Fig. 2.

5-HT_2Areceptor knockout male and female mice exhibit chronic unpredictable stress (CUS)-evoked behavioral despair on the tail suspension test (TST) and forced swim test (FST). WT and 5-$\text{H}{\text{T}}_{2\text{A}}^{-/-}$ male and female mice were subjected to a CUS paradigm as illustrated in the schematic (A) for 24 days, which incorporated a weekly TST (CUS days 2, 8, 12 and 19 correspond to week 0, 1, 2 and 3 respectively) and FST (CUS days 3, 7, 14 and 21 correspond to week 0, 1, 2 and 3 respectively). The non-stressed control WT and 5-$\text{H}{\text{T}}_{2\text{A}}^{-/-}$ male and female mice were left undisturbed, with the exception of an FST test performed at day 21 and weekly body-weight measurements. The CUS regime was completed on day 24 and the readouts consisted of behavioral analysis, serum profiling and gene expression analysis in the prefrontal cortex (PFC) and hippocampus (A). Measurements of time spent immobile revealed significant increases in immobility time on the TST and FST following CUS in both WT and 5-$\text{H}{\text{T}}_{2\text{A}}^{-/-}$ male (B – TST; D - FST) and female (C – TST) mice commencing from week 1 and sustained till week three as compared to respective week 0 immobility times. Measurement of immobility time on the FST in WT and 5-$\text{H}{\text{T}}_{2\text{A}}^{-/-}$ female mice following CUS revealed a main effect of CUS, but no significance in Bonferroni post-hoc comparisons between weeks 1–3 to week 0 (E). Results are expressed as the mean ± SEM (n = 12–15/group). (*p < 0.05 as compared to WT at week 0, ^$p < 0.05 as compared to 5-$\text{H}{\text{T}}_{2\text{A}}^{-/-}$ mice compared to week 0, Repeated measures Two-way ANOVA analysis, Bonferroni post-hoc test). Shown is a schematic (F) for the FST treatment performed on day 21 in both non-stressed and CUS administered WT and 5-$\text{H}{\text{T}}_{2\text{A}}^{-/-}$ male and female mice. Measurement of time spent immobile revealed a significant increase in immobility time in both male (G) and female (H) WT and 5-$\text{H}{\text{T}}_{2\text{A}}^{-/-}$ mice subjected to CUS as compared to their respective non-stressed WT and 5-$\text{H}{\text{T}}_{2\text{A}}^{-/-}$ sex-matched controls (Cntrl). Results are expressed as the mean ± SEM (n = 12–15/group). (*p < 0.05 as compared to non-stressed WT mice controls, ^$p < 0.05 as compared to non-stressed 5-$\text{H}{\text{T}}_{2\text{A}}^{-/-}$ mice controls, Two-way ANOVA analysis, Bonferroni post-hoc test).