Related Experiment Video

Updated: Mar 23, 2026

Polygraphic Recording Procedure for Measuring Sleep in Mice
08:45

Polygraphic Recording Procedure for Measuring Sleep in Mice

Published on: January 25, 2016

25.7K

The hypocretin/orexin system in sleep disorders: preclinical insights and clinical progress

Matthew Chow1, Michelle Cao1

  • 1Department of Psychiatry and Behavioral Sciences, Division of Sleep Medicine, Stanford University School of Medicine, Stanford, CA, USA.

Nature and Science of Sleep
|April 7, 2016
PubMed

Insights

The hypocretin/orexin (HCRT/OX) system is crucial for stable sleep-wake cycles. Disruptions lead to disorders like narcolepsy, prompting new HCRT/OX-targeting treatments.

Area of Science:

  • Neuroscience
  • Sleep Medicine
  • Pharmacology

Background:

  • The hypocretin/orexin (HCRT/OX) system, involving neuropeptides HCRT-1 and -2/OX-A and -B, is vital for regulating wakefulness.
  • This system interacts with monoaminergic, cholinergic, and GABAergic neurons to maintain sleep-wake stability.
  • Deficiency in the HCRT/OX system causes unstable sleep-wake transitions, leading to narcolepsy symptoms like excessive daytime sleepiness and cataplexy.

Purpose of the Study:

  • To review the origin and mechanisms of HCRT/OX receptors.
  • To discuss the clinical progress and therapeutic applications of targeting the HCRT/OX system for sleep disorders.
  • To highlight recent advancements in HCRT/OX agonist and antagonist development.

Main Methods:

  • Literature review of studies on the HCRT/OX system in sleep-wake regulation.
  • Analysis of research on narcolepsy-cataplexy and its link to HCRT/OX deficiency.
  • Examination of preclinical and clinical data for HCRT/OX receptor modulators.

Main Results:

  • The HCRT/OX system plays a fundamental role in maintaining consolidated wakefulness and preventing sleep intrusions.
  • Pharmacological targeting of HCRT/OX receptors has shown promise, with approved medications for insomnia.
  • Research continues to explore agonists and antagonists for various sleep-wake disorders.

Conclusions:

  • The HCRT/OX system is a key regulator of sleep-wake states, and its dysfunction underlies significant neurological disorders.
  • Targeting HCRT/OX receptors offers a promising therapeutic avenue for managing sleep disorders.
  • Continued research into HCRT/OX pharmacology is essential for developing novel treatments.
Keywords:
hypocretininsomnianarcolepsyorexinorexin agonistorexin antagonist

More Related Videos

A Chronic Sleep Fragmentation Model using Vibrating Orbital Rotor to Induce Cognitive Deficit and Anxiety-Like Behavior in Young Wild-Type Mice06:23

A Chronic Sleep Fragmentation Model using Vibrating Orbital Rotor to Induce Cognitive Deficit and Anxiety-Like Behavior in Young Wild-Type Mice

Published on: September 22, 2020

6.2K
Optogenetic Manipulation of Neural Circuits During Monitoring Sleep/wakefulness States in Mice08:58

Optogenetic Manipulation of Neural Circuits During Monitoring Sleep/wakefulness States in Mice

Published on: June 19, 2019

10.6K

Related Concept Videos

Sleep-Wake Cycles01:24

Sleep-Wake Cycles

Sleep is an essential physiological process vital to maintaining overall well-being. The reticular activating system (RAS), a network of neurons in the brainstem, regulates wakefulness and sleep. While it may seem passive, sleep consists of distinct cycles, each with its unique characteristics and functions. Two key sleep phases are non-rapid eye movement (NREM) and  rapid eye movement (REM).
NREM Sleep
NREM sleep comprises four progressive stages that seamlessly merge:
3.2K
Narcolepsy01:07

Narcolepsy

Narcolepsy is a chronic sleep disorder characterized by pervasive, uncontrolled sleepiness and other sleep disturbances. One of its hallmark symptoms is an abrupt transition to REM sleep upon falling asleep, which causes symptoms typically associated with this phase to occur unexpectedly during wakefulness. These include the following symptoms, which typically last from a minute or two to half an hour.
728
Understanding Sleep01:11

Understanding Sleep

Sleep, an essential biological state, involves significant reductions in physical activity, sensory awareness, and interaction with the environment. This complex physiological process is primarily regulated by specific brain regions, notably the hypothalamus and pons, which govern the sleep-wake cycle or circadian rhythm.
The circadian rhythm, a nearly 24-hour cycle, is deeply influenced by environmental light cues. Light exposure directly affects the hypothalamus, which in turn regulates...
1.8K
REM Sleep Behavior Disorder01:15

REM Sleep Behavior Disorder

REM Sleep Behavior Disorder (RBD) is a sleep disorder characterized by the absence of muscle paralysis that normally occurs during the REM phase of sleep. This absence allows individuals to physically act out their dreams, which are often vivid and disturbing. Common behaviors exhibited during episodes include kicking, punching, and yelling. These actions can be dangerous, potentially leading to injuries for the person with RBD or their bed partner.
RBD is significantly associated with...
2.4K
Substance Use Disorders Affecting Sleep01:24

Substance Use Disorders Affecting Sleep

Substance use disorders involve a pattern of using drugs more extensively than intended and continuing use despite harmful consequences. This includes legal substances like alcohol and nicotine, as well as illegal drugs. These disorders often involve both physical and psychological dependence, reflecting compulsive use of substances that significantly alter thoughts, feelings, and behaviors, contributing to a major public health issue.
Understanding the concepts of physical dependence,...
524
Sedatives and Hypnotics Drugs: Miscellaneous Agents01:17

Sedatives and Hypnotics Drugs: Miscellaneous Agents

Sedatives and hypnotics encompass a wide range of substances, each with its unique mechanism of action, uses, and potential adverse effects.
Melatonin congeners like ramelteon (Rozerem) and tasimelteon (Hetlioz) selectively bind to melatonin receptors (MT1 and MT2) and thus mimic the actions of melatonin, a hormone that regulates sleep-wake cycles. Tasimelteon is primarily used for non-24-hour sleep-wake disorder, common in blind patients. They are also used to treat conditions like insomnia...
801