Evidence map›Paper›PMID 29950444›Full record

ArticleScience translational medicine2018

Opiates increase the number of hypocretin-producing cells in human and mouse brain and reverse cataplexy in a mouse model of narcolepsy.

Thomas C Thannickal, Joshi John, Ling Shan, Dick F Swaab, Ming-Fung Wu, Lalini Ramanathan, Ronald McGregor, Keng-Tee Chew, Marcia Cornford, Akihiro Yamanaka and 5 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science translational medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed, 1 pooled it
6.5field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

76 citing papers in PubMed, 1 synthesis or guideline pooled it, 139 citations in OpenAlex.

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  5. Narcolepsy is (not) an autoimmune disease.Nature reviews. Neurology · 2026
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16 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 6 institutions in 3 countries.

Thomas C ThannickalNeuropsychiatric Institute and Brain Research Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.ORCID 0000-0003-1623-9545
Joshi JohnNeuropsychiatric Institute and Brain Research Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.ORCID 0000-0003-2856-0942
Ling ShanNeuropsychiatric Institute and Brain Research Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.ORCID 0000-0002-4765-2474
Dick F SwaabNetherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, Netherlands.ORCID 0000-0002-9665-7845
Ming-Fung WuNeuropsychiatric Institute and Brain Research Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.ORCID 0000-0002-7591-8743
Lalini RamanathanNeuropsychiatric Institute and Brain Research Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.ORCID 0000-0002-4092-8511
Ronald McGregorNeuropsychiatric Institute and Brain Research Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.ORCID 0000-0001-8856-7455
Keng-Tee ChewNeuropsychiatric Institute and Brain Research Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.ORCID 0000-0003-2000-065X
Marcia CornfordDepartment of Pathology, Harbor University of California, Los Angeles, Medical Center, Torrance, CA 90509, USA.
Akihiro YamanakaDepartment of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
Ayumu InutsukaDepartment of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.ORCID 0000-0001-6503-5501
Rolf FronczekLeiden University Medical Centre, Department of Neurology, Leiden, Netherlands.ORCID 0000-0002-1935-7603
Gert Jan LammersLeiden University Medical Centre, Department of Neurology, Leiden, Netherlands.
Paul F WorleyThe Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Jerome M SiegelNeuropsychiatric Institute and Brain Research Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. jsiegel@ucla.edu.ORCID 0000-0003-2898-0111
Neuropsychiatric Research Institute · USLeiden University · NLNagoya University · JPJohns Hopkins University · USNetherlands Institute for Neuroscience · NLUCLA Medical Center · US

Funding

Role of hypocretin in opiate addiction and withdrawalR01DA034748 · NIDA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SIEGEL, JEROME M · 2014 to 2024
$6.3M
De novo Synthesis and MemoryR35NS097966 · NINDS · JOHNS HOPKINS UNIVERSITY · PI WORLEY, PAUL F · 2017 to 2024
$4.3M
Environmental determinants of human sleep timing, duration and continuity: studies in hunter gatherersR01HL148574 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SIEGEL, JEROME M · 2019 to 2023
$3.6M
What Causes Human Narcolepsy?I01BX001753 · VA · VA GREATER LOS ANGELES HEALTHCARE SYSTEM · PI SIEGEL, JEROME M · 2013 to 2020
–
BLRD VA I01 BX001753BLRD VA IK6 BX005245NHLBI NIH HHS R01 HL148574NIDA NIH HHS R01 DA034748NINDS NIH HHS R35 NS097966
6 · The paper itself

Abstract

The changes in brain function that perpetuate opiate addiction are unclear. In our studies of human narcolepsy, a disease caused by loss of immunohistochemically detected hypocretin (orexin) neurons, we encountered a control brain (from an apparently neurologically normal individual) with 50% more hypocretin neurons than other control human brains that we had studied. We discovered that this individual was a heroin addict. Studying five postmortem brains from heroin addicts, we report that the brain tissue had, on average, 54% more immunohistochemically detected neurons producing hypocretin than did control brains from neurologically normal subjects. Similar increases in hypocretin-producing cells could be induced in wild-type mice by long-term (but not short-term) administration of morphine. The increased number of detected hypocretin neurons was not due to neurogenesis and outlasted morphine administration by several weeks. The number of neurons containing melanin-concentrating hormone, which are in the same hypothalamic region as hypocretin-producing cells, did not change in response to morphine administration. Morphine administration restored the population of detected hypocretin cells to normal numbers in transgenic mice in which these neurons had been partially depleted. Morphine administration also decreased cataplexy in mice made narcoleptic by the depletion of hypocretin neurons. These findings suggest that opiate agonists may have a role in the treatment of narcolepsy, a disorder caused by hypocretin neuron loss, and that increased numbers of hypocretin-producing cells may play a role in maintaining opiate addiction.

Indexed as

AnimalsBrainCataplexyCell CountDisease Models, AnimalDose-Response Relationship, DrugHeroinHumansMaleMice, Inbred C57BLMorphineNarcolepsyNeurogenesisNeuronsOpiate AlkaloidsOrexinsHeroinMorphineOpiate AlkaloidsOrexins

Identifiers

PMID29950444
PMCPMC8235614
OpenAlexW2809819218

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.