Neuroanatomical patterns of the μ, δ, and κ opioid receptors of rat brain as determined by quantitative in vitro autoradiography

Highly specific radioligands and quantitative autoradiography reveal strikingly different neuroanatomical patterns for the μ, δ, and κ opioid receptors of rat brain. The μ receptors are most densely localized in patches in the striatum, layers I and III of the cortex, the pyramidal cell layer of the hippocampal formation, specific nuclei of the thalamus, the pars reticulata of the substantia nigra, the interpeduncular nucleus, and the locus coeruleus. In contrast, δ receptors are highly confined, exhibiting selective localization in layers I, II, and VIa of the neocortex, a diffuse pattern in the striatum, and moderate concentration in the pars reticulata of the substantia nigra and in the interpeduncular nucleus. δ receptors are absent in most other brain structures. This distribution is unexpected in that the enkephalins, the putative endogenous ligands of the δ receptor, occur essentially throughout the brain. The κ receptors of rat brain exhibit a third pattern distinct from that of the μ and δ receptors. κ receptors occur at low density in patches in the striatum and at particularly high density in the nucleus accumbens, along the pyramidal and molecular layers of the hippocampus, in the granular cell layer of the dentate gyrus, specific midline nuclei of the thalamus, and hindbrain regions, κ receptors appear to be uniformly distributed across regions in the neocortex with the exception of layer III, which revealed only trace levels of binding. An important conclusion of the present study is that δ receptors occur at high density only in the forebrain and in two midbrain structures, whereas μ and κ receptors exhibit discrete patterns in most major brain regions.