Figure 4.

The reduced psychomotor effect of morphine in β-arr2−/− mice is similarly returned to +/+ levels by inhibiting JNK. These data are presented in the same format as in Figure 2 showing both the distance traveled over time in the line graphs and total locomotion in the accompanying bar graphs (ai) A 3-day protocol of successive morphine (10 mg/kg s.c.) treatment of β-arr2+/+ mice resulted in an enhanced locomotor response to the same dose of morphine by day 3 (p<0.01 day 1 vs day 3, F_1,5=16.972). (aii) Conversely, similarly treated β-Arr2−/− mice showed no such increase (p=0.41 day 1 vs day 3, F_1,6=0.765). (bi) Administration of SP6 (30 mg/kg i.p.), 60 min before each morphine injection had no effect on the locomotor sensitization in β-arr2+/+ mice (p<0.05 day 1 vs day 3, F_1,9=6.866) but reversed the lack of sensitization in the β-arr2−/− mice (p<0.05 day 1 vs day 3, F_1,5=6.989) to wild-type levels. (c, d) Mice treated with fentanyl (0.2 mg/kg s.c.) showed locomotor sensitization (p<0.001 day 1 vs day 3, F_1,23=63.235), that was unaffected by β-arrestin 2 deletion or SP6 administration (vehicle; p=0.93 day × genotype, F_1,23=0.007, SP6; p=0.25 day × genotype × injection, F_1,23=1.382). ^*p<0.05, ^**p<0.01.