OPIATE ACTION ON SEPTO HIPPOCAMPAL NEURONS

阿片类药物对海马隔神经元的作用

• 批准号: 2123199
• 负责人: Meenakshi Alreja
• 金额: $ 10.44万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-07-01 至 2000-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2123199
• 关键词: G protein; acetylcholine; antidromic impulse; brain mapping; brain septal area; central neural pathway /tract; electrophysiology; gamma aminobutyrate; hippocampus; histology; intercellular connection; laboratory rat; membrane potentials; neural information processing; neurochemistry; opiate alkaloid; opioid receptor; voltage /patch clamp

The overall goal of the proposed research is to characterize cellular and molecular mechanisms underlying the actions of opiates in the rat septal area. The septal area is part of the septo-hippocampal complex and contains amongst the highest densities of mu and delta opiate receptor subtypes in the brain, comparable to that in the nucleus accumbens. While opiate actions have been extensively studied in the hippocampus and in the nucleus accumbens, the septal area has remained relatively unexplored. Opiate actions in the septal area are likely to be significant with respect to the addictive properties of opiates as the septal area supports self-stimulation behavior and is anatomically linked to reward pathways. The proposed research will use electrophysiological methods in conjunction with anatomical and molecular approaches to study opiate actions in the medial and lateral divisions of the septal area. The specific aims of the proposed research are: AIM 1. Identification and characterization of opiate-responsive neurons in the septal area. Opiate-responsive neurons in brain slices of the septal area will be characterized using electrophysiological anatomical, and neuropharmacological approaches. In the medial septum and the diagonal band of Broca (MSDB), effects of opiates will be tested on antidromically- identified cholinergic and GABAergic septo-hippocampal projection neurons. In the lateral septum (LS), studies will focus on orthodromically- identified GABAergic somatospiny projection neurons which receive input from hypothalamic enkephalinergic fibers. AIM 2. Effects of opiates on synaptic interactions within the septal area. The effect of opiates on synaptic interactions within each of the two septal divisions (e.g. interactions between cholinergic and GABAergic MSDB neurons) and between the lateral and medial septal divisions (e.g. interactions between GABAergic neurons in the two divisions) will be investigated. It is postulated that these synaptic interactions will determine the net effect of opiates on septal projection neurons. AIM 3. Analysis of the signal transduction pathways underlying opiate actions in the septal area. The ionic mechanisms underlying opiate responses in the septal area, role of specific G proteins and opiate interactions with second messenger pathways will be investigated. In summary, the proposed studies on the basic mechanisms underlying the physiological actions of opiates on septal neurons will provide a framework for understanding the contribution of the septal area to the addictive properties of opiates.

拟议研究的总体目标是表征细胞和 阿片类药物对大鼠鼻中隔作用的分子机制 区域。间隔区是间隔海马复合体的一部分 含有密度最高的 mu 和 delta 阿片受体 大脑中的亚型，与伏隔核中的亚型相当。尽管 阿片类药物的作用已在海马体和大脑皮层中得到了广泛的研究。 伏隔核中，间隔区域相对而言尚未被探索。 阿片类药物对中隔区域的作用可能对以下情况很重要： 考虑到阿片类药物的成瘾特性，因为隔膜区域支持 自我刺激行为，并且在解剖学上与奖励途径相关。 拟议的研究将结合使用电生理学方法 使用解剖学和分子方法来研究阿片类药物的作用 间隔区的内侧和外侧划分。该计划的具体目标 拟议的研究是： 目的 1. 鸦片反应神经元的鉴定和表征 间隔区。间隔脑切片中的阿片反应神经元 将使用电生理解剖学来表征该区域，并且 神经药理学方法。在内侧隔膜和对角线 布罗卡带（MSDB），阿片类药物的作用将在反作用上进行测试 鉴定出胆碱能和 GABA 能隔膜海马投射神经元。 在侧隔膜（LS）中，研究将集中于顺向- 识别出接收输入的 GABA 能体棘投射神经元 来自下丘脑脑啡肽能纤维。 目的 2.阿片类药物对间隔区内突触相互作用的影响。 阿片类药物对两者内突触相互作用的影响 间隔分裂（例如胆碱能和 GABA 能 MSDB 之间的相互作用 神经元）以及外侧和内侧间隔部分之间（例如 两个部分中 GABA 能神经元之间的相互作用）将是 调查了。据推测，这些突触相互作用将 确定阿片类药物对间隔投射神经元的净效应。 AIM 3.阿片类药物信号转导途径分析 间隔区的动作。阿片类药物的离子机制 间隔区域的反应、特定 G 蛋白和阿片类药物的作用 将研究与第二信使途径的相互作用。 总之，拟议的基本机制研究 阿片类药物对间隔神经元的生理作用将提供 了解间隔区对 阿片类药物的成瘾特性。