Kowsar Jundishapur J Nat Pharm Prod 2228-7876 16 2 2021 3 30 10.5812/jjnpp.67765 Rahimeh Bargi Division of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Mahmoud Hosseini Division of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Fereshteh Asgharzadeh Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Majid Khazaei Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Mohammad Naser Shafei Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Farimah Beheshti Neuroscience Research Center, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran, Department of Physiology, School of Paramedical Sciences, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran Research Article 2019 5 11 2018 6 9 2021 3 30 2021 05 31 Background : Blood-brain barrier (BBB), as well-known protection for the brain, plays an active role in normal homeostasis. It might be changed by a range of inflammatory mediators to have a role in sickness behaviors. Objectives : Regarding the anti-inflammatory effects of thymoquinone (TQ), its protection against BBB permeability, as a possible mechanism for protective effects against sickness behaviors elicited by lipopolysaccharide (LPS), was evaluated in rats. Methods : The animals were grouped as follows and treated (n = 10 in each): (1) control (saline); (2) LPS 1 mg/kg, was injected two hours before behavioral tests for two weeks; (3-5) 2, 5, and 10 mg/kg TQ, respectively was injected 30 min before LPS injection. Open-field (OF), elevated plus-maze (EPM) and Forced Swimming test (FST) were done. Finally, the animals were anesthetized to evaluate for BBB permeability using Evans blue (EB) dye method. Results : Compared with control, LPS decreased the peripheral distance and crossing and also total crossing and distance in OF, (P < 0.01 - P < 0.001). The central crossing and distance and central time in all three treatment groups were more than LPS (P < 0.05 - P < 0.001). LPS also reduced the entries and the time spent in the open arm while increased the time spent in the closed arm in EPM (P < 0.05 - P < 0.001). The effects of LPS were reversed by TQ (P < 0.05 - P < 0.001). In FST, the immobility time and active time were increased and decreased by LPS compared with control (P < 0.001), respectively. In all three TQ-treated groups, the active and climbing times were more while the immobility time was fewer than the LPS (P < 0.05 - P < 0.001). The animals of the LPS group showed more EB dye content in their brain tissue than the control group (P < 0.05 - P < 0.001). TQ significantly reduced EB dye content of the brain tissues (P < 0.05 - P < 0.001). Conclusions : According to this study, protection against BBB permeability as a possible mechanism for the protective effects of TQ against sickness behaviors induced by LPS might be suggested. https://sites.kowsarpub.com/jjnpp/articles/67765.html https://jjnpp.kowsarpub.com/cdn/dl/e522d316-914e-11eb-af88-3beae39493f4 Blood-Brain Barrier Thymoquinone Sickness Behavior Lipopolysaccharide