4.3 Article

Combining D-cycloserine with appetitive extinction learning modulates CrossMak amygdala activity during recall

Journal

NEUROBIOLOGY OF LEARNING AND MEMORY
Volume 142, Issue -, Pages 209-217

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nlm.2017.05.008

Keywords

D-cycloserine; Pavlovian conditioning; Extinction recall; Amygdala; vmPFC; Reward

Funding

  1. Bundesminis-terium fur Bildung and Forschung [AS 01 GV0612]
  2. NeuroCure Cluster of Excellence
  3. Deutsche Forschungsgemeinschaft [FS FOR1617/SCHL1969/2-2]
  4. Elsa-Neumann scholarship

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Appetitive Pavlovian conditioning plays a crucial role in the pathogenesis of drug addiction and conditioned reward cues can trigger craving and relapse even after long phases of abstinence. Promising pre clinical work showed that the NMDA-receptor partial agonist D-cycloserine (DCS) facilitates Pavlovian extinction learning of fear and drug cues. Furthermore, DCS-augmented exposure therapy seems to be beneficial in various anxiety disorders, while the supposed working mechanism of DCS during human appetitive or aversive extinction learning is still not confirmed. To test the hypothesis that DCS administration before extinction training improves extinction learning, healthy adults (n = 32) underwent conditioning, extinction, and extinction recall on three successive days in a randomized, double-blind, placebo-controlled fMRI design. Monetary wins and losses served as unconditioned stimuli during conditioning to probe appetitive and aversive learning. An oral dose of 50 mg of DCS or placebo was administered 1 h before extinction training and DCS effects during extinction recall were evaluated on a behavioral and neuronal level. We found attenuated amygdala activation in the DCS compared to the placebo group during recall of the extinguished appetitive cue, along with evidence for enhanced functional amygdala-vmPFC coupling in the DCS group. While the absence of additional physiological measures of conditioned responses during recall in this study prevent the evaluation of a behavioral DC5 effect, our neuronal findings are in accordance with recent theories linking successful extinction recall in humans to modulatory top down influences from the vmPFC that inhibit amygdala activation. Our results should encourage further translational studies concerning the usefulness of DCS to target maladaptive Pavlovian reward associations. (C) 2017 Elsevier Inc. All rights reserved.

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