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Updated: Jan 21, 2026

Contextual and Cued Fear Conditioning Test Using a Video Analyzing System in Mice
Published on: March 1, 2014
Dopaminergic D1 receptor signalling is necessary, but not sufficient for cued fear memory destabilisation
Charlotte R Flavell1, Jonathan L C Lee2
1School of Psychology, University of Birmingham, Hills Building, Edgbaston, Birmingham, B15 2TT, UK.
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.
Insights
Targeting memory reconsolidation shows promise for fear disorders. Nefiracetam combined with mifepristone, dependent on dopamine D1 receptors, aids memory disruption without increasing fear.
Area of Science:
- Neuroscience
- Pharmacology
- Psychiatry
Background:
- Memory reconsolidation targeting is a key strategy for fear-related disorders.
- Effective fear memory destabilization via reactivation is crucial for therapeutic success.
Purpose of the Study:
- Investigate the role of dopamine D1 receptors in cued fear memory destabilization.
- Assess the potential of pharmacological interventions for memory reconsolidation disruption.
Main Methods:
- Systemic administration of drugs targeting dopamine D1 receptors.
- Utilized nefiracetam and mifepristone to assess memory destabilization and reconsolidation disruption.
- Evaluated effects on fear memory expression and extinction learning.
Main Results:
- Direct dopamine D1 receptor agonism alone did not destabilize fear memory for disruption.
- Nefiracetam facilitated mifepristone-induced amnesia, contingent on dopamine D1 receptor activation.
- Combined nefiracetam and mifepristone did not enhance fear reduction during extinction; mifepristone alone showed some fear reduction.
Conclusions:
- Combination pharmacological treatments can target memory destabilization and impair reconsolidation.
- This approach offers therapeutic potential for fear memory disorders without increasing maladaptive fear.
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