Zarrindast Mohammad-Reza, Asgari-Afshar Ali, Sahebgharani Mousa
Department of Pharmacology, School of Medicine and Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran.
Behav Pharmacol. 2007 May;18(3):177-84. doi: 10.1097/FBP.0b013e32813c5462.
In this study, the effects of dopamine receptor antagonists and nitric oxide agents on morphine-induced sensitization in the formalin test in mice have been investigated. Repeated daily intraperitoneal administration of morphine (30 mg/kg for 3 days) followed by a 11-day wash out period increased morphine-induced antinociception in the formalin test, which may be due to sensitization. The antinociceptive response to higher doses of morphine (6 and 9 mg/kg) but not 3 mg/kg was significantly increased in sensitized animals compared with control groups. Pretreatment of animals with an opioid receptor antagonist, naloxone (4 mg/kg), during repeated administration of morphine, attenuated the morphine-induced sensitization. In the second part of the study, the animals received SCH23390 (D1 receptor antagonist), sulpiride (D2 receptor antagonist), L-Arg (nitric oxide precursor) and NG-nitro-L-Arg methylester (nitric oxide synthase inhibitor) during repeated morphine administration, to evaluate the role of dopamine receptor antagonists and nitric oxide agents in this phenomenon. Pretreatment of animals with NG-nitro-L-Arg methylester (20 mg/kg) and sulpiride (100 mg/kg) during morphine sensitization decreased the antinociceptive response to higher doses of morphine in the formalin test. It is concluded that D2 dopamine receptor and nitric oxide mechanisms may be involved at least partly in morphine-induced sensitization in the formalin test.
在本研究中，已对多巴胺受体拮抗剂和一氧化氮制剂对小鼠福尔马林试验中吗啡诱导的敏化作用进行了研究。每天重复腹腔注射吗啡（30毫克/千克，共3天），随后经过11天的洗脱期，在福尔马林试验中增加了吗啡诱导的抗伤害感受，这可能是由于敏化作用。与对照组相比，致敏动物对较高剂量吗啡（6和9毫克/千克，但不是3毫克/千克）的抗伤害感受反应显著增加。在重复注射吗啡期间，用阿片受体拮抗剂纳洛酮（4毫克/千克）对动物进行预处理，可减弱吗啡诱导的敏化作用。在研究的第二部分，在重复注射吗啡期间，给动物注射SCH23390（D1受体拮抗剂）、舒必利（D2受体拮抗剂）、L-精氨酸（一氧化氮前体）和NG-硝基-L-精氨酸甲酯（一氧化氮合酶抑制剂），以评估多巴胺受体拮抗剂和一氧化氮制剂在这一现象中的作用。在吗啡致敏期间，用NG-硝基-L-精氨酸甲酯（20毫克/千克）和舒必利（100毫克/千克）对动物进行预处理，可降低福尔马林试验中对较高剂量吗啡的抗伤害感受反应。得出的结论是，D2多巴胺受体和一氧化氮机制可能至少部分参与了福尔马林试验中吗啡诱导的敏化作用。
