Fig. 3

Treatment by AMPA receptor modulator CX516 rescues hyperactivity and increased rearing behavior in Scn2a^KO/+ mice. CX516, a specific AMPA receptor positive allosteric modulator, was intraperitoneally administered 10 min before submitting WT and Scn2a^KO/+ mice to the open field task. a The traveled distance decreased significantly over time regardless of the genotype and presence/absence of treatment (time-genotype-treatment interaction: F_2,120 = 1.575, NS; time effect: F_2,120 = 16.195, p < 0.001). A significant genotype-treatment interaction was observed, CX516 leading to a significant decrease in traveled distance specifically in the Scn2a^KO/+ group (genotype-treatment interaction: F_1,120 = 12.285, p < 0.001; post-hoc WT_{saline_vs_CX}: F_1,65 = 0.001, NS; KO_{saline_vs_CX}: F_1,65 = 32.406, p < 0.001). Saline injected Scn2a^KO/+ mice (KO/+) traveled significantly longer distances than their WT (+/+) littermates whereas CX516-treated Scn2a^KO/+ mice traveled significantly shorter distances (post-hoc saline_{WT_vs_KO}: F_1,65 = 4.582, p < 0.05; CX_{WT_vs_KO}: F_1,65 = 5.428, p < 0.05). b The rearing count slightly, yet significantly increased over time regardless of the genotype and presence/absence of treatment (time-genotype-treatment interaction: F_2,120 = 2.212, NS; time effect: F_2,120 = 4.646, p < 0.05). A significant genotype-treatment interaction was observed, CX516 leading to a significant decrease in rearing count specifically in the Scn2a^KO/+ group (genotype-treatment interaction: F_1,120 = 23.418, p < 0.001; post-hoc WT_{saline_vs_CX}: F_1,65 = 2.492, NS; KO_{saline_vs_CX}: F_1,65 = 21.676, p < 0.001). Saline injected Scn2a^KO/+ mice reared significantly more than their WT littermates (post-hoc saline_{WT_vs_KO}: F_1,65 = 90.141, p < 0.001), and although a significant improvement was seen in the CX516-treated Scn2a^KO/+ mice, their rearing count remaining significantly higher than in controls (CX_{WT_vs_KO}: F_1,65 = 17.427, p < 0.001). c The time spent in the center increased significantly over time, was significantly increased in the Scn2a^KO/+ mice and treatment with CX516 led to a mild yet significant decrease regardless of genotype and time (time-genotype-treatment interaction: F_2,120 = 0.351, NS; time effect: F_2,120 = 7.583, p < 0.001; genotype effect: F_2,120 = 24.710, p < 0.001; drug effect: F_2,120 = 4.920, p < 0.05). The test was conducted using N = 11 mice per genotype and per condition (saline and CX516 at 40 mg/kg). Values are expressed as mean ± standard error of the mean. Statistical significance was assessed using three-way ANOVA for time, genotype and treatment effects, followed by one-way ANOVA post-hoc test when a significant interaction was observed (a, b) with significance set at *p < 0.05, **p < 0.01, and ***p < 0.001