Overcoming boundary conditions for object location memory destabilization in male rats involves dopamine D1 receptor activation

Neurobiol Learn Mem. 2024 Dec 16:217:108017. doi: 10.1016/j.nlm.2024.108017. Online ahead of print.

Abstract

Consolidated long-term memories can undergo strength or content modification via protein synthesis-dependent reconsolidation. This is the process by which a reminder cue initiates reactivation of the memory trace, triggering destabilization. Older and more strongly encoded spatial memories can resist destabilization due to biological boundary conditions. The present study investigated the role of dopamine (DA) at D1 receptors (D1Rs) in object location memory destabilization and overcoming boundary conditions for older ("remote"; tested with a 48-h rather than a 24-h delay between sample and reactivation) memory destabilization. Using male rats in a modified object location task, we found that administering the D1R antagonist SCH23390 (0.1 mg/kg, i.p.) prior to reactivation blocked destabilization of recently encoded memories, as well as novelty-induced destabilization of remote memories. Using remote parameters, systemically administered D1R agonist SKF38393 (5 mg/kg, i.p.) induced destabilization of remote object location memories in the absence of salient novelty. Intra-dorsal hippocampus administration of SCH23390 (2 μg/μL) also blocked destabilization of remote object location memories when a salient novel cue was present. These results are consistent with previous findings implicating DA in memory destabilization as well as demonstrate a role for D1-receptor activation in the destabilization of boundary condition protected-object location memories.

Keywords: Boundary conditions; D1 receptors; Dopamine; Memory destabilization; Object location memory; Salient novelty.