Limits...
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.


Related in: MedlinePlus

The effect of combined AP-5/SCH23390 infusion to impair responding was critically dependent on memory reactivation. A, The combined infusion significantly impaired lever pressing at test (as shown in Fig. 6, presented again here for clarity); however, coadministration of AP-5/SCH23390 (n = 7) did not significantly impair lever pressing if given in the absence of memory reactivation, compared with non-reactivated PBS infused controls (n = 5). B, Combined infusion of AP-5/SCH23390 also had a reactivation-dependent effect on nosepoking. Nosepoking was moderately impaired in the reactivated infusion group; however, the reactivation dependence of the effect is primarily driven by low responding in the non-reactivated vehicle group. Data are represented as mean + SEM.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4596086&req=5

Figure 7: The effect of combined AP-5/SCH23390 infusion to impair responding was critically dependent on memory reactivation. A, The combined infusion significantly impaired lever pressing at test (as shown in Fig. 6, presented again here for clarity); however, coadministration of AP-5/SCH23390 (n = 7) did not significantly impair lever pressing if given in the absence of memory reactivation, compared with non-reactivated PBS infused controls (n = 5). B, Combined infusion of AP-5/SCH23390 also had a reactivation-dependent effect on nosepoking. Nosepoking was moderately impaired in the reactivated infusion group; however, the reactivation dependence of the effect is primarily driven by low responding in the non-reactivated vehicle group. Data are represented as mean + SEM.

Mentions: Combined analysis of lever pressing at test, for both reactivated and non-reactivated groups, revealed a reactivation-dependent effect of AP-5/SCH23390 infusion (Fig. 7A; Treatment × Reactivation: F(1,20) = 6.82, p = 0.017ee), with no main effects of Treatment (F(1,20) = 1.03, p = 0.323ee) or Reactivation (F(1,20) = 0.03, p = 0.868ee). Analysis of simple effects showed significantly reduced lever pressing in rats infused with AP-5/SCH23390 immediately prior to the VR5 reactivation compared with their PBS-infused controls (F(1,10) = 14.1, p = 0.004ee); importantly, there was no significant effect of AP-5/SCH23390 infusion on lever pressing in non-reactivated rats (F(1,10) = 0.83, p = 0.385ee), suggesting reconsolidation was disrupted by the infusion. Orthogonal simple effects showed no significant difference between reactivated and non-reactivated groups given either PBS (F(1,9) = 4.44, p=0.064ee) or AP-5/SCH23390 (F(1,11) = 3.22, p = 0.100ee).


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

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

The effect of combined AP-5/SCH23390 infusion to impair responding was critically dependent on memory reactivation. A, The combined infusion significantly impaired lever pressing at test (as shown in Fig. 6, presented again here for clarity); however, coadministration of AP-5/SCH23390 (n = 7) did not significantly impair lever pressing if given in the absence of memory reactivation, compared with non-reactivated PBS infused controls (n = 5). B, Combined infusion of AP-5/SCH23390 also had a reactivation-dependent effect on nosepoking. Nosepoking was moderately impaired in the reactivated infusion group; however, the reactivation dependence of the effect is primarily driven by low responding in the non-reactivated vehicle group. Data are represented as mean + SEM.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 7: The effect of combined AP-5/SCH23390 infusion to impair responding was critically dependent on memory reactivation. A, The combined infusion significantly impaired lever pressing at test (as shown in Fig. 6, presented again here for clarity); however, coadministration of AP-5/SCH23390 (n = 7) did not significantly impair lever pressing if given in the absence of memory reactivation, compared with non-reactivated PBS infused controls (n = 5). B, Combined infusion of AP-5/SCH23390 also had a reactivation-dependent effect on nosepoking. Nosepoking was moderately impaired in the reactivated infusion group; however, the reactivation dependence of the effect is primarily driven by low responding in the non-reactivated vehicle group. Data are represented as mean + SEM.
Mentions: Combined analysis of lever pressing at test, for both reactivated and non-reactivated groups, revealed a reactivation-dependent effect of AP-5/SCH23390 infusion (Fig. 7A; Treatment × Reactivation: F(1,20) = 6.82, p = 0.017ee), with no main effects of Treatment (F(1,20) = 1.03, p = 0.323ee) or Reactivation (F(1,20) = 0.03, p = 0.868ee). Analysis of simple effects showed significantly reduced lever pressing in rats infused with AP-5/SCH23390 immediately prior to the VR5 reactivation compared with their PBS-infused controls (F(1,10) = 14.1, p = 0.004ee); importantly, there was no significant effect of AP-5/SCH23390 infusion on lever pressing in non-reactivated rats (F(1,10) = 0.83, p = 0.385ee), suggesting reconsolidation was disrupted by the infusion. Orthogonal simple effects showed no significant difference between reactivated and non-reactivated groups given either PBS (F(1,9) = 4.44, p=0.064ee) or AP-5/SCH23390 (F(1,11) = 3.22, p = 0.100ee).

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.


Related in: MedlinePlus