A specific prelimbic-nucleus accumbens pathway controls resilience versus vulnerability to food addiction (2020)

Nat Commun. 2020 Feb 7;11(1):782. doi: 10.1038/s41467-020-14458-y.

Domingo-Rodriguez L1, Ruiz de Azua I2,3, Dominguez E4, Senabre E1, Serra I5, Kummer S1, Navandar M6, Baddenhausen S2, Hofmann C2,7, Andero R8,9,10, Gerber S6, Navarrete M5, Dierssen M4,11, Lutz B2,3, Martín-García E1,8, Maldonado R12,13.


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.

PMID: 32034128

PMCID: PMC7005839

DOI: 10.1038/s41467-020-14458-y