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

Publication date: 2 February 2018 Source:Progress in Neuro-Psychopharmacology and Biological Psychiatry, Volume 81 Author(s): Adriano Zager, Wesley Nogueira Brandão, Rafael Oliveira Margatho, Jean Pierre Peron, Sergio Tufik, Monica Levy Andersen, Birgitte Rahbek Kornum, João Palermo-Neto 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 (90mg/Kg) and, 30min later, received a single saline or LPS (2mg/Kg) administration, and were submitted to the open field and elevated plus maze test 2h later. After 24h, 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+ CD45high cells induced by LPS. Our results indicate that Modafinil pretreatment also decreased the IL-1β gene upregulation caused by LPS in brain areas, which is possibly correlated with the preventive behav...
Source: Progress in Neuro Psychopharmacology and Biological Psychiatry - Category: Psychiatry Source Type: research