The NMDA agonist D-cycloserine facilitates fear memory consolidation in humans.
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.
Kalisch
Raffael
R
Functional Imaging Laboratory, Wellcome Department of Imaging Neuroscience, University College London, London, UK. rkalisch@uke.uni-hamburg.de
Holt
Beatrice
B
Petrovic
Predrag
P
De Martino
Benedetto
B
Klöppel
Stefan
S
Büchel
Christian
C
Dolan
Raymond J
RJ
D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology; D000328:Adult; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D003523:Cycloserine / Q000008:administration & dosage*; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D011939:Mental Recall / Q000187:drug effects / Q000502:physiology*; D016202:N-Methylaspartate / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists*
D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D003523:Cycloserine