Effects of Paraxanthine and Caffeine on Sleep, Locomotor Activity, and Body Temperature in Orexin/Ataxin-3 Transgenic Narcoleptic Mice
Identifieur interne : 000B77 ( Ncbi/Merge ); précédent : 000B76; suivant : 000B78Effects of Paraxanthine and Caffeine on Sleep, Locomotor Activity, and Body Temperature in Orexin/Ataxin-3 Transgenic Narcoleptic Mice
Auteurs : Masashi Okuro [États-Unis] ; Nobuhiro Fujiki [États-Unis] ; Nozomu Kotorii [États-Unis] ; Yuji Ishimaru [États-Unis] ; Pierre Sokoloff [France] ; Seiji Nishino [États-Unis]Source :
- Sleep [ 0161-8105 ] ; 2010.
Abstract
Caffeine, an adenosine A1 and A2a receptor antagonist, is a widely consumed stimulant and also used for the treatment of hypersomnia; however, the wake-promoting potency of caffeine is often not strong enough, and high doses may induce side effects. Caffeine is metabolized to paraxanthine, theobromine, and theophylline. Paraxanthine is a central nervous stimulant and exhibits higher potency at A1 and A2 receptors, but has lower toxicity and lesser anxiogenic effects than caffeine.
We evaluated the wake-promoting efficacy of paraxanthine, caffeine, and a reference wake-promoting compound, modafinil, in a mice model of narcolepsy, a prototypical disease model of hypersomnia. Orexin/ataxin-3 transgenic (TG) and wild-type (WT) mice were subjected to oral administration (at ZT 2 and ZT14) of 3 doses of paraxanthine, caffeine, modafinil, or vehicle.
Paraxanthine, caffeine, and modafinil significantly promoted wakefulness in both WT and narcoleptic TG mice and proportionally reduced NREM and REM sleep in both genotypes. The wake-promoting potency of 100 mg/kg p.o. of paraxanthine during the light period administration roughly corresponds to that of 200 mg/kg p.o. of modafinil. The wake-promoting potency of paraxanthine is greater and longer lasting than that of the equimolar concentration of caffeine, when the drugs were administered during the light period. The wake-promotion by paraxanthine, caffeine, and modafinil are associated with an increase in locomotor activity and body temperature. However, the higher doses of caffeine and modafinil, but not paraxanthine, induced hypothermia and reduced locomotor activity, thereby confirming the lower toxicity of paraxanthine. Behavioral evaluations of anxiety levels in WT mice revealed that paraxanthine induced less anxiety than caffeine did.
Because it is also reported to provide neuroprotection, paraxanthine may be a better wake-promoting agent for hypersomnia associated with neurodegenerative diseases.
Okuro M; Fujiki N; Kotorii N; Ishimaru Y; Sokoloff P; Nishino S. Effects of paraxanthine and caffeine on sleep, locomotor activity, and body temperature in orexin/ataxin-3 transgenic narcoleptic mice.
