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. 2018 Jul 2;8:124. doi: 10.1038/s41398-018-0171-1

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 2 — a Effect of CUS on time spent in the center of the open field. Two way ANOVA revealed a significant genotype by CUS interaction (F[1,70] = 6.08, p = 0.016. Post hoc comparisons of simple main with Bonferroni correction effects indicated a significant difference between Ahi1+/+ and Ahi1+/− control mice (p < 0.005), and between CUS-exposed Ahi1+/+ and Ahi1+/+ controls (p < 0.01), but not between CUS-exposed Ahi1+/− and Ahi1+/− controls. *p < 0.05, **p < 0.005; b Effect of CUS on light-dark box preference. Significant main effect of genotype was detected on two-way ANOVA (F[1,70] = 20.18, p = 0.00003), indicating that Ahi1+/− mice spent longer in the open area of the dark-light box than Ahi1+/+ mice. Post hoc comparisons of simple main effects with Bonferroni correction revealed that Ahi1+/− control mice spent longer in the light zone than Ahi1+/+ controls (p < 0.0001), and CUS-exposed Ahi1+/+ mice spent longer in the light zone than Ahi1+/+ controls (p < 0.05), suggesting that the CUS protocol decreased the anxiety of these mice. No such effect was observed in CUS-exposed Ahi1+/− mice. *p < 0.05, ***p < 0.0001; c Effects of CUS on time spent in the open arms of the elevated plus maze. Significant main effect of genotype (F[1,70] = 6.869, p = 0.011) on two-way ANOVA, indicating that Ahi1+/− mice spent longer in the open arms of the elevated plus maze than Ahi1+/+ mice, suggesting reduced anxiety of these mice. Post hoc comparisons of simple main effects with Bonferroni correction indicated that Ahi1+/− mice spent longer in the open arms compared to Ahi1+/+ controls (p < 0.01), and that CUS-exposed Ahi1+/+ mice spent longer in the open arms compared to Ahi1+/+ controls (p < 0.05). No similar effect was observed in the CUS-exposed Ahi1+/− mice. *p < 0.05 d Effect of CUS in the stress-induced hyperthermia test. Two-way ANOVA revealed a significant main effect of genotype (F[1,63] = 4.203, p = 0.045), indicating that Ahi1+/+ mice manifested attenuated hyperthermia. CUS blunted hyperthermia in Ahi1+/+ mice, but had no effect on Ahi1+/− mice, reflected in a significant CUS by genotype interaction (F[1,63] = 5.001, p = 0.029). Post hoc tests of simple main effects with Bonferroni correction indicated that CUS-exposed Ahi1+/+ mice displayed a blunted response to acute stress compared to both CUS-exposed Ahi1+/− mice (p < 0.05) and Ahi1+/+ controls (p < 0.05). There was no significant difference between CUS-exposed Ahi1+/− mice and Ahi1+/− control mice. *p < 0.05