ETHANOL AND AGING: CHOLINERGIC RELATIONSHIPS

本项目旨在研究乙醇（ETOH）和老化的影响 单独和组合对Fischer 344的中枢胆碱能功能的影响 大鼠 纵向和同步实验将检查基本的 从繁殖中获得的大鼠在ETOH和/或老化后的胆碱能变化 在受控条件下保存的库存。 纵向研究 将在研究开始后4、12、20和28个月使用大鼠， 而同时进行的实验将使用相同年龄的大鼠， 两项单独的研究，其中将在 同时还研究与讨论 关于中枢神经系统敏感性的基本信息， 耐受性、身体依赖性、血液ETOH水平、ETOH清除率和 将收集急性给予ETOH的不同年龄大鼠的病理学， 短期（20天）或长期（6个月）慢性ETOH暴露（基础） 问题研究 其他研究将检查中枢胆碱能变化是否 发生在大脑皮层、海马体、纹状体和脑干 在与基础研究相似的条件下对大鼠进行了研究。 这些 研究将测量大脑乙酰胆碱（ACh）的水平和周转率， 叫做探索研究 随后，Begavuirak Correlate 研究将确定小说中与时间和强度相关的变化， 行为快速反应时间测量，与神经化学 措施 最后，将检查大脑中ACh变化的原因 在机制研究中，血浆胆碱，肝脏和大脑 磷脂酰胆碱、突触体胆碱摄取和毒蕈碱/烟碱 受体测量是在与本发明相同的条件下进行的。 基础研究。 根据现有的文献和试点研究， 首席研究员，拟议的研究可能会提供有价值的 关于急性和慢性ETOH期间中枢胆碱能变化的信息 暴露，老化过程中，以及ETOH与 老化过程

This project is designed to study the effects of ethanol (ETOH) and aging alone and in combination on central cholinergic function of Fischer 344 rats. Both longitudinal and simultaneous experiments will examine basic cholinergic changes after ETOH and/or aging in rats obtained from breeding stock maintained under controlled conditions. The longitudinal studies will use rats at 4, 12, 20, and 28 months after the beginning of the study, whereas the simultaneous experiments will use the same aged rats timed for two individual studies in which rats of various ages will be studied at the same time. Basic information on central nervous system sensitivity, tolerance, physical dependence, blood ETOH levels, ETOH clearance and pathology will be gathered in rats of different ages given ETOH acutely or in short-term (20-day) or long-term (6-month) chronic ETOH exposure (Basic) studies. Other studies will examine whether central cholinergic changes occur in the cerebral cortex, hippocampus, corpus striatum, and brainstem of rats under conditions similar to those in the Basic studies. These studies will measure brain levels and turnover of acetylcholine (ACh) and are called Discovery studies. Following these, Begavuirak Correlate studies will determine time- and intensity-related changes in a novel behavioral fast reaction-time measure, in comparison with the neurochemical measures. Finally, the causes of ACh changes in the brain will be examined in Mechanism studies in which plasma choline, liver and brain phosphatidylcholine, synaptosomal choline uptake and muscarinic/nicotinic receptor measurements are followed under the same conditions as in the Basic study. Based upon available literature and pilot studies by the principal investigator, the proposed studies are likely to provide valuable information about central cholinergic changes during acute and chronic ETOH exposure, during aging, and during periods when ETOH interacts with the aging process.