ELECTRON-MICROSCOPIC DISTRIBUTION OF MU-OPIOID RECEPTORS ON NORADRENERGIC NEURONS OF THE LOCUS-COERULEUS

The distribution of mu opioid receptors was examined by light and elec tron microscopic autoradiography in the locus coeruleus of the rat fol lowing in vitro labelling with the iodinated agonist [(125)l]FK-33824. At the light microscopic level, specific mu opioid binding sites were concentrated over the perikarya and dendrites of neurons that were ty rosine hydroxylase-immunopositive in adjacent sections. Accordingly, b oth the number of tyrosine hydroxylase-immunoreactive neurons and the density of labelled mu receptors decreased markedly throughout the ros trocaudal extent of the nucleus following treatment with the catechola minergic neurotoxin 6-hydroxydopamine. By electron microscopy, specifi cally labelled receptors were detected both inside and on the surface of locus coeruleus neurons. Intracellular sites were found by resoluti on circle analysis to be highly concentrated within the endoplasmic re ticulum and Golgi apparatus, suggesting that the ligand recognizes bot h glycosylated and preglycosylated forms of receptor. The remainder we re found mainly over the cytoplasmic matrix or intracytoplasmic vesicl es, and were attributed to newly synthesized or recycled receptors in transit. Cell surface receptors were present over both dendritic and p erikaryal membranes of noradrenergic cells, These were most highly con centrated opposite abutting axon terminals, suggesting the existence o f receptor 'hot spots' at sites of putative endogenous ligand release. However, only a small proportion of these sites was associated with s ynaptic specializations. Furthermore, an important contingent was dete cted opposite non-axonal elements, such as dendrites and glial cells, suggesting that mu opioid ligands act mainly parasynaptically on locus coeruleus neurons. Finally, similar to 5% of labelled receptors were associated with axoglial interfaces, indicating that a minor action of mu opioids in the locus may be presynaptic and/or glial.