Kusztos R D, Ingram D K, Spangler E L, London E D
Neuroimaging and Drug Action Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
Neurobiol Aging. 1996 May-Jun;17(3):453-7. doi: 10.1016/0197-4580(96)00032-2.
Previous studies have suggested that aging is associated with impaired behavioral performance and with decrements of N-methyl-D-aspartate (NMDA) receptors in the rat hippo-campus. Other studies have indicated that chronic treatment with nimodipine, a Ca2+ channel antagonist, prevents the age-related decline in performance by rats in behavioral tasks. Therefore, we tested whether nimodipine altered binding of [3H]CGS 19755 to hippocampal NMDA receptors in rats whose performance on a 14-unit T maze had been tested previously (14). No significant age difference was observed in [3H]CGS 19755 binding in hippocampi from old Fischer-344 rats (27 months) as compared with mature but not senescent rats (9 months); however, old rats that received chronic treatment with a low dose of nimodipine (20 mg pellets implanted subcutaneously twice during 70 days of treatment) showed higher levels of binding. A high dose of nimodipine (40 mg pellets implanted by the same route and at the same times as the low dose) was without effect on [3H]CGS 19755 binding, although aged rats given this treatment performed better in the maze than rats that received no nimodipine or the low dose. In a second experiment comparing hippocampi of young (4 months) and old (24 months) rats, saturation studies confirmed the lack of an age difference in [3H]CGS 19755 binding. The findings suggest that neither the age-related decline in maze performance nor the enhancement of behavior by nimodipine depend upon changes in hippocampal NMDA receptors.
先前的研究表明，衰老与行为表现受损以及大鼠海马中N-甲基-D-天冬氨酸（NMDA）受体数量减少有关。其他研究表明，用钙通道拮抗剂尼莫地平进行长期治疗可防止大鼠在行为任务中的表现出现与年龄相关的下降。因此，我们测试了尼莫地平是否会改变先前已测试过在14单元T迷宫中表现的大鼠海马中[3H]CGS 19755与NMDA受体的结合。与成熟但未衰老的大鼠（9个月）相比，在老年Fischer-344大鼠（27个月）的海马中，未观察到[3H]CGS 19755结合存在显著的年龄差异；然而，接受低剂量尼莫地平长期治疗的老年大鼠（在70天治疗期间皮下植入两次20 mg药丸）显示出更高的结合水平。高剂量的尼莫地平（通过与低剂量相同的途径和相同时间植入40 mg药丸）对[3H]CGS 19755结合没有影响，尽管接受这种治疗的老年大鼠在迷宫中的表现比未接受尼莫地平或低剂量的大鼠更好。在第二项比较年轻（4个月）和老年（24个月）大鼠海马的实验中，饱和研究证实了[3H]CGS 19755结合不存在年龄差异。这些发现表明，与年龄相关的迷宫表现下降和尼莫地平对行为的增强作用均不依赖于海马NMDA受体的变化。
