Neuroscience Research Institute, Department of Neurobiology, School of Basic Medical Sciences, Peking University, 38 Xueyuan Road, 100083, Beijing, People's Republic of China.
Neurochem Res. 2011 Mar;36(3):383-91. doi: 10.1007/s11064-010-0342-9. Epub 2010 Dec 9.
Drug addiction, as well as learning and memory, share common mechanisms in terms of neural circuits and intracellular signaling pathways. In the present study, the role of N-methyl-D-aspartate (NMDA) receptors, particularly those containing NR2B subunits, in morphine-induced conditioned place preference (CPP) and Morris water maze (MWM) learning and memory task was investigated. CPP was used as a paradigm for assessing the rewarding effect of morphine, and MWM was used to measure spatial learning and memory in male Sprague-Dawley rats. We found that ifenprodil, an antagonist highly selective for NR2B-containing NMDA receptors, dose-dependently blocked the development, maintenance and reinstatement of morphine-induced CPP, without evident impairment of the acquisition and retrieval of spatial memory in the MWM task. However, the consolidation of spatial memory was disrupted by a high dose (10 mg/kg) of ifenprodil. These results clearly demonstrate that NR2B-containing NMDA receptors are actively involved in addiction memory induced by morphine conditioning, but not in the acquisition and retrieval of spatial learning and memory. In conclusion, NR2B-containing NMDA receptors can be considered potential targets for the treatment of opiate addiction.
药物成瘾与学习和记忆在神经回路和细胞内信号通路方面具有共同的机制。本研究旨在探讨 N-甲基-D-天冬氨酸（NMDA）受体，特别是含有 NR2B 亚基的 NMDA 受体，在吗啡诱导的条件性位置偏爱（CPP）和 Morris 水迷宫（MWM）学习和记忆任务中的作用。CPP 被用作评估吗啡奖赏效应的范例，MWM 被用于测量雄性 Sprague-Dawley 大鼠的空间学习和记忆。我们发现，ifenprodil（一种高度选择性的 NR2B 包含 NMDA 受体拮抗剂）剂量依赖性地阻断了吗啡诱导的 CPP 的发展、维持和再现，而对 MWM 任务中空间记忆的获得和检索没有明显的损害。然而，高剂量（10mg/kg）的 ifenprodil 破坏了空间记忆的巩固。这些结果清楚地表明，NR2B 包含的 NMDA 受体积极参与吗啡条件作用诱导的成瘾记忆，但不参与空间学习和记忆的获得和检索。总之，NR2B 包含的 NMDA 受体可被视为治疗阿片类成瘾的潜在靶点。
