Reduction in responding for sucrose and cocaine reinforcement by disruption of memory reconsolidation

Research output: Contribution to journalArticle

Colleges, School and Institutes

Abstract

Stored memories are dynamic and, when reactivated, can undergo a process of destabilization and reconsolidation to update them with new information. Reconsolidation has been shown for a variety of experimental settings; most recently for well-learned instrumental memories, a class of memory previously thought not to undergo reconsolidation. Here we tested, in rats, whether a weakly-trained lever-pressing memory destabilized following a shift in reinforcement contingency. We show that lever-pressing memory for both sucrose and cocaine reinforcement destabilized under appropriate conditions, and that the reconsolidation of this memory was impaired by systemic administration of the NMDA receptor (NMDAR) antagonist [5R,10S]-[+]-5-methyl-10,1-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801). We went on to investigate the potential role of the nucleus accumbens (NAc) in the reconsolidation of sucrose-reinforced instrumental memories, showing that co-infusion of the NMDAR antagonist 2-amino-5-phosphonopentanoic acid (AP-5) and the dopamine-1 receptor (D1R) antagonist 7-chloro-3-methyl-1-phenyl-1,2,4,5-tetrahydro-3-benzazepin-8-ol (SCH23390) into the NAc prior to memory reactivation impaired reconsolidation; however, there was no effect when these drugs were infused alone. Further investigation of this effect suggests the combined infusion disrupted the reconsolidation of pavlovian components of memory, and we hypothesize that coactivation of accumbal D1Rs and NMDARs may contribute to both the destabilization and reconsolidation of appetitive memory. Our work demonstrates that weakly-trained instrumental memories undergo reconsolidation under similar parameters to well-trained ones, and also suggests that receptor coactivation in the NAc may contribute to memory destabilization. Furthermore, it provides an important demonstration of the therapeutic potential of reconsolidation-based treatments that target the instrumental components of memory in maladaptive drug seeking.
Significance Statement: This research adds to the growing body of evidence that instrumental memories (memories of interactions with the world) undergo reconsolidation, a class of memory previously not thought to undergo reconsolidation. Furthermore, we suggest that there may be a role for coactivation of accumbal D1Rs and NMDARs in the destabilization and reconsolidation of appetitive memory. Our work also extends to include reconsolidation disruption of responding for cocaine self-administration. This provides proof of principle that impairing the reconsolidation of instrumental memory can diminish the instrumental components of drug seeking, and demonstrates the potential viability of reconsolidation-based therapies for maladaptive memory disorders.

Details

Original languageEnglish
Pages (from-to)1-17
Number of pages17
JournaleNeuro
Volume2
Issue number2
Publication statusPublished - 11 Mar 2015

Keywords

  • cocaine, dopamine, NMDAR, nucleus accumbens, reconsolidation, sucrose