TABLE 1.
Opioid antinociceptive tolerance using an 8-h model
Mice were either repeatedly administered vehicle over 8 h and then challenged with the opioid (vehicle + opioid) or repeatedly administered opioid over 8 h and then challenged with the opioid (opioid + opioid) as well as vehicle intracerebroventricularly. Meperidine (40 mg/kg s.c.), morphine (10 mg/kg s.c.), and fentanyl (0.2 mg/kg s.c.) were administered every 2 h for a total of four injections, with test doses of the opioid administered 2 h after the last injection. DAMGO (25.7 ng/kg i.c.v.) was administered every 1 h for a total of eight injections, with test doses of DAMGO administered 1 h after the last injection. All opioid + opioid groups received vehicle intracerebroventricular injections before the opioid test doses. Thirty minutes (20 min for DAMGO) after test doses were administered, tail-immersion latencies were determined for construction of dose-response curves as well as calculation of ED50 values and potency ratios.
| Treatment | ED50 Value (95% CL) | Potency Ratio (95% CL) | |
|---|---|---|---|
| Vehicle + meperidine | 15.1 mg/kg (11.3, 20.1) | ||
| Meperidine + meperidine | 41.9 mg/kg (37.1, 47.3) | vs. vehicle + meperidine | 2.73 (2.29, 3.23) |
| Vehicle + fentanyl | 0.089 mg/kg (0.08, 0.1) | ||
| Fentanyl + fentanyl | 0.292 mg/kg (0.26, 0.33) | vs. vehicle + fentanyl | 3.50 (3.09, 3.92) |
| Vehicle + morphine | 3.5 mg/kg (2.9, 4.2) | ||
| Morphine + morphine | 16.3 mg/kg (13.4, 19.8) | vs. vehicle + morphine | 4.55 (3.77, 5.69) |
| Vehicle + DAMGO | 11.3 ng/kg (10.3, 12.3) | ||
| DAMGO + DAMGO | 28.3 ng/kg (25.7, 36.0) | vs. vehicle + DAMGO | 2.42 (2.13, 2.73) |