Fig. 5: A single PA-915 administration exerted long-lasting antidepressant-like effects in susceptible (SUS) mice after repeated exposure to social defeat stress.

(A) SUS mice received a single injection of PA-915 (30 mg/kg, i.p.), ketamine (20 mg/kg, i.p.) or vehicle treatment on day 0, and fluoxetine (20 mg/kg, i.p.) once daily for 14 consecutive days (days 0–13). The mice and naïve control mice were subjected to the sucrose preference test on days 0, 7, 14, 28, and 56. Statistical significance was assessed using repeated measures two-way ANOVA (n = 13–22, time × treatment, F_{(16, 304)} = 1.91, p = 0.019; time, F_{(3.64, 276.7)} = 0.33, p = 0.84; treatment, F_{(4, 776)} = 51.46, p < 0.01) followed by Dunnett’s multiple comparisons test. *p < 0.05, **p  <  0.01. The values are expressed as means ± SEM from two independent experiments. (B, C) Morphological analysis of the dendritic spines in the medial prefrontal cortex in SUS mice received PA-915 (30 mg/kg, i.p.) or vehicle treatment and naïve control mice. Representative images of Golgi-stained pyramidal neurons in the medial prefrontal cortex on days 1 and 56. Scale bar, 10 µm. (B) Quantification of the number of total spines. Statistical significance was assessed using one-way ANOVA (n = 7 (day 1), n = 4 (day 56), day 1: F_{(2, 18)} = 55.74, p = 0.012; day 56: F_{(2, 9)} = 8.24, p < 0.01) followed by the Tukey-Kramer test. *p < 0.05, **p < 0.01. Values are expressed as means ± SEM.