title: Effects of caerulein and CCK antagonists on tolerance induced to morphine antinociception in mice.
abstract: Different groups of mice received one daily dose (50 mg/kg) of morphine subcutaneously (SC) for 3, 4 or 5 days to develop tolerance to the opioid. The antinociceptive response of morphine (9 mg/kg) was tested in the hot-plate test 24 h after the last dose of the drug. Tolerance to morphine was obtained in all groups. The group of mice that received morphine for 4 days was employed for the rest of the experiments. Pretreatment of animals with a single dose of caerulein (0.025, 0.05, and 0.1 mg/kg, SC) 30 min prior to receiving morphine (50 mg/kg; during the development of tolerance to the opioid) on day 1, 2, 3, 4 or 5 of morphine administration potentiate antinociception induced by morphine (test dose of 9 mg/kg). The dose of 0.05 mg/kg of caerulein, used 30 min before morphine administration on day 3, was also used to evaluate the effects of antagonists on caerulein-induced decrease in tolerance. The selective cholecystokinin (CCK) receptor antagonists, MK-329 [1-methyl-3-(2 indoloyl)amino-5-phenyl-3H-1,4-benzodiazepin-2-one; 0.25 and 0.5 mg/kg] or L-365,260 [3R(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H- 1,4-benzodiazepin-3-yl)-N-(3-methyl-phenyl)urea: 0.25 and 0.5 mg/kg] decreased potentiation of morphine response induced by caerulein. MK-329 or L-365,260, when were injected 35 min before morphine injection during the development of tolerance and on day 3, decreased the tolerance to morphine. A single administration of MK-329 or L-365,260 (in the absence of caerulein) 35 min and 48 h before the test dose of morphine (9 mg/kg) potentiated the antinociception of morphine in nontolerant animals. In conclusion, CCK mechanism(s) may interact with morphine tolerance.
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Iran.
authors.forename: M R
authors.initials: MR
authors.lastname: Zarrindast
authors.forename: A
authors.initials: A
authors.lastname: Zabihi
authors.forename: M
authors.initials: M
authors.lastname: Rezayat
authors.forename: H
authors.initials: H
authors.lastname: Rakhshandeh
authors.forename: M
authors.initials: M
authors.lastname: Ghazi-Khansari
authors.forename: R
authors.initials: R
authors.lastname: Hosseini
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002108:Ceruletide / Q000494:pharmacology*; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D020109:Devazepide; D004361:Drug Tolerance; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin / Q000819:agonists / Q000037:antagonists & inhibitors; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D001570:Benzodiazepinones; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C058121:L 365260; D009020:Morphine; D002108:Ceruletide; D002766:Cholecystokinin; D020109:Devazepide