The wake-promoting drug Modafinil prevents motor impairment in sickness behavior induced by LPS in mice: Role for dopaminergic D1 receptor

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dc.contributor.author Zager, Adriano
dc.contributor.author Brandao, Wesley Nogueira
dc.contributor.author Margatho, Rafael Oliveira
dc.contributor.author Peron, Jean Pierre
dc.contributor.author Tufik, Sergio [UNIFESP]
dc.contributor.author Andersen, Monica Levy [UNIFESP]
dc.contributor.author Kornum, Birgitte Rahbek
dc.contributor.author Palermo-Neto, Joao
dc.date.accessioned 2020-07-08T13:09:42Z
dc.date.available 2020-07-08T13:09:42Z
dc.date.issued 2018
dc.identifier http://dx.doi.org/10.1016/j.pnpbp.2017.05.003
dc.identifier.citation Progress In Neuro-Psychopharmacology & Biological Psychiatry. Oxford, v. 81, p. 468-476, 2018.
dc.identifier.issn 0278-5846
dc.identifier.uri https://repositorio.unifesp.br/handle/11600/54147
dc.description.abstract The wake-promoting drug Modafinil has been used for many years for treatment of Narcolepsy and Excessive Daytime Sleepiness, due to a dopamine-related psychostimulant action. Recent studies have indicated that Modafinil prevents neuroinflammation in animal models. Thus, the aim of the present study was to evaluate the effect of Modafinil pretreatment in the Lipopolysaccharide (LPS)-induced sickness and depressive-like behaviors. Adult male C57BL/6J mice were pretreated with Vehicle or Modafinil (90 mg/Kg) and, 30 min later, received a single saline or LPS (2 mg/Kg) administration, and were submitted to the open field and elevated plus maze test 2 h later. After 24 h, mice were subjected to tail suspension test, followed by either flow cytometry with whole brain for CD11b(+) CD45(+) cells or qPCR in brain areas for cytokine gene expression. Modafinil treatment prevented the LPS-induced motor impairment, anxiety-like and depressive-like behaviors, as well as the increase in brain CD11b(+) CD45(high) cells induced by LPS. Our results indicate that Modafinil pretreatment also decreased the IL-1 beta gene upregulation caused by LPS in brain areas, which is possibly correlated with the preventive behavioral effects. The pharmacological blockage of the dopaminergic D1R by the drug SCH-23390 counteracted the effect of Modafinil on locomotion and anxiety-like behavior, but not on depressive-like behavior and brain immune cells. The dopaminergic D1 receptor signaling is essential to the Modafinil effects on LPS-induced alterations in locomotion and anxiety, but not on depression and brain macrophages. This evidence suggests that Modafinil treatment might be useful to prevent inflammation-related behavioral alterations, possibly due to a neuroimmune mechanism. en
dc.description.sponsorship CNPq
dc.description.sponsorship FAPESP
dc.description.sponsorship AFIP (Associacao Fundo de Incentivo a Pesquisa)
dc.format.extent 468-476
dc.language.iso eng
dc.publisher Pergamon-Elsevier Science Ltd
dc.relation.ispartof Progress In Neuro-Psychopharmacology & Biological Psychiatry
dc.rights Acesso restrito
dc.subject Modafinil en
dc.subject Lipopolysaccharide en
dc.subject Sickness behavior en
dc.subject Neuroinflammation en
dc.subject Dopaminergic D1 receptor en
dc.title The wake-promoting drug Modafinil prevents motor impairment in sickness behavior induced by LPS in mice: Role for dopaminergic D1 receptor en
dc.type Artigo
dc.description.affiliation Univ Sao Paulo, Sch Vet Med, Dept Pathol, Neuroimmunomodulat Res Grp, Sao Paulo, Brazil
dc.description.affiliation Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Neuroimmune Interact Lab, Sao Paulo, Brazil
dc.description.affiliation Univ Fed Sao Paulo UNIFESP EPM, Dept Psychobiol, Sao Paulo, Brazil
dc.description.affiliation Glostrup Res Inst, Rigshosp, Dept Clin Biochem, Mol Sleep Lab, Glostrup, Denmark
dc.description.affiliationUnifesp Univ Fed Sao Paulo UNIFESP EPM, Dept Psychobiol, Sao Paulo, Brazil
dc.description.sponsorshipID FAPESP: 09/51886-3, 2013/18921-5
dc.identifier.doi 10.1016/j.pnpbp.2017.05.003
dc.description.source Web of Science
dc.identifier.wos WOS:000414901100051
dc.coverage Oxford
dc.citation.volume 81



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