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.
Highlights
When the effort to obtain one single pellet was increased to FR to 5 (FR5), the progressive increase of the number of reinforcers was significantly reduced in Glu-CB1-KO as compared to WT, leading to a reduced number of reinforcers over the entire FR5 period
We describe a novel neurobiological mechanism underlying the resilience and vulnerability to food addiction-like behavior targeting excitatory glutamatergic transmission in PL-nucleus accumbens (NAc) core projection, which appears to be modulated by the endocannabinoid and the dopaminergic signaling systems
Our findings revealed that the lack of CB1R in dorsal telencephalic glutamatergic neurons induced a strong resilience to food addiction as revealed by the significantly reduced percentage (6.9%) of addicted mice in the mutant group
Summary
The aim of this study was to decipher the neurobiological mechanisms underlying the resilience and the vulnerability to develop food addiction-like behavior
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