The Hypocretins/Orexins: Master Regulators of Arousal and Hyperarousal

Abstract

(from the chapter) The hypocretins (Herts)-also known as "orexins"-are a pair of neuropeptides well known for their role in promoting wakefulness. Shortly after their discovery, multiple laboratories identified the crucial link between dysfunction of the Hcrt system and narcolepsy in mice, dogs, and humans. Therefore, much research has focused on the wake-promoting properties of Herts and why their absence leads to a narcoleptic phenotype. Indeed, drugs that directly target the Hcrt system are currently under development to treat human patients with insomnia and other sleep disorders. However, research also indicates that Herts play roles in behavioral phenotypes beyond wakefulness, regulating other arousal-related behaviors such as brain reward and motivation, stress/anxiety, food intake, sexual behavior, and attention. In this chapter, we review the role of Herts in mediating arousal-related behaviors in addition to wakefulness, with a special emphasis on the recently discovered role of Herts in mediating the stress response and in regulating reward circuitry in the brain. These multiple roles of Herts in arousal-related behaviors should be considered when contemplating the role of Herts in narcolepsy, and also when targeting the Hcrt system to treat narcolepsy and other sleep disorders. (PsycINFO Database Record (c) 2012 APA, all rights reserved).