The involvement of the orexin system in the obsessive compulsive subtype of gaming behavior in acute and chronic stress in rats

Introduction. Game addiction, particularly its obsessive-compulsive subtype, often co-occurs with anxiety disorders. The aim of the study was to evaluate the role of the brain’s orexin system in the development of compulsive behavior modeling a component of addiction under acute and chronic stress. Materials and methods. Experiments were conducted on 64 male Wistar rats. Chronic stress was modeled through social isolation, while acute stress involved a life threat (observation of a conspecific’s death). Compulsive behavior was assessed using a ball-digging test. Results. Animals received intranasal administration of selective orexin receptor antagonists: SB-408124 (OX1R) or TCS-OX2-29 (OX2R), over a period of 7 days. Both types of stress significantly increased compulsive activity. Under chronic stress, blockade of OX2R receptors (TCS-OX2-29) markedly reduced the level of compulsive actions, while both antagonists decreased the scores to the control group level after acute stress. Discussion. Thus, the orexin system, primarily through OX2R, is involved in the pathogenesis of stress-induced compulsive behavior. Conclusion. Intranasal orexin receptor antagonists may serve as a promising basis for developing interventions for stress-dependent obsessive-compulsive spectrum disorders.