; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D009025:Morpholines / Q000494:pharmacology*; D009483:Neuropsychological Tests; D000077593:Reboxetine; D018036:Selenium Compounds; D013647:Task Performance and Analysis; D014796:Visual Perception / Q000187:drug effects / Q000502:physiology
chemical_list: D018759:Adrenergic Uptake Inhibitors; D009025:Morpholines; D018036:Selenium Compounds; C477347:cupric selenide; D000077593:Reboxetine