Pharmacological studies on dementia

本研究旨在建立一种可用于评价促智药作用的痴呆模型。1.大鼠工作记忆在3-panel runway装置中采用重复获取程序进行评估，东莨菪碱或AF 64 A给药、海马或嗅球损毁以及脑缺血均显著损害大鼠的工作记忆。毒扁豆碱和具有中枢胆碱能活性的促智药如米那普林、阿米定、四氢氨基吖啶、WEB 1881等均能明显改善东莨菪碱或海马损伤所致的工作记忆障碍。而不是S-腺苷-L-甲硫氨酸（SAM）。2.嗅球切除可明显损害大鼠在3水平开放装置中的延迟匹配杠杆定位任务，毒扁豆碱可逆转这种损害。3.作为一种体外脑缺血模型，将大鼠海马和皮质切片（450 μ m厚）在缺氧+低血糖溶液中孵育20分钟，并在接下来的6小时内洗出。然后<14>在45分钟的时间内测量30 mM KCl诱导的组织的β-C-2-脱氧葡萄糖（2-DG）摄取。缺氧+低血糖20 min后，脑片2-DG摄取减少。降低腺苷酸环化酶活性、肌醇磷酸周转或钙离子内流可有效保护脑葡萄糖利用率的降低。

It was attempted to establish dementia models useful for evaluating the effect of nootropic drugs in rats.1.Working memory of the rat assessed in a 3-panel runway apparatus, using a repeated acquisition procedure, was significantly impaired by an administration of scopolamine or AF64A, lesioning of the hippocampus or olfactory bulb and cerebral ischemia. The impairment of working memory induced by either scopolamine or hippocampal lesions was significantly ameliorated by physostigmine and many nootropic drugs possessing central cholinergic activity, such as minaprine, amiridin, tetrahydroaminoacridine, WEB1881 and so on, but. not by S-adenosyl-L-methionine(SAM). In contrast, the memory impairment induced by cerebral ischemia was ameliorated not merely by these nootropic drugs but also by SAM.2.The delayed matching to lever location task of rats in a 3-level aperant apparatus was markedly impaired by olfactory bulbectomy and this impairment was reversed by physostigmine.3.As an in vitro model of cerebral ischemia, rat hippocampus and cortex slices (450mum thick) were incubated for 20 minutes in a hypoxia + hypoglycemia solution and washed out for the next 6 hours. and then 3OmM KCI-induced ^<14>C-2-deoxyglucose(2-DG) uptake of the tissue was measured for a period of 45 minutes. The 2-DG uptake of these slices decreased after being subjected to hypoxia + hypoglycemia for 20 minutes. This decrease in the cerebral glucose utilization was effectively protected by the treatments reducing the adenylate cyclase activity, inositol hosphate turnover or the influx of Ca ion into the cell.