Exposure to high-energy diet reduces cue-evoked dopamine in obesity-resistant but not obesity-prone female rats.

The mesolimbic dopamine system is a critical neural pathway that contributes to reward processing and motivation through the release of dopamine in the nucleus accumbens (NAc) from neurons originating in the ventral tegmental area. Various factors, like intake of palatable foods and obesity, can alter dopamine release and subsequent behaviors. In this study, using a polygenic rat model of obesity, we investigated if the mesolimbic dopamine system responds differently after exposure to high-energy (HE) diet in female rats that are obesity-prone (DIO) or obesity-resistant (DR). We approached this by combining a Pavlovian conditioning paradigm - in which the presentation of a rewarding sugar pellet was preceded by a light cue - and in vivo fiber photometry. Results revealed a significant decrease in cue-evoked dopamine in DR rats after HE diet exposure, contrasting with the unchanged response in DIO rats. This reduction in dopamine activity may signify reduced salience for the sucrose-reward in DR rats, potentially serving as an adaptive mechanism preventing excessive overeating and weight gain, consistent with the lack of body weight gain when consuming high-energy diet. Moreover, DR rats exhibited lower reward-seeking behavior compared to DIO rats, indicating a differential, but innate, responsiveness to the rewarding stimuli between the obesity-prone and -resistance phenotypes. In conclusion, the study offers new evidence showing that dopamine signaling in the NAc responds differently following exposure to HE diet in DIO and DR rats, shedding light on potential adaptive mechanisms that protect against excessive weight gain and altered motivation for rewards. Understanding these mechanisms could offer insights into managing obesity-related behaviors and associated neurobiological responses in an obesogenic environment.