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

doi:10.1126/sciadv.aax7060

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^*

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

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 language	English
Article number	eaax7060
Pages (from-to)	1-13
Number of pages	13
Journal	Science Advances
Volume	6
Issue number	19
DOIs	https://doi.org/10.1126/sciadv.aax7060
Publication status	Published - 6 May 2020

Funding

We would like to thank Y. Gouwenberg for AAV packaging and K. A. Jonkman, I. Koutlas, and N. Milićević for help with behavioral experiments and immunohistochemical stainings. This study was funded by an NWO VIDI grant (016.168.313) to E.V. and M.C.v.d.O., a VIDI grant (016.Vidi.188.022) to N.J.M., and an Amsterdam Neuroscience PoC grant (8-722 PoC-CIA-2017) to M.C.v.d.O. and N.J.M.

Funders	Funder number
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	8-722 PoC-CIA-2017, 016.168.313, 016.Vidi.188.022

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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title = "A persistent alcohol cue memory trace drives relapse to alcohol seeking after prolonged abstinence",

abstract = "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.",

author = "Esther Visser and Matos, \{Mariana R.\} and \{van der Loo\}, \{Rolinka J.\} and Marchant, \{Nathan J.\} and \{de Vries\}, \{Taco J.\} and Smit, \{August B.\} and \{van den Oever\}, \{Michel C.\}",

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T1 - A persistent alcohol cue memory trace drives relapse to alcohol seeking after prolonged abstinence

AU - Visser, Esther

AU - Matos, Mariana R.

AU - van der Loo, Rolinka J.

AU - Marchant, Nathan J.

AU - de Vries, Taco J.

AU - Smit, August B.

AU - van den Oever, Michel C.

PY - 2020/5/6

Y1 - 2020/5/6

N2 - 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.

AB - 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.

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

Abstract

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UN SDGs

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