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

Author(s)

Zager, Adriano ^[1] ; Brandao, Wesley Nogueira ^[2] ; Margatho, Rafael Oliveira ^[1] ; Peron, Jean Pierre ^[2] ; Tufik, Sergio ^[3] ; Andersen, Monica Levy ^[3] ; Kornum, Birgitte Rahbek ^[4] ; Palermo-Neto, Joao ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Vet Med, Dept Pathol, Neuroimmunomodulat Res Grp, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Neuroimmune Interact Lab, Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo UNIFESP EPM, Dept Psychobiol, Sao Paulo - Brazil

^[4] Glostrup Res Inst, Rigshosp, Dept Clin Biochem, Mol Sleep Lab, Glostrup - Denmark

• Document type: Journal article
• Source: PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY; v. 81, p. 468-476, FEB 2 2018.
• Web of Science Citations: 7

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. (AU)

• FAPESP's process: 13/18921-5 - Effects of modafinil on immunity, neuroinflammation and development of experimental autoimmune encephalomyelitis in mice
• Grantee: Adriano Zager
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 09/51886-3 - Neuroimmunomodulation: drugs, stress and cytokines on nervous, endocrine and immune systems relationships
• Grantee: João Palermo Neto
• Support Opportunities: Research Projects - Thematic Grants