L-DOPA improves extinction memory retrieval after successful fear extinction

Psychopharmacology (Berl). 2019 Dec;236(12):3401-3412. doi: 10.1007/s00213-019-05301-4. Epub 2019 Jun 26.

Abstract

Rationale: A promising strategy to prevent a return of fear after exposure-based therapy in anxiety disorders is to pharmacologically enhance the extinction memory consolidation presumed to occur after exposure. Accumulating evidence suggests that the effect of a number of pharmacological consolidation enhancers depends on a successful fear reduction during exposure. Here, we employed the dopamine precursor L-DOPA to clarify whether its documented potential to enhance extinction memory consolidation is dependent on successful fear extinction.

Methods: In two double-blind, randomized and placebo-controlled experiments (experiment 1: N = 79, experiment 2: N = 32) comprising fear conditioning (day 1), extinction followed by administration of 150 mg L-DOPA or placebo (day 2) and a memory test (day 3) in healthy male adults, conditioned responses were assessed as differential skin conductance responses. We tested whether the effect of L-DOPA on conditioned responses at test depended on conditioned responses at the end of extinction in an experiment with a short (10 trials, experiment 1) and long (25 trials, experiment 2) extinction session.

Results: In both experiments, the effect of L-DOPA was dependent on conditioned responses at the end of extinction. That is, post-extinction L-DOPA compared to placebo administration reduced conditioned responses at test only in participants showing a complete reduction of conditioned fear at the end of extinction.

Conclusion: The results support the potential use of L-DOPA as a pharmacological adjunct to exposure treatment, but point towards a common boundary condition for pharmacological consolidation enhancers: a successful reduction of fear in the exposure session.

Keywords: Anxiety; Cognitive-behavioural therapy; Dopamine; Exposure treatment; Extinction; Fear conditioning; Memory consolidation; Post-traumatic stress disorder.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Conditioning, Classical / drug effects*
  • Conditioning, Classical / physiology
  • Dopamine Agents / pharmacology
  • Double-Blind Method
  • Extinction, Psychological / drug effects*
  • Extinction, Psychological / physiology
  • Fear / drug effects*
  • Fear / physiology
  • Fear / psychology*
  • Humans
  • Levodopa / pharmacology*
  • Male
  • Memory Consolidation / drug effects*
  • Memory Consolidation / physiology
  • Photic Stimulation / methods
  • Young Adult

Substances

  • Dopamine Agents
  • Levodopa