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A neural substrate of compulsive alcohol use
Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten.ORCID-id: 0000-0001-5726-4814
Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten. Univ Elect Sci & Technol China, Peoples R China.
Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten.
Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten.
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2021 (engelsk)Inngår i: Science Advances, E-ISSN 2375-2548, Vol. 7, nr 34, artikkel-id eabg9045Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
American Association for the Advancement of Science , 2021. Vol. 7, nr 34, artikkel-id eabg9045
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Identifikatorer
URN: urn:nbn:se:liu:diva-178772DOI: 10.1126/sciadv.abg9045ISI: 000686461400012PubMedID: 34407947OAI: oai:DiVA.org:liu-178772DiVA, id: diva2:1589821
Merknad

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

Tilgjengelig fra: 2021-09-01 Laget: 2021-09-01 Sist oppdatert: 2021-12-29

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