ABSTRACT Feeding is regulated by energy homeostatic and pleasure-induced rewarding signals. Palatable food intake modifies serotonergic (5-HT) and dopaminergic (DA) pathways in nucleus accumbens, inducing neuronal maladaptations that favor hyperphagia for high-energy dense food and consequent obesity. Chronic stress is an environmental condition that increases the preference for palatable food by modulating brain DA and 5-HT metabolism. Objective: To evaluate the association between changes in accumbal 5-HT and DA metabolism and the effects of chronic stress, palatable food intake and their interaction with satiety/hunger condition. Methods: Wistar rats were housed in pairs (non-stressed) or individually (stressed), fed with chow or chocolate milk plus chow (Ch) for 2 weeks (4 groups); then 6 animals/group were 48 h fasted or maintained ad libitum; the rest were fasted and re-fed for 2 h either with chow or Ch. Results: Rats with prolonged high-energy density food intake and re-fed with chow showed reduced 5-HT metabolism, although there was no association with animals’ feeding behavior. In contrast, after re-fed with palatable food, stressed chow-fed rats had increased 5-HT turnover, which decreased in Ch re-fed rats, supporting that palatable food might induce positive mood changes related to high extracellular 5-HT in limbic regions. Discussion: Rats with prolonged palatable food intake exhibited high accumbal DA turnover independently of stress exposure, supporting its relation with the development of high-energy dense food hyperphagia. As accumbal 5-HT and DA metabolism changed due to fasting or re-feeding, alterations could represent the interaction of energy homeostatic and hedonic feeding signaling in animals.