ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2002
Hypocretins (orexins) regulate serotonin neurons in the dorsal raphe nucleus by excitatory direct and inhibitory indirect actions.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 150 papers.
What it found
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Who cites it
150 citing papers in PubMed, 386 citations in OpenAlex.
- Hypothalamic control of arousal.Reviews in endocrine & metabolic disorders · 2026Review
- Lateral hypothalamus to dorsal raphe nucleus projections modulate intraspecific attack behavior in male mice.iScience · 2026Article
- Awakening Recovery: Enhancing Orexinergic Tone After Acute CNS Damage.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Found in translation: orexin receptor antagonism for the treatment of opioid use disorder.Translational psychiatry · 2025Review
- Chronic Fluoxetine Treatment Desensitizes Serotoninergic Inhibition of GABAergic Inputs and Intrinsic Excitability of Dorsal Raphe Serotonin Neurons.Brain sciences · 2025Article
- Emerging medications and pharmacological treatment approaches for substance use disorders.Pharmacology, biochemistry, and behavior · 2025Review
- The role of orexin and MCH neurons in the hypothalamus in sleep-wake regulation and learning-forgetting balance.Frontiers in neuroscience · 2025Review
- Interaction of serotonin/GLP-1 circuitry in a dual preclinical model for psychiatric disorders and metabolic dysfunction.Psychiatry research · 2024Article
- Interactions between Lateral Hypothalamic Orexin and Dorsal Raphe Circuitry in Energy Balance.Brain sciences · 2024Article
- Association between RMTg Neuropeptide Genes and Negative Effect during Alcohol Withdrawal in Mice.International journal of molecular sciences · 2024Article
- Review
- Simulating combined monoaminergic depletions in a PD animal model through a bio-constrained differential equations system.Frontiers in computational neuroscience · 2024Article
- Prolonged stress alters the PC1/PC2 ratio in the rat lateral hypothalamus, implicating impaired orexin maturation.Iranian journal of basic medical sciences · 2024Article
- Unraveling the serotonin saga: from discovery to weight regulation and beyond - a comprehensive scientific review.Cell & bioscience · 2023Review
- Obsessive-compulsive disorder: Etiology, neuropathology, and cognitive dysfunction.Brain and behavior · 2023Review
- Characteristics of Seltorexant-Innovative Agent Targeting Orexin System for the Treatment of Depression and Anxiety.Molecules (Basel, Switzerland) · 2023Review
- Use of experimental medicine approaches for the development of novel psychiatric treatments based on orexin receptor modulation.Neuroscience and biobehavioral reviews · 2023Review
- Orexin, Sleep, Sympathetic Neural Activity, and Cardiovascular Function.Hypertension (Dallas, Tex. : 1979) · 2022Review
- Daridorexant: A New Dual Orexin Receptor Antagonist for Insomnia.The Journal of pharmacy technology : jPT : official publication of the Association of Pharmacy Technicians · 2022Review
- A study on the effect of JNJ-10397049 on proliferation and differentiation of neural precursor cells.Anatomy & cell biology · 2022Article
90 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The hypocretins (hcrt1 and hcrt2) are expressed by a discrete population of hypothalamic neurons projecting to many regions of the CNS, including the dorsal raphe nucleus (DRN), where serotonin (5-HT) neurons are concentrated. In this study, we investigated responses to hcrts in 216 physiologically identified 5-HT and non-5-HT neurons of the DRN using intracellular and whole-cell recording in rat brain slices. Hcrt1 and hcrt2 induced similar amplitude and dose-dependent inward currents in most 5-HT neurons tested (EC50, approximately 250 nm). This inward current was not blocked by the fast Na+ channel blocker TTX or in a Ca2+-free solution, indicating a direct postsynaptic action. The hcrt-induced inward current reversed near -18 mV and was primarily dependent on external Na+ but not on external or internal Ca2+, features typical of Na+/K+ nonselective cation channels. At higher concentrations, hcrts also increased spontaneous postsynaptic currents in 5-HT neurons (EC50, approximately 450-600 nm), which were TTX-sensitive and mostly blocked by the GABA(A) antagonist bicuculline, indicating increased impulse flow in local GABA interneurons. Accordingly, hcrts were found to increase the basal firing of presumptive GABA interneurons. Immunolabeling showed that hcrt fibers projected to both 5-HT and GABA neurons in the DRN. We conclude that hcrts act directly to excite 5-HT neurons primarily via a TTX-insensitive, Na+/K+ nonselective cation current, and indirectly to activate local inhibitory GABA inputs to 5-HT cells. The greater potency of hcrts in direct excitation compared with indirect inhibition suggests a negative feedback function for the latter at higher levels of hcrt activity.
Indexed as
Identifiers
12417670PMC6758063W2121147520What OpenQuestion holds
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.