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Roles of Orexins and Orexin Receptors in Central Regulation of Feeding Behavior and Energy Homeostasis

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Orexins were initially recognized as regulators of feeding behavior due to their exclusively production in the lateral hypothalamic area (LHA), a feeding center. Subsequently, the finding that orexin deficiency causes narcolepsy in humans and animals suggested that these hypothalamic neuropeptides play a critical role in regulating and maintaining sleep/wakefulness states. Proper maintenance of arousal during food searching and intake is essential for an animal's survival. Therefore, feeding behavior and sleep/wakefulness states are appropriately coordinated. For example, when faced with reduced food availability, animals adapt with a longer wakefulness period, which disrupts the normal circadian pattern of activity. The discovery that orexin neurons are regulated by peripheral metabolic cues, including ghrelin, leptin and glucose, suggests that they might have important roles as a link between energy homeostasis and sleep/wakefulness states. Recent studies on afferent (input) systems of orexin neurons further suggest roles of orexin and orexin receptors in the coordination of feeding, arousal and emotion.

Keywords: Amygdala; REM-sleep; Ventromedial hypothalamus; body mass index; cerebrospinal fluid (CSF); wakefulness

Document Type: Research Article


Affiliations: Department of Pharmacology, Institute of Basic Medical Science, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan and ERATO Yanagisawa Orphan Receptor Project, Japan Science and Technology Corporation, Tokyo 135-0064, Japan.

Publication date: 2006-06-01

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  • CNS & Neurological Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in neurological and central nervous system (CNS) disorders e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will contain a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in neurological and CNS disorders. As the discovery, identification, characterization and validation of novel human drug targets for neurological and CNS drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.
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