Fig. 3: Reversal of KO behavioral phenotypes by risperidone and diazepam.
The behavior of WT, HT, or KO mice administered with 0.3 mg/kg risperidone i.p was compared that of control mice administered with saline in: a–c PPI trials with significant effects of risperidone in the 77–110, 77–120, and 83–110 dB prepulse-pulse trials (F1,92 = 19.20, p < 0.001; F1,92 = 16.80, p < 0.001; and F1,92 = 15.71, p < 0.001, respectively), and significant effects of genotype in the 77–110 and 77–120 dB prepulse-pulse trials (F2,92 = 8.04, p < 0.001; and F2,92 = 3.53, p < 0.05, respectively). Saline group: WT male n = 21, HT male n = 25, KO male n = 21; risperidone group: WT male n = 10, HT male n = 10, KO male n = 10. d Locomotor activity test with significant effects of risperidone (F1,95 = 49.87, p < 0.0001) and of genotype (F2,95 = 51.78, p < 0.0001). Saline group: WT male n = 11, HT male n = 11, KO male n = 11; risperidone group: WT male n = 10, HT male n = 13, KO male n = 10. e Behavioral stereotypy test based on rears and climbs with significant effects of risperidone (F1,60 = 72.57, p < 0.0001) and of genotype (F2,60 = 25.33, p < 0.0001). Saline group: WT male n = 11, HT male n = 11, KO male n = 11; risperidone group: WT male n = 10, HT male n = 13, KO male n = 10. f Morris water maze test with significant effect of genotype (F2,54 = 6.20, p < 0.01). Saline group: WT male n = 10, HT male n = 10, KO male n = 10; risperidone group: WT male n = 10, HT male n = 10, KO male n = 10. g Tail-suspension test with significant effects of risperidone (F1,59 = 32.92, p < 0.0001) and of genotype (F2,59 = 43.82, p < 0.0001). Saline group: WT male n = 11, HT male n = 10, KO male n = 11; risperidone group: WT male n = 10, HT male n = 13, KO male n = 10. h Elevated-plus maze test with significant effect of risperidone (F1,96 = 13.29, p < 0.001). Saline group: WT male n = 12, HT male n = 25, KO male n = 16; risperidone group: WT male n = 12, HT male n = 25, KO male n = 12. i Audiogenic epilepsy with significant effects of diazepam (F3,87 = 12.47, p < 0.001). Saline group: KO male n = 16, KO female n = 16; 0.1 mg/kg diazepam group: KO male n = 11, KO female n = 11; 0.3 mg/kg diazepam group: KO male n = 11, KO female n = 10; 0.5 mg/kg diazepam group: KO male n = 10, KO female n = 10. Latency periods were capped at the maximum cutoff of 60 seconds. In (a–h), ‘+’ denotes animals administered with 0.3 mg/kg risperidone i.p, and ‘−’ animals administered with saline i.p. In (i), the different groups were treated with 0–0.5 mg/kg diazepam i.p. WT is represented by green dots, HT by orange dots, and KO by red dots except in (i) where KO mice reaching the 60-s cutoff are represented by red open circles. Average y values ± SEM in the different plots are represented by horizontal bars. Statistical analysis was performed using two-way ANOVA with Dunnett’s post-hoc test; *p < 0.05, **p < 0.01, and ***p < 0.001 in all the post-hoc tests