Url:
PubMed: 20614853
PubMed Central: 2894435
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 000557
- to stream Pmc, to step Curation: 000554
- to stream Pmc, to step Checkpoint: 000764
Links to Exploration step
PMC:2894435Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Effects of Paraxanthine and Caffeine on Sleep, Locomotor Activity, and Body Temperature in Orexin/Ataxin-3 Transgenic Narcoleptic Mice</title><author><name sortKey="Okuro, Masashi" sort="Okuro, Masashi" uniqKey="Okuro M" first="Masashi" last="Okuro">Masashi Okuro</name><affiliation wicri:level="2"><nlm:aff id="aff1">Sleep and Circadian Neurobiology Laboratory, Stanford University, Stanford University Center for Narcolepsy, Palo Alto, CA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Sleep and Circadian Neurobiology Laboratory, Stanford University, Stanford University Center for Narcolepsy, Palo Alto</wicri:cityArea></affiliation></author><author><name sortKey="Fujiki, Nobuhiro" sort="Fujiki, Nobuhiro" uniqKey="Fujiki N" first="Nobuhiro" last="Fujiki">Nobuhiro Fujiki</name><affiliation wicri:level="2"><nlm:aff id="aff1">Sleep and Circadian Neurobiology Laboratory, Stanford University, Stanford University Center for Narcolepsy, Palo Alto, CA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Sleep and Circadian Neurobiology Laboratory, Stanford University, Stanford University Center for Narcolepsy, Palo Alto</wicri:cityArea></affiliation></author><author><name sortKey="Kotorii, Nozomu" sort="Kotorii, Nozomu" uniqKey="Kotorii N" first="Nozomu" last="Kotorii">Nozomu Kotorii</name><affiliation wicri:level="2"><nlm:aff id="aff1">Sleep and Circadian Neurobiology Laboratory, Stanford University, Stanford University Center for Narcolepsy, Palo Alto, CA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Sleep and Circadian Neurobiology Laboratory, Stanford University, Stanford University Center for Narcolepsy, Palo Alto</wicri:cityArea></affiliation></author><author><name sortKey="Ishimaru, Yuji" sort="Ishimaru, Yuji" uniqKey="Ishimaru Y" first="Yuji" last="Ishimaru">Yuji Ishimaru</name><affiliation wicri:level="2"><nlm:aff id="aff1">Sleep and Circadian Neurobiology Laboratory, Stanford University, Stanford University Center for Narcolepsy, Palo Alto, CA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Sleep and Circadian Neurobiology Laboratory, Stanford University, Stanford University Center for Narcolepsy, Palo Alto</wicri:cityArea></affiliation></author><author><name sortKey="Sokoloff, Pierre" sort="Sokoloff, Pierre" uniqKey="Sokoloff P" first="Pierre" last="Sokoloff">Pierre Sokoloff</name><affiliation wicri:level="3"><nlm:aff id="aff2">Pierre Fabre Research Institute, Neurology-Psychiatry Department, Castres, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Pierre Fabre Research Institute, Neurology-Psychiatry Department, Castres</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Castres</settlement></placeName></affiliation></author><author><name sortKey="Nishino, Seiji" sort="Nishino, Seiji" uniqKey="Nishino S" first="Seiji" last="Nishino">Seiji Nishino</name><affiliation wicri:level="2"><nlm:aff id="aff1">Sleep and Circadian Neurobiology Laboratory, Stanford University, Stanford University Center for Narcolepsy, Palo Alto, CA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Sleep and Circadian Neurobiology Laboratory, Stanford University, Stanford University Center for Narcolepsy, Palo Alto</wicri:cityArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">20614853</idno><idno type="pmc">2894435</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2894435</idno><idno type="RBID">PMC:2894435</idno><date when="2010">2010</date><idno type="wicri:Area/Pmc/Corpus">000557</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000557</idno><idno type="wicri:Area/Pmc/Curation">000554</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000554</idno><idno type="wicri:Area/Pmc/Checkpoint">000764</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000764</idno><idno type="wicri:Area/Ncbi/Merge">000B77</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Effects of Paraxanthine and Caffeine on Sleep, Locomotor Activity, and Body Temperature in Orexin/Ataxin-3 Transgenic