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 ED₅₀ 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. (C) 2000 Elsevier Science Inc.