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. 2019 Sep 18;9:235. doi: 10.1038/s41398-019-0569-4

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© The Author(s) 2019

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. 4 — Two-way ANOVA with Tukey post hoc test was performed (females (M): N.Ch. Adnp^+/+ N = 5–7; N.Ch. Adnp^+/− N = 4–6; +Ch. Adnp^+/+ N = 6–9; +Ch. Adnp^+/− N = 4–7; +Ch. Adnp^+/+ PACAP N = 5–8; +Ch. Adnp^+/− PACAP N = 4–7). a Adnp^+/− female male mice exhibit markedly increased total distance traveled in the open field apparatus, further increased by stress-challenge and reduced by PACAP treatment. In stress-challenged females, main effects for genotype (F(1,15) = 14.358, p = 0.002) and interaction (F(1,15) = 5.541, p = 0.033) were found, with significant differences between PACAP- and vehicle-treated Adnp^+/− mice (*p < 0.05), and Adnp^+/+ vs. Adnp^+/− mice (***p < 0.001). In vehicle-treated females, significant main genotype (F(1,15) = 26.946, p < 0.001) and treatment (F(1,15) = 10.137, p = 0.006) effects were found, with significant differences between non-challenged Adnp^+/+ and Adnp^+/− mice (*p < 0.05), challenged vs. non-challenged Adnp^+/− mice (*p < 0.05), and challenged Adnp^+/+ vs. Adnp^+/− mice (***p < 0.001). b In female mice, stress-challenged Adnp^+/− mice spent substantially more time in the open arms compared with non-challenged Adnp^+/− mice, challenged Adnp^+/+ mice, and challenged PACAP-treated Adnp^+/− mice. In stress-challenged females, main effects for treatment (F(1,27) = 7.823, p = 0.009) and interaction (F(1,27) = 5.779, p = 0.023) were found, with a significant difference between PACAP- and vehicle-treated Adnp^+/− mice (**p < 0.01), as well as Adnp^+/+ vs. Adnp^+/− mice (*p < 0.05). In vehicle-treated females, a main effect for stress-challenge was found (F(1,25) = 15.297, p < 0.001), with a significant difference between non-challenged and challenged Adnp^+/− mice (***p < 0.001), as well as challenged Adnp^+/+ vs. Adnp^+/− mice (*p < 0.05). c For all experimental groups in the study (total N = 30), plasma cortisol levels were positively correlated with the D2 score in the elevated plus maze test (Spearman’s correlation, r = 0.379, *p < 0.05)