Flood J F, Morley J E, La Reginna M
Geriatric Research Education and Clinical Center (GRECC), VA Medical Center, St. Louis, MO 63106.
Neurobiol Aging. 1993 Mar-Apr;14(2):159-66. doi: 10.1016/0197-4580(93)90092-p.
The P/8 line of the senescence accelerated mouse (SAM) model exhibits characteristics of aging early in its lifespan including an early onset of impaired learning and memory which becomes progressively worse with age. Age-matched controls of the R/1 line do not show impaired learning and memory. We report age-related changes in the drug dosage needed to improve 1 week retention in the P/8 but not R/1 line. The results indicate that 8-month-old P/8 mice show a reduced sensitivity to memory enhancing doses of cholinomimetics and an increased sensitivity to a serotonin antagonist compared to 4-month-old mice. By 12 months of age, improvement of retention required still higher doses of cholinomimetics and even lower doses of the serotonin antagonist. Higher doses of an opioid antagonist and a dopamine agonist were needed to improve retention in 12-month-old mice. A GABA antagonist and an alpha noradrenergic agonist improved retention at the same dose in mice 4, 8, and 12 months of age.
衰老加速小鼠（SAM）模型的P/8品系在其寿命早期就表现出衰老特征，包括学习和记忆受损的早期发作，且随着年龄增长逐渐恶化。R/1品系的年龄匹配对照组未表现出学习和记忆受损。我们报告了改善P/8品系而非R/1品系1周记忆保持所需药物剂量的年龄相关变化。结果表明，与4个月大的小鼠相比，8个月大的P/8小鼠对增强记忆剂量的拟胆碱药敏感性降低，对5-羟色胺拮抗剂敏感性增加。到12个月大时，改善记忆保持需要更高剂量的拟胆碱药和更低剂量的5-羟色胺拮抗剂。在12个月大的小鼠中，需要更高剂量的阿片类拮抗剂和多巴胺激动剂来改善记忆保持。γ-氨基丁酸拮抗剂和α-去甲肾上腺素能激动剂在4、8和12个月大的小鼠中以相同剂量改善记忆保持。
