Intermittency and Predictability of a Cafeteria Diet Shape Food Intake, Adiposity, and Neurobehavioral Outcomes in Rats

Background/Objective: Highly palatable foods are pleasurable and motivational stimuli that activate the brain’s reward system and can induce overeating in the absence of physiological needs. This study investigated how different access patterns to a cafeteria diet influence food intake, body weight-related parameters, and metabolic and neurobehavioral outcomes. Methods: At postnatal day 31, forty male Wistar rats were assigned to a standard diet or a cafeteria diet with continuous, predictable intermittent, or unpredictable intermittent access. After 10 weeks, the open-field and sucrose-preference tests assessed exploratory and anxiety-like behaviors and reward-related responses, respectively. Body composition, serum biochemical parameters, neurotransmitter content, and mRNA and protein levels were analyzed in reward-related brain regions. Results: Intermittent access increased food intake on cafeteria days compared with continuous access, with unpredictable access yielding the highest intake. Continuous-access rats exhibited higher final body weight and fat accumulation than chow-fed Control rats. Despite similar body weight, both intermittent-access groups had higher visceral adiposity, obesity indices, and adverse metabolic outcomes than the Control group. All cafeteria-fed rats displayed anxiety-like behavior, and all groups preferred sucrose except the continuous-access group. Molecular analyses revealed region-specific differences in gene expression related to neuroplasticity, stress response, and epigenetic regulation that varied with access pattern and predictability. Conclusions: Our results suggest that, beyond diet composition, the pattern and predictability of food access are key determinants of feeding behavior. Intermittent access increases the motivational value of the cafeteria diet, promoting overeating and driving reward- and stress-related neuroadaptations with potential metabolic and mental health implications.