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.

TreatmentED50 Value (95% CL)Potency Ratio (95% CL)
Vehicle + meperidine15.1 mg/kg (11.3, 20.1)
Meperidine + meperidine41.9 mg/kg (37.1, 47.3)vs. vehicle + meperidine2.73 (2.29, 3.23)
Vehicle + fentanyl0.089 mg/kg (0.08, 0.1)
Fentanyl + fentanyl0.292 mg/kg (0.26, 0.33)vs. vehicle + fentanyl3.50 (3.09, 3.92)
Vehicle + morphine3.5 mg/kg (2.9, 4.2)
Morphine + morphine16.3 mg/kg (13.4, 19.8)vs. vehicle + morphine4.55 (3.77, 5.69)
Vehicle + DAMGO11.3 ng/kg (10.3, 12.3)
DAMGO + DAMGO28.3 ng/kg (25.7, 36.0)vs. vehicle + DAMGO2.42 (2.13, 2.73)