DRUGS OF ABUSE STUDIED THROUGH CHICK BRAIN MEMORY SYS

主要目的是：（1）开发和测试一个小鸡学习系统 用于行为药理学神经化学研究 阿片类药物的作用机制，以及（2）使用该系统来阐明 阿片类药物在中枢神经系统中的作用与学习和记忆 为了增加对药物作用机制的了解， 虐待 小鸡1-3天postthatch有许多优势， 研究，但迄今为止，很少有研究报告阿片类药物的影响 学习和记忆的能力 更精确地发现 阿片类药物影响学习和记忆本身是有价值的， 这也是阿片类药物依赖性发展的一个模式。 同时进行的具体研究领域是： 以下内容： 1. 分析鸡脑的主要解剖区域， 主要阿片类药物和阿片受体;即，使用高性能 液相色谱分析主要代谢产物的 3母体阿片分子，并使用高度 对三种主要类型的阿片受体有选择性。 结果 将有助于指导和解释行为药理学 使用阿片类药物对小鸡进行的实验（下文2）。 2. 测试3个主要类别的阿片类药物的遗忘效果 在某些大脑部位，并调查记忆的哪个阶段（S） 形成受到3个主要类别的遗忘阿片类药物的影响。 阿片类药物的选择将部分取决于已知的 对哺乳动物有效，部分是因为我们绘制了阿片类药物的图谱， 和阿片受体（上文1）。 3. 研究神经化学作用和时间过程， 一些阿片类药物被发现是有效的遗忘剂。 作为主要 焦点，测试LTM形成对蛋白质合成的依赖性 通过使用体外方法：测试阿片类药物是否 药物显著减少蛋白质的合成， 由小鸡的一次试验训练引起的。 我们假设 大脑的测量结果将与行为端非常接近， 点，即，在适当条件下给予阿片类药物 产生健忘症，会大大减少正常训练- 诱导蛋白质合成增加。 此外，确定 鸡脑中主要阿片类药物的半衰期;将其与时间进行比较- 这些阿片类药物对记忆的影响曲线， 并更好地了解相关机制。 这个项目是基于一个组合的方法和专业知识， 鸡的一次性辨别学习的PI，阿片类药物 和阿片系统的行为实验，和神经化学 研究记忆形成机制的技术， 阿片类药物的作用。

The main aims are (1) to develop and test a chick learning system for behavioral-pharmacological-neurochemical studies of effects an mechanisms of opioids, and (2) to use this system to elucidat actions of opioids in the CNS in relation to learning and memory in order to increase understanding of the mechanisms of drug abuse. Chicks 1-3 days posthatch have many advantages for such research, but to date few studies have reported effects of opioids on learning and memory in th chick. Finding more precisely how opioids affect learning and memory would be valuable in itself and also as a model for the development of dependence on opiates. Specific lines of research to be undertaken in parallel are the following: 1. Analyze major anatomical regions of chick brain for several main opioids and for opioid receptors; i.e., use high performance liquid chromatography to analyze major metabolic products of the 3 parent opioid molecules, and use radioligands that are highly selective for the 3 major types of opioid receptors. The results will help to guide and interpret behavioral-pharmacological experiments using opioid agents with chicks (2 below). 2. Test opioids of the 3 main classes for amnestic effectiveness at certain brain sites, and investigate which stage(s) of memory formation are affected by amnestic opioids of the 3 main classes. Choice of opioid agents will be determined in part by those known to be effective in mammals and in part by our mapping of opioids and opioid receptors (1 above). 3. Investigate the neurochemical actions and time courses for some opioids found to be effective amnestic agents. As a major focus, test the dependence of LTM formation on protein synthesis by using an in vitro approach: test whether opioid amnestic agents reduce significantly the synthesis of proteins that are induced by one-trial training in the chick. We hypothesize that the brain measurements will closely parallel the behavioral end points, i.e., the opioid agents, given under appropriate conditions to produce amnesia, will significantly reduce the normal training- induced increase in synthesis of proteins. Also, determine the half-life of major opioids in chick brain; compare these with time- effect curves of these opioids on memory to see how they are related and to better understand the mechanisms involved. This project is based on a combination of mehods and expertise of the PIs with one-trial discrimination learning in the chick, opioids and opioid systems in behavioral experiments, and neurochemical techniques to study mechanisms of memory formation and of opioid effects.