EFFECT OF CNS LESIONS ON DRUG ACTION

兔瞬膜的巴甫洛夫条件反射 反应，角膜第六神经反射，通常被认为是 提供了一个可靠的测量联想学习和记忆。 该模型系统将用于识别解剖路径 以及参与学习和记忆的神经化学系统， 研究行为和神经化学过程， 药物可以改变学习和记忆。 实验将 在三个主要目标下进行， 这些基本过程的额外知识来源的方法。 目标1将检查那些被认为是 在收购中发挥重要或关键作用，和/或 条件反应的表现。 这将包括一个彻底的 对最近提出的小脑是必不可少的建议的审查 通过使用皮质（第六叶）学习运动行为 和小脑皮质下（间位）病变， 由利多卡因输注产生的可逆性损伤。 的 然后将采用可逆性损伤来确定是否 插入语对于条件句的习得是必不可少的 应答 这些可逆性病变也将用于识别 条件反应和非条件反应的其他途径。 目的 2将检查3 H-和14 C-2-脱氧-D-葡萄糖的摄取， 采用定量放射自显影的双同位素技术， 识别大脑中不同的激活区域， 有条件和无条件的连续呈现 刺激和是否这种神经元异突触促进 活动可以预测随后的学习速度。 比如说， 一些药物对学习的影响似乎是次要的， 它们增加或减少这种异突触的能力 便利化 AIM 3将使用脑室内注射药物 激活或抑制cAMP系统，以检查 这第二信使在学习和药物的影响， 学习 这样的知识应该提供线索， 与人类学习和记忆障碍有关的神经系统 (e.g.,阿尔茨海默氏症），并确定药物， 有效地治疗。

Pavlovian conditioning of the rabbit's nictitating membrane response, a corneal-VIth nerve reflex, is generally agreed to provide a reliable measure of associative learning and memory. This model system will be used to identify the anatomical pathways and neurochemical systems involved in learning and memory and to examine the behavioral and neurochemical processes through which drugs act to alter learning and memory. Experiments will be carried out under three major aims that will provide converging approaches to origin additional knowledge of these basic processes. Aim 1 will examine those brain regions that have been suggested to play an essential or important role in the acquisition and/or performance of conditioned responses. This will include a thorough examination of recent proposals that the cerebellum is essential for the learning of motor acts by the use of cortical (VIth lobe) and subcortical (interpositus) lesions of the cerebellum and from reversible lesions produced by infusion of lidocaine. The reversible lesion will then be employed to establish whether interpositus is essential for the acquisition of conditioned responses. These reversible lesions will also be used to identify other pathways of the conditioned and unconditioned response. Aim 2 will examine the uptake of 3H- and 14C-2-deoxy-D-glucose in a double isotope technique employing quantitative autoradiography to identify the areas of brain that are differentially activated by the contiguous presentation of a conditioned and unconditioned stimulus and whether such heterosynaptic facilitation of neuronal activity can predict subsequent rates of learning. For example, the effect of some drugs on learning appear to be secondary to their ability to increase or decrease such heterosynaptic facilitation. Aim 3 will use intraventricular injections of drugs that activate or inhibit the cAMP system to examine the role of this second messenger in learning and in the effects of drugs on learning. Such knowledge should provide clues concerning the neural systems involved in human disorders of learning and memory (e.g., Alzheimer's disease) and identify the drugs that might be effective in their treatment.