FFAR1−/− mice showed reduced cocaine-induced locomotor responses. Mice were placed in an open-field test chamber for 63 min for habituation purpose (left panels in A–D). Then, cocaine was i.p.-injected, and mice were returned to the test chamber for an additional 33 min (middle panels in A–D). Cocaine injection (20 mg/kg, i.p.) induced significant acute enhancement of locomotor activity in both FFAR1+/+ and −/− mice. *p < 0.05, **p < 0.01, ***p < 0.001 versus the basal (pre-cocaine injection) values (60–63 min time points) (Dunnett’s test). However, FFAR1−/− mice showed reduced cocaine-evoked acute locomotor responses analyzed in terms of the three parameters (right panels in A–C), but −/− mice showed enhanced ambulation in the center region after cocaine injection (right panel in D). Two-way ANOVA with repeated measures indicated significant effects of genotype [F(1, 116) = 9.32, p < 0.01 (A), F(1, 116) = 15.9, p < 0.001 (B), F(1, 116) = 43, p < 0.001 (C), F(1, 116) = 12.1, p < 0.001 (D)] and time [F(5, 116) = 18.7, p < 0.001 (A), F(5, 116) = 17.7, p < 0.001 (B), F(5, 116) = 43, p < 0.001 (C), F(5, 116) = 11.8, p < 0.001 (D)]. Since significant interactions between genotype and time were not detected in A–D, each area under the curve (AUC) value, calculated for 13 min (A–C) and 33 min (D) after acute cocaine injection, was compared between +/+ and −/− mice. #
p < 0.05, ###
p < 0.001 vs. +/+ mice (Student’s t-test). +/+: n = 9–11 for +/+ mice, and n = 11 for −/− mice.