Figure 3.

The extent of chronic analgesic tolerance after repeated exposure to SNC80 is attenuated in arrestin 2 KO mice. Arrestin 2 WT and KO mice were injected with equipotent doses of SNC80 (10 mg·kg⁻¹ for WT, and 3 mg·kg⁻¹ for KO) daily for 5 days, and tested daily, 45 min following each injection (A, n = 10 per WT group, n = 12 per KO group; two‐way RM ANOVA P < 0.05 time, genotype and interaction; ^* P < 0.05 as compared to WT‐SNC80 group). We also treated mice daily but only tested on the first and the fifth day of treatment (B, n = 8 per group; two‐way RM ANOVA, P < 0.05 genotype × time interaction, ^* P < 0.05 as compared to day 1, and as compared to WT‐SNC80 on day 5); or on the first and tenth day of treatment (C, n = 5–6 per group; two‐way RM ANOVA, P < 0.05 genotype and time). Unlike SNC80, tolerance to repeated ARM390 treatment was unaltered in arrestin 2 KO mice (D). WT and KO mice were injected with ARM390 (10 mg·kg⁻¹, p.o.) daily for 5 days, and tested 45 min following each injection. n = 6 per group, two‐way RM ANOVA P < 0.05 for time only.