Figure 6
Exploratory and locomotor behavior in 2 month-old male C57Bl/6 mice was assessed by total distance moved in the novel cage test (A) or in the activity chamber (B–D). Mice were either injected and then immediately tested (acute groups in A–C), or injected daily for one week prior to testing (chronic groups in D). Data are shown as mean ± SEM. (A) Dose–response for each of the three compounds vs. total distance moved from 0 to 60 min in the novel cage test expressed as % of vehicle exposed mice (n = 3 mice per group). Two-way ANOVA had FInteraction (4, 18) = 9.068, P = 0.0003; FDose (2, 18) = 14.91, P = 0.0002; and FCompound (2, 18) = 21.89, P < 0.0001. Tukey’s multiple comparison test was significantly different for rac-2MeGln vs. (R)-2MeGlu (****P < 0.0001) and vs. (S)-2MeGlu (***P = 0.0002). (B) Time course of activity chamber distance moved following acute 100 mg/kg had two-way repeated measures ANOVA with FInteraction (87, 580) = 1.879, P < 0.0001; FTime (29, 580) = 11.44, P < 0.0001; and FExposure (3, 20) = 2.906, P = 0.0600 (n = 6 mice per group). Dunnett's multiple comparisons test had multiple early time points that were significantly different between vehicle and (R)-2MeGlu or between vehicle and (S)-2MeGlu (*P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001); vehicle was not significantly different from rac-2MeGln at any time point. (C) Time course of activity chamber distance moved following acute 30 mg/kg had two-way repeated measures ANOVA with FInteraction (87, 580) = 0.9328, P = 0.6493; FTime (29, 580) = 20.13, P < 0.0001; and FExposure (3, 20) = 1.805, P = 0.1786 (n = 6 mice per group). Dunnett's multiple comparisons test had one time point that was significantly different between vehicle and (R)-2MeGlu (*P < 0.05) or between vehicle and rac-2MeGln (#P < 0.05); vehicle was not significantly different from (S)-2MeGlu at any time point. (D) Time course of activity chamber distance moved following chronic 10 mg/kg per day for one week had two-way repeated measures ANOVA with FInteraction (87, 986) = 1.22, P = 0.0912; FTime (29, 986) = 62.35, P < 0.0001; and FExposure (3, 34) = 1.122, P = 0.3536; (n = 6 mice per group). One vehicle group mouse and one (S)-2MeGlu group mouse were outliers using the ROUT method; they were removed from analysis.
