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. Author manuscript; available in PMC: 2021 Oct 30.
Published in final edited form as: Mol Psychiatry. 2020 Nov 24;26(8):4066–4084. doi: 10.1038/s41380-020-00958-2

Figure 2.

Figure 2

Class I HDAC inhibition via MS275 normalizes manic-like behavior in ClockΔ19 mice. Male (A-F) and female (G-L) Wt and ClockΔ19 mice were treated with the Class I HDAC inhibitor, MS275 (n=15 male; n=10 female), or the Class IIa HDAC inhibitor, MC1568 (n=10 male; n=10 female), and tested for exploratory drive and avoidance behavior in the dark/light box (A, G), EPM (B, H), and open field test (C, I), behavior despair in the FST (D, E, J, K), and locomotor response to novelty (F, L). Vehicle-treated male ClockΔ19 mice (n=15) showed increased time in the light side of the dark/light box (A), increased time in the open arm of the EPM (B), increased center time in the open field (C), increased latency to immobility (D) and decreased immobility time in the FST (E), and increased locomotor response to novelty (F) compared to Wt mice (n=15). Treatment of male ClockΔ19 mice with MS275 normalized time spent in the light side of the dark/light box (A), center time in the open field test (C), and latency to immobility in the FST (D). There were no effects in the EPM (B), in the FST (E), or locomotor response to novelty (F). Treatment of male ClockΔ19 mice with MC1568 normalized latency to immobility (D) and immobility time (E) in the FST, with no effect on time spent in the light side of the dark/light box (A), open arm time in the EPM (B), center time in the open field (C), or locomotor response to novelty (F). MS275 and MC1568 both had no effect on male Wt mice (A-F). Vehicle-treated female ClockΔ19 mice (n=10) showed increased time spent on the light side of the dark/light box (G), increased time in the open arm of the EPM (H), increased center time in the open field (I), increased latency to immobility in the FST (J), and increased locomotor response to novelty (L), with no effect on immobility time in the FST (K). Treatment of female ClockΔ19 mice with MS275 normalized open arm time in the EPM (H) and center time in the open field (I). There was no effect in the dark/light box (G) and on the latency to immobility in the FST (J), with no effect on immobility time in the FST (K) or locomotor response to novelty (L). Treatment of female ClockΔ19 mice with MC1568 normalized open arm time in the EPM (H), with no effects on time spent in the light side of the dark/light box (G), center time in the open field test (I), latency to immobility in the FST (J), immobility time in the FST (K), or locomotor response to novelty (L). Both MS275 and MC1568 treatment increased time spent in the open arm of the EPM in Wt mice (H). Data is represented as mean ± SEM. Data in A-E and G-K were analyzed using two-way ANOVA followed by Tukey’s post hoc tests if significant interaction. Data in F and L were analyzed using two-way repeated measures ANOVA. *p <0.05, **p<0.01, ***p<0.001, ****p<0.0001, with lines between bars representing significant differences between those groups.