A persistent alcohol cue memory trace drives relapse to alcohol seeking after prolonged abstinence

Esther Visser, Mariana R. Matos, Rolinka J. van der Loo, Nathan J. Marchant, Taco J. de Vries, August B. Smit, Michel C. van den Oever

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Scopus)


Alcohol use disorder is characterized by a high risk of relapse during periods of abstinence. Relapse is often triggered by retrieval of persistent alcohol memories upon exposure to alcohol-associated environmental cues, but little is known about the neuronal circuitry that supports the long-term storage of alcohol cue associations. We found that a small ensemble of neurons in the medial prefrontal cortex (mPFC) of mice was activated during cue-paired alcohol self-administration (SA) and that selective suppression of these neurons 1 month later attenuated cue-induced relapse to alcohol seeking. Inhibition of alcohol seeking was specific to these neurons as suppression of a non–alcohol-related or sucrose SA–activated mPFC ensemble did not affect relapse behavior. Hence, the mPFC neuronal ensemble activated during cue-paired alcohol consumption functions as a lasting memory trace that mediates cue-evoked relapse long after cessation of alcohol intake, thereby providing a potential target for treatment of alcohol relapse vulnerability.

Original languageEnglish
Article numbereaax7060
Pages (from-to)1-13
Number of pages13
JournalScience advances
Issue number19
Publication statusPublished - 6 May 2020

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