Figure 3.
Glutamate and dopamine level elevation is prevented in NOX2-deficient mice. A–D, Time-dependent effect of ketamine or saline injection on extracellular glutamate (GLU; A, B) and dopamine (DA; C, D) levels was determined by microdialysis in the prefrontal cortex of WT (A, C) and KO NOX2 (B, D) mice. Data are expressed as the percentage of baseline (as described in Materials and Methods). E, F, Concentration of glutamate (E) and dopamine (F) in WT and KO NOX2 mice at basal level or 30 min after saline or ketamine injection. ***p < 0.001 using two-way ANOVA for repeated measures followed by Tukey's post hoc test (n = 6 WT saline and ketamine; n = 4 KO NOX2 saline and ketamine). For glutamate analysis: two-way ANOVA for repeated measures in KO NOX2 saline versus KO NOX2 ketamine: Ftr(1,66) = 2.259, p = 0.184; Ftime (t)(11,66) = 1.882, p = 0.058; Ftr×t(11,66) = 0.568, p = 0.847; in WT ketamine versus KO NOX2 ketamine: Fgen(1,88) = 10268.736, p < 0.001; Ft(11,88) = 345.017, p < 0.001; Ft×gen(11,88) = 327.118, p < 0.001; in WT ketamine versus KO NOX2 saline: Ftr(1,88) = 7557.223, p < 0.001; Ft(11,88) = 358.748, p < 0.001; Ft×tr(11,88) = 329.535, p < 0.001; in WT saline versus KO NOX2 ketamine: Ftr(1,88) = 15.944, p = 0.004; Ft(11,88) = 2.118, p = 0.027; Ftr×t(11,88) = 0.551, p = 0.863; however, Tukey's post hoc test did not reveal any significant difference for treatment and time; in WT saline versus KO NOX2 saline: Fgen(1,88) = 0.00160, p = 0.969; Ft(11,88) = 2.011, p = 0.036; Fgen×t(11,88) = 0.443, p = 0.932; however, Tukey's post hoc test did not reveal any significant difference for genotype and time; in WT ketamine versus WT saline: Ftr(1,110) = 16,702.806, p < 0.001; Ft(11,110) = 529.138, p < 0.001; Ftr×t(11,110) = 505.459, p < 0.001. For dopamine analysis: two-way ANOVA for repeated measures in KO NOX2 saline versus KO NOX2 ketamine: Ftr(1,66) = 0.00525, p = 0.945; Ft(11,66) = 0.633, p = 0.749; Ftr×t(11,66) = 0.440, p = 0.932; in WT ketamine versus KO NOX2 saline: Ftr(1,88) = 360.147, p < 0.001; Ft(11,88) = 16.156, p < 0.001; Ft×tr(11,88) = 14.890, p < 0.001; in WT saline versus KO NOX2 ketamine: Ftr(1,88) = 0.00714, p = 0.935; Ft(11,88) = 0.480, p = 0.911; Ftr×t(11,88) = 0.37, p = 0.965; in WT saline versus KO NOX2 saline: Fgen(1,88) = 0.00000392, p = 0.998; Ft(11,88) = 0.31, p = 0.982; Fgen×t(11,88) = 0.234, p = 0.994; in WT ketamine versus WT saline: Ftr(1,110) = 530.505, p < 0.001; Ft(11,110) = 20.573, p < 0.001; Ftr×t(11,110) = 18.919, p < 0.001; WT ketamine versus KO NOX2 ketamine: Fgen(1,88) = 331.637, p < 0.001; Ft(11,88) = 16.311, p < 0.001; Ft×gen(11,88) = 15.508, p < 0.001.