This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.This project examined the localization of group I metabotropic glutamate receptors (mGluRs) in the rat nucleus accumbens, a key subcortical structure involved in reward and drug addiction. During the past year, efforts have been devoted towards understanding changes in the subcellular and subsynaptic localization of mGluR1a and mGluR5 in various groups of animals chronically and acutely treated with cocaine. Surprisingly, in spite of previously reported changes in glutamate release in the accumbens of cocaine-treated rats, we could not demonstrate significant reorganization of the localization of the two group I mGluRs in cocaine-treated animals. In both normal and drug-challenged animals, the two group I mGluRs were largely expressed extrasynaptically on the plasma membrane of accumbal neurons, and there was no major change in the proportion of internalized receptors in response to the different cocaine treatments. These observations are contrary to those reported for ionotropic AMPA glutamate receptors which display a fast and profound synaptic reorganization in response to cocaine administration. These findings demonstrate that the trafficking of AMPA receptors is more sensitive to physiological and pathological changes in extracellular glutamate levels than group I mGluRs. However, in line with many other G-protein-coupled receptors, we demonstrated that mGluR1a and mGluR5 display a significant level of internalization in response to local application of the group I mGluRs agonist, DHPG, indicating that group I mGluRs are capable of internalization in response to acute agonist application. In an ongoing last series of experiments, we use tract-tracing method combined with the pre-embedding immunogold technique to characterize the perisynaptic localization of group I mGluRs at specific glutamatergic synapses from the cerebral cortex, amygdala and thalamus in the rat nucleus accumbens. Findings of this project provide important localization data that will help elucidate the role of group I mGluRs in addiction to drugs of abuse.
Showing the most recent 10 out of 912 publications
