The Orexin/Hypocretin System

The Orexin/Hypocretin System

Functional Roles and Therapeutic Potential

1st Edition - January 3, 2019

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  • Editors: Jim Fadel, Joshua Burk
  • Paperback ISBN: 9780128137512
  • eBook ISBN: 9780128137529

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The Orexins/Hypocretins System: Functional Roles and Therapeutic Potential summarizes research on both the physiological functioning of orexins, their impact on homeostatic processes, and related disorders. The book encompasses the effects on appetite, sleep, substance abuse, cognition, and anxiety. Additionally, it examines new therapeutic approaches utilizing orexins, including utilization of orexin receptors for drug development. It is essential reading for neuroscience researchers interested in brain-behavior relationships, as well as psychiatrists, endocrinologists and pharmacologists.

Key Features

  • Provides an overview of new research on orexins/hypocretins
  • Includes an overview of intracellular signaling and orexin physiology
  • Discusses the effects on arousal, appetite, cognition, addiction and anxiety
  • Examines orexin based therapies and their potential use in disorders
  • Explores orexin receptors for drug development


Researchers, clinicians, postdoctoral fellows and graduate students in behavioral neuroscience, clinical neuroscience, neuroendocrinology, pharmacology, psychiatry, and psychology

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

Product details

  • No. of pages: 188
  • Language: English
  • Copyright: © Academic Press 2019
  • Published: January 3, 2019
  • Imprint: Academic Press
  • Paperback ISBN: 9780128137512
  • eBook ISBN: 9780128137529

About the Editors

Jim Fadel

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).

Affiliations and Expertise

Professor, Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine

Joshua Burk

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.

Affiliations and Expertise

Professor and Chair, Department of Psychology, College of William and Mary

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