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. 2014 Jun 4;39(11):2506–2518. doi: 10.1038/npp.2014.105

Figure 2.

Figure 2

Stimulation of the 5-HT7 receptor improves the behavioral phenotype in a mouse model of Rett syndrome. (a) Vehicle-injected RTT mice (RTT, Veh) spent significantly less time in the light compartment in the Light/Dark test compared with wild-type controls (wt, Veh), thus confirming increased anxiety-like behaviors. Treatment with LP-211 restored wt-like levels of anxiety-like behaviors in RTT mice. (b) RTT mice displayed a higher number of transitions between the two compartments during the Light/Dark test compared with wt controls. The LP-211 treatment rescued the hyperactive phenotype of RTT mice, thus confirming the anxiolytic properties of the treatment. (c) RTT mice buried significantly less marbles in the Marble Burying test compared with wt controls, thus suggesting decreased digging/exploratory behavior in a novel environment. LP-211 significantly increased this parameter. A normalization of performance was thus observed in RTT mice who received the LP-211 treatment. (d) In the Dowel test, RTT mice displayed significantly shorter latencies to fall from a dowel during the second trial compared to wt controls, thus confirming impaired motor learning capacities. LP-211 significantly improved the performance of RTT mice in this test. (e) Dowel test results were confirmed on a second cohort of mice. Comparable genotype and treatment effects were found on days 6 and 12, after a 5-day long wash-out period, thus suggesting lasting effects of a 7-day long treatment with LP-211 in RTT mice. (f) RTT mice showed increased inactivity after 70 min of exposure to a novel cage compared with wt controls. The LP-211 treatment completely rescued the hypoactive phenotype of RTT mice. (g) In the spatial novelty preference task, RTT mice showed decreased discrimination of the novel arm compared to wt controls. The LP-211 treatment completely restored the hippocampal-dependent short-term spatial memory of RTT mice in this non-aversive task. LP-211 or vehicle were i.p. injected for 6 (a–d) or 7 (e–g) consecutive days. Data are mean±SEM. Statistical significance was calculated by two-way ANOVA with Tukey's post hoc test. €, wt, Veh vs RTT, Veh; p<0.05; *, RTT, Veh vs RTT, LP-211, p<0.05, after post hoc comparisons on the genotype*treatment or genotype*treatment*repeated measures interactions.