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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Effects of caerulein and CCK antagonists on tolerance induced to morphine antinociception in mice.
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Effects of caerulein and CCK antagonists on tolerance induced to morphine antinociception in mice.

机译：Caerulein和CCK拮抗剂对小鼠吗啡抗伤害感受的耐受性的影响。

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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.
机译：不同组的小鼠皮下（SC）每天服用一次剂量（50 mg / kg）的吗啡，持续3、4或5天，以产生对阿片类药物的耐受性。最后一剂药后24小时，在热板试验中测试了吗啡（9 mg / kg）的镇痛反应。在所有组中均获得了对吗啡的耐受性。在其余的实验中使用接受吗啡4天的小鼠组。在第1、2、3天接受吗啡（50 mg / kg;在对阿片类药物的耐受性发展期间）之前30分钟，用单剂量的花青素（0.025、0.05和0.1 mg / kg，SC）对动物进行预处理，4或5剂吗啡给药可增强吗啡诱导的抗伤害作用（测试剂量为9 mg / kg）。在第3天吗啡给药前30分钟使用0.05 mg / kg的菜青素剂量，还用于评估拮抗剂对菜青素诱导的耐受性降低的影响。选择性胆囊收缩素（CCK）受体拮抗剂，MK-329 [1-甲基-3-（2吲哚基）氨基-5-苯基-3H-1,4-苯并二氮杂-2-酮; 0.25和0.5 mg / kg]或L-365,260 [3R（+）-N-（2,3-二氢-1-甲基-2-氧代-5-苯基-1H-1,4-苯并二氮杂-3-基） -N-（3-甲基-苯基）脲：0.25和0.5 mg / kg]降低了由菜青素诱导的吗啡反应增强。 MK-329或L-365,260，在耐受性发展期间和吗啡注射前35分钟注射，并在第3天降低了对吗啡的耐受性。在非耐受性动物中，在吗啡试验剂量（9 mg / kg）之前35分钟和48小时单次施用MK-329或L-365,260（在不存在青霉素的情况下）可增强吗啡的抗伤害感受性。总之，CCK机制可能与吗啡耐受性相互作用。

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