title: Involvement of amygdalar protein kinase A, but not calcium/calmodulin-dependent protein kinase II, in the reconsolidation of cocaine-related contextual memories in rats.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Psychology, University of North Carolina, CB# 3270, Davie Hall, Chapel Hill, NC, 27599-3270, USA.
authors.forename: Amy A
authors.initials: AA
authors.lastname: Arguello
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Hodges
authors.forename: Audrey M
authors.initials: AM
authors.lastname: Wells
authors.forename: Honorio
authors.initials: H
authors.lastname: Lara
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Xie
authors.forename: Rita A
authors.initials: RA
authors.lastname: Fuchs
mesh_terms: D000679:Amygdala / Q000201:enzymology* / Q000502:physiology; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D001921:Brain / Q000033:anatomy & histology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D003042:Cocaine / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D003627:Data Interpretation, Statistical; D058999:Drug-Seeking Behavior / Q000187:drug effects; D005108:Extinction, Psychological / Q000187:drug effects; D005502:Food; D008297:Male; D008568:Memory / Q000187:drug effects*; D008845:Microinjections; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D012646:Self Administration; D013449:Sulfonamides / Q000494:pharmacology; D000096926:Benzenesulfonamides
chemical_list: D001596:Benzylamines; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D003042:Cocaine; D017868:Cyclic AMP-Dependent Protein Kinases; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; C072105:KN 93; D000096926:Benzenesulfonamides