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Acute morphine withdrawal syndrome was induced in adult male rats by s.c. administration of morphine (10 mg/kg) and naloxone (1 mg/kg) at 8.00 a.m. withdrawal signs were observed throughout the following two hours. Atropine (2 mg/kg) administered 1 h before drug treatment was also used. To evaluate the effects of clonidine, mianserin and cyproheptadine, rats were pre-treated with each drug (1, 5, 10 mg/kg) 30 min before s.c. administration of morphine and naloxone. Finally, mianserin was also administered (5, 10 mg/kg) 30 min before morphine (10 mg/kg) and naloxone (1 mg/kg). Effectiveness of mianserin and clonidine was monitored in terms of level of withdrawal signs before and after drug administration. According to the effects of pre-treatment, the half-maximal effective dose (ED50) of the drugs was estimated and the dose producing 50% of maximal effect (ED50) was observed. All three drugs at ED50s significantly reduced the intensity of the observed withdrawal signs (P < 0.01). Cyproheptadine at ED50 (20 mg/kg) failed to attenuate the withdrawal signs. Mianserin at ED50 (5 mg/kg) reduced the withdrawal signs at 1 h after drug administration (P < 0.05), but at ED50 (10 mg/kg) the reduction of withdrawal signs did not reach the level of significance. However, clonidine at ED50 (5 mg/kg) reduced the withdrawal signs of morphine withdrawal up to 3 h after its administration (P < 0.01) but the effects of higher doses (10 and 20 mg/kg) of the drug

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