ETHANOL AND AGING: CHOLINERGIC RELATIONSHIPS

本项目旨在研究乙醇(Etoh)和衰老的影响。 单独及联合应用对Fischer 344中枢胆碱能功能的影响 老鼠。纵向和同步实验都将检验基本的 饲养大鼠乙醇和/或衰老后胆碱能变化 库存维持在受控条件下。纵向研究 将在研究开始后的4、12、20和28个月使用大鼠， 鉴于同时进行的实验将使用相同年龄的大鼠 在两项单独研究中，不同年龄的大鼠将在 同样的时间。关于中枢神经系统敏感性的基本信息， 耐受性、身体依赖性、血液乙醇水平、乙醇清除和 病理将收集不同年龄段的大鼠急性给予乙醇或 短期(20天)或长期(6个月)慢性乙醇暴露(基础) 学习。其他研究将检查中枢胆碱能变化 发生于大脑皮层、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实验。这些 研究将测量大脑中乙酰胆碱(ACh)的水平和周转情况 被称为探索研究。接下来，Begavuirak将 研究将确定一部小说中与时间和强度相关的变化 行为快速反应时测量方法与神经化学方法的比较 措施。最后，我们将研究大脑ACh变化的原因。 在血浆胆碱、肝脏和脑的机制研究中 磷脂酰胆碱、突触体胆碱摄取与毒碱/烟碱 受体测量是在相同的条件下进行的 基础研究。基于可获得的文献和由 首席调查员，拟议的研究可能会提供有价值的 急慢性无水乙醇中枢性胆碱能变化的信息 暴露，在老化期间，在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.