Non-peptidergic OP4 receptor agonist inhibits morphine antinociception but does not influence morphine dependence.
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.
Kotlinska
Jolanta
J
Department of Pharmacodynamics, Medical Academy PL 20-081 Lublin, Staszica 4, Poland. jolka@pandceum.am.lublin.pl
Wichmann
Juergen
J
Rafalski
Piotr
P
Talarek
Sylwia
S
Dylag
Tomasz
T
Silberring
Jerzy
J
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
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