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Arc controls alcohol cue relapse by a central amygdala mechanism

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 targ...

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Main Authors: Pagano, Roberto (Author) , Salamian, Ahmad (Author) , Zielinski, Janusz (Author) , Beroun, Anna (Author) , Nalberczak-Skóra, Maria (Author) , Skonieczna, Edyta (Author) , Cały, Anna (Author) , Tay, Nicole (Author) , Banaschewski, Tobias (Author) , Desrivières, Sylvane (Author) , Grigis, Antoine (Author) , Garavan, Hugh (Author) , Heinz, Andreas (Author) , Brühl, Rüdiger (Author) , Martinot, Jean-Luc (Author) , Martinot, Marie-Laure Paillère (Author) , Artiges, Eric (Author) , Nees, Frauke (Author) , Orfanos, Dimitri Papadopoulos (Author) , Poustka, Luise (Author) , Hohmann, Sarah (Author) , Fröhner, Juliane (Author) , Smolka, Michael (Author) , Vaidya, Nilakshi (Author) , Walter, Henrik (Author) , Whelan, Robert (Author) , Kalita, Katarzyna (Author) , Bito, Haruhiko (Author) , Müller, Christian P. (Author) , Schumann, Gunter (Author) , Okuno, Hiroyuki (Author) , Radwanska, Kasia (Author)
Format: Article (Journal)
Language:English
Published: 2023
In: Molecular psychiatry
Year: 2023, Volume: 28, Issue: 2, Pages: 733-745
ISSN:1476-5578
DOI:10.1038/s41380-022-01849-4
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41380-022-01849-4
Verlag, lizenzpflichtig, Volltext: http://www.nature.com/articles/s41380-022-01849-4
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Author Notes:Roberto Pagano, Ahmad Salamian, Janusz Zielinski, Anna Beroun, Maria Nalberczak-Skóra, Edyta Skonieczna, Anna Cały, Nicole Tay, Tobias Banaschewski, Sylvane Desrivières, Antoine Grigis, Hugh Garavan, Andreas Heinz, Rüdiger Brühl, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Eric Artiges, Frauke Nees, Dimitri Papadopoulos Orfanos, Luise Poustka, Sarah Hohmann, Juliane H. Fröhner, Michael N. Smolka, Nilakshi Vaidya, Henrik Walter, Robert Whelan, Katarzyna Kalita, Haruhiko Bito, Christian P. Müller, Gunter Schumann, Hiroyuki Okuno and Kasia Radwanska
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Summary: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.
Item Description:Online veröffentlicht: 10. November 2022
Gesehen am 16.07.2024
Physical Description:Online Resource
ISSN:1476-5578
DOI:10.1038/s41380-022-01849-4

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