Maldonado R, Valverde O, Derrien M, Tejedor-Real P, Roques B P
Département de Pharmacochimie Moléculaire et Structurale, U 266 INSERM, URA D1500 CNRS, Université René Descartes, Faculté de Pharmacie, Paris, France.
Pharmacol Biochem Behav. 1994 Jun;48(2):363-9. doi: 10.1016/0091-3057(94)90539-8.
The aim of this study was to investigate the possible interaction between neuronal cholecystokinin (CCK) and opiate dependence. Rats were made dependent to morphine and the ability of cholecystokinin-octapeptide (CCK-8) and Tyr(SO3H)-gNle-mGly-Trp-(NMe)Nle-Asp-Phe-NH2 (BC 264), a selective agonist of CCK-B receptors, to induce signs of morphine withdrawal after ICV injection was tested. Behavioral responses were compared to those occurring during the naloxone-precipitated morphine withdrawal syndrome. In contrast to naloxone, CCK-8 (0.1, 1, and 10 micrograms, ICV) did not precipitate any sign of withdrawal. BC 264 (0.1, 1, and 10 micrograms, ICV) induced a strong hyperlocomotion and wet dog shakes in morphine-dependent rats, the latter effect also observed in nondependent animals. In rats receiving acute morphine, BC 264 induced an opposite effect (i.e., blockade of morphine-induced hyperactivity). Taken together, these results suggest that CCK plays only a minor role in the expression of morphine physical dependence.
本研究的目的是探讨神经元胆囊收缩素（CCK）与阿片类药物依赖之间可能的相互作用。使大鼠对吗啡产生依赖，并测试胆囊收缩素八肽（CCK-8）和CCK-B受体的选择性激动剂Tyr(SO3H)-gNle-mGly-Trp-(NMe)Nle-Asp-Phe-NH2（BC 264）在脑室内注射后诱导吗啡戒断症状的能力。将行为反应与纳洛酮诱发的吗啡戒断综合征期间出现的反应进行比较。与纳洛酮不同，CCK-8（0.1、1和10微克，脑室内注射）未诱发任何戒断症状。BC 264（0.1、1和10微克，脑室内注射）在吗啡依赖的大鼠中诱发强烈的运动亢进和湿狗样抖动，在非依赖动物中也观察到后一种效应。在接受急性吗啡的大鼠中，BC 264产生相反的效应（即阻断吗啡诱发的活动亢进）。综上所述，这些结果表明CCK在吗啡身体依赖的表达中仅起次要作用。
