Localization of mu-opioid receptors to locus coeruleus-projecting neurons in the rostral medulla: morphological substrates and synaptic organization.

Abstract

The increase in discharge activity of locus coeruleus (LC) neurons following precipitated opiate withdrawal has been reported to be caused, in part, by excitatory amino acid release most likely originating from the nucleus paragigantocellularis lateralis (PGCl) in the rostral ventral medulla. Activation of glutamate-containing neurons in the PGCl may depend on changes in the occupancy of opioid receptive sites located on LC-projecting neurons which subsequently effect excitatory amino acid release in the LC during opiate withdrawal. To determine whether the mu-opioid receptor (MOR) is localized to plasmalemmal sites of LC-projecting neurons in the PGCl, we combined retrograde transport of the protein-gold tracer, wheat germ agglutinin-conjugated to inactive horseradish peroxidase (WGA-AU-apoHRP), from the LC with immunocytochemical detection of MOR in the same section of tissue throughout the rostral medulla. Light microscopic analysis indicated that neurons containing either the retrograde tracer or immunoperoxidase labeling for the MOR were numerous throughout the ventral medulla and that individual PGCl neurons contained both WGA-Au-apoHRP as well as MOR. By electron microscopy, WGA-Au-apoHRP was commonly identified in lysosomes within somata and large proximal dendrites. The somata contained either spherical or invaginated nuclei and were often surrounded by numerous myelinated axons. Gold deposits could also be identified in the cytoplasm of smaller dendritic processes in the PGCl, although these were not necessarily associated with lysosomes. The smaller dendritic processes were often the target of afferent input by axon terminals containing heterogeneous types of synaptic vesicles. Of 150 cellular profiles exhibiting WGA-Au-apoHRP retrograde labeling, 31% contained immunoperoxidase labeling for MOR. These results indicate that the MOR is distributed along plasmalemmal sites of morphologically diverse neurons in the PGCl which project to the LC.