Zarrindast Mohammad-Reza, Torkaman-Boutorabi Anahita
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.
Eur J Pharmacol. 2003 Jul 18;473(1):19-25. doi: 10.1016/s0014-2999(03)01913-7.
In the present study, the effects of imipramine and/or alpha-adrenoceptor agents on naloxone-induced jumping in morphine-dependent mice were examined. In the first set of experiments, the drugs were used before naloxone injection, to test their effects on the expression of jumping. Administration of imipramine (10-60 mg/kg) 15 min before naloxone increased the number of jumping in mice. Injection of the alpha2-adrenoceptor agonist, clonidine (0.1 mg/kg), or alpha1-adrenoceptor agonist, phenylephrine (4 mg/kg), themselves neither altered naloxone-induced jumping nor influenced the imipramine response. The alpha2-adrenoceptor antagonist, yohimbine (4 mg/kg), itself but not the alpha1-adrenoceptor antagonist, prazosin (1 mg/kg), increased jumping and decreased the imipramine effect. In the second set of experiments, imipramine and/or the alpha-adrenoceptor drugs were injected during the development of morphine dependence. Imipramine (10-40 mg/kg) increased the development of dependence and increased jumping was seen. Clonidine did not influence the imipramine effect. Phenylephrine was lethal in combination with imipramine. Both yohimbine and prazosin decreased the effect of imipramine. Imipramine and phenylephrine but not clonidine, yohimbine or prazosin decreased locomotion. It is concluded an alpha2-adrenoceptor mechanism may be involved in the influence of imipramine on the expression and development of naloxone-induced withdrawal signs in mice.
在本研究中，检测了丙咪嗪和/或α-肾上腺素受体药物对纳洛酮诱发的吗啡依赖小鼠跳跃反应的影响。在第一组实验中，在注射纳洛酮之前使用这些药物，以测试它们对跳跃反应表达的影响。在纳洛酮注射前15分钟给予丙咪嗪（10 - 60毫克/千克）可增加小鼠的跳跃次数。注射α2-肾上腺素受体激动剂可乐定（0.1毫克/千克）或α1-肾上腺素受体激动剂去氧肾上腺素（4毫克/千克），本身既不改变纳洛酮诱发的跳跃反应，也不影响丙咪嗪的反应。α2-肾上腺素受体拮抗剂育亨宾（4毫克/千克）本身可增加跳跃次数并降低丙咪嗪的作用，但α1-肾上腺素受体拮抗剂哌唑嗪（1毫克/千克）则无此作用。在第二组实验中，在吗啡依赖形成过程中注射丙咪嗪和/或α-肾上腺素受体药物。丙咪嗪（10 - 40毫克/千克）增加了依赖的形成，并出现跳跃次数增加。可乐定不影响丙咪嗪的作用。去氧肾上腺素与丙咪嗪联合使用是致命的。育亨宾和哌唑嗪均降低了丙咪嗪的作用。丙咪嗪和去氧肾上腺素可降低运动能力，但可乐定、育亨宾或哌唑嗪则无此作用。得出结论：α2-肾上腺素受体机制可能参与了丙咪嗪对小鼠纳洛酮诱发的戒断症状的表达和形成的影响。
