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Fig. 3 Amylovis-201 attenuated Dizocilpine-induced learning impairment in mice through σ1 agonism: dose-response effects in the (a) spontaneous alternation and (b) step-through passive avoidance. (c,d) Blockade of Amylovis-201 effect by NE-100 in each test. Mice received Amylovis-201 (0.01–1 mg/kg PO) 10 min before Dizocilpine (0.15 mg/kg IP), 20 min before the Y-maze session in (a,c) or passive avoidance training in (b,d). In (c,d), NE-100 was administered at 1 mg/kg IP simultaneously with the lowest active dose of Amylovis-201, i.e., 0.03 mg/kg PO in the Y-maze in (d) and 0.1 mg/kg in the passive avoidance test in (e). Abbreviations: V, vehicle solution (physiological saline); Dizo, Dizocilpine; A, Amylovis-201; N, NE-100. Data show mean ± SEM of the number of animals indicated within or below the columns. ANOVAs: F(5,50) = 12.19, P < 0.0001 in (a); F(4,46) = 22.76, P < 0.0001 in (c). Kruskal-Wallis ANOVAs: H = 19.29, P = 0.0017 in (b); H = 23.86, P < 0.0001 in (d). ∗ P < 0.05, ∗∗ P < 0.01, ∗∗∗ P < 0.001 vs. (V+V)-treated mice; # P < 0.05, ## P < 0.01 vs. (Dizo+V)-treated mice; oo P < 0.01 vs. (Dizo+A)-treated mice; Dunnett's test in (a,c), Dunn's test in (b,d).