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

• DOI: 10.1038/s41467-020-14458-y
• Publication Date: 2020-02-07T11:04:14Z
• Authors: Laura Domingo-Rod...; 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
• Keywords: Mice, Knockout; 0303 health sciences; Receptors, Dopamine D2; Science; Gene Expression Profiling; Q; Addiction; Prefrontal Cortex; Feeding Behavior; Synaptic Transmission; Article; Nucleus Accumbens; Up-Regulation; 3. Good health; Disease Models, Animal; 03 medical and health sciences; Gene Expression Regulation; Receptor, Cannabinoid, CB1; Behavioural genetics ; Addiction; Neural Pathways; Behavioural genetics; Animals; Food Addiction

Abstract Food addiction is linked to obesity and eating disorders characterized by a loss of behavioral control compulsive food intake. Here, using mouse model, we report that the lack cannabinoid type-1 receptor in dorsal telencephalic glutamatergic neurons prevents development addiction-like behavior, which associated with enhanced synaptic excitatory transmission medial prefrontal cortex (mPFC) nucleus accumbens (NAc). In contrast, chemogenetic inhibition neuronal activity mPFC-NAc pathway induces seeking. Transcriptomic analysis genetic manipulation identified increased dopamine D2 expression promotes phenotype. Our study unravels new neurobiological mechanism underlying resilience vulnerability addiction, could pave way towards novel efficient interventions for this disorder.