ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Role of the hypocretin (orexin) receptor 2 (Hcrt-r2) in the regulation of hypocretin level and cataplexy.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Are orexins-hypocretins the culprit for rapid eye movement sleep behavior disorder in narcolepsy?Sleep · 2024Article
- Opioid-induced neuroanatomical, microglial and behavioral changes are blocked by suvorexant without diminishing opioid analgesia.Nature. Mental health · 2024Article
- Hypocretin/Orexin Interactions with Norepinephrine Contribute to the Opiate Withdrawal Syndrome.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Pleasure, addiction, and hypocretin (orexin).Handbook of clinical neurology · 2021Review
- Article
- Narcolepsy and influenza vaccination-induced autoimmunity.Annals of translational medicine · 2017Article
- Mechanistic insights into influenza vaccine-associated narcolepsy.Human vaccines & immunotherapeutics · 2016Article
- To ingest or rest? Specialized roles of lateral hypothalamic area neurons in coordinating energy balance.Frontiers in systems neuroscience · 2015Review
- Cataplexy--clinical aspects, pathophysiology and management strategy.Nature reviews. Neurology · 2014Review
- Orexin 1 receptor antagonists in compulsive behavior and anxiety: possible therapeutic use.Frontiers in neuroscience · 2014Review
- Orexin/hypocretin system modulates amygdala-dependent threat learning through the locus coeruleus.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Relation of melanin concentrating hormone levels to sleep, emotion and hypocretin levels.Sleep · 2013Article
- Human hypocretin and melanin-concentrating hormone levels are linked to emotion and social interaction.Nature communications · 2013Article
- Highly specific role of hypocretin (orexin) neurons: differential activation as a function of diurnal phase, operant reinforcement versus operant avoidance and light level.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2011Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Hypocretin receptor-2 (Hcrt-r2)-mutated dogs exhibit all the major symptoms of human narcolepsy and respond to drugs that increase or decrease cataplexy as do narcoleptic humans; yet, unlike narcoleptic humans, the narcoleptic dogs have normal hypocretin levels. We find that drugs that reduce or increase cataplexy in the narcoleptic dogs, greatly increase and decrease, respectively, hypocretin levels in normal dogs. The effects of these drugs on heart rate and blood pressure, which were considerable, were not correlated with their effects on cataplexy. Administration of these drugs to Hcrt-r2-mutated dogs produced indistinguishable changes in heart rate and blood pressure, indicating that neither central nor peripheral Hcrt-r2 is required for these cardiovascular effects. However, in contrast to the marked Hcrt level changes in the normal dogs, these drugs did not alter hypocretin levels in the Hcrt-r2 mutants. We conclude that Hcrt-r2 is a vital element in a feedback loop integrating Hcrt, acetylcholine, and norepinephrine function. In the absence of functional Hcrt-r2, Hcrt levels are not affected by monoaminergic and cholinergic drugs, despite the strong modulation of cataplexy by these drugs. Conversely, strong transient reductions of Hcrt level by these drugs do not produce episodes of cataplexy in normal dogs. The Hcrt-r2 mutation causes drug-induced cataplexy by virtue of its long-term effect on the functioning of other brain systems, rather than by increasing the magnitude of phasic changes in Hcrt level. A similar mechanism may be operative in spontaneous cataplexy in narcoleptic dogs as well as in narcoleptic humans.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.