Although originally implicated in appetite and sleep/wakefulness, the hypothalamic orexin (hypocretin) system has now been demonstrably linked with motivated behavior. This highly plastic system responds to reward-associated environmental stimuli and becomes pathologically overactive in addicted states. Here, we provide a brief overview of the roles of the orexin system in reward-seeking and addiction, as well as potential therapeutic opportunities for substance use disorders based on normalizing orexin function.
