Opioid receptors in rat neostriatum: radioautographic distribution at the electron microscopic level

The distribution of mu-opioid receptors, selectively labeled in vitro with a monoiodinated Met-enkephalin analog [( 125I]FK 33-824), was analyzed by light and electron microscopic radioautography in sections from the neostriatum of the rat. In the light microscope, patches of high receptor densities were detected amidst a moderately labeled matrix. The number of silver grains, as counted in 1-micron thick plastic-embedded sections, was 3 times greater inside the patches than in the intervening matrix. In both compartments, the proportion of labeled binding sites associated with the neuropil was significantly higher (greater than 70%) than that associated with nerve cell bodies or myelinated fascicles. Quantitative analyses of electron microscopic radioautographs revealed that the majority of silver grains corresponding to specifically bound [125I]FK molecules originated from radioactive sources associated with apposed neuronal membranes. Of the total number of specific binding sites, 53% was associated with axodendritic, 18% with axoaxonic and 3% with axosomatic interfaces. The occurrence of multiple labeled foci along the plasma membrane of certain perikarya and dendrites suggested that some of the binding sites might be associated with somato/dendritic elements. The high incidence of labeling along axoaxonic interfaces indicated that others were linked to the membrane of axons and/or axon terminals. A major finding of the present study was that only a small proportion of specific FK binding sites (7% of total) was associated with synaptic junctions. Labeled synapses were primarily of the asymmetric type and were found predominantly on dendritic branches and spines. A few were observed on nerve cell bodies. Labeled symmetric synapses were rare and encountered exclusively on dendritic branches. The high frequency with which specifically labeled binding sites were found to be associated with neuronal interfaces involving axonal processes strongly suggests that even if non-junctional these binding sites correspond to functional receptors. Whether these receptors are activated by endogenous ligand molecules released by the labeled terminals themselves or from terminals located at a distance from the labeled interfaces remains to be determined.