Abstract # 1864 Modafinil prevents sickness behavior induced by LPS in mice: Role for dopaminergic D1 receptor

Modafinil is a psychostimulant drug that is used to treat Narcolepsy and Excessive Daytime Sleepiness, due to a dopamine-related action. Recent studies indicated that Modafinil prevents inflammation in animal models of neurodegeneration. However, the effect of Modafinil on the behavioral changes induced by systemic inflammation is still unknown. Thus, the aim of the present study was to evaluate the effect of Modafinil pretreatment in the Lipopolysaccharide (LPS)-induced sickness behavior, and determine the role of dopaminergic D1 receptor in this phenomenon. Adult male C57BL/6J mice were pretreated with Vehicle or Modafinil and, 30 min later, received a single saline or LPS administration, followed by open field and elevated plus maze test 2 h later. Modafinil treatment prevented the LPS-induced increases in immobility and anxiety-like behavior. The pharmacological blockage of the dopaminergic D1R by the drug SCH-23390 counteracted the preventive effect of Modafinil on locomotion and anxiety-like behavior. Our results indicate that Modafinil pretreatment prevented the behavioral inhibition of an acute LPS challenge. The dopaminergic D1 receptor signaling is essential to the Modafinil effects on locomotion and anxiety. This evidence suggests that Modafinil treatment may be useful to prevent inflammation-related behavioral inhibition, possibly due to a neuroimmune mechanism.