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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.


Schematic of the brain. Black dots indicate the location of injector tips for reactivated PBS (A), AP-5 (B), SCH23390 (C), AP-5/SCH23390 (D), MK-801 (E) infused groups and non-reactivated PBS (F), and AP-5/SCH23390 (G) controls. H, Diagram showing location of notable brain regions surrounding the infusion site. Numbers (right) signify millimeters from bregma. All injectors were located within the NAc.
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Figure 1: Schematic of the brain. Black dots indicate the location of injector tips for reactivated PBS (A), AP-5 (B), SCH23390 (C), AP-5/SCH23390 (D), MK-801 (E) infused groups and non-reactivated PBS (F), and AP-5/SCH23390 (G) controls. H, Diagram showing location of notable brain regions surrounding the infusion site. Numbers (right) signify millimeters from bregma. All injectors were located within the NAc.

Mentions: Eighty rats were implanted bilaterally with stainless steel cannulae (11 mm, 22 gauge; Coopers Needleworks). Cannulae were directed at the NAc region of the brain using a stereotaxic frame: AP +1.5 mm, ML ±1.8 mm from bregma, DV −1.8 mm from skull surface (Paxinos and Watson, 2009). Stainless steel stylets extending 1 mm past the end of the guide cannulae were inserted post-surgery in order to maintain patency until infusion. Prior to reactivation, stylets were removed and injectors (28 gauge; Plastics One) inserted into the guide cannulae, extending 6 mm past the end of the guide cannulae to a final DV −7.8 mm. PBS vehicle, MK-801, AP-5, SCH23390, or combined AP-5/SCH23390 (see Drugs, below) was infused into the NAc immediately prior to reactivation. At the end of the experiment, cannulated rats were killed, their brains extracted freshly and fixed in 4% paraformaldehyde. Brains were sectioned then stained using cresyl violet and the locations of injectors confirmed using light microscopy (Fig. 1).


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

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

Schematic of the brain. Black dots indicate the location of injector tips for reactivated PBS (A), AP-5 (B), SCH23390 (C), AP-5/SCH23390 (D), MK-801 (E) infused groups and non-reactivated PBS (F), and AP-5/SCH23390 (G) controls. H, Diagram showing location of notable brain regions surrounding the infusion site. Numbers (right) signify millimeters from bregma. All injectors were located within the NAc.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Schematic of the brain. Black dots indicate the location of injector tips for reactivated PBS (A), AP-5 (B), SCH23390 (C), AP-5/SCH23390 (D), MK-801 (E) infused groups and non-reactivated PBS (F), and AP-5/SCH23390 (G) controls. H, Diagram showing location of notable brain regions surrounding the infusion site. Numbers (right) signify millimeters from bregma. All injectors were located within the NAc.
Mentions: Eighty rats were implanted bilaterally with stainless steel cannulae (11 mm, 22 gauge; Coopers Needleworks). Cannulae were directed at the NAc region of the brain using a stereotaxic frame: AP +1.5 mm, ML ±1.8 mm from bregma, DV −1.8 mm from skull surface (Paxinos and Watson, 2009). Stainless steel stylets extending 1 mm past the end of the guide cannulae were inserted post-surgery in order to maintain patency until infusion. Prior to reactivation, stylets were removed and injectors (28 gauge; Plastics One) inserted into the guide cannulae, extending 6 mm past the end of the guide cannulae to a final DV −7.8 mm. PBS vehicle, MK-801, AP-5, SCH23390, or combined AP-5/SCH23390 (see Drugs, below) was infused into the NAc immediately prior to reactivation. At the end of the experiment, cannulated rats were killed, their brains extracted freshly and fixed in 4% paraformaldehyde. Brains were sectioned then stained using cresyl violet and the locations of injectors confirmed using light microscopy (Fig. 1).

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.