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Reduction in Responding for Sucrose and Cocaine Reinforcement by Disruption of Memory Reconsolidation(1,2,3).

Exton-McGuinness MT, Lee JL - eNeuro (2015)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Psychology, University of Birmingham , B15 2TT, United Kingdom.

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.

No MeSH data available.


Treatment with systemic MK-801 was without effect on pr-STM. A, Three hours after reactivation MK-801 treated rats (n = 7) showed no significant difference in lever pressing compared with vehicle controls (n = 9). B, MK-801 had no significant effect on short-term nosepoking behavior 3 h after reactivation. Data are represented as mean number of lever presses + SEM.
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Figure 3: Treatment with systemic MK-801 was without effect on pr-STM. A, Three hours after reactivation MK-801 treated rats (n = 7) showed no significant difference in lever pressing compared with vehicle controls (n = 9). B, MK-801 had no significant effect on short-term nosepoking behavior 3 h after reactivation. Data are represented as mean number of lever presses + SEM.

Mentions: An additional group of rats were trained, injected and reactivated as above and their memory tested 3 h after receiving the VR5 reactivation session in order to assess pr-STM. This test controls for any effect of drug treatment on behavioral expression, which may impact later long-term recall. If an impairment in long-term memory is due to disruption of reconsolidation, then short-term memory should be intact. Both treatment groups learned to lever press similarly during training (data not shown; Training: F(1,14) = 461.37, p < 0.001g; Treatment: F(1,14) = 1.08, p = 0.317g; Training × Treatment: F(1,14) = 0.58, p = 0.461g). There was no significant effect of MK-801 on lever-pressing performance during either the VR5 reactivation (Saline: 91.2 ± 4.5; MK-801: 100.9 ± 4.5; F(1,14) = 2.24, p = 0.157h) or pr-STM test (Fig. 3A; F(1,14) = 0.38, p = 0.548i). Thus, pr-STM was unimpaired by MK-801 treatment prior to the VR5 reactivation.


Reduction in Responding for Sucrose and Cocaine Reinforcement by Disruption of Memory Reconsolidation(1,2,3).

Exton-McGuinness MT, Lee JL - eNeuro (2015)

Treatment with systemic MK-801 was without effect on pr-STM. A, Three hours after reactivation MK-801 treated rats (n = 7) showed no significant difference in lever pressing compared with vehicle controls (n = 9). B, MK-801 had no significant effect on short-term nosepoking behavior 3 h after reactivation. Data are represented as mean number of lever presses + SEM.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4596086&req=5

Figure 3: Treatment with systemic MK-801 was without effect on pr-STM. A, Three hours after reactivation MK-801 treated rats (n = 7) showed no significant difference in lever pressing compared with vehicle controls (n = 9). B, MK-801 had no significant effect on short-term nosepoking behavior 3 h after reactivation. Data are represented as mean number of lever presses + SEM.
Mentions: An additional group of rats were trained, injected and reactivated as above and their memory tested 3 h after receiving the VR5 reactivation session in order to assess pr-STM. This test controls for any effect of drug treatment on behavioral expression, which may impact later long-term recall. If an impairment in long-term memory is due to disruption of reconsolidation, then short-term memory should be intact. Both treatment groups learned to lever press similarly during training (data not shown; Training: F(1,14) = 461.37, p < 0.001g; Treatment: F(1,14) = 1.08, p = 0.317g; Training × Treatment: F(1,14) = 0.58, p = 0.461g). There was no significant effect of MK-801 on lever-pressing performance during either the VR5 reactivation (Saline: 91.2 ± 4.5; MK-801: 100.9 ± 4.5; F(1,14) = 2.24, p = 0.157h) or pr-STM test (Fig. 3A; F(1,14) = 0.38, p = 0.548i). Thus, pr-STM was unimpaired by MK-801 treatment prior to the VR5 reactivation.

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Psychology, University of Birmingham , B15 2TT, United Kingdom.

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.

No MeSH data available.