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. 2018 Oct 2;11:353. doi: 10.3389/fnmol.2018.00353

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Copyright © 2018 Costa, Sardone, Bonaccorso, D’Antoni, Spatuzza, Gulisano, Tropea, Puzzo, Leopoldo, Lacivita, Catania and Ciranna.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Acute in vivo administration of LP-211 improved memory and reduced stereotyped behavior in Fmr1 KO mice. (A) Exploration times of familiar and novel object during T2 (after a 24-h retention interval) show that Fmr1 KO mice treated with vehicle present an impairment of memory (higher amount of time exploring the familiar vs. the novel object; p < 0.0001) that is rescued by treatment with LP-211 (3 mg/kg 30 min before T1). WT + vehicle = 11; Fmr1 KO + vehicle = 12; WT + LP-211 = 10; Fmr1 KO + LP-211 = 10. (B) Analysis of the discrimination (D) index confirms that the impairment of recognition memory in Fmr1 KO (P = 0.015 vs. WT) is rescued by LP-211 (P = 0.02 vs. Fmr1 KO + LP-211). A difference from 0 is depicted with hashes (^#p < 0.05) (C) Latency to first approach to the novel object and (D) total exploration time are comparable in the 4 groups of mice. (E) Fmr1 KO treated with vehicle buried a higher number of marbles compared to WT (P = 0.002). This stereotypic behavior was rescued by treatment with LP-211 (3 mg/kg 30 min before test). WT + vehicle = 11; WT + LP-211 = 10; Fmr1 KO + vehicle = 12; Fmr1 KO + LP-211 = 10 for novel object recognition (NOR; A–D) and Marble Burying (E) tasks. (F) Time spent in the center of the arena and (G) the number of crosses into the center is comparable in the four groups of mice. (H–I) General locomotor activity analyzed as horizontal activity and vertical activity (rearing) is not modified by genotype and treatment. (J) The increase in stereotyped behavior such as grooming in Fmr1 KO mice (P < 0.0001) is rescued by treatment with LP-211. (K) Fmr1 KO mice show a decrease of spontaneous freezing behavior compared to WT littermates (P = 0.036) that is rescued by LP-211. (L) Defecation is comparable in the four groups of mice. WT + vehicle = 10; WT + LP-211 = 12; Fmr1 KO + vehicle = 12; Fmr1 KO + LP-211 = 14 for Open field (OF) test. Data are expressed as mean ± SEM. *Significant difference (p < 0.05 by one-way ANOVA with Bonferroni’s multiple comparisons test); ^#difference with zero (one-sample t-test).