Fig. 6.

Effect of the D4-selective dopamine receptor antagonist L-745,870 on amphetamine-mediated locomotor activity. Coloboma (A) and control mice (B) were treated with saline or 4 mg/kg amphetamine and challenged with L-745,870. Compared to vehicle treatment, amphetamine significantly increased locomotor activity in control mice (***p < 0.001) but significantly reduced locomotor activity in coloboma mice (**p<0.005). There was a significant effect of genotype (F_1,12 = 54.9, p < 0.0001) and dose of L-745,870 (F_3,36 = 4.1, p < 0.05) on amphetamine-mediated locomotor activity whereby L-745,870 reduced amphetamine-mediated locomotor activity in both control and coloboma mice overall. Post hoc analyses demonstrated a significant decrease in amphetamine-mediated locomotor activity after treatment with 1 mg/kg L-745,870 in coloboma mice (*p < 0.05). There was a significant effect of genotype after treatment with L-745,870 alone (F_1,12 = 55.0, p < 0.0001) without significant effect of dose or genotype × dose interactions. However, post hoc analyses demonstrated a significant reduction in locomotor activity of coloboma mice at 5 mg/kg L-745,870 (*p < 0.05). Data are beam breaks accumulated in 1 hr following drug treatment and are expressed as mean ± SEM (n = 7/genotype/dose).