Fig. 5: Effects of acute memantine administration on hyperactivity and hippocampus-dependent learning in Xpnpep1–/– mice.

a–c Open-field activities of 6- to 7-week-old male mice were measured 30 min after saline or memantine injection. Representative activity traces during the entire test period (a), locomotor activities of mice at 5-min intervals (b), and total distance moved during the 30-min open-field test (c). n = 13 (+/+, Sal), 13 (+/+, Mem), 14 (–/–, Sal), and 12 (–/–, Mem). Genotype, F(1, 48) = 24.723, p < 0.001; treatment, F(1, 48) = 15.375, p < 0.001; interaction, F(1, 48) = 10.117, p < 0.001. d–f Acute memantine injection reduced hyperactivity in female Xpnpep1–/– mice. Sample path recordings (d), distance moved over 5 min time bins (e), and locomotor activity during the entire test period (f). n = 8 (+/+, Sal), 10 (+/+, Mem), 6 (–/–, Sal), and 10 (–/–, Mem). Genotype, F(1, 30) = 34.488, p < 0.001; treatment, F(1, 30) = 15.440, p < 0.001; interaction, F(1, 30) = 23.255, p < 0.001. g Experimental designs of the novel object recognition (NOR), object location memory (OLM), and contextual fear conditioning (CFC) tests. Saline or memantine was administered 1 h before the acquisition period. NOR and CFC tests were performed by male mice, and the OLM test was performed by female mice. h Representative tracks of movement patterns during the test period of the NOR test. i Acute memantine injection had no effect on NOR in male Xpnpep1–/– mice. n = 13 (+/+, Sal), 13 (+/+, Mem), 14 (–/–, Sal), and 12 (–/–, Mem). Genotype, F(1, 48) = 18.617, p < 0.001; treatment, F(1, 48) = 3.283, p = 0.076; interaction, F(1, 48) = 0.032, p = 0.86. j Representative exploratory tracks of female mice during the test period of the OLM test. k Preference index for the moved object in the OLM test. n = 8 (+/+, Sal), 7 (+/+, Mem), 7 (–/–, Sal), and 7 (–/–, Mem). Genotype, F(1, 25) = 16.357, p < 0.001; treatment, F(1, 25) = 1.171, p = 0.290; interaction, F(1, 25) = 0.0008, p = 0.98. l Percentage of time spent freezing during contextual exposure in the testing period of the CFC test. n = 13 (+/+, Sal), 13 (+/+, Mem), 14 (–/–, Sal), and 11 (–/–, Mem). Genotype, F(1, 47) = 42.035, p < 0.001; treatment, F(1, 47) = 0.118, p = 0.733; interaction, F(1, 47) = 0.128, p = 0.722. c, f, i, k, and l) *p < 0.05; ***p < 0.001; n.s., not significant (p ≥ 0.05); two-way ANOVA with the Tukey multiple comparison test.