Narcoleptic Mice</title><author><name sortKey="Okuro, Masashi" sort="Okuro, Masashi" uniqKey="Okuro M" first="Masashi" last="Okuro">Masashi Okuro</name><affiliation wicri:level="2"><nlm:aff id="aff1">Sleep and Circadian Neurobiology Laboratory, Stanford University, Stanford University Center for Narcolepsy, Palo Alto, CA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Sleep and Circadian Neurobiology Laboratory, Stanford University, Stanford University Center for Narcolepsy, Palo Alto</wicri:cityArea></affiliation></author><author><name sortKey="Fujiki, Nobuhiro" sort="Fujiki, Nobuhiro" uniqKey="Fujiki N" first="Nobuhiro" last="Fujiki">Nobuhiro Fujiki</name><affiliation wicri:level="2"><nlm:aff id="aff1">Sleep and Circadian Neurobiology Laboratory, Stanford University, Stanford University Center for Narcolepsy, Palo Alto, CA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Sleep and Circadian Neurobiology Laboratory, Stanford University, Stanford University Center for Narcolepsy, Palo Alto</wicri:cityArea></affiliation></author><author><name sortKey="Kotorii, Nozomu" sort="Kotorii, Nozomu" uniqKey="Kotorii N" first="Nozomu" last="Kotorii">Nozomu Kotorii</name><affiliation wicri:level="2"><nlm:aff id="aff1">Sleep and Circadian Neurobiology Laboratory, Stanford University, Stanford University Center for Narcolepsy, Palo Alto, CA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Sleep and Circadian Neurobiology Laboratory, Stanford University, Stanford University Center for Narcolepsy, Palo Alto</wicri:cityArea></affiliation></author><author><name sortKey="Ishimaru, Yuji" sort="Ishimaru, Yuji" uniqKey="Ishimaru Y" first="Yuji" last="Ishimaru">Yuji Ishimaru</name><affiliation wicri:level="2"><nlm:aff id="aff1">Sleep and Circadian Neurobiology Laboratory, Stanford University, Stanford University Center for Narcolepsy, Palo Alto, CA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Sleep and Circadian Neurobiology Laboratory, Stanford University, Stanford University Center for Narcolepsy, Palo Alto</wicri:cityArea></affiliation></author><author><name sortKey="Sokoloff, Pierre" sort="Sokoloff, Pierre" uniqKey="Sokoloff P" first="Pierre" last="Sokoloff">Pierre Sokoloff</name><affiliation wicri:level="3"><nlm:aff id="aff2">Pierre Fabre Research Institute, Neurology-Psychiatry Department, Castres, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Pierre Fabre Research Institute, Neurology-Psychiatry Department, Castres</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Castres</settlement></placeName></affiliation></author><author><name sortKey="Nishino, Seiji" sort="Nishino, Seiji" uniqKey="Nishino S" first="Seiji" last="Nishino">Seiji Nishino</name><affiliation wicri:level="2"><nlm:aff id="aff1">Sleep and Circadian Neurobiology Laboratory, Stanford University, Stanford University Center for Narcolepsy, Palo Alto, CA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Sleep and Circadian Neurobiology Laboratory, Stanford University, Stanford University Center for Narcolepsy, Palo Alto</wicri:cityArea></affiliation></author></analytic><series><title level="j">Sleep</title><idno type="ISSN">0161-8105</idno><idno type="eISSN">1550-9109</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Study Objective:</title><p>Caffeine, an adenosine A1 and A2a receptor antagonist, is a widely consumed stimulant and also used for the treatment of hypersomnia; however, the wake-promoting potency of caffeine is often not strong enough, and high doses may induce side effects. Caffeine is metabolized to paraxanthine, theobromine, and theophylline. Paraxanthine is a central nervous stimulant and exhibits higher potency at A1 and A2 receptors, but has lower toxicity and lesser anxiogenic effects than caffeine.</p></sec><sec><title>Design:</title><p>We evaluated the wake-promoting efficacy of paraxanthine, caffeine, and a reference wake-promoting compound, modafinil, in a mice model of narcolepsy, a prototypical disease model of hypersomnia. Orexin/ataxin-3 transgenic (TG) and wild-type (WT) mice were subjected to oral administration (at ZT 2 and ZT14) of 3 doses of paraxanthine, caffeine, modafinil, or vehicle.