LOCALIZATION METABOTROPIC GLUTAMATE RECEPTORS IN NORMAL/COCAINE-TREATED ANIMALS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 有重要的药理学和行为学证据表明，伏核中的I类代谢性谷氨酸受体(mGluR1a和mGluR5)在精神刺激剂成瘾的神经化学和病理生理机制中起重要作用。这些受体很可能通过调节外源性谷氨酸能输入来调节它们的功能效应，这些输入冲击伏核外壳和核心的投射神经元。然而，伏隔核的谷氨酸能输入来自多个来源，包括前额叶皮质、丘脑和杏仁核。 在过去的资助期间，我们使用解剖学和免疫细胞化学技术分析了mGluR1a和mGluR5亚型在这些不同谷氨酸能突触中在大鼠伏隔核中的亚细胞定位。由于谷氨酸在伏隔核中的来源多种多样，深入了解I组mGluR在特定突触的定位将有助于更好地了解这些受体在伏核兴奋性传递调节中的功能作用，并可能为I组mGluR药物成瘾的治疗方法识别特定的靶点。 我们的发现表明，这两组mGluR在皮质、丘脑和杏仁核谷氨酸能突触上的分布不同，从而提供了伏隔神经元中这些受体的详细图谱。综上所述，这些发现表明，这两组mGluRs分布广泛，但根据伏隔核谷氨酸能输入的不同来源，以高度特异的方式组织。

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.