Milanés M V, Marín M T, Laorden M L
Department of Pharmacology, University School of Medicine, Murcia, Spain.
Can J Physiol Pharmacol. 2001 Oct;79(10):885-91.
The purpose of our study was to examine the effects of D1-and D2-dopamine receptors blockade on the changes in the ventricular content of catecholamines in rats withdrawn from morphine. Rats were given morphine by subcutaneous (s.c.) implantation of morphine pellets for 5 days. On the eighth day, morphine withdrawal was induced by s.c. administration of naloxone (1 mg/kg), and rats were killed 30 min later. Pretreatment with SCH 23390 (dopamine D1, D5 receptor antagonist) 15 min prior to naloxone administration suppressed some the behavioural signs of morphine withdrawal, whereas eticlopride (dopamine D2, D3, D4 receptor antagonist) did not. In addition, biochemical analysis indicate that SCH 23390 completely abolished the withdrawal-induced increase in noradrenaline and dopamine turnover in the right ventricle. By contrast, eticlopride did not block the hyperactivity of catecholaminergic neurons in the heart during morphine withdrawal. These data suggest that the hyperactivity of catecholaminergic neurons in the heart during morphine withdrawal is dependent upon D1 dopamine receptor activation. In addition, our results exclude the involvement of D2 dopamine receptors.
我们研究的目的是检验D1和D2多巴胺受体阻断对吗啡戒断大鼠心室儿茶酚胺含量变化的影响。通过皮下植入吗啡丸粒给大鼠注射吗啡,持续5天。在第8天,通过皮下注射纳洛酮(1mg/kg)诱导吗啡戒断,30分钟后处死大鼠。在注射纳洛酮前15分钟用SCH 23390(多巴胺D1、D5受体拮抗剂)预处理可抑制吗啡戒断的一些行为体征,而多潘立酮(多巴胺D2、D3、D4受体拮抗剂)则不能。此外,生化分析表明,SCH 23390完全消除了戒断引起的右心室去甲肾上腺素和多巴胺周转率的增加。相比之下,多潘立酮并未阻断吗啡戒断期间心脏中儿茶酚胺能神经元的活动亢进。这些数据表明,吗啡戒断期间心脏中儿茶酚胺能神经元的活动亢进依赖于D1多巴胺受体激活。此外,我们的结果排除了D2多巴胺受体的参与。