Dopamine D1 receptor activation is involved in overcoming boundary conditions for destabilizing and updating object memories.

Abstract

Consolidated long-term memories can be modified when destabilized at reactivation (RA). This must be followed by an upregulation of protein synthesis to return the memory to a stable state. Reconsolidation is suggested to maintain the relevance of stored memories, preserving behavioral flexibility. Older or strongly encoded memories resist reconsolidation because of biological boundary conditions and destabilization of such memories is more likely in the presence of prediction error at reactivation. The neurotransmitter dopamine (DA), which has been implicated in prediction error, has been linked to destabilization using appetitive or aversive memory paradigms. However, more neutral memories also undergo modification to adapt to changing environments. Evidence suggests that a salient novel cue presented at reactivation can trigger destabilization of boundary condition-protected object memories, but DA has not yet been implicated in this process. Using male rats in a modified spontaneous object recognition task, we report that systemic administration of the D1 receptor (D1R) antagonist SCH23390 blocked recently encoded and novelty-induced relatively remote object memory destabilization. Further, systemic administration of the D1R agonist SKF38393 promoted destabilization of relatively remote memory traces in the absence of salient novelty at reactivation. Finally, systemic D1R antagonism and agonism blocked and promoted integrative memory updating, respectively, in the postreactivation object memory modification task. This work therefore advances current knowledge related to the role of DA in the dynamic nature of memory storage. (PsycInfo Database Record (c) 2025 APA, all rights reserved).