ro-64-6198 and 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.

Topics: Animals; Behavior, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Drug Interactions; Escape Reaction; Hypnotics and Sedatives; Imidazoles; Male; Mice; Morphine; Morphine Dependence; Motor Activity; Naloxone; Narcotic Antagonists; Nociceptin; Nociceptin Receptor; Opioid Peptides; Pain Measurement; Pentobarbital; Psychomotor Performance; Receptors, Opioid; Spiro Compounds; Time Factors