title: Effects of cholecystokinin receptor agonist and antagonists on morphine dependence in mice.
abstract: In the present study, the effect of cholecystokinin agonists and antagonists on dependence to morphine in mice has been investigated. Mice were treated subcutaneously with morphine (50, 50 and 75 mg/kg) three times daily for 2-4 days, and a last dose of morphine (50 mg/kg) was administered on day 3, 4 or 5. Withdrawal syndrome (jumping) was precipitated by naloxone (2.5, 5 and 10 mg/kg) which was administered intraperitoneally 2 hr after the last dose of morphine. To study the effects of cholecystokinin receptor agonists or antagonists, 10 injection of morphine (3 administrations each day) for dependence and a dose of 5 mg/kg of naloxone for withdrawal induction were employed. Cholecystokinin-8 (0.001-0.01 mg/kg), low doses of the cholecystokinin agonists caerulein (0.00001 and 0.0001 mg/kg) and, unsulfated cholecystokinin (but not high doses) as well as the antagonists MK-329 (0.5-1 mg/kg) and L-365,260 (0.5-1 mg/kg) elicit reduction of the nalaxone-induced jumping. The inhibition of jumping induced by caerulein was reduced with the selective cholecystokinin antagonists MK-329 and L-365,260. It is concluded that cholecystokinin mechanism(s) may be involved in morphine dependence, that the agonists may act on a presynaptic receptors and that the antagonists may work on postsynaptic receptors.
authors.affiliation: Department of Pharmacology, Tehran University of Medical Sciences, Iran.
authors.forename: M R
authors.initials: MR
authors.lastname: Zarrindast
authors.forename: A
authors.initials: A
authors.lastname: Malekzadeh
authors.forename: M
authors.initials: M
authors.lastname: Rezayat
authors.forename: M
authors.initials: M
authors.lastname: Ghazi-Khansari
mesh_terms: D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002108:Ceruletide / Q000494:pharmacology; D002766:Cholecystokinin / Q000031:analogs & derivatives / Q000494:pharmacology; D020109:Devazepide; D004347:Drug Interactions; D006727:Hormone Antagonists / Q000494:pharmacology; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology; D009021:Morphine Dependence / Q000188:drug therapy*; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D011949:Receptors, Cholecystokinin / Q000819:agonists* / Q000037:antagonists & inhibitors*; D013375:Substance Withdrawal Syndrome
chemical_list: D001570:Benzodiazepinones; D006727:Hormone Antagonists; D009292:Narcotic Antagonists; D011949:Receptors, Cholecystokinin; D009270:Naloxone; D009020:Morphine; D002108:Ceruletide; D002766:Cholecystokinin; D020109:Devazepide