TABLE 1.
Summary of effects of the four KOR agonists on behaviors and KOR phosphorylation in male CD-1 mice and KOR internalization in male KOR-tdT mice.
| U50,488H | MOM-SalB | nalfurafine | 42B | |
| Analgesia in the formalin test (A50 value) | Yes (0.58 mg/kg) |
Yes (17.0 μg/kg) |
Yes (5.8 μg/kg) |
Yes (2.08 mg/kg) |
| Inhibition of 48/80-induced scratch (A50 value) | Yes (2.07 mg/kg) |
Yes (70.2 μg/kg) |
Yes (8.0 μg/kg) |
Yes (2.95 mg/kg) |
| CPA (doses used) | Yes (0.25–10 mg/kg) |
Yes (10–300 μg/kg) |
No (0.25–20 μg/kg) |
No (1, 3, 5 mg/kg) |
| Motor incoordination (dose(s) used) | Yes (5 mg/kg) |
Yes (200 μg/kg) |
Slight effect (20 μg/kg) |
Yes (3, 5 mg/kg) |
| Inhibition of novelty-induced hyper-locomotion (dose used) | Yes (5 mg/kg) |
Yes (200 μg/kg) |
No (20 μg/kg) |
Yes (5 mg/kg) |
| KOR phosphorylation in the brain (dose used) | Yes (5 mg/kg) |
Yes (200 μg/kg) |
No (20 μg/kg) |
Yes (5 mg/kg) |
| KOR internalization in the VTA (dose used) | Yes (5 mg/kg) |
Yes (200 μg/kg) |
No (20 μg/kg) |
Yes (5 mg/kg) |
Results of CPA, motor incoordination, hypolocomotion, KOR phosphorylation, and KOR internalization were obtained at doses (in parentheses) that produce maximal analgesic effect in the formalin test and maximal inhibitory effects on compound 48/80-induced scratch behavior [Reproduced from Chen et al. (2022a)].