Effect of fasting on dopamine neurotransmission in subregions of the nucleus accumbens in male and female mice

Diets high in saturated fat (HFD) disrupt dopamine neurotransmission, whereas fasting alters tonic and phasic dopamine release to drive motivation and food consumption. However, functional compartments in the nucleus accumbens (NAc) influencing these effects are not well characterized, and sex comparisons have not been made. This study sought to determine whether consumption of a HFD, sex, or being fed versus fasted altered baseline dopamine release and reuptake throughout NAc subregions. Male and female C57BL/6 mice were fed a control diet or nutrient matched HFD for six weeks. Ex-vivo fast-scan cyclic voltammetry revealed females had significantly slower dopamine reuptake in the NAc core than males when fed ad lib control diet. Fasting enhanced dopamine release and reuptake in the NAc core but not the medioventral shell. Further, being fasted versus fed significantly increased dopamine release throughout the NAc core in control males but specifically promoted release and reuptake in only the ventrolateral core of HF-fed males, effects which were lacking in females. Finally, fasting promoted dopamine release and reuptake in the rostral NAc core of controls and more caudally in HFD groups. These data support that dopamine neurotransmission is heterogeneous in NAc subregions and suggest the ventrolateral core is responsive to energy state. Furthermore, a rostrocaudal gradient in the NAc core might control valence responses to fasting that could promote overeating after chronic HFD consumption.