Domingo Rodriguez, Laura, 1992-Ruiz de Azua, IñigoDomínguez, EduardoSenabre, EricSerra, IreneKummer, Sami, 1985-Navandar, MohitBaddenhausen, SarahHofmann, ClementineAndero, RaülGerber, SusanneNavarrete, MartaDierssen, MaraLutz, BeatMartín García, Elena, 1975-Maldonado, Rafael, 1961-2020-03-112020-03-112020Domingo-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-y2041-1723http://hdl.handle.net/10230/43855Food 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.application/pdfeng© 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/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41467-020-14458-yAddictionBehavioural geneticsinfo:eu-repo/semantics/openAccess