Abstract: Objective To investigate the relationship between lycopene exposure and neurobehavior and its mechanism in mice exposed to drinking water fluoride.Methods Sixty adult mice were randomly divided into six groups(ten animals in each group):control group,lycopene group,sodium fluoride(NaF) group,NaF plus low,medium,high dose lycopene groups.After 6 months' treatment,fluoride ion selective electrode method was used to determine the fluorine concentrations of urine,blood and hippocampus.Spectrophotometry was used to determine the activities of superoxide dismutase(SOD),glutathione peroxidease(GSH-PX),catalase(CAT),and the contents of malondialdehyde(MDA) in serum and hippocampus.We also examined neurobehavioral abnormalities with WT-200 water maze.Results Compared with the control group,NaF administration induced a decrease in body weight markedly(P<0.05);the fluorine concentrations of urine,blood,and hippocampus were 2.06±0.47,13.40±0.35,and 0.52±0.21 mg/kg and increased markedly(P<0.05).At the same time,NaF administration induced oxidative stress indicated by elevated levels of MDA in serum and brain tissues(P<0.05).Moreover,significantly decreased activities of SOD,GSH-PX,CAT were observed in the tissues examined(P<0.05).Compared with NaF group,the fluorine concentrations of urine,blood,and hippocampus(2.06±0.47,13.40±0.35,and 0.52±0.21 mg/kg) decreased in NaF plus high dose lycopene group(P<0.05).The induced oxidative stress and the alterations in antioxidant system were normalized by the oral administration of medium and high dose lycopene treatment(P<0.05).Compared with the control group,the escape time and activity time were 20.84±0.72 s and 16.11±0.77 s(P<0.05) in NaF group.Compared with NaF group,the escape time and activity time(14.01±0.82 s and 7.38±0.37 s) decreased in high dose lycopene group(P<0.05).Conclusion Lycopene administration could minimize toxic effects of fluoride,indicating its free radical scavenging and powerful antioxidant activities.