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OREXIN ANTAGONISTS FOR NEUROPSYCHIATRIC DISEASE: PROGRESS AND POTENTIAL PITFALLS

Authors :
Jiann W Yeoh
Erin J Campbell
Morgan H James
Brett A Graham
Christopher V Dayas
Source :
Frontiers in Neuroscience, Vol 8 (2014)
Publication Year :
2014
Publisher :
Frontiers Media S.A., 2014.

Abstract

The tight regulation of sleep/wake states is critical for mental and physiological wellbeing. For example, dysregulation of sleep/wake systems predisposes individuals to metabolic disorders such as obesity and psychiatric problems, including depression. Contributing to this understanding, the last decade has seen significant advances in our appreciation of the complex interactions between brain systems that control the transition between sleep and wake states. A pivotal moment in this pathway to discovery was the description of a group of neurons in the lateral hypothalamus (LH) that express the neuropeptides orexin A and B (hypocretin, Hcrt-1 and Hcrt-2). Orexin neurons were quickly placed at centre stage with the demonstration that loss of normal orexin function is associated with the development of narcolepsy – a condition in which sufferers fail to maintain normal levels of daytime wakefulness. Since these initial seminal findings, much progress has been made in our understanding of the physiology and function of the orexin system. For example, the orexin system has been identified as a key modulator of autonomic and neuroendocrine function, arousal and reward and attention. Notably, studies in animals suggest that dysregulation of orexin function is associated with neuropsychiatric states such as addiction and mood disorders including depression and anxiety. This review discusses the progress associated with therapeutic attempts to restore orexin system function and treat neuropsychiatric conditions such as addiction, depression and anxiety. We also highlight potential pitfalls and challenges associated with targeting this system to treat these neuropsychiatric states.

Details

Language :
English
ISSN :
1662453X
Volume :
8
Database :
Directory of Open Access Journals
Journal :
Frontiers in Neuroscience
Publication Type :
Academic Journal
Accession number :
edsdoj.98d7c49c09448898e64462549f6500a
Document Type :
article
Full Text :
https://doi.org/10.3389/fnins.2014.00036