Objectives:ZZKetamine has been reported to have antidepressant effects or psychotomimetic effects. The aim of this study was to investigatethe behavioral effects of ketamine treatment at various sub-anesthetic doses in adolescent and adult naïve mice.

Methods:ZZIn each experiment for adolescent and adult mice, a total of 60 male Institute of Cancer Research mice were randomly dividedinto 6 groups, which were intraperitoneally treated with physiological saline, 10, 20, 30, 40, and 50 mg/kg ketamine for consecutive3 days. At 1 day after last injection, the locomotor and depressive-like behaviors were evaluated in mice, using open field test (OFT)and forced swim test (FST), respectively.

Results:ZZIn case of adolescent mice, ketamine dose was negatively correlated with total distance traveled in the OFT (Spearman’srho = -0.27, p = 0.039). In case of adult mice, we found significant positive correlation between ketamine dose and duration of immobilityin the FST (Spearman’s rho = 0.45, p < 0.001). Immobility time in the 50 mg/kg ketamine-treated mice was significantly higher comparedto the saline-treated mice (Dunnett’s post-hoc test, p = 0.012).

Conclusions:ZZWe found that the repeated treatment with ketamine could decrease the locomotor or prolong the duration of immobilityin mice as the dose of ketamine increased. Our findings suggest that sub-anesthetic doses of ketamine might induce schizophrenia-like negative symptoms but not antidepressant effects in naïve laboratory animals.