Fig. 6.

Decreased responsiveness to AMPH in KO mice compared with WT mice. A, time course of locomotor activity induced by 3 mg/kg AMPH or Sal in WT and KO mice. Mice were given an injection of Sal to reduce injection stress 2 h before either AMPH (3 mg/kg) or Sal, and locomotor activity was recorded for 4 h as described under Materials and Methods. A two-way ANOVA (genotype × time) comparing AMPH-treated WT and KO mice revealed a significant main effect of genotype [F(1,1076) = 28.31, p < 0.0001], time [F(75,1076) = 17.45, p < 0.0001], and a significant interaction effect of genotype and time [F(75,1076) = 1.602, p < 0.001]. KO mice exhibited significantly lower locomotor activity in response to 3 mg/kg AMPH than WT mice (n = 8-9). Bar, significant values determined by post hoc Bonferroni analysis. ^*, p < 0.05 for all values except for 50 min (^**, p < 0.01). B, mice were given an injection of Sal 2 h before the test injection of Sal or AMPH at doses of 1, 2, 3, 5, or 7 mg/kg. Locomotor activity was summed over 80 min. A two-way ANOVA (genotype × dose) revealed a significant main effect of AMPH dose [F(5, 87) = 61.49, p < 0.01] and a significant interaction effect of genotype and dose [F(5, 87) = 4.79, p < 0.05]. Post hoc Bonferroni analysis indicated that AMPH significantly stimulated locomotor activity in WT mice at doses of 1, 2, 3, 5, and 7 mg/kg compared with their Sal injection (n = 6-12), whereas KO mice showed stimulation only at doses of 3, 5, and 7 mg/kg AMPH (n = 6-13). In addition, the Sal-treated KO mice consistently exhibited higher locomotor activity than Sal-treated WT mice (Student's t test, p < 0.05, n = 11-13). ^*, p < 0.05; ^**, p < 0.01, AMPH versus Sal within each genotype; #, p < 0.05, WT versus KO within each dose of AMPH.