ArticleSleep2015
Insomnia Caused by Serotonin Depletion is Due to Hypothermia.
Article in Sleep, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 55 citations in OpenAlex.
- Ginsenoside Rg1 alleviates PCPA-induced insomnia by inhibiting NLRP3 inflammasome activation and pyroptosis through the Nrf2/HO-1 pathway in mice.Psychopharmacology · 2025Article
- Neurochemical Insights into the Role of Tryptophan Metabolites and Kynurenine Pathway in Insomnia and its Psychological and Neurological Comorbidities.Molecular neurobiology · 2025Review
- Behavioral and circuit principles of temperature gradient navigation.Current biology : CB · 2025Article
- Spatial differences in gene expression across the dorsal raphe nucleus in a model of early Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2025Article
- Serotonergic dysfunction may mediate the relationship between alcohol consumption and Alzheimer's disease.Pharmacological research · 2024Review
- A midbrain GABAergic circuit constrains wakefulness in a mouse model of stress.Nature communications · 2024Article
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- Seizures Cause Prolonged Impairment of Ventilation, COThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
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- PtNPs/Short MWCNT-PEDOT: PSS-Modified Microelectrode Array to Detect Neuronal Firing Patterns in the Dorsal Raphe Nucleus and Hippocampus of Insomnia Rats.Micromachines · 2022Article
- An estrogen-sensitive hypothalamus-midbrain neural circuit controls thermogenesis and physical activity.Science advances · 2022Article
- Gut microbiota-generated short-chain fatty acids are involved in para-chlorophenylalanine-induced cognitive disorders.Frontiers in microbiology · 2022Article
- A Century Searching for the Neurons Necessary for Wakefulness.Frontiers in neuroscience · 2022Review
- Nyctinastic herbs decoction improves para-chlorophenylalanine-induced insomnia by regulating the expression level of neurotransmitters.Annals of translational medicine · 2021Article
- Impact of Insomnia Symptoms on the Clinical Presentation of Depressive Symptoms: A Cross-Sectional Population Study.Frontiers in neurology · 2021Article
- Comparative pharmacokinetics of six major compounds in normal and insomnia rats after oral administration of Ziziphi Spinosae Semen aqueous extract.Journal of pharmaceutical analysis · 2020Article
- Role of serotonergic dorsal raphe neurons in hypercapnia-induced arousals.Nature communications · 2020Article
- Selective activation of serotoninergic dorsal raphe neurons facilitates sleep through anxiolysis.Sleep · 2020Article
- Self-reported insomnia as a marker for anxiety and depression among migraineurs: a population-based cross-sectional study.Scientific reports · 2019Article
- Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
STUDY
objectiveSerotonin (5-hydroxytryptamine, 5-HT) neurons are now thought to promote wakefulness. Early experiments using the tryptophan hydroxylase inhibitor para-chlorophenylalanine (PCPA) had led to the opposite conclusion, that 5-HT causes sleep, but those studies were subsequently contradicted by electrophysiological and behavioral data. Here we tested the hypothesis that the difference in conclusions was due to failure of early PCPA experiments to control for the recently recognized role of 5-HT in thermoregulation.
designAdult male C57BL/6N mice were treated with PCPA (800 mg/kg intraperitoneally for 5 d; n = 15) or saline (n = 15), and housed at 20 °C (normal room temperature) or at 33 °C (thermoneutral for mice) for 24 h. In a separate set of experiments, mice were exposed to 4 °C for 4 h to characterize their ability to thermoregulate. MEASUREMENTS AND
resultsPCPA treatment reduced brain 5-HT to less than 12% of that of controls. PCPA-treated mice housed at 20 °C spent significantly more time awake than controls. However, core body temperature decreased from 36.5 °C to 35.1 °C. When housed at 33 °C, body temperature remained normal, and total sleep duration, sleep architecture, and time in each vigilance state were the same as controls. When challenged with 4 °C, PCPA-treated mice experienced a precipitous drop in body temperature, whereas control mice maintained a normal body temperature.
conclusionsThese results indicate that early experiments using para-chlorophenylalanine that led to the conclusion that 5-hydroxytryptamine (5-HT) causes sleep were likely confounded by hypothermia. Temperature controls should be considered in experiments using 5-HT depletion.
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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.