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

We assessed the withdrawal intensity in acutely morphine-dependent mice usi ng a pretreatment with escalating doses of naloxone. All animals received a single dose of morphine (100 mg/kg) for the induction of acute opioid depe ndency. Group 1 (control) received three injections of normal saline and th en naloxone 0.8 mg/kg. Group 2 received increasing pretreatment doses of na loxone (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 3 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 gr oup 1 exhibited significantly more jumps after 0.8 mg/kg of naloxone as com pared with group 2. The number of jumps in response to naloxone between gro ups 1 and 2 and groups 2 and 3 was not significantly different. The results show that pretreatment with increasing naloxone doses significantly reduce d the withdrawal intensity as compared with the control group; whereas pret reatment with repeated low antagonist did not reduce it significantly. (C) 2000 Elsevier Science Inc. All rights reserved.