title: Analgesic effect of the direct D2 dopamine receptor agonist RU 24926 and cross tolerance with morphine.
abstract: The direct D2 dopamine receptor agonist RU 24926, administered subcutaneously to mice, elicited, starting at the dose of 0.125 mg/kg, a dose dependent analgesic effect, assessed as the jump latency from a hot plate (55 degrees C). The analgesic effect induced by 0.25 mg/kg RU 24926 was dose dependently antagonized by the preferential D2 dopamine receptor antagonist haloperidol (ID50 = 15.1 +/- 3.3 micrograms/kg sc) as well as by the opioid receptor antagonist naloxone (ID50 = 0.59 +/- 0.17 mg/kg sc). The reversion of RU 24926-induced analgesia by naloxone was not accompanied by a reversion of hypothermia. Semi-chronic administration of RU 24926 (2.5 mg/kg, sc, 3 times a day for 3 days) completely desensitized to the analgesic effect induced by a 0.25 mg/kg test dose of RU 24926 and partially reduced the analgesic effect of low doses of morphine (0.5, 1, 1.5 mg/kg). Conversely, semi-chronic administration of morphine (32 mg/kg sc, twice daily for 4 days) completely desensitized the analgesic effect induced by a 2 mg/kg test dose of morphine and partially reduced the analgesic effect of RU 24926 (0.25, 0.5 and 1 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Unité de Neuropsychopharmacologie Expérimentale, CNRS URA 1969, Faculté de Médecine et Pharmacie de Rouen, Saint-Etienne-du-Rouvray, France.
authors.forename: C
authors.initials: C
authors.lastname: Suaudeau
authors.forename: J
authors.initials: J
authors.lastname: Costentin
mesh_terms: D000698:Analgesia; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D010627:Phenethylamines / Q000494:pharmacology*; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D013997:Time Factors
chemical_list: D010627:Phenethylamines; D017448:Receptors, Dopamine D2; D009270:Naloxone; C025254:RU 24926; D009020:Morphine