Abstract
Rationale
Contextual control over drug relapse depends on the successful reconsolidation and retention of context-response–cocaine associations in long-term memory stores. The basolateral amygdala (BLA) plays a critical role in cocaine memory reconsolidation and subsequent drug context-induced cocaine-seeking behavior; however, less is known about the cellular mechanisms of this phenomenon.
Objectives
The present study evaluated the hypothesis that protein kinase A (PKA) and calcium/calmodulin-dependent protein kinase II (CaMKII) activation in the BLA is necessary for the reconsolidation of context-response–cocaine memories that promote subsequent drug context-induced cocaine-seeking behavior.
Methods
Rats were trained to lever-press for cocaine infusions in a distinct context, followed by extinction training in a different context. Rats were then briefly re-exposed to the previously cocaine-paired context or an unpaired context in order to reactivate cocaine-related contextual memories and initiate their reconsolidation or to provide a similar behavioral experience without explicit cocaine-related memory reactivation, respectively. Immediately after this session, rats received bilateral microinfusions of vehicle, the PKA inhibitor, Rp-adenosine 3’,5’-cyclic monophosphorothioate triethylammonium salt (Rp-cAMPS), or the CaMKII inhibitor, KN-93, into the BLA or the posterior caudate putamen (anatomical control region). Rats were then tested for cocaine-seeking behavior (responses on the previously cocaine-paired lever) in the cocaine-paired context and the extinction context.
Results
Intra-BLA infusion of Rp-cAMPS, but not KN-93, following cocaine memory reconsolidation impaired subsequent cocaine-seeking behavior in a dose-dependent, site-specific, and memory reactivation-dependent fashion.
Conclusions
PKA, but not CaMKII, activation in the BLA is critical for cocaine memory re-stabilization processes that facilitate subsequent drug context-induced instrumental cocaine-seeking behavior.
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Acknowledgments
This work was supported by NIDA grants R01 DA025646, T32 DA007244, and F31 DA028051. The authors thank Christopher Hanlin and Andrew Reittinger for excellent technical assistance. The authors have no conflicts of interest to disclose.
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Arguello, A.A., Hodges, M.A., Wells, A.M. et al. Involvement of amygdalar protein kinase A, but not calcium/calmodulin-dependent protein kinase II, in the reconsolidation of cocaine-related contextual memories in rats. Psychopharmacology 231, 55–65 (2014). https://doi.org/10.1007/s00213-013-3203-9
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DOI: https://doi.org/10.1007/s00213-013-3203-9