Arc controls alcohol cue relapse by a central amygdala mechanism

Pagano R, Salamian A, Zielinski J, Beroun A, Nalberczak-Skóra M, Skonieczna E, Cały A, Tay N, Banaschewski T, Desrivières S, Grigis A, Garavan H, Heinz A, Brühl R, Martinot JL, Martinot MLP, Artiges E, Nees F, Orfanos DP, Poustka L, Hohmann S, Fröhner JH, Smolka MN, Vaidya N, Walter H, Whelan R, Kalita K, Bito H, Müller CP, Schumann G, Okuno H, Radwanska K (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Molecular Psychiatry Springer Nature

DOI: 10.1038/s41380-022-01849-4

Abstract

Alcohol use disorder (AUD) is a chronic and fatal disease. The main impediment of the AUD therapy is a high probability of relapse to alcohol abuse even after prolonged abstinence. The molecular mechanisms of cue-induced relapse are not well established, despite the fact that they may offer new targets for the treatment of AUD. Using a comprehensive animal model of AUD, virally-mediated and amygdala-targeted genetic manipulations by CRISPR/Cas9 technology and ex vivo electrophysiology, we identify a mechanism that selectively controls cue-induced alcohol relapse and AUD symptom severity. This mechanism is based on activity-regulated cytoskeleton-associated protein (Arc)/ARG3.1-dependent plasticity of the amygdala synapses. In humans, we identified single nucleotide polymorphisms in the ARC gene and their methylation predicting not only amygdala size, but also frequency of alcohol use, even at the onset of regular consumption. Targeting Arc during alcohol cue exposure may thus be a selective new mechanism for relapse prevention.

Authors with CRIS profile

Peter Christian Müller Professur für Suchtmedizin

Involved external institutions

Polska Akademia Nauk (PAN) / Polish Academy of Sciences PL Poland (PL) King’s College London GB United Kingdom (GB) Universitätsklinikum Mannheim DE Germany (DE) Freie Universität Berlin DE Germany (DE) École Polytechnique - Université Paris-Saclay FR France (FR) Universitätsklinikum Göttingen DE Germany (DE) Technische Universität Dresden DE Germany (DE) Charité - Universitätsmedizin Berlin DE Germany (DE) Kagoshima University JP Japan (JP) University of Vermont US United States (USA) (US) Physikalisch-Technische Bundesanstalt (PTB) DE Germany (DE) National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM) FR France (FR) Trinity College Dublin IE Ireland (IE)

How to cite

APA:

Pagano, R., Salamian, A., Zielinski, J., Beroun, A., Nalberczak-Skóra, M., Skonieczna, E.,... Radwanska, K. (2022). Arc controls alcohol cue relapse by a central amygdala mechanism. Molecular Psychiatry. https://doi.org/10.1038/s41380-022-01849-4

MLA:

Pagano, Roberto, et al. "Arc controls alcohol cue relapse by a central amygdala mechanism." Molecular Psychiatry (2022).

BibTeX: Download