The wake-promoting drug Modafinil prevents the depressive-like behavior induced by LPS in mice

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 some animal models. Thus, the aim of the present study was to evaluate the effect of Modafinil pretreatment in the Lipopolysaccharide (LPS)-induced depressive-like behavior. Adult male C57BL/6J mice were pretreated with Vehicle or Modafinil (Stavigile, Libbs; 90 mg/kg, i.p.) and, 30 minutes later, received a single saline or LPS administration (E.coli serotype 0127:B8; 2 mg/kg, i.p.), and were submitted to a 2% sucrose preference test during the next 24 hours. After this period, mice were subjected to tail suspension test, followed by flow cytometry with whole brain for CD11b+CD45+ cells. Modafinil treatment prevented the LPS-induced impairment in sucrose preference (anhedonia), as well as prevented the increased immobility in tail suspension test induced by LPS (learned helplessness). In addition, LPS challenge markedly increased the number of CNS-infiltrating macrophages (CD11b+CD45High), but not microglia (CD11b+CD45low), an effect that was prevented by Modafinil pretreatment (p 0.05). Our results indicate that Modafinill pretreatment was able to prevent the depressive-like effects of an acute LPS injection, a finding that is possibly linked with the CNS-infiltrating macrophages. This evidence suggests that Modafinil treatment might be useful to prevent inflammation-related depression, possibly due to a neuroimmune mechanism.