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

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, although. 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.

Publication DOI: https://doi.org/10.1007/s00213-019-05338-5
Divisions: Life & Health Sciences > Biosciences
Life & Health Sciences
Additional Information: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Uncontrolled Keywords: reconsolidation,destabilisation,dopamine,nefiracetam,fear,extinction,mifepristone,glucocorticoid
Full Text Link: https://www.bio ... 0.1101/564674v1
Related URLs: https://link.sp ... 213-019-05338-5 (Publisher URL)
PURE Output Type: Article
Published Date: 2019-12-01
Published Online Date: 2019-08-07
Accepted Date: 2019-07-15
Authors: Flavell, Charlotte ( 0000-0003-0345-0237)
Lee, Jonathan

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