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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.


Systemic MK-801 impaired the reconsolidation of a weakly-learned lever-pressing memory for sucrose reinforcement following a shift to a VR5 schedule during reactivation. A, MK-801 (n = 9) administered prior to the VR5 reactivation significantly impaired lever-pressing performance in a reactivation-dependent manner at test the next day. Performance of reactivated MK-801 rats was impaired compared to reactivated saline controls (n = 7); however, there was no significant difference between non-reactivated rats administered saline (n = 8) or MK-801 (n = 7). B, MK-801 treatment had no significant effect on long-term nosepoking behavior regardless of reactivation. Data are represented as mean + SEM.
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Figure 2: Systemic MK-801 impaired the reconsolidation of a weakly-learned lever-pressing memory for sucrose reinforcement following a shift to a VR5 schedule during reactivation. A, MK-801 (n = 9) administered prior to the VR5 reactivation significantly impaired lever-pressing performance in a reactivation-dependent manner at test the next day. Performance of reactivated MK-801 rats was impaired compared to reactivated saline controls (n = 7); however, there was no significant difference between non-reactivated rats administered saline (n = 8) or MK-801 (n = 7). B, MK-801 treatment had no significant effect on long-term nosepoking behavior regardless of reactivation. Data are represented as mean + SEM.

Mentions: In a test of long-term memory, 24 h after drug administration and reactivation (Fig. 2A), there was a reactivation-dependent effect of MK-801 on lever pressing (Treatment × Reactivation: F(1,27) = 4.53, p = 0.042c) with no significant main effects of treatment (F(1,27) = 0.55, p = 0.464c) or reactivation (F(1,27) = 0.01, p = 0.908c). Analysis of simple main effects showed significantly reduced lever pressing in MK-801-treated reactivated rats compared to reactivated saline controls (F(1,14) = 6.02, p = 0.028c); however, there was no effect of drug treatment in the non-reactivated groups (F(1,13) = 0.71, p = 0.415c). This suggests reconsolidation was impaired by systemic MK-801, and by inference that the VR5 reactivation successfully destabilized lever-pressing memory, as there was no significant effect of MK-801 in the absence of reactivation. Orthogonal simple effects showed no significant difference in lever pressing between reactivated and non-reactivated saline- (F(1,13) = 1.88, p = 0.194c) or MK-801- (F(1,14) = 2.91, p = 0.110c) treated animals.


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

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

Systemic MK-801 impaired the reconsolidation of a weakly-learned lever-pressing memory for sucrose reinforcement following a shift to a VR5 schedule during reactivation. A, MK-801 (n = 9) administered prior to the VR5 reactivation significantly impaired lever-pressing performance in a reactivation-dependent manner at test the next day. Performance of reactivated MK-801 rats was impaired compared to reactivated saline controls (n = 7); however, there was no significant difference between non-reactivated rats administered saline (n = 8) or MK-801 (n = 7). B, MK-801 treatment had no significant effect on long-term nosepoking behavior regardless of reactivation. 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 2: Systemic MK-801 impaired the reconsolidation of a weakly-learned lever-pressing memory for sucrose reinforcement following a shift to a VR5 schedule during reactivation. A, MK-801 (n = 9) administered prior to the VR5 reactivation significantly impaired lever-pressing performance in a reactivation-dependent manner at test the next day. Performance of reactivated MK-801 rats was impaired compared to reactivated saline controls (n = 7); however, there was no significant difference between non-reactivated rats administered saline (n = 8) or MK-801 (n = 7). B, MK-801 treatment had no significant effect on long-term nosepoking behavior regardless of reactivation. Data are represented as mean + SEM.
Mentions: In a test of long-term memory, 24 h after drug administration and reactivation (Fig. 2A), there was a reactivation-dependent effect of MK-801 on lever pressing (Treatment × Reactivation: F(1,27) = 4.53, p = 0.042c) with no significant main effects of treatment (F(1,27) = 0.55, p = 0.464c) or reactivation (F(1,27) = 0.01, p = 0.908c). Analysis of simple main effects showed significantly reduced lever pressing in MK-801-treated reactivated rats compared to reactivated saline controls (F(1,14) = 6.02, p = 0.028c); however, there was no effect of drug treatment in the non-reactivated groups (F(1,13) = 0.71, p = 0.415c). This suggests reconsolidation was impaired by systemic MK-801, and by inference that the VR5 reactivation successfully destabilized lever-pressing memory, as there was no significant effect of MK-801 in the absence of reactivation. Orthogonal simple effects showed no significant difference in lever pressing between reactivated and non-reactivated saline- (F(1,13) = 1.88, p = 0.194c) or MK-801- (F(1,14) = 2.91, p = 0.110c) treated animals.

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.