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

Claudia Ebrahimi1, Stefan P Koch1, Eva Friedel1

  • 1Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany.

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D-cycloserine (DCS) may enhance extinction learning by reducing amygdala activation during recall of appetitive cues. This suggests DCS could help target maladaptive reward associations in addiction and anxiety disorders.

Keywords:
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Area of Science:

  • Neuroscience
  • Psychopharmacology
  • Addiction Research

Background:

  • Appetitive Pavlovian conditioning is key in drug addiction, with cues triggering relapse.
  • D-cycloserine (DCS), an NMDA-receptor partial agonist, shows promise in facilitating extinction learning for fear and drug cues.
  • The mechanism of DCS in human appetitive extinction learning remains unclear.

Purpose of the Study:

  • To investigate if DCS administration before extinction training improves extinction learning in healthy adults.
  • To evaluate the behavioral and neuronal effects of DCS during extinction recall.
  • To test the hypothesis that DCS enhances extinction recall by modulating brain activity.

Main Methods:

  • A randomized, double-blind, placebo-controlled fMRI study with 32 healthy adults.
  • Participants underwent conditioning, extinction, and extinction recall over three days.
  • Monetary wins/losses served as stimuli; DCS or placebo was given before extinction training.

Main Results:

  • DCS group showed attenuated amygdala activation during recall of appetitive cues compared to placebo.
  • Evidence of enhanced functional amygdala-ventromedial prefrontal cortex (vmPFC) coupling was observed in the DCS group.
  • Behavioral effects of DCS were not evaluated due to lack of physiological measures.

Conclusions:

  • Neuronal findings support theories linking successful extinction recall to vmPFC top-down inhibition of amygdala activation.
  • DCS may modulate brain activity to facilitate extinction recall of appetitive cues.
  • Further translational studies are encouraged to explore DCS for maladaptive Pavlovian reward associations.