A trend of attenuation of the metamphetamine-induced hyperactive responses in Sept4Tg/+mice. (A, B) The responses of Sept4+/+ and Sept4Tg/+ mice to the administration of a dopaminergic psychostimulant metamphetamine (MAP) assessed in the open field test. The test was conducted with the same cohort of 9-month-old mice in the same apparatus (cf. Figure 3. Note that aging has reduced the activity level before MAP injection while extending the center time.). Each of the Sept4+/+ and Sept4Tg/+ cohorts was divided into two subgroups and intraperitoneally injected with either MAP in saline (open and closed circles, n = 10, 7) or saline (open and closed triangles, n = 9, 7) at 60 min and observed for 120 min. The metamphetamine-driven surge of the total distance traveled (A) and the center time (B) of Sept4Tg/+ mice tended to be less than those of Sept4+/+ mice. [(A) F1,29 = 0.53, p = 0.47, drug effect, F1,29 = 30.14, p < 0.0001, genotype × drug interaction, F1,29 = 0.13, p = 0.72, genotype × time interaction, F23,667 = 1.13, p = 0.31, drug × time interaction, F23,667 = 8.28, p < 0.0001, genotype × drug × time interaction, p = 0.46, (B) F1,29 = 0.92, p = 0.35, drug effect, F1,29 = 19.37, p = 0.0001, genotype × drug interaction, F1,29 = 0.62, p = 0.44, genotype × time interaction, F23,667 = 1.34, p = 0.13, drug × time interaction, F23,667 = 7.49, p < 0.0001, genotype × drug × time interaction, p = 0.21].