OPIATE ACTION ON SEPTO HIPPOCAMPAL NEURONS

拟议研究的总体目标是表征细胞和 阿片类药物对大鼠隔区作用的分子机制 区域。隔区是隔-海马区复合体的一部分， 含有密度最高的Mu和增量阿片受体 大脑中的亚型，与伏隔核中的亚型相当。而当 阿片类药物的作用在海马体和 伏隔核的隔区相对来说还没有被探索过。 隔区的阿片类药物作用可能显著。 关于阿片类药物作为隔区支持物的成瘾特性 自我刺激行为，在解剖学上与奖励途径有关。 拟议中的研究将结合使用电生理学方法。 用解剖学和分子学方法研究阿片类药物的作用 隔区的内侧和外侧分支。《公约》的具体目标 建议的研究包括： 目的1.大鼠脑内阿片类反应神经元的鉴定和特征 隔区。隔区脑片上的阿片反应神经元 区域将使用电生理解剖学来表征，以及 神经药理学方法。在内侧隔和斜角线 Broca of Broca(MSDB)，阿片类药物的作用将在对流- 鉴定出胆碱能和GABA能隔-海马投射神经元。 在外侧隔(LS)，研究将集中在正畸- 已识别的接受输入的GABA能躯体脊髓投射神经元 来自下丘脑的脑啡肽能纤维。 目的2.阿片类药物对隔区突触相互作用的影响。 阿片类药物对两者之间突触相互作用的影响 隔分区(例如胆碱能和GABA能MSDB之间的相互作用 神经元)以及隔外侧和内侧分支之间(例如， 两个部门的GABA能神经元之间的相互作用将是 调查过了。据推测，这些突触相互作用将 确定阿片类药物对隔区投射神经元的净影响。 目的3.分析阿片类药物潜在的信号转导途径 隔区的动作。阿片类药物的离子机制 隔区的反应、特异性G蛋白和阿片剂的作用 与第二信使通路的相互作用将被研究。 总而言之，拟议的关于基础的基本机制的研究 阿片类药物对隔区神经元的生理作用将提供 了解隔区对脑电活动的影响的框架 鸦片类药物的成瘾特性。

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.