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Activation of exchange protein activated by cAMP in the rat basolateral amygdala impairs reconsolidation of a memory associated with self-administered cocaine.
PLoS One. 2014; 9(9):e107359.Plos

Abstract

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 cocaine self-administration. Rats were trained to lever press for cocaine on an FR-1 schedule, in which each cocaine delivery was paired with a tone+light cue. Lever pressing was then extinguished in the absence of cue presentations and cocaine delivery. Following the last day of extinction, rats were put in a novel context, in which the conditioned cue was presented to reactivate the cocaine-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 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 cocaine-cue memories and reduce the ability of the cue to produce reinstatement of cocaine-seeking behavior.

Authors+Show Affiliations

Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, United States of America.Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, United States of America.Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, United States of America.Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, United States of America.Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, United States of America.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25259911

Citation

Wan, Xun, et al. "Activation of Exchange Protein Activated By cAMP in the Rat Basolateral Amygdala Impairs Reconsolidation of a Memory Associated With Self-administered Cocaine." PloS One, vol. 9, no. 9, 2014, pp. e107359.
Wan X, Torregrossa MM, Sanchez H, et al. Activation of exchange protein activated by cAMP in the rat basolateral amygdala impairs reconsolidation of a memory associated with self-administered cocaine. PLoS One. 2014;9(9):e107359.
Wan, X., Torregrossa, M. M., Sanchez, H., Nairn, A. C., & Taylor, J. R. (2014). Activation of exchange protein activated by cAMP in the rat basolateral amygdala impairs reconsolidation of a memory associated with self-administered cocaine. PloS One, 9(9), e107359. https://doi.org/10.1371/journal.pone.0107359
Wan X, et al. Activation of Exchange Protein Activated By cAMP in the Rat Basolateral Amygdala Impairs Reconsolidation of a Memory Associated With Self-administered Cocaine. PLoS One. 2014;9(9):e107359. PubMed PMID: 25259911.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of exchange protein activated by cAMP in the rat basolateral amygdala impairs reconsolidation of a memory associated with self-administered cocaine. AU - Wan,Xun, AU - Torregrossa,Mary M, AU - Sanchez,Hayde, AU - Nairn,Angus C, AU - Taylor,Jane R, Y1 - 2014/09/26/ PY - 2014/07/03/received PY - 2014/08/07/accepted PY - 2014/9/27/entrez PY - 2014/9/27/pubmed PY - 2015/6/11/medline SP - e107359 EP - e107359 JF - PloS one JO - PLoS One VL - 9 IS - 9 N2 - 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 cocaine self-administration. Rats were trained to lever press for cocaine on an FR-1 schedule, in which each cocaine delivery was paired with a tone+light cue. Lever pressing was then extinguished in the absence of cue presentations and cocaine delivery. Following the last day of extinction, rats were put in a novel context, in which the conditioned cue was presented to reactivate the cocaine-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 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 cocaine-cue memories and reduce the ability of the cue to produce reinstatement of cocaine-seeking behavior. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/25259911/Activation_of_exchange_protein_activated_by_cAMP_in_the_rat_basolateral_amygdala_impairs_reconsolidation_of_a_memory_associated_with_self_administered_cocaine_ L2 - https://dx.plos.org/10.1371/journal.pone.0107359 DB - PRIME DP - Unbound Medicine ER -