Tina B Lonsdorf1, Jan Haaker, Tahmine Fadai, Raffael Kalisch. 1. Institute for Systems Neuroscience, University Medical Center Hamburg-Eppendorf (UKE), Martinistrasse 52, 20246, Hamburg, Germany, t.lonsdorf@uke.de.
Abstract
RATIONALE: 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. OBJECTIVES: 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.
RCT Entities:
RATIONALE: 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. OBJECTIVES: 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: Raffael Kalisch; Beatrice Holt; Predrag Petrovic; Benedetto De Martino; Stefan Klöppel; Christian Büchel; Raymond J Dolan Journal: Cereb Cortex Date: 2008-05-13 Impact factor: 5.357