Development of a rat model for Gaming Disorder: reward system analysis and validation with Fluoxetine treatment

Gaming Disorder (GD) is a psychopathological condition that primarily affects adolescents, characterized by compulsive gaming behavior, loss of control, and psychopathological symptoms such as social anxiety and depression. Despite the recognition of the disorder by the International Classification of Diseases-11th Revision (ICD-11) in 2018, a specific animal model for GD is still lacking. This thesis proposes a novel animal model of GD, developed using Wistar Kyoto rats trained for five to six weeks on a touch-screen platform designed to simulate typical behaviors associated with the disorder. The results show that rats exposed to the GD protocol exhibit behavioral traits similar to those observed in humans, such as hyperactivity and loss of control, which are consistently maintained over time. Neurobiological analysis revealed significant alterations in neuronal activity in key brain regions, such as the prelimbic cortex, orbitofrontal cortex, and amygdala, suggesting dysfunctions in reward and decision-making circuits. Furthermore, the examination of neurotransmitters, including orexin, dopamine, and serotonin, showed alterations both at the brain and peripheral levels, indicating involvement of reward systems and emotional regulation. Fluoxetine administration, a selective serotonin reuptake inhibitor, significantly reduced compulsive behaviors in GD rats, suggesting its effectiveness in improving control over gaming behavior and emotional dysregulation associated with the disorder. In summary, the proposed animal model provides an innovative tool to explore the neurobiological mechanisms underlying GD and to test potential therapeutic interventions, such as Fluoxetine, paving the way for future clinical research on the treatment of this emerging disorder.