Prefrontal accumbens neural dynamics abnormalities in mice vulnerable to develop food addiction

Food addiction is characterized by a loss of behavioral control over food intake and is closely associated with several eating disorders, including obesity and binge eating. Despite its high prevalence, the underlying neural mechanisms of food addiction are still unresolved. We trained mice in an operant paradigm for 110 days to promote the development of food addiction. Then, we classified mice as addicted and extreme non-addicted based on three addiction criteria and recorded neural activities in the prelimbic medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) core through electrophysiology in vivo. Addicted mice presented disrupted mPFC-to-NAc signaling at high frequencies (hfo 150-200 Hz) during decision-making to obtain food. Moreover, addicted mice exhibited reduced low gamma oscillations and theta-gamma coupling in the NAc during reward expectancy. Disrupted mPFC-to-NAc connectivity and gamma synchrony in the NAc correlated with increased reinforcement levels, unraveling the functional relevance of these alterations. The cannabinoid type-1 (CB1) receptor antagonist rimonabant rescued neural alterations observed in the addicted mice.Reinforcement levels were reduced after rimonabant administration and the directionality of signals and oscillatory activity in the NAc were reversed in addicted mice during decision-making and reward expectation, respectively. These findings suggest that disrupted mPFC-NAc neural dynamics are candidate mechanisms underlying specific behavioral alterations associated with food addiction. The elucidation of these novel communication mechanisms between the mPFC and the NAc will provide advances towards future development of new therapeutic interventions for food addiction and related disorders.