ENDOGENOUS OPIOIDS: THEIR ROLE IN LTP IN DENTATE GYRUS

内源性阿片类药物：它们在齿状回 LTP 中的作用

• 批准号: 2119034
• 负责人: DARRELL V LEWIS
• 金额: $ 11.87万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-07-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2119034
• 关键词: behavioral medicine; dentate gyrus; drug addiction; drug addiction antagonist; drug interactions; electrophysiology; endogenous opioid; enkephalins; granule cell; laboratory rat; learning; memory; naloxone; neural transmission; neuropeptide receptor; neuropeptides; neuropharmacology; opioid receptor; synapses

Opioid peptides are present in presynaptic terminals in several areas of the limbic system, but their role in synaptic transmission remains obscure. In the dentate gyrus, the gateway into the hippocampus, opioid peptides appear to be crucial for long term potentiation (LTP) of the synapse between the lateral perforant path (LPP) and the principal neurons of the dentate, the dentate granule cells. Understanding the cellular and molecular mechanisms of opioid induced LTP in the dentate would give insights into the role of opioids and opioid receptors in learning, memory and, perhaps, also into the conditioning that sustains opiate addiction. The model will be the dentate gyrus in the rat hippocampal slice. In the rat dentate, enkephalin is present in the terminals of the LPP and the opioid antagonist, naloxone, blocks LTP of the LPP to granule cell synapse. The goal is to determine how enkephalin release from the LPP acts to produce LTP in the dentate. The hypothesis is that release of enkephalin from the LPP terminals facilities LTP by suppressing GABAergic inhibition of the dentate neurons. This hypothesis will be tested using both extracellular and intracellular recording techniques in the hippocampal slice. The specific aims are: 1) Determine if a more specific opioid antagonist than naloxone can be used to block dentate LTP. The effects of more specific opioid antagonists will be tested; 2) Determine if blockade of GABAergic inhibition eliminates the opioid dependent component of LTP. This would be expected if opioids are acting by disinhibiting the granule cells; 3) Test whether release of enkephalin from the LPP increases depolarization of granule cells during a stimulus train; and 4) Determine if release of enkephalin from the LPP suppresses inhibitory postsynaptic potentials in dentate granule cells.

阿片类肽存在于突触前末端的几个地区 边缘系统，但它们在突触传播中的作用仍然存在 朦胧。 在齿状回中，进入海马的门户，阿片类药物 肽似乎对于长期增强（LTP）至关重要 横向穿孔路径（LPP）与主的突触 齿状神经元，齿状颗粒细胞。 了解 阿片类药物诱导的LTP的细胞和分子机制 将深入了解阿片类药物和阿片受体在 学习，记忆，也许也进入维持的条件 鸦片成瘾。 该模型将是大鼠的齿状回 海马切片。 在大鼠牙齿中，enkephalin存在于 LPP的末端和阿片类拮抗剂Naloxone阻止了LTP的LTP LPP到颗粒细胞突触。 目标是确定如何 Enkephalin从LPP释放起作用，在齿状物中产生LTP。 这 假设是从LPP终端释放ankephalin 设施LTP通过抑制GABA能抑制齿状 神经元。 该假设将使用细胞外和 海马切片中的细胞内记录技术。 这 具体目的是：1）确定是否更具体的阿片类药物拮抗剂 纳洛酮可用于阻止牙齿LTP。 更多的影响 将测试特定的阿片类拮抗剂； 2）确定是否封锁 GABA能抑制消除了LTP的阿片类药物依赖性成分。 如果阿片类药物通过抑制 颗粒细胞； 3）测试是否从LPP释放ankephalin 在刺激训练期间增加颗粒细胞的去极化；和 4）确定从LPP中释放Enkephalin是否会抑制抑制作用 齿状颗粒细胞中的突触后电位。