5-HT levels in the hippocampus of 5-HT4R KO mice with the C57BL/6 J-background. (A) Tissue 5-HT and 5-HIAA levels in the hippocampus and raphe nuclei. Data are expressed as the mean ± SEM (n = 7 or 8). N.S., not significant for unpaired t-tests. (B) Fluoxetine (Flx)-induced increase in extracellular 5-HT concentrations in the hippocampus. After equilibration, dialysate samples were collected every 20 min with either fluoxetine (22 mg/kg) or saline (Sal) administered at time zero. The average value of seven basal samples for each animal was defined as 100% and used for normalization. Data are expressed as the mean ± SEM (n = 4 for fluoxetine, n = 3 for saline). Main effect of group: P = 0.0499; main effect of time point: P < 0.0001; interaction of group and time point: P < 0.0001. P value was determined by two-way ANOVA for repeated measures. * P < 0.01 [WT(Sal) vs WT(Flx)] for post hoc Bonferroni’s test after two-way ANOVA; N.S, not significant [WT(Flx) vs KO(Flx)] for post hoc Bonferroni’s test at every time point after two-way ANOVA. (C) Tissue 5-HT and 5-HIAA levels in the hippocampus after chronic fluoxetine treatment. Fluoxetine (22 mg/kg) was administered for 3 weeks. Data are expressed as the mean ± SEM (n = 7 or 8). Main effect of drug: #P < 0.0001 (5-HT), #P < 0.0001 (5-HIAA); main effect of genotype: P = 0.9734 (5-HT), P = 0.0423 (5-HIAA); interaction of drug and genotype: P = 0.9790 (5-HT), P = 0.3243 (5-HIAA); P values determined by two-way ANOVA.