Fig. 4.

Locomotor activity after acute cocaine treatment. Mice were habituated to the open field for 1 h, given saline or cocaine (i.p.), and immediately returned to the open field for 2 h. Effects of saline, 10, 15, or 20 mg/kg cocaine on open field activity in WT (A,B) or dtg (C,D) mice. Both WT (A) and dtg (C) mice display dose-dependent increases in locomotor activity following administration of cocaine. RMANOVA for distance traveled for the first h before drug injection was not significant. RMANOVA over the 2 h post-injection period revealed significant main effects of time [F_23,851 = 47.528, p<0.001] and a significant time by treatment interaction [F_69,851 = 10.612, p<0.001]. No significant time by genotype or time by genotype by treatment interactions were discerned. Bonferroni corrected pair-wise comparisons for the time by treatment effects revealed that WT and dtg mice had enhanced locomotor responses to 10, 15, and 20 mg/kg cocaine at 5, 10, 15, and 20 min post-injection (ps<0.04) relative to the vehicle controls. Cumulative total distance traveled during 20 min before and following drug injection is presented for WT (B) and dtg (D) mice. RMANOVA for distance traveled 20 min pre- and post-injection revealed significant effects of time [F_1,37 = 91.633, p<0.001] and a significant time by dose interaction [F_3,37 = 35.421, p<0.001]. No effects of genotype were observed. Bonferroni corrected pair-wise comparisons confirmed that WT and dtg animals did not differ in locomotor activities prior to or following cocaine administration. Behavioral responses to both 15 and 20 mg/kg cocaine were augmented relative to animals given vehicle (ps<0.02) or 10 mg/kg cocaine (ps<0.04). At 0 mg/kg cocaine: N=12 WT and 4 dtg mice, 10 mg/kg cocaine: N=4 WT and 4 dtg mice, 15 mg/kg cocaine: N=4 WT and 5 dtg mice, 20 mg/kg cocaine: N=5 WT and 7 dtg mice were tested; +p<0.05, within genotype from vehicle.