Dopaminergic D1 receptor signalling is necessary, but not sufficient for cued fear memory destabilisation

Flavell, Charlotte R.; Lee, Jonathan L. C.

doi:10.1007/s00213-019-05338-5

Cited by 21Memory and Neural MechanismsMemory Processes and InfluencesNeurotransmitter Receptor Influence on Behavior

Dopaminergic D1 receptor signalling is necessary, but not sufficient for cued fear memory destabilisation

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Flavell, Charlotte R., Lee, Jonathan L. C.·2019·Psychopharmacology

DOI 10.1007/s00213-019-05338-5PMC PMC6892761

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Abstract

RATIONALE: Pharmacological targeting of memory reconsolidation is a promising therapeutic strategy for the treatment of fear memory-related disorders. However, the success of reconsolidation-based approaches depends upon the effective destabilisation of the fear memory by memory reactivation. OBJECTIVES: Here, we aimed to determine the functional involvement of dopamine D1 receptors in cued fear memory destabilisation, using systemic drug administration. RESULTS: We observed that direct D1 receptor agonism was not sufficient to stimulate tone fear memory destabilisation to facilitate reconsolidation disruption by the glucocorticoid receptor antagonist mifepristone. Instead, administration of the nootropic nefiracetam did facilitate mifepristone-induced amnesia, in a manner that was dependent upon dopamine D1 receptor activation. Finally, while the combined treatment with nefiracetam and mifepristone did not confer fear-reducing effects under conditions of extinction learning, there was some evidence that mifepristone reduces fear expression irrespective of memory reactivation parameters. CONCLUSIONS: The use of combination pharmacological treatment to stimulate memory destabilisation and impair reconsolidation has potential therapeutic benefits, without risking a maladaptive increase of fear.

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Dopamine is required for the destabilisation of both appetitive and aversive memories.
“it also appears that dopamine is required for the destabilisation of both appetitive (Merlo et al., 2015) and aversive memories (Flavell and Lee, 2019).”
From Retrieval-Dependent Mechanisms Affecting Emotional Memory Persistence: Reconsolidation, Extinction, and the Space in Between (2020) · cites this paper as Flavell and Lee, 2019
The Discussion reports that D1 receptor activation was necessary for cued fear memory destabilisation under the study’s experimental conditions: blocking D1 receptors prevented nefiracetam’s facilitative effect. This supports the aversive-memory portion attributed to Flavell and Lee, but the claim extends that finding beyond cued fear memories. The appetitive-memory portion is attributed to Merlo et al., not to this source. (LLM, conf=0.85)
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Dopaminergic signalling does not appear to be sufficient to induce memory destabilisation, as enhancing dopaminergic signalling with the D1 dopamine receptor agonist SKF38393 did not induce destabilisation of a strong fear memory under reactivation conditions that would normally destabilise a weaker memory.
“However, dopaminergic signalling does not appear to be sufficient to induce memory destabilisation, as enhancing dopaminergic signalling with the D1 dopamine receptor agonist SKF38393 did not induce destabilisation of a strong fear memory under reactivation conditions that would normally destabilise a weaker memory (Flavell and Lee, 2019).”
From Retrieval-Dependent Mechanisms Affecting Emotional Memory Persistence: Reconsolidation, Extinction, and the Space in Between (2020) · cites this paper as Flavell and Lee, 2019
Administration of nefiracetam, a pharmacological agent that enhances LVGCC calcium currents, enhances the destabilisation of fear memory.
“Additionally, the administration of nefiracetam, a pharmacological agent that enhances LVGCC calcium currents (Yoshii and Watabe, 1994), was shown to enhance the destabilisation of fear memory (Flavell and Lee, 2019).”
From Retrieval-Dependent Mechanisms Affecting Emotional Memory Persistence: Reconsolidation, Extinction, and the Space in Between (2020) · cites this paper as Flavell and Lee, 2019

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Authors: Flavell, C. R., & Lee, J. L. C.
Affiliations: University of Birmingham (GB)
Corresponding author: Lee, Jonathan L. C.
ORCID: Lee, Jonathan L. C.
Venue: Psychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2019-08-07
Volume: 236
Issue: 12
Pages: 3667-3676
ISSN: 0033-3158 (ISSN-L)
1432-2072
DOI: 10.1007/s00213-019-05338-5
PMC: PMC6892761
OpenAlex: W2964501849
Cited by: 21
References: 70
Citations by year: 2026: 4 · 2025: 3 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 1 · 2020: 6
FWCI: 1.45
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0 (tdm)
creativecommons.org/licenses/by/4.0 (vor)
Locations: Psychopharmacology (publishedVersion, cc-by)
bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Aston Publications Explorer (Aston University) (submittedVersion)
University of Birmingham Research Portal (University of Birmingham) (submittedVersion, cc-by)
Funders: Leverhulme Trust (RPG-2015-006)
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: dopamine D1 receptor, fear memory reconsolidation, memory reactivation, mifepristone, glucocorticoid receptor, nefiracetam, nootropic drugs, fear extinction, fear expression, combination pharmacotherapy
MeSH terms: Animals, Cues, Extinction, Psychological, Fear, Hormone Antagonists, Male, Memory, Memory Disorders, Signal Transduction, Mifepristone, Receptors, Dopamine D1, Nootropic Agents, Rats

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Dopaminergic D1 receptor signalling is necessary, but not sufficient for cued fear memory destabilisation

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