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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| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2023
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| In: |
Molecular psychiatry
Year: 2023, Jahrgang: 28, Heft: 2, Pages: 733-745 |
| ISSN: | 1476-5578 |
| DOI: | 10.1038/s41380-022-01849-4 |
| Online-Zugang: | 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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| Verfasserangaben: | 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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| 245 | 1 | 0 | |a Arc controls alcohol cue relapse by a central amygdala mechanism |c 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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| 520 | |a 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. | ||
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