Opiate receptor localization in rat cerebral cortex

Abstract

The differential distributions of [3H]naloxone-labeled and [3H]D-Ala-D-Leu-enkephalin-labeled opiate receptors in rat cerebral cortex were localized autoradiographically and quantified by grain counting and computerized densitometry. In addition, receptor distributions were compared to terminal patterns of thalamocortical projections labeled by axoplasmic transport of [3H]amino acids. Opiate receptors labeled with [3H]naloxone in a mu ligand selectivity pattern show striking laminar heterogeneity and are densest in limbic cortical areas, intermediate in the motor cortex, and fewest in the primary sensory areas. By contrast, opiate receptors labeled with [3H]D-Ala2-D-Leu5-enkephalin in a delta ligand selectivity pattern are much more homogeneously distributed across both regions and laminae within regions. Mu receptors in most cortical areas have density peaks in layers I and VI and each peak shows a density gradient that is sloped within the layer so that the highest densities are at the most superficial and the deepest portions of cortex. In addition, there is an intermediate peak whose laminar position varies depending on the area in which it is found. In rostral agranular cortex, including limbic and motor areas, the [3H]naloxone binding peaks are in layers I, III, and VI. In primary somatosensory cortex, the intermediate peak is in layer Va and in most of remaining homotypical cortex it is in layer IV. Some areas have only bilaminar labeling, in superficial and deep layers; these include portions of the sulcal and retrosplenial cortices. Piriform and entorhinal cortices have dense [3H]naloxone binding only in the deepest layer and show a descending gradient of density toward the superficial layer. The positions of the mu receptor peaks were compared with termination patterns of projections originating in the thalamus. Close correspondence was found between receptor binding in the prelimbic, primary somatosensory, and entorhinal areas and projection terminations arising from the thalamic mediodorsal, posterior, and central medial nuclei, respectively. Although regional variations in [3H]D-Ala2-D-Leu5-enkephalin-labeled receptor density are uncommon, a gradual decrease in the number of sites along the dorsomedial wall of the cortex from anterior cingulate to caudal retrosplenial limbic cortex can be observed. Laminar variations in binding density are small as well; higher concentrations of the peptide binding sites are usually found in the deep cortical layers. These findings emphasize aspects of opiate receptor architecture which may be relevant to identifying cortical "opiatergic" neurocircuitry and raise the possibility of opiate modulation of thalamocortical transmission.