Abstract
The consolidation of newly acquired memories involves the temporal transition from a recent, less stable trace to a more permanent consolidated form. Opiates possess potent rewarding effects and produce powerful associative memories. The activation of these memories is associated with opiate abuse relapse phenomena and the persistence of compulsive opiate dependence. However, the neuronal, molecular and temporal mechanisms by which associative opiate reward memories are consolidated are not currently understood. We report that the consolidation of associative opiate reward memories involves a temporal and molecular switch between the basolateral nucleus of the amygdala (BLA) (early consolidation phase) to the medial prefrontal cortex (mPFC) (late consolidation phase). We demonstrate at the molecular, behavioral and neuronal levels that the consolidation of a recently acquired opiate reward memory involves an extracellular signal-related kinase (ERK)-dependent phosphorylation process within the BLA. In contrast, later-stage consolidation of a newly acquired memory is dependent upon a calcium-calmodulin-dependent (CaMKII), ERK-independent, mechanism in the mPFC, over a 12 hr temporal gradient. In addition, using in vivo multi-unit neuronal recordings in the mPFC, we report that protein synthesis within the BLA modulates the consolidation of opiate-reward memory in neuronal mPFC sub-populations, via the same temporal dynamic.
Highlights
Opiates are powerfully addictive drugs that create potent associative memories
We report that intra-basolateral amygdala (BLA) or medial prefrontal cortex (mPFC) protein synthesis or extracellular signal-related kinase (ERK)/ calmodulin-dependent kinase II (CaMKII) inhibition blocks the consolidation of acute opiate reward memory through a temporal gradient: recent opiate reward memory requires BLA-dependent consolidation whereas remote memory consolidation switches to an mPFC-dependent substrate
We found that protein synthesis inhibition within the BLA during early phase memory consolidation, blocked the subsequent neuronal expression of morphine-related associative firing increases when tested in the conditioned place preference (CPP) paradigm
Summary
Opiates are powerfully addictive drugs that create potent associative memories. the persistence of opiate addiction is in large part due to the ability of opiate-related memories to trigger compulsive drug seeking and relapse, even years after abstinence. M-opiate receptor sensitive dopamine (DA) substrates within the ventral tegmental area (VTA), send projections directly to neuronal populations within the BLA [12], suggesting that opiate-related activation of DAergic VTA outputs may first target associative neuronal substrates within the BLA [9] Both the encoding and recall of reward and aversion-related associative memory involves functional interactions between the BLA and mPFC. We have reported recently that pharmacological inactivation of the BLA prior to the acquisition of associative opiate reward learning, leads to a disinhibition of mPFC neuronal population activity and a concomitant acceleration in the behavioral extinction of a previously acquired associative opiate reward memory. The potential role for functional interactions between the BLA and mPFC during the consolidation of reward-related memories is not currently understood
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