BENZODIAZEPINES, LONG-TERM POTENTIATION, AND MEMORY

苯二氮卓类药物、长时程增强和记忆

• 批准号: 2250406
• 负责人: JOHN R LARSON
• 金额: $ 9.95万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 1998-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2250406
• 关键词: NMDA receptors; benzodiazepine receptor; benzodiazepines; dosage; electroencephalography; evoked potentials; hippocampus; injection /infusion; laboratory rat; long term memory; long term potentiation; neural inhibition; olfactions; psychopharmacology; short term memory; synapses

Chronic recording studies of hippocampus in freely moving rats have identified patterns of neuronal activity that approximate electrical stimulation paradigms known to be very effective in inducing long-term potentiation (LTP). Given the considerable evidence linking LTP to memory, the observed naturally occurring patterns could be part of the process whereby information is encoded in brain networks. The proposed work will test if this hypothesis accounts for the amnestic effects of benzodiazepines, a class of drugs widely used for the treatment of anxiety. Thus, the experiments will ask if benzodiazepines disrupt three LTP-related physiological events and do so at dosages sufficient to impair encoding into long-term memory. The specific goals of the program are as follows: one, determine if the previously observed suppression of LTP by diazepam is due to the enhancing effect of the drug on inhibitory potentials; two, test if amnestic doses of diazepam are sufficient to block induction of LTP in intact rats; three, test if amnestic doses of diazepam block LTP-related patterns of neuronal activity in acute and/or chronic rats; four, compare relative potencies of different benzodiazepines on LTP-related events with their reported potencies on memory encoding; five, assess effects of different dosages of benzodiazepines on performance variables and the acquisition and retention of memory in an olfactory task. The data from these specific aims should make it feasible to test specific predictions, about dose- dependent relationships between the physiological and behavioral effects of benzodiazepines using chronic recording techniques. In general, the experiments will provide tests of hypothesized relationships between LTP and memory and should increase understanding of the amnestic effects of a clinically important class of drugs.

对自由活动的大鼠海马体的长期记录研究 确定了近似于电的神经元活动模式 众所周知，刺激范式对于诱导长期效果非常有效 增强作用（LTP）。 鉴于大量证据表明 LTP 与 记忆中，观察到的自然发生的模式可能是记忆的一部分 信息在大脑网络中编码的过程。 拟议的 工作将测试这个假设是否解释了记忆删除的影响 苯二氮卓类药物，一类广泛用于治疗的药物 焦虑。 因此，实验将询问苯二氮卓类药物是否会破坏三个 LTP 相关的生理事件，并且剂量足以 损害长期记忆的编码。 该计划的具体目标 如下：一、判断是否之前观察到的抑制 安定对 LTP 的影响是由于该药物对 LTP 的增强作用 抑制潜力；二、测试地西泮的遗忘剂量是否为 足以阻断完整大鼠中 LTP 的诱导；三、测试是否 遗忘剂量的地西泮可阻断 LTP 相关的神经元模式 急性和/或慢性大鼠的活性；四、比较相对效力 不同苯二氮卓类药物对 LTP 相关事件的影响及其报道 记忆编码的效力；五、评估不同剂量的效果 苯二氮卓类药物对性能变量的影响以及获取和 在嗅觉任务中保留记忆。 这些具体数据 目标应该使测试有关剂量的具体预测成为可能 生理效应和行为效应之间的依赖关系 使用慢性记录技术测定苯二氮卓类药物。 一般来说， 实验将提供 LTP 之间假设关系的检验 和记忆，应该增加对遗忘效应的理解 一类临床上重要的药物。