ULTRASTRUCTURAL IMMUNOCYTOCHEMICAL LOCALIZATION OF MU-OPIOID RECEPTORS IN RAT NUCLEUS-ACCUMBENS - EXTRASYNAPTIC PLASMALEMMAL DISTRIBUTION AND ASSOCIATION WITH LEU(5)-ENKEPHALIN

mu-Opioid receptors and their endogenous ligands, including Leu(5)-enk ephalin (LE), are distributed abundantly in the nucleus accumbens (NAC ), a region implicated in mechanisms of opiate reinforcement. We used immunoperoxidase and/or immunogold-silver methods to define ultrastruc tural sites for functions ascribed to mu-opioid receptors and potentia l sites for activation by LE in the NAC. An antipeptide antibody raise d against an 18 aminoacid sequence of the cloned mu-opioid receptor (M OR) C terminus showed that MOR-like immunoreactivity (MOR-LI) was loca lized predominantly to extrasynaptic sites along neuronal plasma membr anes, The majority of neuronal profiles containing MOR-LI were dendrit es and dendritic spines, The dendritic plasma membranes immunolabeled for MOR were near sites of synaptic input from LE-labeled terminals an d other unlabeled terminals forming either inhibitory or excitatory ty pe synapses, Unmyelinated axons and axon terminals were also intensely but less frequently immunoreactive for MOR. Observed sites for potent ial axonal associations with LE included coexistence of MOR and LE wit hin the same terminal, as well as close appositions between differenti ally labeled axons, Astrocytic processes rarely contained detectable M OR-LI, but also were sometimes observed in apposition to LE-labeled te rminals. We conclude that in the rat NAC, MOR is localized prominently to extrasynaptic neuronal and more rarely to glial plasma membranes t hat are readily accessible to released LE and possibly other opioid pe ptides and opiate drugs, The close affiliation of MOR with spines rece iving excitatory synapses and dendrites receiving inhibitory synapses provides the first direct morphological evidence that MOR selectively modulates postsynaptic responses to cortical and other afferents.