Fig. 4.

Either fewer μ receptors or the absence of β-arrestin2 diminishes psychomotor stimulation by morphine. (A) Morphine (10 mg/Kg s.c.) stimulated locomotor activity in WT mice averaged over the 3 days of conditioning (*p < 0.001, n = 8, paired t-test compared to saline). This effect was not seen in μ-/- mice in which morphine had no effect on the averaged locomotion (n = 7). By contrast, morphine stimulated locomotion in β-arr2-/- mice (*p < 0.01, paired t-test, n = 8), but the average distance travelled was less than that of WT mice (#p < 0.01, unpaired t-test). (B) Morphine (10 mg/Kg) was without effect on distance travelled by μ-/- mice (n = 7) on all days of conditioning. (C) Morphine (3 mg/Kg) administration to WT mice (n = 8) showed modest increase on distance travelled on days 2 and 3 of conditioning (*p < 0.05, two-way ANOVA, post hoc Bonferroni test). (D) At a higher dose morphine (10 mg/Kg s.c.) increased distance travelled on all 3 days and this effect exhibited sensitization (*p < 0.0001, two-way ANOVA, post hoc Bonferroni test; n = 8). (E) The locomotor effect of morphine (10 mg/Kg) was diminished in μ+/- mice (n = 8) and there was no sensitisation (*p < 0.01 on day 1, p < 0.0001 on day 2 and 3, two-way ANOVA, post hoc Bonferroni test). (F) A higher dose of morphine (30 mg/Kg) enhanced locomotion, but there was no effect of time over the 3 days of conditioning (*p < 0.0001, two-way ANOVA, post hoc Bonferroni test; n = 8). Morphine (3 mg/Kg) had no effect on distance travelled by β-arr2-/- mice on days 1-3 (n = 8). (G) At a higher dose morphine (10 mg/Kg) increased distance travelled by β-arr2-/- mice on all 3 days and this effect exhibited sensitization (*p < 0.01 on day 1, p < 0.0001 on day 2 and 3, two-way ANOVA, post hoc Bonferroni test; n = 8).