Fig. 3.

Suppression of withdrawal behavior by 6β-naltrexol in juvenile mice. (A) 6β-Naltrexol prevents a dependence behavior, withdrawal jumping, when delivered in combination with morphine. Total jumps were counted over a period of 15 minutes starting immediately after the injection of naloxone to induce withdrawal. We used a two-concentration ramping procedure for the morphine injections with commensurate ramping of 6β-naltrexol (see Materials and Methods). Data are plotted using the higher of the two drug concentrations. Asterisks indicate a significant difference compared with morphine-treated animals with no 6β-naltrexol; *P < 0.05; **P < 0.01. Numbers below the data-points indicate n values. (B) Kaplan-Meier plots indicating a progressive delay in time to first jump with increasing 6β-naltrexol. Note that all concentrations of 6β-naltrexol result in a significant delay relative to morphine alone (P < 0.05 by log-ratio test). (C) Inhibition of weight gain by morphine is alleviated by 6β-naltrexol. The mass of each mouse was determined before and after the 6-day morphine dosing schedule and the percentage weight change was determined. Asterisk indicates significant difference from animals that received morphine but no (“0”) 6β-naltrexol (P < 0.05). n = the same as indicated in (A). In (C), drug concentration is reported as a ratio of 6β-naltrexol to morphine to emphasize the combination treatment.