</p></sec><sec><title>Results:</title><p>Paraxanthine, caffeine, and modafinil significantly promoted wakefulness in both WT and narcoleptic TG mice and proportionally reduced NREM and REM sleep in both genotypes. The wake-promoting potency of 100 mg/kg p.o. of paraxanthine during the light period administration roughly corresponds to that of 200 mg/kg p.o. of modafinil. The wake-promoting potency of paraxanthine is greater and longer lasting than that of the equimolar concentration of caffeine, when the drugs were administered during the light period. The wake-promotion by paraxanthine, caffeine, and modafinil are associated with an increase in locomotor activity and body temperature. However, the higher doses of caffeine and modafinil, but not paraxanthine, induced hypothermia and reduced locomotor activity, thereby confirming the lower toxicity of paraxanthine. Behavioral evaluations of anxiety levels in WT mice revealed that paraxanthine induced less anxiety than caffeine did.</p></sec><sec><title>Conclusions:</title><p>Because it is also reported to provide neuroprotection, paraxanthine may be a better wake-promoting agent for hypersomnia associated with neurodegenerative diseases.</p></sec><sec><title>Citation:</title><p>Okuro M; Fujiki N; Kotorii N; Ishimaru Y; Sokoloff P; Nishino S. Effects of paraxanthine and caffeine on sleep, locomotor activity, and body temperature in orexin/ataxin-3 transgenic narcoleptic mice. <italic>SLEEP</italic> 2010;33(7):930-942.</p></sec></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Sleep</journal-id><journal-id journal-id-type="publisher-id">Sleep</journal-id><journal-title-group><journal-title>Sleep</journal-title></journal-title-group><issn pub-type="ppub">0161-8105</issn><issn pub-type="epub">1550-9109</issn><publisher><publisher-name>Associated Professional Sleep Societies, LLC</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">20614853</article-id><article-id pub-id-type="pmc">2894435</article-id><article-categories><subj-group subj-group-type="heading"><subject>Effects of Stimulants on Narcoleptic Mice</subject></subj-group></article-categories><title-group><article-title>Effects of Paraxanthine and Caffeine on Sleep, Locomotor Activity, and Body Temperature in Orexin/Ataxin-3 Transgenic Narcoleptic Mice</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Okuro</surname><given-names>Masashi</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Fujiki</surname><given-names>Nobuhiro</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kotorii</surname><given-names>Nozomu</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ishimaru</surname><given-names>Yuji</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Sokoloff</surname><given-names>Pierre</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Nishino</surname><given-names>Seiji</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="corresp" rid="cor1"></xref></contrib><aff id="aff1"><label>1</label>Sleep and Circadian Neurobiology Laboratory, Stanford University, Stanford University Center for Narcolepsy, Palo Alto, CA</aff><aff id="aff2"><label>2</label>Pierre Fabre Research Institute, Neurology-Psychiatry Department, Castres, France</aff></contrib-group><author-notes><corresp id="cor1">Address correspondence to: Seiji Nishino MD, PhD,
<addr-line>Sleep and Circadian Neurobiology Laboratory, Stanford University, MSLS Bldg Room P213, 1201 Welch Road, Palo Alto, CA 94304</addr-line><phone>(650) 723-3724</phone><fax>(650) 723-5873</fax><email>nishino@stanford.edu</email></corresp></author-notes><pub-date pub-type="ppub"><day>1</day><month>7</month><year>2010</year></pub-date><volume>33</volume><issue>7</issue><fpage>930</fpage><lpage>942</lpage><history><date date-type="received"><month>9</month><year>2009</year></date><date date-type="rev-recd"><month>2</month><year>2010</year></date><date date-type="accepted"><month>2</month><year>2010</year></date></history><permissions><copyright-statement>© 2010 Associated Professional Sleep Societies, LLC.