Fig. 1.
Effect of extended morphine dosing on the development of tolerance. Groups of CD-1 mice (n = 60) were s.c. injected with saline (control group, n = 20) or the indicated morphine dose (5, 10, 20, or 40 mg/kg) twice daily (0830 hours and 2030 hours). Each morphine group started with 60 mice. Ten mice were removed from each group on days 7, 15, 21, 28, 39, and 43 for determination of their respective morphine ED50 values as described in Methods and were then removed from the study. bid, twice daily.