ArticleSleep2020
Striatal histamine mechanism in the pathogenesis of restless legs syndrome.
Article in Sleep, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
7 citing papers in PubMed, 2 syntheses or guidelines pooled it, 12 citations in OpenAlex.
- Treatment of restless legs syndrome and periodic limb movement disorder: an American Academy of Sleep Medicine clinical practice guideline.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2025Guideline
- Putative Animal Models of Restless Legs Syndrome: A Systematic Review and Evaluation of Their Face and Construct Validity.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Pooled it
- Histamine Modulation of the Basal Ganglia Circuitry in the Motor Symptoms of Parkinson's Disease.CNS neuroscience & therapeutics · 2025Review
- Review of the role of the endogenous opioid and melanocortin systems in the restless legs syndrome.Brain : a journal of neurology · 2024Article
- Effects of iron-deficient diet on sleep onset and spinal reflexes in a rodent model of Restless Legs Syndrome.Frontiers in neurology · 2023Article
- A Narrative Review of the Lesser Known Medications for Treatment of Restless Legs Syndrome and Pathogenetic Implications for Their Use.Tremor and other hyperkinetic movements (New York, N.Y.) · 2023Review
- Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
STUDY
objectivesRestless legs syndrome (RLS) has been hypothesized to be generated by abnormal striatal dopamine transmission. Dopaminergic drugs are effective for the treatment of RLS. However, long-term use of dopaminergic drugs causes adverse effects. We used iron-deficient (ID) and iron-replacement (IR) rats to address the neuropathology of RLS and to determine if a histamine H3 receptor (H3R) antagonist might be a useful treatment. Histamine H3R antagonists have been shown to decrease motor activity.
methodsControl and ID rats were surgically implanted with electrodes for polysomnographic recording. After 3 days of baseline polysomnographic recordings, rats were systemically injected with the H3R agonist, α-methylhistamine, and antagonist, thioperamide. Recordings were continued after drug injection. Striatal H3R levels from control, ID, and IR rats were determined by western blots. Blood from control, ID, and IR rats was collected for the measurement of hematocrit levels.
resultsα-Methylhistamine and thioperamide increased and decreased motor activity, respectively, in control rats. In ID rats, α-methylhistamine had no effect on motor activity, whereas thioperamide decreased periodic leg movement (PLM) in sleep. Sleep-wake states were not significantly altered under any conditions. Striatal H3R levels were highest in ID rats, moderate to low in IR rats, and lowest in control rats. Striatal H3R levels were also found to positively and negatively correlate with PLM in sleep and hematocrit levels, respectively.
conclusionsA striatal histamine mechanism may be involved in ID anemia-induced RLS. Histamine H3R antagonists may be useful for the treatment of RLS.
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Registered trials
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