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

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

Author Zager, Adriano Google Scholar
Brandao, Wesley Nogueira Google Scholar
Margatho, Rafael Oliveira Google Scholar
Peron, Jean Pierre Google Scholar
Tufik, Sergio Autor UNIFESP Google Scholar
Andersen, Monica Levy Autor UNIFESP Google Scholar
Kornum, Birgitte Rahbek Google Scholar
Palermo-Neto, Joao Google Scholar
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.
Keywords Modafinil
Sickness behavior
Dopaminergic D1 receptor
xmlui.dri2xhtml.METS-1.0.item-coverage Oxford
Language English
Sponsor CNPq
AFIP (Associacao Fundo de Incentivo a Pesquisa)
Grant number FAPESP: 09/51886-3, 2013/18921-5
Date 2018
Published in Progress In Neuro-Psychopharmacology & Biological Psychiatry. Oxford, v. 81, p. 468-476, 2018.
ISSN 0278-5846 (Sherpa/Romeo, impact factor)
Publisher Pergamon-Elsevier Science Ltd
Extent 468-476
Access rights Closed access
Type Article
Web of Science ID WOS:000414901100051

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