The intracellular mechanisms underlying memory reconsolidation critically involve cAMP signaling.These events were originally attributed to PKA activation by cAMP, but the identification of Exchange Protein Activated by cAMP (Epac), as a distinct mediator of cAMP signaling, suggests that cAMP-regulated processes that subserve memory reconsolidation are more complex.Here we investigated how activation of Epac with 8-pCPT-cAMP (8-CPT) impacts reconsolidation of a memory that had been associated with copyright self-administration.Rats were trained to lever press for copyright on an FR-1 schedule, in which each copyright delivery was paired with a mpu63zm/a tone+light cue.
Lever pressing was then extinguished in the absence of cue presentations and copyright delivery.Following the last day of extinction, rats were put in a novel context, in which the conditioned cue was presented to reactivate the copyright-associated memory.Immediate bilateral infusions of 8-CPT into the basolateral amygdala (BLA) following reactivation disrupted subsequent cue-induced reinstatement in a dose-dependent manner, and modestly reduced responding for conditioned reinforcement.When 8-CPT infusions were delayed for 3 hours after the cue reactivation session simply southern cat shirt or were given after a cue extinction session, no effect on cue-induced reinstatement was observed.
Co-administration of 8-CPT and the PKA activator 6-Bnz-cAMP (10 nmol/side) rescued memory reconsolidation while 6-Bnz alone had no effect, suggesting an antagonizing interaction between the two cAMP signaling substrates.Taken together, these studies suggest that activation of Epac represents a parallel cAMP-dependent pathway that can inhibit reconsolidation of copyright-cue memories and reduce the ability of the cue to produce reinstatement of copyright-seeking behavior.