</copyright-statement></permissions><abstract><sec><title>Study Objective:</title><p>Caffeine, an adenosine A1 and A2a receptor antagonist, is a widely consumed stimulant and also used for the treatment of hypersomnia; however, the wake-promoting potency of caffeine is often not strong enough, and high doses may induce side effects. Caffeine is metabolized to paraxanthine, theobromine, and theophylline. Paraxanthine is a central nervous stimulant and exhibits higher potency at A1 and A2 receptors, but has lower toxicity and lesser anxiogenic effects than caffeine.</p></sec><sec><title>Design:</title><p>We evaluated the wake-promoting efficacy of paraxanthine, caffeine, and a reference wake-promoting compound, modafinil, in a mice model of narcolepsy, a prototypical disease model of hypersomnia. Orexin/ataxin-3 transgenic (TG) and wild-type (WT) mice were subjected to oral administration (at ZT 2 and ZT14) of 3 doses of paraxanthine, caffeine, modafinil, or vehicle.</p></sec><sec><title>Results:</title><p>Paraxanthine, caffeine, and modafinil significantly promoted wakefulness in both WT and narcoleptic TG mice and proportionally reduced NREM and REM sleep in both genotypes. The wake-promoting potency of 100 mg/kg p.o. of paraxanthine during the light period administration roughly corresponds to that of 200 mg/kg p.o. of modafinil. The wake-promoting potency of paraxanthine is greater and longer lasting than that of the equimolar concentration of caffeine, when the drugs were administered during the light period. The wake-promotion by paraxanthine, caffeine, and modafinil are associated with an increase in locomotor activity and body temperature. However, the higher doses of caffeine and modafinil, but not paraxanthine, induced hypothermia and reduced locomotor activity, thereby confirming the lower toxicity of paraxanthine. Behavioral evaluations of anxiety levels in WT mice revealed that paraxanthine induced less anxiety than caffeine did.</p></sec><sec><title>Conclusions:</title><p>Because it is also reported to provide neuroprotection, paraxanthine may be a better wake-promoting agent for hypersomnia associated with neurodegenerative diseases.</p></sec><sec><title>Citation:</title><p>Okuro M; Fujiki N; Kotorii N; Ishimaru Y; Sokoloff P; Nishino S. Effects of paraxanthine and caffeine on sleep, locomotor activity, and body temperature in orexin/ataxin-3 transgenic narcoleptic mice. <italic>SLEEP</italic> 2010;33(7):930-942.</p></sec></abstract><kwd-group><kwd>Narcolepsy</kwd><kwd>caffeine</kwd><kwd>paraxanthine</kwd><kwd>cataplexy</kwd><kwd>modafinil</kwd><kwd>mice</kwd></kwd-group></article-meta></front></pmc><affiliations><list><country><li>France</li><li>États-Unis</li></country><region><li>Californie</li><li>Midi-Pyrénées</li><li>Occitanie (région administrative)</li></region><settlement><li>Castres</li></settlement></list><tree><country name="États-Unis"><region name="Californie"><name sortKey="Okuro, Masashi" sort="Okuro, Masashi" uniqKey="Okuro M" first="Masashi" last="Okuro">Masashi Okuro</name></region><name sortKey="Fujiki, Nobuhiro" sort="Fujiki, Nobuhiro" uniqKey="Fujiki N" first="Nobuhiro" last="Fujiki">Nobuhiro Fujiki</name><name sortKey="Ishimaru, Yuji" sort="Ishimaru, Yuji" uniqKey="Ishimaru Y" first="Yuji" last="Ishimaru">Yuji Ishimaru</name><name sortKey="Kotorii, Nozomu" sort="Kotorii, Nozomu" uniqKey="Kotorii N" first="Nozomu" last="Kotorii">Nozomu Kotorii</name><name sortKey="Nishino, Seiji" sort="Nishino, Seiji" uniqKey="Nishino S" first="Seiji" last="Nishino">Seiji Nishino</name></country><country name="France"><region name="Occitanie (région administrative)"><name sortKey="Sokoloff, Pierre" sort="Sokoloff, Pierre" uniqKey="Sokoloff P" first="Pierre" last="Sokoloff">Pierre Sokoloff</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonFranceV1/Data/Ncbi/Merge
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000B77 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd -nk 000B77 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= ParkinsonFranceV1
|flux= Ncbi
|étape= Merge
|type= RBID
|clé= PMC:2894435
|texte= Effects of Paraxanthine and Caffeine on Sleep, Locomotor Activity, and Body Temperature in Orexin/Ataxin-3 Transgenic Narcoleptic Mice
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/RBID.i -Sk "pubmed:20614853" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd \
| NlmPubMed2Wicri -a ParkinsonFranceV1
| This area was generated with Dilib version V0.6.29. |  |