title: Non-peptidergic OP4 receptor agonist inhibits morphine antinociception but does not influence morphine dependence.
abstract: The non-peptidergic opioid receptor-like 1 (ORL1, OP4) receptor ligand, Ro 64-6198 [(1S,3aS)-8-(2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl)-1-phenyl-1,3,8-triaza-spiro[4,5]decan-4-one], is a full agonist of the OP4 receptor. The aim of this study was to evaluate whether this compound influences morphine antinociception and dependence in mice. Ro 64-6198 inhibits the acute analgesic effect of morphine in the tail-immersion test, however, when given chronically during the acquisition of morphine dependence, development of this dependence is not prevented. The acute injection of Ro 64-6198 suppresses withdrawal escape jumps in morphine dependent mice, though this effect may be a result of the loss of locomotor activity induced by this compound and/or its myorelaxant action. The study provides evidence that stimulation of the OP4 receptor suppresses acute morphine antinociception, but is not sufficient to inhibit the development of morphine dependence in mice.
authors.affiliation: Department of Pharmacodynamics, Medical Academy PL 20-081 Lublin, Staszica 4, Poland. jolka@pandceum.am.lublin.pl
authors.forename: Jolanta
authors.initials: J
authors.lastname: Kotlinska
authors.forename: Juergen
authors.initials: J
authors.lastname: Wichmann
authors.forename: Piotr
authors.initials: P
authors.lastname: Rafalski
authors.forename: Sylwia
authors.initials: S
authors.lastname: Talarek
authors.forename: Tomasz
authors.initials: T
authors.lastname: Dylag
authors.forename: Jerzy
authors.initials: J
authors.lastname: Silberring
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D004924:Escape Reaction / Q000187:drug effects; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009020:Morphine / Q000037:antagonists & inhibitors*; D009021:Morphine Dependence; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D018847:Opioid Peptides / Q000378:metabolism; D010147:Pain Measurement / Q000187:drug effects; D010424:Pentobarbital / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects; D011957:Receptors, Opioid / Q000819:agonists*; D013141:Spiro Compounds / Q000494:pharmacology*; D013997:Time Factors; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D006993:Hypnotics and Sedatives; D007093:Imidazoles; D009020:Morphine; D009270:Naloxone; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D010424:Pentobarbital; D011957:Receptors, Opioid; D013141:Spiro Compounds; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C408068:Ro 64-6198; C000722287:Oprl1 protein, mouse