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

TY - JOUR

T1 - Dopaminergic D1 receptor signalling is necessary, but not sufficient for cued fear memory destabilisation

AU - Flavell, Charlotte

AU - Lee, Joff

PY - 2019/12

Y1 - 2019/12

N2 - 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.

AB - 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.

KW - Destabilisation

KW - Dopamine

KW - Extinction

KW - Fear

KW - Glucocorticoid

KW - Mifepristone

KW - Nefiracetam

KW - Reconsolidation

UR - http://www.scopus.com/inward/record.url?scp=85070224409&partnerID=8YFLogxK

U2 - 10.1007/s00213-019-05338-5

DO - 10.1007/s00213-019-05338-5

M3 - Article

C2 - 31392356

VL - 236

SP - 3667

EP - 3676

JO - Psychopharmacology

JF - Psychopharmacology

SN - 0033-3158

IS - 12

ER -