Central and peripheral monoamine changes in a rat model of Gaming Disorder

Gaming Disorder (GD) is a mental disorder primarily affecting adolescents. Prolonged video game use can lead to behavioral alterations, such as loss of control, increased compulsivity, and symptoms of depression and anxiety. Studies in humans have shown changes in brain areas involved in emotional regulation and reward circuits, including the lateral hypothalamus (LH), ventral tegmental area (VTA), and dorsal (DRN) and median (MnR) raphe nuclei. These alterations appear to be linked to disrupted activity of orexin- (ORX), dopamine- (DA), and serotonin- (5-HT) positive (+) neurons. Our laboratory developed a rat model that mimics some symptoms of GD. Using immunohistochemistry and high-performance liquid chromatography, we analyzed ORX, DA, and 5-HT levels in rats exposed to the GD protocol. Compared to control groups, GD rats of both sexes exhibited a decreased density and number of ORX+, DA+, and 5-HT+ cells in the analyzed nuclei. Additionally, the reduction in DA+ and 5-HT+ neurons was associated with peripheral changes in their plasma levels and alterations in the tryptophan signaling pathway, accompanied by an increase in its inflammatory metabolites. These three systems are crucial for proper brain function, decision-making regulation, and the processing of emotional and reward-related stimuli. Our findings support the hypothesis that neurotransmitter dysfunction plays a key role in GD and provide a foundation for further research on the cerebral and behavioral changes observed in GD patients.