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

L-DOPA improves extinction memory retrieval after successful fear extinction.

Author information

1
Neuroimaging Center (NIC), Focus Program Translational Neuroscience (FTN), Johannes Gutenberg University Medical Center, Langenbeckstr. 1, 55131, Mainz, Germany. a.m.v.gerlicher@uva.nl.
2
Deutsches Resilienz Zentrum (DRZ), Johannes Gutenberg University Medical Center, Untere Zahlbacher Str. 8, 55131, Mainz, Germany. a.m.v.gerlicher@uva.nl.
3
Department of Clinical Psychology, University of Amsterdam, Nieuwe Achtergracht 129B, 1018 WS, Amsterdam, The Netherlands. a.m.v.gerlicher@uva.nl.
4
Deutsches Resilienz Zentrum (DRZ), Johannes Gutenberg University Medical Center, Untere Zahlbacher Str. 8, 55131, Mainz, Germany.
5
Department of Psychiatry and Psychotherapy, Johannes Gutenberg University Medical Center, Untere Zahlbacher Str. 8, 55131, Mainz, Germany.
6
Neuroimaging Center (NIC), Focus Program Translational Neuroscience (FTN), Johannes Gutenberg University Medical Center, Langenbeckstr. 1, 55131, Mainz, Germany.

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

PMID:
31243481
DOI:
10.1007/s00213-019-05301-4

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