The Orexin/Hypocretin System: Functional Roles and Therapeutic Potential

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.

• 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

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).

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.