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

Ebrahimi, C., Koch, S. P., Friedel, E., Crespo, I., Fydrich, T., Ströhle, A., et al. (2017). Combining D-cycloserine with appetitive extinction learning modulates amygdala activity during recall. Neurobiology of Learning and Memory, 142, 209-217. doi:10.1016/j.nlm.2017.05.008.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0004-A748-F Version Permalink: http://hdl.handle.net/21.11116/0000-0004-DB71-6
Genre: Journal Article

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 Creators:
Ebrahimi, Claudia1, Author
Koch, Stefan P.1, Author
Friedel, Eva1, Author
Crespo, Ilsoray1, Author
Fydrich, Thomas2, Author
Ströhle, Andreas1, Author
Heinz, Andreas1, 3, Author
Schlagenhauf, Florian1, 4, Author              
Affiliations:
1Department of Psychiatry and Psychotherapy, Charité University Medicine Berlin, Germany, ou_persistent22              
2Department of Psychology, Humboldt University Berlin, Germany, ou_persistent22              
3NeuroCure Cluster of Excellence, Charité University Medicine Berlin, Germany, ou_persistent22              
4Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549              

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Free keywords: Amygdala; D-cycloserine; Extinction recall; Pavlovian conditioning; Reward; vmPFC
 Abstract: 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 preclinical 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 50mg of DCS or placebo was administered 1h 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 DCS 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.

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Language(s): eng - English
 Dates: 2017-05-072016-12-162017-05-122017-05-132017-07
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1016/j.nlm.2017.05.008
PMID: 28512009
Other: Epub 2017
 Degree: -

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Project name : -
Grant ID : 01GV0612
Funding program : -
Funding organization : German Federal Ministry of Education and Research (BMBF)
Project name : Lern- und Gewöhnungsprozesse als Prädiktoren für die Entwicklung und Aufrechterhaltung alkoholbezogener Störungen / FOR 1617
Grant ID : SCHL1969/2-2
Funding program : -
Funding organization : Deutsche Forschungsgemeinschaft (DFG)
Project name : -
Grant ID : -
Funding program : Elsa-Neumann scholarship
Funding organization : Humboldt Universität zu Berlin
Project name : NeuroCure – Neue Wege in der Erforschung und Behandlung von Erkrankungen des Nervensystems / EXC 2049
Grant ID : -
Funding program : -
Funding organization : Deutsche Forschungsgemeinschaft (DFG)

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Title: Neurobiology of Learning and Memory
  Other : Neurobiol. Learn. Mem.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Orlando, Fla. : Academic Press
Pages: - Volume / Issue: 142 Sequence Number: - Start / End Page: 209 - 217 Identifier: ISSN: 1074-7427
CoNE: https://pure.mpg.de/cone/journals/resource/954926963939