A specific prelimbic-nucleus accumbens pathway controls resilience versus vulnerability to food addiction

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  • dc.contributor.author Domingo Rodriguez, Laura, 1992-
  • dc.contributor.author Ruiz de Azua, Iñigo
  • dc.contributor.author Domínguez, Eduardo
  • dc.contributor.author Senabre, Eric
  • dc.contributor.author Serra, Irene
  • dc.contributor.author Kummer, Sami, 1985-
  • dc.contributor.author Navandar, Mohit
  • dc.contributor.author Baddenhausen, Sarah
  • dc.contributor.author Hofmann, Clementine
  • dc.contributor.author Andero, Raül
  • dc.contributor.author Gerber, Susanne
  • dc.contributor.author Navarrete, Marta
  • dc.contributor.author Dierssen, Mara
  • dc.contributor.author Lutz, Beat
  • dc.contributor.author Martín García, Elena, 1975-
  • dc.contributor.author Maldonado, Rafael, 1961-
  • dc.date.accessioned 2020-03-11T08:34:14Z
  • dc.date.available 2020-03-11T08:34:14Z
  • dc.date.issued 2020
  • dc.description.abstract Food addiction is linked to obesity and eating disorders and is characterized by a loss of behavioral control and compulsive food intake. Here, using a food addiction mouse model, we report that the lack of cannabinoid type-1 receptor in dorsal telencephalic glutamatergic neurons prevents the development of food addiction-like behavior, which is associated with enhanced synaptic excitatory transmission in the medial prefrontal cortex (mPFC) and in the nucleus accumbens (NAc). In contrast, chemogenetic inhibition of neuronal activity in the mPFC-NAc pathway induces compulsive food seeking. Transcriptomic analysis and genetic manipulation identified that increased dopamine D2 receptor expression in the mPFC-NAc pathway promotes the addiction-like phenotype. Our study unravels a new neurobiological mechanism underlying resilience and vulnerability to the development of food addiction, which could pave the way towards novel and efficient interventions for this disorder.
  • dc.description.sponsorship This work was supported by the Spanish Ministerio de Economía y Competitividad-MINECO (#SAF2017-84060-R-AEI/FEDER-UE), the Spanish Instituto de Salud Carlos III, RETICS-RTA (#RD12/0028/0023), the Generalitat de Catalunya, AGAUR (#2017 SGR-669), ICREA-Acadèmia (#2015) and the Spanish Ministerio de Sanidad, Servicios Sociales e Igualdad, Plan Nacional Sobre Drogas (#PNSD-2017I068) to R.M., Fundació La Marató-TV3 (#2016/20-30) to E.M-G., the German Research Foundation (#CRC1193 “Neurobiology of Resilience”, TP A05 and B04) to B.L. and S.G., and the Boehringer Ingelheim Foundation to B.L., S.G. and I.R.A. The work of M.N.A was supported by the Emergent AI Center funded by the Carl-Zeiss-Stiftung. NARSAD Young Investigator Award (#22434), MINECO Ramón y Cajal (#RYC- 2014-15784) and (#SAF2016-76565-R) and Fondo Europeo de Desarrollo Regional (FEDER) to R.A. DIUE Generalitat de Catalunya (#2017 SGR 595), MINECO (#SAF2016-79956-R), EU (#Era Net Neuron PCIN-2013-060), Fundació La Marató-TV3 (#2016/20-31), CRG acknowledges support of the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) to the EMBL partnership, the Center of Excellence Severo Ochoa (#SEV-2012-0208), the CERCA Programme/Generalitat de Catalunya, the CIBER of Rare Diseases of the ISCIII to M.D. MINECO Ramón y Cajal (#RYC-2016-20414), AGAUR (#2017 SGR 926), (#RTI2018-094887-B-I00) and Fondo Europeo de Desarrollo Regional (FEDER) to M.N.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Domingo-Rodriguez L, Ruiz de Azua I, Dominguez E, Senabre E, Serra I, Kummer S, Navandar M, Baddenhausen S, Hofmann C, Andero R, Gerber S, Navarrete M, Dierssen M, Lutz B, Martín-García E, Maldonado R. A specific prelimbic-nucleus accumbens pathway controls resilience versus vulnerability to food addiction. Nat Commun. 2020; 11(1):782. DOI: 10.1038/s41467-020-14458-y
  • dc.identifier.doi http://dx.doi.org/10.1038/s41467-020-14458-y
  • dc.identifier.issn 2041-1723
  • dc.identifier.uri http://hdl.handle.net/10230/43855
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Nat Commun. 2020; 11(1):782
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/SAF2017-84060-R
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-79956-R
  • dc.rights © The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Addiction
  • dc.subject.keyword Behavioural genetics
  • dc.title A specific prelimbic-nucleus accumbens pathway controls resilience versus vulnerability to food addiction
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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