title: Where are the mu receptors that mediate opioid analgesia? An autoradiographic 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.
authors.affiliation: Research Service, VA Medical Center, Portland, OR.
authors.forename: J K
authors.initials: JK
authors.lastname: Belknap
authors.forename: S E
authors.initials: SE
authors.lastname: Laursen
authors.forename: K E
authors.initials: KE
authors.lastname: Sampson
authors.forename: A
authors.initials: A
authors.lastname: Wilkie
mesh_terms: D000818:Animals; D001345:Autoradiography; D004305:Dose-Response Relationship, Drug; D007981:Levorphanol / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D009619:Nociceptors / Q000187:drug effects*; D010487:Periaqueductal Gray / Q000187:drug effects*; D011903:Raphe Nuclei / Q000187:drug effects*; D011957:Receptors, Opioid / Q000187:drug effects* / Q000235:genetics; D017450:Receptors, Opioid, mu; D012641:Selection, Genetic; D012684:Sensory Thresholds / Q000187:drug effects
chemical_list: D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D007981:Levorphanol