Fig. 1: Prophylactic effects of (R)-ketamine, not its metabolites, on CRS model of depression.
A Treatment schedule. (R)-ketamine (10 mg/kg) or saline (10 ml/kg) was i.p. injected to adult mice 1 day before chronic restraint stress (CRS) (day 1). Subsequently, mice were subjected to CRS for 7 days (day 2–day 8). Locomotion test (LMT), forced swimming test (FST) and sucrose preference test (SPT) were performed on day 9 and day 10, respectively. The prefrontal cortex (PFC) was collected after the SPT (day 10). B Body weight change (one way ANOVA: F2,27 = 11.02, P = 0.0003). C Locomotion test (one way ANOVA: F2,27 = 0.648, P = 0.531). D FST (one way ANOVA: F2,27 = 7.793, P = 0.002). E SPT (one way ANOVA: F2,27 = 10.75, P = 0.0004). The data represent mean ± SEM (n = 9–11). *P < 0.05, **P < 0.01, ***P < 0.0001. N.S., not significant. F Treatment schedule. (R)-norketamine (R-NKT; 10 mg/kg), (2 R,6 R)-hydroxynorketamine (R-HNK; 10 mg/kg) or saline (10 ml/kg) was i.p. injected to mice 1 day before CRS (day 1). Subsequently, mice were subjected to CRS for 7 days (day 2 -day 8). LMT, FST, and SPT were performed on day 9 and day 10, respectively. G Body weight change (one way ANOVA: F3,28 = 3.221, P = 0.038). H Locomotion test (one way ANOVA: F3,28 = 0.3635, P = 0.780). I FST (one way ANOVA: F3,28 = 3.171, P = 0.040). J SPT (one way ANOVA: F3,28 = 10.59, P < 0.0001). The data represent mean ± SEM (n = 8). *P < 0.05, ***P < 0.001. N.S., not significant.
