Ribeiro Do Couto Bruno, Aguilar Maria A, Manzanedo Carmen, Rodríguez-Arias Marta, Miñarro Jose
Departamento de Psicobiología, Facultad de Psicología, Universidat de València, Avda. Blasco Ibañez, 21, 46010 Valencia, Spain.
Prog Neuropsychopharmacol Biol Psychiatry. 2004 Sep;28(6):1035-43. doi: 10.1016/j.pnpbp.2004.05.038.
Several studies have shown that the systemic administration of a variety of N-methyl-D-aspartate (NMDA) receptor antagonists can block the development or expression of conditioned place preference (CPP) induced by rewarding drugs such as morphine. In the present study, we examined the effects of different doses of two non-competitive NMDA receptor antagonists, MK-801 (0.1, 0.2 and 0.3 mg/kg) and memantine (2.5, 5, 10, 20 and 40 mg/kg), in CPP induced by 40 mg/kg of morphine in male mice. The CPP was carried out with an unbiased procedure in terms of initial spontaneous preference. Animals received the different doses of drugs in the conditioning sessions. MK-801 and memantine, at all doses used, produced neither place preference nor place aversion, but the higher doses of memantine (20 and 40 mg/kg) were able to completely block morphine-induced CPP. The present data show that the NMDA receptor antagonists MK-801 and memantine have no reinforcing properties but memantine is capable of preventing the acquisition of morphine-induced CPP. These results suggest that the development of morphine-induced CPP may be closely related to NMDA receptors and that the glutamatergic system can modulate opiate reward.
多项研究表明，全身给予多种N-甲基-D-天冬氨酸（NMDA）受体拮抗剂可阻断由吗啡等奖赏性药物诱导的条件性位置偏爱（CPP）的形成或表达。在本研究中，我们检测了两种非竞争性NMDA受体拮抗剂不同剂量（MK-801为0.1、0.2和0.3mg/kg，美金刚为2.5、5、10、20和40mg/kg）对雄性小鼠中由40mg/kg吗啡诱导的CPP的影响。CPP实验在初始自发偏爱方面采用无偏程序进行。动物在条件训练阶段接受不同剂量的药物。所用的所有剂量的MK-801和美金刚既未产生位置偏爱也未产生位置厌恶，但较高剂量的美金刚（20和40mg/kg）能够完全阻断吗啡诱导的CPP。目前的数据表明，NMDA受体拮抗剂MK-801和美金刚没有强化特性，但美金刚能够阻止吗啡诱导的CPP的形成。这些结果提示，吗啡诱导的CPP的形成可能与NMDA受体密切相关，并且谷氨酸能系统可调节阿片类奖赏。
