title: Extracellular signal-regulated kinase in the basolateral amygdala, but not the nucleus accumbens core, is critical for context-response-cocaine memory reconsolidation in rats.
abstract: The reconsolidation of cocaine memories following retrieval is necessary for the sustained ability of a cocaine-paired environmental context to elicit cocaine seeking. Extracellular signal-regulated kinase (ERK) is an intracellular signaling molecule involved in nucleus accumbens core (NACc)-mediated reconsolidation of Pavlovian cocaine memories. Here, we used a rodent model of drug context-elicited relapse to test the hypothesis that ERK would be similarly required for the reconsolidation of context-response-cocaine memories that underlie drug context-induced reinstatement of instrumental cocaine-seeking behavior, with a focus on the NACc and on the basolateral amygdala (BLA), another important locus for the reconsolidation of cocaine memories. We show that the mitogen-activated protein kinase (MEK)/ERK1/2 inhibitor, U0126 (1.0 μg/0.5 μl/hemisphere), microinfused bilaterally into the BLA--but not the NACc--immediately after brief re-exposure to a previously cocaine-paired context (that is, cocaine-memory reactivation), significantly attenuated subsequent drug context-induced cocaine seeking relative to vehicle (VEH). This effect in the BLA was associated with a transient inhibition of ERK1/2 phosphorylation, and it depended on memory reactivation given that U0126 administered following exposure to a novel context did not alter subsequent cocaine seeking. Furthermore, similar to U0126, baclofen+muscimol-induced (B+M; 106.8/5.7 ng/0.5 μl/hemisphere) neural inactivation of the NACc, following cocaine-memory reactivation, failed to alter subsequent cocaine seeking. These findings demonstrate that ERK activation in the BLA, but not the NACc, is required for the reconsolidation of context-response-cocaine associative memories. Together with prior research, these results suggest that contextual drug-memory reconsolidation in Pavlovian and instrumental settings involves distinct neuroanatomical mechanisms.
authors.affiliation: Department of Psychology, University of North Carolina, Chapel Hill, NC 27599-3270, USA.
authors.forename: Audrey M
authors.initials: AM
authors.lastname: Wells
authors.forename: Amy A
authors.initials: AA
authors.lastname: Arguello
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Xie
authors.forename: Megan A
authors.initials: MA
authors.lastname: Blanton
authors.forename: Heather C
authors.initials: HC
authors.lastname: Lasseter
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Reittinger
authors.forename: Rita A
authors.initials: RA
authors.lastname: Fuchs
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000201:enzymology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002070:Butadienes / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000201:enzymology / Q000473:pathology; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005108:Extinction, Psychological / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D058786:GABA-B Receptor Agonists / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D009118:Muscimol / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D012646:Self Administration; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002070:Butadienes; D018765:Dopamine Uptake Inhibitors; D004791:Enzyme Inhibitors; D058786:GABA-B Receptor Agonists; D009570:Nitriles; C113580:U 0126; D009118:Muscimol; D048049:Extracellular Signal-Regulated MAP Kinases; D001418:Baclofen; D003042:Cocaine