Obesity is a chronic and relapsing condition, typically driven by overconsumption of foods high in fat and sugar (HFHS). People suffering from diet-induced obesity often continue to overeat despite knowledge of its negative health consequences, resembling a hallmark diagnostic feature of addiction – the persistence of behaviour despite adverse consequences. The transition to compulsive substance use has been linked with changes at glutamatergic synapses in the nucleus accumbens. In this study, we investigated a potential link between such glutamatergic dysregulation and compulsive-like eating using a rat model of diet-induced obesity. Further, we assessed the ability of N-acetylcysteine (NAC), a cysteine pro-drug shown to reduce cocaine, marijuana and cigarette use in some clinical trials to reduce addiction-like behaviour towards highly palatable food in this model. Adult male Sprague-Dawley rats were placed on a HFHS diet (45% kcal/fat) for eight weeks and then separated by weight gain into diet-induced obese (DIO) and diet-resistant (DR) subgroups. Subsequently, behaviour was assessed using operant self-administration and conditioned suppression paradigms. An addiction score was calculated based on three behavioural criteria. DIO and DR rats received either N-acetylcysteine (NAC, 100mg/kp, i.p.) or vehicle subchronically during operant testing.
DIO rats showed persistent eating despite negative consequences as compared to their DR counterparts and received a higher ‘addiction score’. Moreover, nucleus accumbens expression of glutamate proteins GluA1 and xCT was upregulated in DIO rats and the extent of this upregulation predicted performance on the addiction score. Treatment with NAC reduced addiction-like behaviour in DIO rats towards HFHS food.
Collectively, these data suggest that susceptibility to overeating HFHS may predict the development of loss of control over eating behaviour later on and that NAC has potential as an adjunct pharmacotherapy to traditional weight loss treatments.