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.
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.
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.
MK-801 impaired new extinction learning resulting from the non-reinforced reactivation. A, MK-801-injected rats (n = 6) responded significantly more than saline controls at test (n = 8). B, MK-801 treatment had no significant effect on nosepoking at test. Data are represented as mean number of lever presses + SEM.
MK-801 was without effect when administered prior to a brief FR1 reactivation. A, MK-801 (n = 6) and saline-treated (n = 6) groups showed no significant difference in performance at test. B, MK-801 administration was without effect on nosepoking at test. Data are represented as mean + SEM.
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.
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.
Administration of MK-801, prior to a shift to a VR5 schedule of reinforcement, significantly impaired the reconsolidation of long-term lever pressing for cocaine self-administration in a reactivation-dependent manner. A, Lever pressing at test was significantly reduced in rats administered MK-801 prior to the VR5 reactivation (n = 7) compared with both reactivated vehicle-injected rats (n = 7) and the non-reactivated MK-801-treated group (n = 6). Non-reactivated vehicle rats (n = 6) showed similar performance to their reactivated counterparts. B, Treatment with MK-801 had no significant effect on nosepoking behavior regardless of when animals received memory reactivation. Data are represented as mean + SEM.