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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.

High-fat diets are linked with obesity and changes in dopamine neurotransmission. Mounting evidence shows that saturated fat impacts dopamine neurons and their terminal fields, but little is known about the effect a diet high in unsaturated fat has on the dopamine system. This study sought to determine whether fat type, saturated vs. unsaturated, differentially affected body weight, blood glucose regulation, locomotor behavior, and control of dopamine release and uptake at dopamine neuron terminals in the nucleus accumbens (NAc). C57BL/6 mice were fed a control diet or a nutrient-matched diet high in saturated fat (SF), unsaturated flaxseed oil (Flax) or a blend of the two fats. After 6-weeks, mice from each high-fat diet group gained significantly more weight than Controls, but the group fed Flax gained less weight than the SF group and had fasting blood glucose levels similar to Controls. Ex-vivo fast scan cyclic voltammetry revealed the SF group also had significantly slower synaptic dopamine clearance and a reduced capacity for phasic dopamine release in the nucleus accumbens (NAc), but the Flax and Blend groups resembled Controls. These data show that different types of dietary fat have substantially different effects on metabolic phenotype and influence how dopamine terminals in the NAc regulate dopamine neurotransmission. Our data also suggests that a diet high in unsaturated fat may preserve normal metabolic and behavioral parameters as well as dopamine signaling in the NAc.

BACKGROUND Obesity has been linked to behavioral and biochemical changes, such as reduced physical activity, dysregulated dopamine metabolism, and gene expression alterations in the brain. The impact of a continuous high-fat diet and resulting state of obesity may vary depending on sex and genetics. OBJECTIVE The aim of this study was to investigate the impact of a high-fat diet on physical activity, gene expression in the striatum, and dopamine neurochemistry using male and female mice from different strains as a model to examine sex and strain influences on dopamine-mediated behavior and neurobiology. METHODS Male and female mice from the C57BL/6J (B6J) and DBA/2J (D2J) strains were randomly assigned a control low-fat diet with 10% kcal fat or a high-fat diet with 60% kcal fat for 16 weeks. We assessed ambulation and habituation using the open field test; dopamine release and reuptake using ex-vivo fast scan cyclic voltammetry; and striatal mRNA expression of dopamine receptor D2, alpha synuclein, and tyrosine hydroxylase. RESULTS Mice fed a high-fat diet exhibited reduced motor activity, but only obese B6J male mice displayed reduced habituation. Dopamine clearance in the dorsal striatum was reduced only in obese D2J mice, while dopamine clearance in the nucleus accumbens core was reduced only in male obese D2J mice. Striatal dopamine receptor D2 gene expression was upregulated exclusively in obese male B6J mice. CONCLUSION Our study provides evidence for important sex and strain influences on the impact of a high-fat diet and obesity-induced behavior alterations and neurobiology dysregulation in the striatum.

The aim of this review is to explore how metabolic changes induced by diets high in saturated fat (HFD) affect nucleus accumbens (NAc) dopamine neurotransmission and food intake, and to explore how stress and inflammation influence this process. Recent evidence linked diet-induced obesity and HFD with reduced dopamine release and reuptake. Altered dopamine neurotransmission could disrupt satiety circuits between NAc dopamine terminals and projections to the hypothalamus. The NAc directs learning and motivated behaviours based on homeostatic needs and psychological states. Therefore, impaired dopaminergic responses to palatable food could contribute to weight gain by disrupting responses to food cues or stress, which impacts type and quantity of food consumed. Specifically, saturated fat promotes neuronal resistance to anorectic hormones and activation of immune cells that release proinflammatory cytokines. Insulin has been shown to regulate dopamine neurotransmission by enhancing satiety, but less is known about effects of diet-induced stress. Therefore, changes to dopamine signalling due to HFD warrant further examination to characterise crosstalk of cytokines with endocrine and neurotransmitter signals. A HFD promotes a proinflammatory environment that may disrupt neuronal endocrine function and dopamine signalling that could be exacerbated by the hypothalamic–pituitary–adrenal and κ-opioid receptor stress systems. Together, these adaptive changes may dysregulate eating by changing NAc dopamine during hedonic versus homeostatic food intake. This could drive palatable food cravings during energy restriction and hinder weight loss. Understanding links between HFD and dopamine neurotransmission will inform treatment strategies for diet-induced obesity and identify molecular candidates for targeted therapeutics.

Diet-induced obesity reduces dopaminergic neurotransmission in the nucleus accumbens (NAc), and stressful weight loss interventions could promote cravings for palatable foods high in fat and sugar that stimulate dopamine. Activation of κ-opioid receptors (KORs) reduces synaptic dopamine, but contribution of KORs to lower dopamine tone after dietary changes is unknown. Therefore, the purpose of this study was to determine the function of KORs in C57BL/6 mice that consumed a 60% high-fat diet (HFD) for six weeks followed by replacement of HFD with a control 10% fat diet for one day or one week. HFD replacement induced voluntary caloric restriction and weight loss. However, fast-scan cyclic voltammetry revealed no differences in baseline dopamine parameters, whereas sex effects were revealed during KOR stimulation. NAc core dopamine release was reduced by KOR agonism after one day of HFD replacement in females but after one week of HFD replacement in males. Further, elevated plus-maze testing revealed no diet effects during HFD replacement on overt anxiety. These results suggest that KORs reduce NAc dopamine tone and increase food-related anxiety during dietary weight loss interventions that could subsequently promote palatable food cravings and inhibit weight loss.

OBJECTIVES: The objectives of this study were to investigate: 1) home food availability and dietary pattern in the beginning and end of the month, and; 2) brain activation for highly palatable and nutrient-dense food stimuli, among low-income women prone to food insecurity. METHODS: An in-depth exploratory study was conducted with low-income women receiving SNAP (n = 13) involving home food inventories, 24-h diet recalls and brain MRIs at two time points of ‘beginning’ and ‘end’ of month. Upon meeting the following main selection criteria: 1) 18 years or older; 2) no absolute and relative MRI contraindications, women provided their informed consent. Participants’ individual dates of monthly income and benefits receipt were used to define the ‘beginning of the month’ period as 1–7 days within receiving benefits and the ‘end of the month’ period starting 21–30 days following. Interviews and MRI scans were completed during these periods. Functional MRI scans were conducted to measure brain activation in response to both highly palatable and nutrient-dense food image stimuli. The study was approved by the UNC-Greensboro IRB. Frequencies, descriptives, and nonparametric statistical tests were used in analysis and results were considered statistically significant at P