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.
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