title: Induction of delta-opioid receptor function in the midbrain after chronic morphine treatment.
abstract: Delta-opioid receptor (DOPr) activation fails to produce cellular physiological responses in many brain regions, including the periaqueductal gray (PAG), despite neural expression of high densities of the receptor. Previous histochemical studies have demonstrated that a variety of stimuli, including chronic morphine treatment, induce the translocation of DOPr from intracellular pools to the surface membrane of CNS neurons. PAG neurons in slices taken from untreated mice exhibited mu-opioid receptor (MOPr) but not DOPr-mediated presynaptic inhibition of GABAergic synaptic currents. In contrast, after 5-6 d of chronic morphine treatment, DOPr stimulation inhibited synaptic GABA release onto most neurons. Shorter exposure to morphine in vitro (upto 4 h) or in vivo (18 h) did not induce functional DOPr responses. DOPr-mediated presynaptic inhibition could not be induced in slices from untreated animals by increasing synaptic activity in vitro using high extracellular potassium concentrations or activation of protein kinase A. Induction of functional DOPr signaling by chronic morphine required MOPr expression, because no DOPr receptor responses were observed in MOPr knock-out mice. DOPr agonists also had no effect on miniature IPSCs in beta-arrestin-2 knock-out mice after chronic morphine. These results suggest that induction of DOPr-mediated actions in PAG by chronic morphine requires prolonged MOPr stimulation and expression of beta-arrestin-2.
authors.affiliation: Pain Management Research Institute, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales 2065, Australia.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Hack
authors.forename: Elena E
authors.initials: EE
authors.lastname: Bagley
authors.forename: Billy C H
authors.initials: BC
authors.lastname: Chieng
authors.forename: MacDonald J
authors.initials: MJ
authors.lastname: Christie
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D019390:Arrestins / Q000172:deficiency; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000502:physiology; D018684:Glycine Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009020:Morphine / Q000008:administration & dosage*; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000008:administration & dosage*; D009474:Neurons / Q000187:drug effects*; D009842:Oligopeptides / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D010487:Periaqueductal Gray / Q000166:cytology* / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000172:deficiency; D013331:Strychnine / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects; D013997:Time Factors; D014970:Xanthines / Q000494:pharmacology; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: C000605258:Arrb2 protein, mouse; D019390:Arrestins; D018691:Excitatory Amino Acid Antagonists; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D018684:Glycine Agents; D007546:Isoquinolines; D009292:Narcotic Antagonists; D009294:Narcotics; D009842:Oligopeptides; D047428:Protein Kinase Inhibitors; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D013449:Sulfonamides; D014970:Xanthines; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; C089773:phenylalanyl--cysteinyl-tyrosyl-tryptophyl-arginyl-penicillaminyl-threoninamide; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C060208:deltorphin I, Ala(2)-; D005680:gamma-Aminobutyric Acid; D004743:Enkephalin, Leucine; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D009020:Morphine; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D013331:Strychnine; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide