Prolonged Consumption of Sweetened Beverages Lastingly Deteriorates Cognitive Functions and Reward Processing in Mice

Abstract

We investigated the detrimental effects of chronic consumption of sweet or sweetened beverages in mice. We report that consumption of beverages containing small amounts of sucrose during several weeks impaired reward systems. This is evidenced by robust changes in the activation pattern of prefrontal brain regions associated with abnormal risk-taking and delayed establishment of decision-making strategy. Supporting these findings, we find that chronic consumption of low doses of artificial sweeteners such as saccharin disrupts brain regions’ activity engaged in decision-making and reward processes. Consequently, this leads to the rapid development of inflexible decisions, particularly in a subset of vulnerable individuals. Our data also reveal that regular consumption, even at low doses, of sweet or sweeteners dramatically alters brain neurochemistry, i.e., dopamine content and turnover, and high cognitive functions, while sparing metabolic regulations. Our findings suggest that it would be relevant to focus on long-term consequences on the brain of sweet or sweetened beverages in humans, especially as they may go metabolically unnoticed.

Inter-Individual Differences in Cognitive Tasks: Focusing on the Shaping of Decision-Making Strategies

“…Sugar consumption also leads to a decrease of approximately 40% in both the dopaminergic content and expression of the dopaminergic D2 receptor in the PFC, and a 21% reduction in the striatum ( Figure 5 ). We also observed a modulation of neuronal activity in cfos immunochemistry following an appetitive task: sugar consumption reduces the neuronal activity in the PFC and in structures of the reward system (nucleus accumbens, OFC) and increases the activity of the basolateral nucleus of the amygdala (BLA, Hamelin et al, 2021 ).…”

“…Our study has shown that continuous sugar consumption at a low dose (1% in home cage water, i.e., an increase of 25% from the daily amount) leads to behavioral, neurochemical and neuron activation disturbances ( Hamelin et al, 2021 ; Figures 5 , 6 ). Indeed, adult mice that consumed sugar for 5 weeks show decision-making alterations ( Figure 6 ).…”

“…In animal experiments, saccharin is classically used to control for caloric content of sucrose, as it mimics its sweet taste, with no metabolic or caloric consequences ( Carroll et al, 2008 for review). Our recent study shows that in mice, continuous saccharin consumption at low doses (0.1% or 0.012%) leads to an increase of anterior insula activity and alterations of dopaminergic content, dopamine turn-over, and dopaminergic receptor expression in the prefrontal cortex and the dorsal striatum ( Figure 5 ; Hamelin et al, 2021 ).…”

“…In addition, level of 5-HT in the OFC plays a key role during top-down control of decision-making ( van den Bos et al, 2013 ). We showed that exposing continuously healthy mice to sucrose or sweetener changes total DA content in the PFC and striatum, dopaminergic receptor expression and that risk-proneness can be manipulated by sucrose beverage exposure ( Hamelin et al, 2021 ). This pattern of behavior is also observed in animals subjected to ASD: sleep doesn’t change the proportion of risk-prone animals, but rather worsens their tendency for risk-taking ( Pittaras et al, 2018 ) and imbalances the DA and 5-HT system in the OFC and the caudate putamen.…”

“…In our experiments, we showed that risk-averse mice strongly preferred advantageous options during the MGT ( Pittaras E. et al, 2016 ). The magnitude of this preference and the rapidity for establishing it in a particularly non-flexible way was even reinforced after sweetener exposure ( Hamelin et al, 2021 ). However, risk-averse mice did not systematically choose the arm associated with the larger reward and did not earn more pellets than average mice: they reduced exploration of other options, and exhibited rigid behavior.…”