LOCALIZATION METABOTROPIC GLUTAMATE RECEPTORS IN NORMAL/COCAINE-TREATED ANIMALS

正常/可卡因治疗动物中代谢型谷氨酸受体的定位

• 批准号: 8172382
• 负责人: Yoland Smith
• 金额: $ 4.39万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172382
• 关键词: Amygdaloid structure; Animals; Behavioral; Cocaine; Computer Retrieval of Information on Scientific Projects Database; Funding; Glutamates; Grant; Institution; Maps; Mediating; Metabotropic Glutamate Receptors; Neurons; Nucleus Accumbens; Play; Prefrontal Cortex; Rattus; Regulation; Research; Research Personnel; Resources; Role; Site; Source; Synapses; Techniques; Thalamic structure; Therapeutic; United States National Institutes of Health; addiction; drug of abuse; neurochemistry; psychostimulant; receptor; transmission process

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. There is significant pharmacological and behavioral evidence that group I metabotropic glutamate receptors (mGluR1a and mGluR5) in the nucleus accumbens play an important role in the neurochemical and pathophysiological mechanisms that underlie addiction to psychostimulants. These receptors most likely mediate their functional effects through the regulation of extrinsic glutamatergic inputs that impinge upon projection neurons in the shell and core of the nucleus accumbens. However, glutamatergic inputs to the accumbens originate from multiple sources, including the prefrontal cortex, thalamus and amygdala. During the past funding period, we have used anatomical and immunocytochemical techniques to analyze the subcellular localization of mGluR1a and mGluR5 subtypes at these different glutamatergic synapses in the rat nucleus accumbens. Because of the multifarious origin of glutamate in the nucleus accumbens, a deep understanding of the localization of group I mGluRs at specific synapses will allow to better understand the functional role of these receptors in the regulation of excitatory transmission in the accumbens, and possibly identify specific target sites for group I mGluR therapeutic approaches in addiction to drugs of abuse. Our findings revealed that the two group I mGluRs are differentially distributed at cortical, thalamic and amygdala glutamatergic synapses, thereby providing a detailed map of these receptors in accumbens neurons. Together, these findings demonstrate that the two group I mGluRs are widely distributed, but organized in a highly specific fashion in relation to the different sources of glutamatergic inputs to the nucleus accumbens.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 有重要的药理学和行为证据表明，I组代谢型谷氨酸受体（MGLUR1A和MGLUR5）在伏隔核中，在神经化学和病理生理机制中起着重要作用，这些机制是基于精神临床成瘾剂的基础的神经化学和病理生理机制。这些受体最有可能通过调节外部谷氨酸能输入来介导其功能效应，这些外部谷氨酸能输入会影响伏隔核的壳和核心的投影神经元。然而，伏隔的谷氨酸能输入来自多种来源，包括前额叶皮层，丘脑和杏仁核。 在过去的资金期间，我们使用解剖学和免疫细胞化学技术来分析在这些不同的谷氨酸能突触中，MGLUR1A和MGLUR5亚型的亚细胞定位。由于谷氨酸在伏隔核中的多种起源，对在特定突触中I组的定位有深入的理解将使这些受体在调节伏隔的兴奋性传播中的功能作用，并可能识别出I组MGLUR治疗方法对滥用药物的特定目标方法。 我们的发现表明，这两组I mglurs在皮质，丘脑和杏仁核谷氨酸胶质塔突触中分布差分分布，从而在伏隔神经元中提供了这些受体的详细图。总之，这些发现表明，这两组I mglurs被广泛分布，但与具有谷氨酸能输入的不同来源的高度特异性方式组织。