Obesogenic diets are known to induce obesity and changes in food intake in experimental animals. Obesity negatively affects the peripheral metabolism and neural aspects, such as changes in eating behavior. In obese animals, dopamine (DA) receptor levels are reduced. Dopamine is one of the main peptides involved in the motivation and pleasure of eating. A combination of naltrexone/bupropion (NB) has shown promise in controlling metabolic alterations, but there are few studies on how they modulate dopaminergic expression. Naltrexone/bupropion, in addition to reducing food intake and body weight, can modify tyrosine hydroxylase (Th) and Dopamine receptor D2 (Drd2) levels in the mesolimbic areas of rats submitted to a high-fat diet (HF). The study evaluated the effect of NB on food intake, body weight, and expression levels of TH, Drd1a, and Drd2, in the nucleus accumbens and striatum of rats fed on HF. Wistar rats were grouped according to diet: Standard (n = 20) and High-fat diet (n = 20). The food intake and body weight were analyzed. The gene expression of Th, Drd1a, and Drd2 was evaluated using real-time Polymerase Chain Reaction (PCR). NB (1 mg/kg) and (20 mg/kg) reduced food intake and body weight. It increased Drd2 expression in rats on HF diet and increased Th in rats on both experimental diets. The level of Drd1a was unchanged. We concluded that body weight reduction may be associated with decreased food intake in response to the increased Drd2 expression in the mesolimbic areas of rats that received a high-fat diet.

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