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

Charlotte R. Flavell, View ORCID ProfileJonathan L. C. Lee
doi: https://doi.org/10.1101/564674
Charlotte R. Flavell
University of Birmingham, School of Psychology
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Jonathan L. C. Lee
University of Birmingham, School of Psychology
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Abstract

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. Here, we show that the nootropic nefiracetam stimulates tone fear memory destabilisation to facilitate reconsolidation disruption by the glucocorticoid receptor antagonist mifepristone. Moreover, the enhancing effect of nefiracetam was dependent upon dopamine D1 receptor activation, although direct D1 receptor agonism was not sufficient to facilitate destabilisation. 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. Therefore, 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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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted March 01, 2019.
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Dopaminergic signalling is necessary, but not sufficient for cued fear memory destabilisation
Charlotte R. Flavell, Jonathan L. C. Lee
bioRxiv 564674; doi: https://doi.org/10.1101/564674
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Dopaminergic signalling is necessary, but not sufficient for cued fear memory destabilisation
Charlotte R. Flavell, Jonathan L. C. Lee
bioRxiv 564674; doi: https://doi.org/10.1101/564674

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