Fig. 4.
Clozapine alone or in combination with valproate (VPA) induces reelin promoter demethylation in mouse FC but not in liver. Mice were pretreated for 7 days with vehicle (open bars) or MET (5.2 mmol/kg twice a day) (filled bars) followed by 3 days with vehicle. After termination of MET treatment, VPA (0.5 mmol/kg, shaded bar), CLZ (15 μmol/kg, checkered bars), or a combination of CLZ with VPA (strip bars) were administered s.c. twice a day for 3 days. Reelin promoter methylation was measured 2 h after the last injection. The data represent the mean ± SE of three animals per group. *, P < 0.05 when CLZ treated mice were compared with the respective VEH-treated mice. **, P < 0.01 when CLZ + VPA-treated mice were compared with either VEH- or VEH+ VPA-treated mice. One-way ANOVA followed by Bonferroni comparison. ¥, Cytosine methylation of reelin promoter was determined as described in Fig. 1.