This study uses a food addiction mouse model to investigate the neurobiological mechanisms underlying resilience and vulnerability to food addiction. The findings reveal that a lack of cannabinoid type-1 receptor (CB1R) in dorsal telencephalic glutamatergic neurons prevents food addiction-like behavior, associated with enhanced excitatory synaptic transmission in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAC). Conversely, chemogenetic inhibition of the mPFC-NAc pathway induces compulsive food seeking. Transcriptomic analysis identified increased dopamine D2 receptor expression in the mPFC-NAc pathway as promoting the addiction-like phenotype. The study uncovers a novel neurobiological mechanism for resilience and vulnerability to food addiction, with implications for future interventions.

Laura Domingo-Rodriguez, Inigo Ruiz de Azua, Eduardo Dominguez, Eric Senabre, Irene Serra, Sami Kummer, Mohit Navandar, Sarah Baddenhausen, Clementine Hofmann, Raul Andero, Susanne Gerber, Marta Navarrete, Mara Dierssen, Beat Lutz, Elena Martín-García, Rafael Maldonado