Disruption of alcohol-related memories by mTORC1 inhibition prevents relapse

Abstract

a r t I C l e S Alcohol abuse is a worldwide problem with concomitant medical, social and economic burdens 1 for which pharmacotherapeutic approaches are limited 2 . Most patients with alcoholism will relapse within the first year of abstinence 3 , highlighting relapse as an important clinical issue. A main cause of relapse is cue-induced drug craving 4 , a process in which a cue that was previously associated with the reinforcing effects of alcohol elicits craving for alcohol itself, thereby increasing the likelihood of relapse. Thus, erasure of the memory for the cue-drug association is expected to reduce or prevent cue-induced relapse. Current conceptions of memory processes hold that after retrieval of a memory, it is reactivated and undergoes a process of destabilization followed by a process of reconsolidation. After destabilization, a temporary 'reconsolidation window' opens during which the memory becomes labile and can be strengthened or attenuated The mTORC1-mediated signaling pathway is required for the translation of a subset of dendritic proteins 12 and is implicated in synaptic plasticity 12,13 as well as memory processes 12 . Interestingly, mTORC1 has been reported to contribute to memory processes that are involved in cocaine-conditioned place preference and cue-induced reinstatement RESULTS Retrieval of alcohol-associated memories activates mTORC1 To determine whether the mTORC1 signaling pathway is activated after retrieval (reactivation) of alcohol-related memories (that is, during memory reconsolidation), we trained rats to voluntarily consume excessive amounts of alcohol in their home cage for 7 weeks using the intermittent access to 20% alcohol two bottle-choice procedur