title: Morphine-induced changes in delta opioid receptor trafficking are linked to somatosensory processing in the rat spinal cord.
abstract: An in vivo fluorescent deltorphin (Fluo-DLT) internalization assay was used to assess the distribution and regulation of pharmacologically available delta opioid receptors (deltaORs) in the rat lumbar (L4-5) spinal cord. Under basal conditions, intrathecal injection of Fluo-DLT resulted in the labeling of numerous deltaOR-internalizing neurons throughout dorsal and ventral horns. The distribution and number of Fluo-DLT-labeled perikaryal profiles were consistent with that of deltaOR-expressing neurons, as revealed by in situ hybridization and immunohistochemistry, suggesting that a large proportion of these cells was responsive to intrathecally administered deltaOR agonists. Pretreatment of rats with morphine for 48 hr resulted in a selective increase in Fluo-DLT-labeled perikaryal profiles within the dorsal horn. These changes were not accompanied by corresponding augmentations in either deltaOR mRNA or (125)I-deltorphin-II binding levels, suggesting that they were attributable to higher densities of cell surface deltaOR available for internalization rather than to enhanced production of the receptor. Unilateral dorsal rhizotomy also resulted in increased Fluo-DLT internalization in the ipsilateral dorsal horn when compared with the side contralateral to the deafferentation or to non-deafferented controls, suggesting that deltaOR trafficking in dorsal horn neurons may be regulated by afferent inputs. Furthermore, morphine treatment no longer increased Fluo-DLT internalization on either side of the spinal cord after unilateral dorsal rhizotomy, indicating that microOR-induced changes in the cell surface availability of deltaOR depend on the integrity of primary afferent inputs. Together, these results suggest that regulation of deltaOR responsiveness through microOR activation in this region is linked to somatosensory information processing.
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, Québec, Canada H3A 2B4.
authors.forename: Anne
authors.initials: A
authors.lastname: Morinville
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Cahill
authors.forename: Haneen
authors.initials: H
authors.lastname: Aibak
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Rymar
authors.forename: Amynah
authors.initials: A
authors.lastname: Pradhan
authors.forename: Cyrla
authors.initials: C
authors.lastname: Hoffert
authors.forename: Françoise
authors.initials: F
authors.lastname: Mennicken
authors.forename: Thomas
authors.initials: T
authors.lastname: Stroh
authors.forename: Abbas F
authors.initials: AF
authors.lastname: Sadikot
authors.forename: Dajan
authors.initials: D
authors.lastname: O'Donnell
authors.forename: Paul B S
authors.initials: PB
authors.lastname: Clarke
authors.forename: Brian
authors.initials: B
authors.lastname: Collier
authors.forename: James L
authors.initials: JL
authors.lastname: Henry
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Vincent
authors.forename: Alain
authors.initials: A
authors.lastname: Beaudet
mesh_terms: D000818:Animals; D005456:Fluorescent Dyes / Q000737:chemistry / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D017403:In Situ Hybridization; D008161:Lumbosacral Region; D008297:Male; D008856:Microscopy, Fluorescence; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D020671:Posterior Horn Cells / Q000378:metabolism; D021381:Protein Transport; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000096:biosynthesis / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000378:metabolism; D019051:Rhizotomy; D013116:Spinal Cord / Q000033:anatomy & histology / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D005456:Fluorescent Dyes; D009294:Narcotics; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C060208:deltorphin I, Ala(2)-; C060209:deltorphin II, Ala(2)-; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D009020:Morphine