Single dose of l -dopa makes extinction memories context-independent and prevents the return of fear
Open accessAbstract
Significance: Traumatic events can engender persistent excessive fear responses to trauma reminders that may return even after successful treatment. In the psychotherapy of fear or anxiety disorders, patients make safety experiences that generate fear-inhibitory safety memories. Fear, however, frequently returns because safety memory retrieval fails. We find that safety memories can be strengthened and are more easily retrieved when adding a standard anti-Parkinson drug that augments brain levels of the neurotransmitter dopamine directly after a safety experience. In mice and humans, this treatment up-regulates an anti-fear area in the frontal cortex. Our findings open a unique avenue for improving psychotherapy.
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Administration of the dopamine precursor L-DOPA enhances the consolidation of extinction in both mice and humans.
“administration of the dopamine precursor L-DOPA enhances the consolidation of extinction in both mice and humans (Haaker et al., 2013).”
From Retrieval-Dependent Mechanisms Affecting Emotional Memory Persistence: Reconsolidation, Extinction, and the Space in Between (2020) · cites this paper as Haaker et al., 2013
Cites
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“Like in the dopamine-dependent formation of long-term fear (13) and other memories (12), the dopaminergic midbrain is thus a likely candidate for participating in the boosting of extinction memory consolidation by L-dopa.”
BackgroundSeeking a Spotless Mind: Extinction, Deconsolidation, and Erasure of Fear Memory
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Singewald, N., Schmuckermair, C., Whittle, N., Holmes, A., & Ressler, K. J. (2015) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.12.004 · Cited by 390 · see citing works
“…volunteers Fear conditioning paradigm, L-DOPA po following extinction training Protection from renewal (skin conductance responses) (Haaker et al., 2013) PTSD (treatment-refractory) 2 single oral MDMA prior to 8h therapy session (3–5 weeks apart, patients also received therapy…”
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Self-citationHDAC inhibitors as cognitive enhancers in fear, anxiety and trauma therapy: Where do we stand?
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“Furthermore, the administration of the dopamine precursor L-DOPA enhances the consolidation of extinction in both mice and humans (Haaker et al., 2013).”
BackgroundA precision medicine approach to pharmacological adjuncts to extinction: A call to broaden research
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New pharmacological strategies for augmenting extinction learning in anxiety disorders
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“…with the groups of R. Kalisch and H.C. Pape we could show that administration of L-DOPA, a bioprecursor of dopamine, is able to augment extinction memory in extinction-competent mice and humans and importantly reduces relapse rates of fear reactions in both species (Haaker et al., 2013).”
BackgroundSelf-citation
- Authors
- Haaker, J., Gaburro, S., Sah, A., Gartmann, N., Lonsdorf, T. B., Meier, K., Singewald, N., Pape, H.-C., Morellini, F., & Kalisch, R.
- Affiliations
- University Medical Center Hamburg-Eppendorf (DE)
- University of Münster (DE)
- Universität Innsbruck (AT)
- Institute for Systems Neuroscience, University Medical Center Hamburg-Eppendorf (UKE), 20246 Hamburg, Germany;
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-06-10
- Volume
- 110
- Issue
- 26
- Pages
- E2428-36
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3696794
- OpenAlex
- W1998065705
- Cited by
- 166
- References
- 12
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 14 · 2023: 10 · 2022: 12 · 2021: 12 · 2020: 16 · 2019: 18 · 2018: 12 · 2017: 13 · 2016: 12 · 2015: 13 · 2014: 12 · 2013: 6
- FWCI
- 7.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (SFB-TR58, KA1623/3-1)
- Austrian Science Fund (F4410, W 1206, W 1206-B18)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- L-DOPA, memory extinction, return of fear, contextual memory, fear extinction, extinction memory consolidation, dopamine, ventromedial prefrontal cortex, amygdala, resting-state functional connectivity, midbrain dopaminergic system, anxiety treatment
- MeSH terms
- Adult, Amygdala, Animals, Extinction, Psychological, Fear, Humans, Levodopa, Male, Memory, Mice, Inbred C57BL, Middle Aged, Prefrontal Cortex, Mice
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