Where are the mu Receptors That Mediate Opioid Analgesia? An Autoradiographical Study in the HAR and LAR Selection Lines

Abstract

One line (strain) of mouse has been selectively bred in our laboratory for 15 generations to exhibit a very high sensitivity to levorphanol-induced analgesia on the hot plate assay (HAR or high antinociceptive response line). Concurrently, a second line (LAR or low antinociceptive response line) has been bred in the opposite direction, i.e., to exhibit a very low sensitivity under the same conditions. This has resulted in a 7-fold difference in sensitivity between HAR and LAR mice as a result of changes in gene frequency. Receptor autoradiographic studies with 3H-DAGO were carried out in the central gray to find receptor populations differing greatly in density between HAR and LAR mice to parallel their in vivo sensitivity differences: such receptors would then be implicated in mediating in vivo analgesia. The caudal portions of the dorsal raphe nucleus (DRN) showed 1.5- to 2-fold differences in density of mu sites, while the periaqueductal gray (PAG) showed relatively small differences. These results strongly suggest that mu receptors in a portion of the DRN are involved in mediating analgesia due to systemically administered opioids in this population of mice.