Reduced accumbens dopamine in Sprague–Dawley rats prone to overeating a fat-rich diet

Abstract Obese humans and animals exhibit reduced functioning of the dopamine (DA) system in the nucleus accumbens (NAc). The question addressed here is whether this change in NAc DA can be detected in Sprague–Dawley rats that are prone to obesity on a fat-rich diet but still at normal body weight. Rats were subgrouped as “obesity-prone” (OP) or “obesity-resistant” (OR), based on their weight gain during 5 days of access to a high-fat diet, and were then shifted to a lower-fat chow diet before microdialysis testing was performed. The OP rats compared to OR rats exhibited markedly reduced basal levels of DA in the NAc. After a high-fat challenge meal, both OP and OR rats showed a significant increase in extracellular DA and its metabolites; however, the NAc DA of the OP rats still remained at reduced levels. Also, the increase in DA and metabolite levels observed in OR rats after systemic administration of a fat emulsion was not evident in the OP rats, which instead showed no change in DA and a decrease in its metabolites. These results demonstrate, first, that fat can stimulate accumbal DA release and, second, that outbred rats prone to overeating and becoming obese on a palatable, fat-rich diet exhibit reduced signaling in the mesolimbic DA system while still at normal weight, suggesting that it may be causally related to their excess consummatory behavior.