Long-term sugar consumption alters extracellular dopamine and acetylcholine levels in the nucleus accumbens shell

High dietary sugar consumption is associated with an increased risk of various diseases, making it imperative to identify the neural, nutritional, and behavioral mechanisms that underlie dietary habits to better understand and improve health. However, little is known about the neural mechanisms underlying prolonged consumption, making it difficult to determine the alterations caused by chronic sucrose intake in reinforcement and memory pathways, including the nucleus accumbens. Previous work in rodents has shown that long-term sugar consumption alters appetitive relearning, potentially leading to increased intake due to a disability in learning new negative consequences associated with the same taste, which possibly involves the mesolimbic dopaminergic system as well as cholinergic signaling. The objective of this study was to evaluate the extracellular levels of dopamine (DA) and acetylcholine (ACh) in the nucleus accumbens shell (NACsh) of adult male Wistar rats during novel (SN), familiar sugar consumption (2 days, SF), and after exposure ad libitum for 14 days to a 10% sugar solution (high-familiar groups, SH). Subsequently, on days 19-21, rats were habituated to the microdialysis chamber; on days 22 and 23, microdialysis was performed during consumption of novel, familiar, or highly familiar sugar. HPLC-EC microdialysis analysis revealed significant differences in the extracellular levels of DA and ACh in the NACsh between the highly familiarized and mildly familiarized groups (SF), and the group exposed to novel sugar. Specifically, baseline NACsh-ACh levels in the SH group were significantly higher and decreased during sugar consumption, whereas the novel sugar group showed a significant increase in ACh during and after sugar consumption; the SF group showed no change in ACh levels. In contrast, DA levels increased significantly during familiar sugar consumption (SF), but there were no changes after long-term consumption (SH) or during novel sugar (SN) consumption. The results demonstrate changes in cholinergic and dopaminergic signaling in the NACsh that negatively correlate with increased familiarity of a highly reinforcing stimulus, such as sugar. Specifically, the decrease in ACh and DA release following high-sugar familiarization suggests neuroadaptation in the NACsh, which could correlate with the inability to form new aversive associations with sweet flavors.