Visualization of multiple opioid-receptor types in rat striatum after specific mesencephalic lesions.

Abstract

In order to gain insight into a possible modulatory role for mu, delta, and kappa opioid receptors of the nigrostriatal dopaminergic pathway, we investigated the topographical organization of the receptors with respect to pre- and postsynaptic membranes. Dopaminergic terminals projecting from the substantia nigra to the corpus striatum were destroyed by unilateral injection of 6-hydroxydopamine into the substantia nigra. Quantitative receptor assays using highly specific radioligands were used to measure the density of striatal mu, delta, and kappa receptors before and after denervation. Denervation caused a 34 +/- 2% loss of striatal mu receptors and a 32 +/- 1% loss of striatal delta receptors on the lesioned side of the brain; in contrast, kappa receptors did not change significantly in density. Quantitative in vitro autoradiography was used to visualize the neuroanatomical pattern of receptors on lesioned and nonlesioned sides of the brain under the light microscope. Loss of mu receptors in striatal patches was striking in the ventrolateral areas of the striatum, whereas the most notable loss of delta receptors was found in the central striatum. Other brain areas did not differ significantly in mu receptor density between the lesioned and nonlesioned sides, as determined by autoradiography. These findings suggest that a high percentage of mu and delta receptors in the striatum are located on the nigrostriatal dopaminergic terminals and support the concept of a modulatory role for mu and delta opioid peptides in the nigrostriatal dopaminergic pathway.