Ingram D K, Garofalo P, Spangler E L, Mantione C R, Odano I, London E D
Molecular Physiology and Genetics Section, Nathan W. Shock Laboratories, National Institute on Aging, Baltimore, MD 21224.
Brain Res. 1992 May 15;580(1-2):273-80. doi: 10.1016/0006-8993(92)90954-8.
About 20 min prior to training in a shock-motivated 14-unit T-maze, young (3-4 months) and aged (24-25 months) male Fischer-344 rats were given s.c. injections of either saline or dizocilpine (MK-801, 0.02 or 0.04 mg/kg), a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor. The aged rats showed a dose-dependent impairment in maze performance. Deficiencies were manifested as increases in errors, in runtime from start to goal, and in the number and duration of shocks received. In contrast, young rats exhibited no detrimental effects of dizocilpine on maze performance. Analysis of [3H]glutamate binding in these rats revealed a marked age-related decline in NMDA receptor binding in hippocampus. A significant correlation was observed between errors in the maze and hippocampal [3H]-glutamate binding, but the correlation was positive, i.e., rats that made the most errors had the highest level of NMDA receptor binding. Thus, compared to young rats, aged rats were more sensitive to the behavioral effects of NMDA receptor antagonism and they showed a hippocampal loss of [3H]glutamate in binding, which may be related to the increased sensitivity to dizocilpine. The positive correlation between poor maze performance and NMDA receptor binding suggests that the behaviors assessed involve complex interactions between NMDA receptors and other neuronal systems in the hippocampus.
在以电击为动机的14单元T型迷宫中训练前约20分钟，给年轻（3 - 4个月）和老年（24 - 25个月）雄性Fischer - 344大鼠皮下注射生理盐水或地卓西平（MK - 801，0.02或0.04 mg/kg），后者是N - 甲基 - D - 天冬氨酸（NMDA）受体的非竞争性拮抗剂。老年大鼠在迷宫任务表现上呈现出剂量依赖性损伤。缺陷表现为错误增加、从起点到终点的运行时间增加以及接受电击的次数和时长增加。相比之下，年轻大鼠未表现出地卓西平对迷宫任务表现的有害影响。对这些大鼠的[3H]谷氨酸结合分析显示，海马体中NMDA受体结合存在明显的年龄相关下降。在迷宫中的错误与海马体[3H] - 谷氨酸结合之间观察到显著相关性，但这种相关性是正相关，即错误最多的大鼠具有最高水平的NMDA受体结合。因此，与年轻大鼠相比，老年大鼠对NMDA受体拮抗的行为效应更敏感，并且它们海马体中[3H]谷氨酸结合减少，这可能与对地卓西平的敏感性增加有关。迷宫任务表现不佳与NMDA受体结合之间的正相关表明，所评估的行为涉及海马体中NMDA受体与其他神经元系统之间的复杂相互作用。
