OPIATE ACTION ON SEPTO HIPPOCAMPAL NEURONS

拟议研究的总体目标是表征细胞和 阿片类药物作用于大鼠隔核的分子机制 区隔区是隔-海马复合体的一部分， 含有最高密度的μ和δ阿片受体 在大脑中的亚型，相当于在脑桥核。而 阿片作用已经在海马体和海马神经元中被广泛研究。 在脑桥核中，间隔区仍然相对未被探索。 隔区的阿片作用可能很重要， 关于阿片类药物的成瘾性，因为中隔区支持 自我刺激行为，在解剖学上与奖励途径有关。 拟议的研究将结合使用电生理学方法 用解剖学和分子学的方法来研究鸦片在大脑中的作用， 隔膜区的内侧和外侧部分。的具体目标 拟议的研究是： AIM 1.海马神经元中阿片反应神经元的鉴定和特征 隔膜区隔区脑片中的阿片反应神经元 将使用电生理解剖学对该区域进行表征，并且 神经药理学方法。在中间隔膜和对角线上 Broca带（MSDB），将测试阿片类药物的作用， 鉴定胆碱能和GABA能隔-海马投射神经元。 在外侧隔（LS），研究将集中在顺向- 确定GABA能体棘投射神经元，其接收输入 下丘脑脑啡肽能纤维 AIM 2.阿片类药物对隔区内突触相互作用的影响。 阿片类药物对两种突触相互作用的影响 隔区（例如胆碱能和GABA能MSDB之间的相互作用 神经元）和外侧和内侧隔部之间（例如， 两个分区中GABA能神经元之间的相互作用）将被 研究了据推测，这些突触相互作用将 确定阿片类药物对隔投射神经元的净效应。 AIM 3.阿片类药物的信号转导途径分析 隔区的活动。阿片类药物的离子机制 隔区的反应，特异性G蛋白和阿片的作用 将研究与第二信使途径的相互作用。 总之，建议的研究的基本机制， 阿片类药物对隔神经元的生理作用将提供 框架，了解中隔区的贡献 鸦片的成瘾性

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.