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A neural substrate of compulsive alcohol use
Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.ORCID iD: 0000-0001-5726-4814
Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Univ Elect Sci & Technol China, Peoples R China.
Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
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2021 (English)In: Science Advances, E-ISSN 2375-2548, Vol. 7, no 34, article id eabg9045Article in journal (Refereed) Published
Abstract [en]

Alcohol 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 PKC delta(+) inhibitory neurons in the lateral subdivision of CeA (CeL) accounted for similar to 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 PKC delta in CeA. These findings identify a previously unknown mechanism for a core element of alcohol addiction and point to a novel candidate therapeutic target.

Place, publisher, year, edition, pages
American Association for the Advancement of Science , 2021. Vol. 7, no 34, article id eabg9045
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Cell and Molecular Biology
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URN: urn:nbn:se:liu:diva-178772DOI: 10.1126/sciadv.abg9045ISI: 000686461400012PubMedID: 34407947OAI: oai:DiVA.org:liu-178772DiVA, id: diva2:1589821
Note

Funding Agencies|Swedish Research CouncilSwedish Research CouncilEuropean Commission [2013-07434, 2019-01138, 2018-02320]; Wallenberg FoundationEuropean Commission; Lions Research Fund; Intramural Research Program, NIDA-NIH

Available from: 2021-09-01 Created: 2021-09-01 Last updated: 2021-12-29

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Domi, EsiXu, LiToivainen, SanneNordeman, AntonHolm, LovisaBarbier, EstelleAugier, EricHeilig, Markus
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Center for Social and Affective NeuroscienceFaculty of Medicine and Health SciencesPsykiatriska kliniken i Linköping
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