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dc.contributor.authorDomi, Esi
dc.contributor.authorXu, Li
dc.contributor.authorToivainen, Sanne
dc.contributor.authorNordeman, Anton
dc.contributor.authorGobbo, Francesco
dc.contributor.authorVenniro, Marco
dc.contributor.authorShaham, Yavin
dc.contributor.authorMessing, Robert O
dc.contributor.authorVisser, Esther
dc.contributor.authorvan den Oever, Michel C
dc.contributor.authorHolm, Lovisa
dc.contributor.authorBarbier, Estelle
dc.contributor.authorAugier, Eric
dc.contributor.authorHeilig, Markus
dc.date.accessioned2021-08-23T18:24:48Z
dc.date.available2021-08-23T18:24:48Z
dc.date.issued2021-08-18
dc.identifier.urihttp://hdl.handle.net/10713/16449
dc.description.abstractAlcohol intake remains controlled in a majority of users but becomes "compulsive," i.e., continues despite adverse consequences, in a minority who develop alcohol addiction. Here, using a footshock-punished alcohol self-administration procedure, we screened a large population of outbred rats to identify those showing compulsivity operationalized as punishment-resistant self-administration. Using unsupervised clustering, we found that this behavior emerged as a stable trait in a subpopulation of rats and was associated with activity of a brain network that included central nucleus of the amygdala (CeA). Activity of PKCδ+ inhibitory neurons in the lateral subdivision of CeA (CeL) accounted for ~75% of variance in punishment-resistant alcohol taking. Activity-dependent tagging, followed by chemogenetic inhibition of neurons activated during punishment-resistant self-administration, suppressed alcohol taking, as did a virally mediated shRNA knockdown of PKCδ in CeA. These findings identify a previously unknown mechanism for a core element of alcohol addiction and point to a novel candidate therapeutic target.en_US
dc.description.urihttps://doi.org/10.1126/sciadv.abg9045en_US
dc.language.isoenen_US
dc.publisherAmerican Association for the Advancement of Scienceen_US
dc.relation.ispartofScience Advancesen_US
dc.rightsCopyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).en_US
dc.subject.meshAlcoholismen_US
dc.subject.meshNeurobiologyen_US
dc.titleA neural substrate of compulsive alcohol useen_US
dc.typeArticleen_US
dc.identifier.doi10.1126/sciadv.abg9045
dc.identifier.pmid34407947
dc.source.volume7
dc.source.issue34
dc.source.countryUnited States


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