Figure 3. Pharmacological and genetic reversal of antinociception of Exoticin.
Reversal of antinociception by selective antagonists in tai-flick(A) and hot-plate(B). Groups of WT mice (n=6) received Exoticin (32mg/kg s.c) and the indicated antagonist. β- Funaltrexamine (β-FNA; 40 mg/kg s. c) and norbinaltorphimine (norBNI; 10 mg/kg s. c) were administered 24 h before agonist testing. Naltrindole (NTI; 0.5 mg/kg s. c), was administered 15 min before Exoticin. All antinociception testing was performed 15 min after the administration of Exoticin. Exoticin antinociception is insensitive to NTI and nor-BNI, whereas antinociception is antagonized by β-FNA (*P<0.05, compared with Vehicle + Exoticin group). Antinociception of Exoticin in WT, E11 KO, and E1/ E11 double KO mice were performed on groups of mice (n=5) for antinociception in the hot-plate (C) and tail flick assay (D) with Exoticin given subcutaneously. Exoticin played significant antinociceptive effects in WT mice (*P<0.05, compared with baseline), however, no antinociception was observed in E11 KO and E1/E11 KO mice, suggesting that the antinociceptive effect of Exoticin is mediated by the E11 MOR-1 variants (#P<0.05, E11 KO + Exoticin compared with WT + Exoticin group). All values are expressed as the mean ± SEM.