Inhibition of ERK1/2 or CRMP2 Disrupts Alcohol Memory Reconsolidation and Prevents Relapse in Rats

Nofar Rahamim, Mirit Liran, Coral Aronovici, Hila Flumin, Tamar Gordon, Nataly Urshansky, Segev Barak*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Relapse to alcohol abuse, often caused by cue-induced alcohol craving, is a major challenge in alcohol addiction treatment. Therefore, disrupting the cue-alcohol memories can suppress relapse. Upon retrieval, memories transiently destabilize before they reconsolidate in a process that requires protein synthesis. Evidence suggests that the mammalian target of rapamycin complex 1 (mTORC1), governing the translation of a subset of dendritic proteins, is crucial for memory reconsolidation. Here, we explored the involvement of two regulatory pathways of mTORC1, phosphoinositide 3-kinase (PI3K)-AKT and extracellular regulated kinase 1/2 (ERK1/2), in the reconsolidation process in a rat (Wistar) model of alcohol self-administration. We found that retrieval of alcohol memories using an odor-taste cue increased ERK1/2 activation in the amygdala, while the PI3K-AKT pathway remained unaffected. Importantly, ERK1/2 inhibition after alcohol memory retrieval impaired alcohol-memory reconsolidation and led to long-lasting relapse suppression. Attenuation of relapse was also induced by post-retrieval administration of lacosamide, an inhibitor of collapsin response mediator protein-2 (CRMP2)—a translational product of mTORC1. Together, our findings indicate the crucial role of ERK1/2 and CRMP2 in the reconsolidation of alcohol memories, with their inhibition as potential treatment targets for relapse prevention.

Original languageEnglish
Article number5478
JournalInternational Journal of Molecular Sciences
Issue number10
StatePublished - May 2024


FundersFunder number
Tel Aviv University
United States-Israel Binational Science Foundation2017022
United States-Israel Binational Science Foundation
Israel Science Foundation508/20
Israel Science Foundation


    • CRMP2
    • ERK1/2
    • addiction
    • alcohol
    • memory reconsolidation
    • signaling


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