Fig. 6: Novel HCN inhibitor MS7710 improves CSDS-induced social, reward, and cognitive deficits. | Molecular Psychiatry

Fig. 6: Novel HCN inhibitor MS7710 improves CSDS-induced social, reward, and cognitive deficits.

From: Design and validation of novel brain-penetrant HCN channel inhibitors to ameliorate social stress-induced susceptible phenotype

Fig. 6: Novel HCN inhibitor MS7710 improves CSDS-induced social, reward, and cognitive deficits.

a Timeline of CSDS and PRLT experimental paradigm. b Schema of SI test. c Social interaction test for male, susceptible mice before injection, and 14 days after IP injection of either saline (n = 11) or 5 mg/kg MS7710 (n = 13). 5 mg/kg MS7710 improved SI ratios (paired t-test: * p = 0.0238), and as compared to saline (Mann-Whitney test: * p = 0.831). d SI test for female, susceptible mice before injection and 14 days after IP injection of either saline (n = 10) or 5 mg/kg MS7710 (n = 9). 5 mg/kg MS7710 improved SI ratios within group (paired t-test: * p = 0.0246). e Schema of PRLT, including placement of SI tests. f PRLT correct choice in percentage during the reversal sessions post-injection for male, control (n = 18), susceptible + saline (n = 11) and susceptible + 5 mg/kg MS7710 mice (n = 13; two-way mixed effects ANOVA: effect of time: F3.336, 129.0 = 63.33, *** p < 0.0001; effect of condition: F2,39 = 4.076, * p = 0.0247; effect of time x condition: F30, 580 = 1.506, * p = 0.0425). The inset depicts the number of sessions until the criteria is reached for each condition (one way ANOVA: F2,39 = 4.539, * p = 0.02; Tukey’s test for multiple comparisons: control vs. susceptible + saline mice: * p = 0.02; susceptible + MS7710 vs. susceptible + saline mice: * p = 0.03). g PRLT correct choice in percentage during the reversal sessions post-injection for female, control (n = 6), susceptible + saline (n = 10) and susceptible + 5 mg/kg MS7710 mice (n = 9; two-way mixed effects ANOVA: effect of time: F3.539, 79.04 = 33.80, *** p < 0.0001; effect of condition: F2,23 = 3.555, * p = 0.0451; effect of time x condition: F30, 355 = 0.7913, ns p = 0.7774). The inset depicts the number of sessions until the criteria are reached for each treatment condition (one-way ANOVA: F2,22 = 4.584, * p = 0.02; Tukey’s test for multiple comparisons: control vs. susceptible + saline mice: ns p = 0.06; susceptible + MS7710 vs. susceptible + saline mice: * p = 0.04). h Pearson correlation of the SI ratio with the number of sessions to reach criteria in the PRLT following reversal for susceptible + 5 mg/kg MS7710 male mice (n = 13, r = 0.3026, p = 0.3149), and i for susceptible + 5 mg/kg MS7710 female mice (n = 9, r = -0.2230, p = 0.5642). Data are presented as mean ± SEM error bars or ribbons. * p < 0.05, ** p < 0.01, *** p < 0.001.

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