title: Morphine-induced analgesia in the rat paw pressure test is blocked by CCK and enhanced by the CCK antagonist MK-329.
abstract: The effects of cholecystokinin octapeptide sulphated (CCK) and the potent CCK antagonist MK-329 (L-364, 718) on analgesia induced by morphine in the paw pressure test in the rat were examined. Both CCK (4-16 micrograms/kg) and MK-329 (0.1-8.0 mg/kg) had no significant effect on thresholds for pain when given alone, whereas morphine (2-16 mg/kg) induced dose-dependent analgesia. Cholecystokinin (4-16 micrograms/kg) abolished the analgesia induced by 8 mg/kg morphine. In contrast, doses of 1 and 2 mg/kg MK-329 enhanced the analgesia induced by 8 and 4 mg/kg morphine, respectively. The present data are consistent with previous reports that CCK blocks, and CCK antagonists enhance, opiate-induced analgesia in response to thermal pain stimuli. In addition, the results show that CCK/opiate interactions extend to mechanical pain stimuli. Recent ligand binding studies have shown that CCK receptors in the spinal cord of the rat (where CCK/opiate interactions are thought to occur) are predominantly of the CCK-B subtype. The drug MK-329 has a relatively weak (micromolar) affinity for CCK-B receptors and a high affinity (nanomolar) for CCK-A receptors. As relatively large doses (1-2 mg/kg) of MK-329 are required to enhance opiate-induced analgesia in the paw pressure test and tail flick test in rats it appears that CCK/opiate interactions in this species involve CCK-B receptors.
authors.affiliation: Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, U.K.
authors.forename: M F
authors.initials: MF
authors.lastname: O'Neill
authors.forename: C T
authors.initials: CT
authors.lastname: Dourish
authors.forename: S D
authors.initials: SD
authors.lastname: Iversen
mesh_terms: D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D020109:Devazepide; D004305:Dose-Response Relationship, Drug; D008297:Male; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010147:Pain Measurement; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
chemical_list: D001570:Benzodiazepinones; D009020:Morphine; D002766:Cholecystokinin; D020109:Devazepide