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Cerebral Cortex Advance Access published online on May 13, 2008
Cerebral Cortex, doi:10.1093/cercor/bhn076
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© 2008 The Authors
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

The NMDA Agonist D-Cycloserine Facilitates Fear Memory Consolidation in Humans

Raffael Kalisch1,2,3, Beatrice Holt1, Predrag Petrovic1, Benedetto De Martino1, Stefan Klöppel1,4, Christian Büchel2,3 and Raymond J. Dolan1

1 Functional Imaging Laboratory, Wellcome Department of Imaging Neuroscience, University College London, London, UK, 2 NeuroImage Nord, Hamburg-Kiel-Lübeck, Germany, 3 Institute for Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany, 4 Department of Psychiatry and Psychotherapy, Albert-Ludwigs-University Freiburg, Freiburg, Germany

Address correspondence to email: rkalisch{at}uke.uni-hamburg.de.

Animal research suggests that the consolidation of fear and extinction memories depends on N-methyl D-aspartate (NMDA)-type glutamate receptors. Using a fear conditioning and extinction paradigm in healthy normal volunteers, we show that postlearning administration of the NMDA partial agonist D-cycloserine (DCS) facilitates fear memory consolidation, evidenced behaviorally by enhanced skin conductance responses, relative to placebo, for presentations of a conditioned stimulus (CS) at a memory test performed 72 h later. DCS also enhanced CS-evoked neural responses in a posterior hippocampus/collateral sulcus region and in the medial prefrontal cortex at test. Our data suggest a role for NMDA receptors in regulating fear memory consolidation in humans.

Key Words: anxiety • conditioning • emotion • fMRI • hippocampus • MPFC


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