Comparative analysis of the subcellular and subsynaptic localization of mGluR1a and mGluR5 metabotropic glutamate receptors in the shell and core of the nucleus accumbens in rat and monkey.

Group I metabotropic glutamate receptors (mGluRs) play critical roles in synaptic plasticity and drug addiction. To characterize potential sites whereby these receptors mediate their effects in the ventral striatum, we studied the subcellular and subsynaptic localization of mGluR1a and mGluR5 in the shell and core of the nucleus accumbens in rat and monkey. In both species, group I mGluRs are mainly postsynaptic in dendrites and spines, with rare presynaptic labeling in unmyelinated axons. Minor, yet significant, differences in proportions of specific immunoreactive elements were found between the accumbens shell and the accumbens core in monkey. At the subsynaptic level, significant differences were found in the proportion of plasma membrane-bound mGluR5 labeling between species. In dendrites, spines, and unmyelinated axons, a significantly larger proportion of mGluR5 labeling was bound to the plasma membrane in rats (50-70%) than in monkeys (30-50%). Conversely, mGluR1a displayed the same pattern of immunogold labeling in the two species. Electron microscopic colocalization studies revealed 30% colocalization of mGluR1a and mGluR5 in dendrites and as much as 50-65% in spines in both compartments of the rat accumbens. Both group I mGluRs were significantly expressed in D1-immunoreactive dendritic processes (60-75% colocalization) and spines (30-50%) of striatal projection neurons as well as dendrites of cholinergic (30-70%) and parvalbumin-containing (70-85%) interneurons. These findings highlight the widespread expression of group I mGluRs in projection neurons and interneurons of the shell and core of the nucleus accumbens, providing a solid foundation for regulatory and therapeutic functions of group I mGluRs in reward-related behaviors and drug addiction.