A method of reducing the opioid withdrawal intensity using progressively increasing doses of naloxone

We assessed the withdrawal intensity in acutely morphine-dependent mice using a pretreatment with escalating doses of naloxone. All animals received a single dose of morphine (100 mg/kg) for the induction of acute opioid dependency. Group 1 (control) received three injections of normal saline and then naloxone 0.8 mg/kg. Group 2 received increasing pretreatment doses of naloxone (0.1, 0.2, and 0.4 mg/kg) and a challenge dose of 0.8 mg/kg. Group 3 received three injections of naloxone 0.1 mg/kg and a challenge dose of 0.8 mg/kg. Groups 4 and 5 were used to verify whether ED(50) found in previous studies was comparable with values obtained in the current experiments. The withdrawal intensity was determined by the number of jumps. The mice of group 1 exhibited significantly more jumps after 0.8 mg/kg of naloxone as compared with group 2. The number of jumps in response to naloxone between groups 1 and 2 and groups 2 and 3 was not significantly different. The results show that pretreatment with increasing naloxone doses significantly reduced the withdrawal intensity as compared with the control group; whereas pretreatment with repeated low antagonist did not reduce it significantly.