L-DOPA improves extinction memory retrieval after successful fear extinction
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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.
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Administration of a pharmacological agent to either disrupt the original memory or enhance extinction may worsen symptoms if the cue exposure session engages the alternative memory process.
“the administration of a pharmacological agent to either disrupt the original memory or enhance extinction may worsen symptoms if the cue exposure session engages the alternative memory process (Price et al., 2009; Gerlicher et al., 2019).”
From Retrieval-Dependent Mechanisms Affecting Emotional Memory Persistence: Reconsolidation, Extinction, and the Space in Between (2020) · cites this paper as Gerlicher et al., 2019
The Introduction explains that a drug intended to enhance extinction may instead strengthen fear memory when exposure reactivates that memory. The Discussion reports greater conditioned fear responses after L-DOPA when extinction was unsuccessful. Our copy does not establish the converse claim that a drug intended to disrupt the original memory may worsen symptoms when exposure engages extinction; the reported outcome is conditioned fear, not clinical symptoms. (LLM, conf=0.86)
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Navigating the garden of forking paths for data exclusions in fear conditioning research
Lonsdorf, T. B., Klingelhöfer-Jens, M., Andreatta, M., Beckers, T., Chalkia, A., Gerlicher, A., Jentsch, V. L., Meir Drexler, S., Mertens, G., Richter, J., et al. (2019) · eLife · doi:10.7554/elife.52465 · Cited by 164 · see citing works
Chmitorz, A., Kurth, K., Mey, L. K., Wenzel, M., Lieb, K., Tüscher, O., Kubiak, T., & Kalisch, R. (2020) · JMIR Mental Health · doi:10.2196/14566 · Cited by 72 · see citing works
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Vaverková, Z., Milton, A. L., & Merlo, E. (2020) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2020.574358 · Cited by 27 · see citing works
“to either disrupt the original memory or enhance extinction may worsen symptoms if the cue exposure session engages the alternative memory process (Price et al., 2009; Gerlicher et al., 2019).”
Background
- Authors
- Gerlicher, A. M. V., Tüscher, O., & Kalisch, R.
- Affiliations
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- Corresponding author
- Gerlicher, A. M. V.
- Venue
- Psychopharmacology
- Published
- 2019-06-26
- Volume
- 236
- Issue
- 12
- Pages
- 3401-3412
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- PMC
- PMC6892771
- OpenAlex
- W2953822305
- Cited by
- 39
- References
- 19
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 4 · 2023: 6 · 2022: 10 · 2021: 5 · 2020: 3 · 2019: 4
- FWCI
- 3.20
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Psychopharmacology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UvA-DARE (University of Amsterdam) (submittedVersion, cc-by)
- Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Deutsche Forschungsgemeinschaft (CRC1193)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- L-DOPA, fear extinction, extinction memory consolidation, exposure therapy, anxiety disorders, fear conditioning, dopamine precursor, skin conductance response, boundary conditions
- MeSH terms
- Memory Consolidation, Adult, Conditioning, Classical, Double-Blind Method, Extinction, Psychological, Fear, Humans, Levodopa, Male, Photic Stimulation, Dopamine Agents, Young Adult
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