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.