Neurochemical alterations in monoaminergic systems induced by excessive sucrose consumption from the juvenile period to adolescence in mice

Abstract

Postweaning to early adulthood is a critical period for neural maturation, with dopamine (DA) and serotonin (5-HT) systems undergoing significant changes. Excessive sucrose (SUC) intake during this period is associated with metabolic and neuropsychiatric disorders; however, its effects on neurodevelopment remain unclear, especially in comparison to noncaloric sweeteners like saccharin (SAC). Therefore, we aimed to investigate the impact of chronic SUC and SAC consumption from postweaning to early adulthood on DA and 5-HT metabolism in the mesocorticolimbic system. Male mice of the Institute of Cancer Research strain received 20 % SUC or 0.2 % SAC ad libitum from postnatal days 21–56. Response to amphetamine (AMP) treatment was determined using the open-field test. The levels of DA, 5-HT, and their metabolites in the mesocorticolimbic system were assessed using high-performance liquid chromatography. Unlike SAC, SUC increased locomotor activity and attenuated the AMP response. SUC and SAC reduced DA levels in the prefrontal cortex (PFC). SUC altered DA turnover in the dorsal striatum and hippocampus, whereas SAC affected the PFC. Differences in the 5-HT/DA ratio further highlighted distinct neurobiological effects. Excessive SUC and SAC consumption during the critical developmental window induces region-specific alterations in DA and 5-HT metabolism, suggesting distinct neural effects of caloric vs. noncaloric sweeteners. These findings emphasize the need for further research on their long-term neurodevelopmental consequences.