The Orexin/Hypocretin System. Functional Roles and Therapeutic Potential

Table of Contents

Part 1: Introduction 1. Hypocretins (orexins): 20 years of dissecting arousal circuits 2. Orexins and motivated behaviors

Part 2: Orexins and Sleep 3. Orexins and the stabilization of wake/sleep states 4. Orexins and narcolepsy in animal models

Part 3: Orexins and Feeding 5. Orexin's role in motivated behavior for food 6. Orexin drives energy expenditure

Part 4. Orexins and Drug Abuse 7. Orexins/hypocretins and addiction 8. Hypocretin 1 receptor regulation of dopaminergic signaling and motivated behavior 9. Orexins and opioid addiction

Part 5: Orexins and Cognition 10. Orexins and cognition: neurochemical and anatomical substrates 11. The hypocretin/orexin system and fear learning

Part 6: Orexins and Psychological Disorders 12. Orexins and anxiety disorders 13. Orexins as targets for treating brain disorders

Authors

Jim R. Fadel Professor, Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine. Jim Fadel is a Professor of Pharmacology, Physiology and Neuroscience at the University of South Carolina School of Medicine. His initial interest in the orexin/hypocretin system began as a postdoctoral fellow with Dr. Ariel Deutch, where he described the anatomical basis for orexin-dopamine interactions and identified orexin neurons as targets of antipsychotic drugs associated with weight gain (Fadel & Deutch, 2002; Fadel et al., 2002). Since then, he has focused extensively on anatomical and neurochemical mechanisms underlying orexin effects on cognition. With his long-time collaborator, Dr. Burk, he has shown that orexins play important roles in regulating attentional functions which stem, in part, from their effects on the basal forebrain cholinergic system (e.g. Fadel & Burk, 2010; Frederick-Duus et al., 2007). Dr. Fadel's lab has also demonstrated loss of orexin neurons in their aged rat model (Kessler et al., 2010), a phenomenon proposed to link age-related alterations in homeostasis with cognition (Stanley & Fadel, 2012; Fadel et al., 2013). Joshua A. Burk Professor and Chair, Department of Psychology, College of William and Mary. Josh Burk is a Professor and Chair of the to Department of Psychological Sciences at the College of William and Mary. His is a neuropsychopharmacologist who studies neural mechanisms involved in attention and impulsivity. He and Dr. Fadel have a long-standing collaboration, which has been supported by two R01 grants. They have shown that blockade of orexin receptors, systemically or by infusion into the basal forebrain disrupts attentional performance (Boschen, Fadel, & Burk, 2009). They discussed the implications of these findings within the existing literature in a review paper (Fadel & Burk, 2010). Most recently, they showed that administration of orexin A can attenuate attentional deficits after a distracter or following loss of basal forebrain corticopetal cholinergic neurons (Zajo, Fadel, & Burk, 2016). They have a number of ongoing studies to understand the role of orexins/hypocretins in cognition associated with their current R01 grant.