Abstract
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.
Highlights
Published: 9 July 2021Obesity prevalence has steadily increased for decades with 42.4% of American adults classified as obese [1]
novelty-induced hypophagia (NIH) testing was used to assess baseline food-related anxiety behaviors induced by consuming a high-fat diet (HFD), whereas the elevated plus-maze (EPM) test was used to assess whether stress induced by HFD replacement promoted general anxiety-like behaviors in addition to baseline food-specific anxiety
Atwo-way analysis of variance (ANOVA) with males and females showed a main effect of diet (F(1,66) = 30.25; p < 0.0001) but not sex (p = 0.5936), and mice consuming HFD consumed significantly less sucrose during the NIH test than controls in males (0.017 ± 0.003 vs. 0.107 ± 0.027 kcals; p = 0.0002) and females (0.031 ± 0.005 vs. 0.108 ± 0.013 kcals; p = 0.0011) (Figure 2a)
Summary
Published: 9 July 2021Obesity prevalence has steadily increased for decades with 42.4% of American adults classified as obese [1]. Animal models showed that replacement of a diet high in saturated fat (HFD) with low-fat food induced anxiety-like behavior and motivation to obtain sucrose and fat [3,4]. This suggests that extended palatable food consumption promotes dietary inflexibility towards non-preferred foods but sudden removal of HFD induces stress and motivation to consume palatable options. Sudden dietary changes that promote stress and food intake could be explained by dopamine neurotransmission in the nucleus accumbens (NAc) that controls cue-induced learning and motivation [7].
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