δ‐opioid receptor is present in presynaptic axon terminals in the rat nucleus locus coeruleus: Relationships with methionine 5 ‐enkephalin

The three classes of opioid receptors, μ, δ, and κ, are distributed within the locus coeruleus (LC) of the rat brain. We have recently shown with immunoelectron microscopy that the μ‐opioid receptor (μOR) is localized prominently to extrasynaptic sites on the plasma membranes of noradrenergic perikarya and dendrites of the LC. To further characterize the cellular distribution of other opioid receptors in this region, in this study, we examined the ultrastructural localization of an antipeptide sequence unique to the δ‐opioid receptor (δOR) in sections that were also dual labeled for methionine‐enkephalin (M‐ENK), an opioid peptide known to be an endogenous ligand of the δOR. Immunoperoxidase labeling for δOR was localized primarily to the plasma membranes of presynaptic axon terminals and was also associated with large dense core vesicles. The δOR‐labeled axon terminals formed both excitatory (asymmetric) and inhibitory (symmetric) type synaptic specializations with unlabeled dendrites and were frequently apposed by astrocytic processes. Dual labeling showed that, of 180 δOR‐labeled axon terminals, 16% showed colocalization with M‐ENK. These formed both types of synaptic junctions. Peroxidase labeling for δOR was also observed occasionally within dendrites, unmyelinated axons, and glial processes. The δOR‐labeled dendrites were usually postsynaptic to unlabeled axon terminals that contained both small clear and large dense core vesicles. These results provide the first ultrastrucutral evidence that, in the LC, δOR may play a role in the presynaptic modulation of release of both excitatory and inhibitory neurotransmitters. They also suggest involvement of δOR in autoregulation of M‐ENK release from axon terminals in this region. J. Comp. Neurol. 388:575–586, 1997. © 1997 Wiley‐Liss, Inc.