Vanderschuren L J, Schoffelmeer A N, De Vries T J
Research Institute Neurosciences Vrije Universiteit, Department of Pharmacology, Faculty of Medicine, Amsterdam, The Netherlands.
Life Sci. 1997;61(26):PL 427-33. doi: 10.1016/s0024-3205(97)01031-x.
Intermittent morphine pretreatment (10 mg/kg/day for 14 days) induced long-lasting (one month post-treatment) sensitization to the locomotor effects of morphine and amphetamine in rats. Co-administration of the non-competitive NMDA-receptor antagonist dizocilpine (MK-801) (0.1 mg/kg) with morphine did not prevent the development of long-term behavioural sensitization. However, this dose of MK-801 did cause long-term sensitization to its own locomotor effects. Co-administration of 0.25 mg/kg MK-801 with morphine caused death in 60% of the animals. In the animals that survived MK-801 plus morphine pretreatment, neither short-term (3 days) nor long-term morphine-induced sensitization was observed. MK-801 alone (0.25 mg/kg/day for 14 days) induced short-term cross-sensitization to morphine. Thus, the development of long-term morphine-induced locomotor sensitization could only be prevented by a dose of MK-801 that yields a lethal combination with morphine. In addition, MK-801 induced sensitization to its own locomotor effects and cross-sensitization to morphine. These findings seriously question whether MK-801 can be used to study the development of morphine-induced behavioural sensitization.
间歇性吗啡预处理（10毫克/千克/天，持续14天）可诱导大鼠对吗啡和苯丙胺的运动效应产生长期（治疗后一个月）的敏感性。将非竞争性NMDA受体拮抗剂地佐环平（MK-801）（0.1毫克/千克）与吗啡联合使用并不能阻止长期行为敏感性的发展。然而，这个剂量的MK-801确实会导致对其自身运动效应的长期敏感性。将0.25毫克/千克的MK-801与吗啡联合使用会导致60%的动物死亡。在MK-801加吗啡预处理后存活的动物中，未观察到短期（3天）或长期吗啡诱导的敏感性。单独使用MK-801（0.25毫克/千克/天，持续14天）可诱导对吗啡的短期交叉敏感性。因此，只有与吗啡产生致死组合剂量的MK-801才能阻止长期吗啡诱导的运动敏感性的发展。此外，MK-801可诱导对其自身运动效应的敏感性以及对吗啡的交叉敏感性。这些发现严重质疑MK-801是否可用于研究吗啡诱导的行为敏感性的发展。
