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.


Combined infusion of AP-5/SCH23390 significantly impaired behavioral activity when administered immediately prior to the VR5 reactivation. A, Coinfusion of AP-5/SCH23390 (n = 6) significantly impaired lever pressing at test compared with PBS controls (n = 6). Infusions of MK-801 (n = 6), AP-5 (n = 5), or SCH23390 (n = 6) alone were without significant long-term effect on lever pressing. B, There was no significant evidence for any long-term impairment in nosepoking with any infusion. Data are represented as mean + SEM.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Combined infusion of AP-5/SCH23390 significantly impaired behavioral activity when administered immediately prior to the VR5 reactivation. A, Coinfusion of AP-5/SCH23390 (n = 6) significantly impaired lever pressing at test compared with PBS controls (n = 6). Infusions of MK-801 (n = 6), AP-5 (n = 5), or SCH23390 (n = 6) alone were without significant long-term effect on lever pressing. B, There was no significant evidence for any long-term impairment in nosepoking with any infusion. Data are represented as mean + SEM.

Mentions: At test, 24 h after reactivation, although an overall ANOVA did not provide conclusive evidence for a long-term effect of infusion (F(4,24) = 2.60, p = 0.06z), planned comparisons revealed a significant reduction in lever pressing in rats previously infused with the AP-5/SCH23390 in combination compared to PBS vehicle controls (Fig. 6A; F(1,10) = 14.1, p = 0.004z). In contrast, similar planned comparisons did not show any lever-pressing impairment at test in rats given infusions of MK-801 (F(1,10) = 0.05, p = 0.823z), AP-5 (F(1,9) = 0.65, p = 0.441z) or SCH23390 (F(1,10) = 0.03, p = 0.871z) alone (Fig. 6A).


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

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

Combined infusion of AP-5/SCH23390 significantly impaired behavioral activity when administered immediately prior to the VR5 reactivation. A, Coinfusion of AP-5/SCH23390 (n = 6) significantly impaired lever pressing at test compared with PBS controls (n = 6). Infusions of MK-801 (n = 6), AP-5 (n = 5), or SCH23390 (n = 6) alone were without significant long-term effect on lever pressing. B, There was no significant evidence for any long-term impairment in nosepoking with any infusion. 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 6: Combined infusion of AP-5/SCH23390 significantly impaired behavioral activity when administered immediately prior to the VR5 reactivation. A, Coinfusion of AP-5/SCH23390 (n = 6) significantly impaired lever pressing at test compared with PBS controls (n = 6). Infusions of MK-801 (n = 6), AP-5 (n = 5), or SCH23390 (n = 6) alone were without significant long-term effect on lever pressing. B, There was no significant evidence for any long-term impairment in nosepoking with any infusion. Data are represented as mean + SEM.
Mentions: At test, 24 h after reactivation, although an overall ANOVA did not provide conclusive evidence for a long-term effect of infusion (F(4,24) = 2.60, p = 0.06z), planned comparisons revealed a significant reduction in lever pressing in rats previously infused with the AP-5/SCH23390 in combination compared to PBS vehicle controls (Fig. 6A; F(1,10) = 14.1, p = 0.004z). In contrast, similar planned comparisons did not show any lever-pressing impairment at test in rats given infusions of MK-801 (F(1,10) = 0.05, p = 0.823z), AP-5 (F(1,9) = 0.65, p = 0.441z) or SCH23390 (F(1,10) = 0.03, p = 0.871z) alone (Fig. 6A).

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.