Harro J, Oreland L
Department of Medical Pharmacology, Uppsala University, Sweden.
Pharmacol Biochem Behav. 1993 Mar;44(3):509-17. doi: 10.1016/0091-3057(93)90160-u.
CCK receptor agonists and antagonists have repeatedly been demonstrated to improve and impair, respectively, learning and memory functions. However, all studies to date have exploited avoidance paradigms. In the present study, the effect of some CCK receptor agonists and antagonists on the ability to learn an appetitively motivated task and to influence spatial working memory was investigated. In the first experiment, drugs were given immediately after each training session in the radial maze and the animals were tested, drug-free, during a 2-week period. After the initial treatments with caerulein, an unselective CCK receptor agonist (100 ng/kg SC), the animals were slightly less successful to obtain food pellets during the sessions on the first 2 days; whereas proglumide, an unselective CCK receptor antagonist (1 mg/kg SC) was without any effect. However, on the following days, all the three groups of rats (saline, caerulein, and proglumide) performed in a similar way. In the second experiment, drugs were given before each test session to well-trained animals. Scopolamine (0.15 and 0.3 mg/kg IP), the reference amnestic drug, produced dose-dependent impairment of working memory in the radial maze test. Proglumide (1 and 10 mg/kg SC) and devazepide, (a selective CCK-A receptor antagonist; 0.01 and 1 mg/kg SC), as well as caerulein (0.01, 0.1 and 1 microgram/kg SC) and CCK-4 (a selective CCK-B receptor agonist; 25 and 50 micrograms/kg SC) had no reliable effect.(ABSTRACT TRUNCATED AT 250 WORDS)
胆囊收缩素(CCK)受体激动剂和拮抗剂已被反复证明分别能改善和损害学习与记忆功能。然而,迄今为止所有研究都采用了回避范式。在本研究中,研究了一些CCK受体激动剂和拮抗剂对学习一项以食欲为动机的任务的能力以及对空间工作记忆的影响。在第一个实验中,每次在放射状迷宫训练后立即给药,然后在为期2周的时间内对动物进行无药物测试。在用未选择性的CCK受体激动剂雨蛙素(100纳克/千克,皮下注射)进行初始治疗后,动物在前两天的训练中获取食丸的成功率略低;而未选择性的CCK受体拮抗剂丙谷胺(1毫克/千克,皮下注射)则没有任何效果。然而,在接下来的几天里,三组大鼠(生理盐水组、雨蛙素组和丙谷胺组)的表现相似。在第二个实验中,对训练有素的动物在每次测试前给药。参比遗忘药物东莨菪碱(0.15和0.3毫克/千克,腹腔注射)在放射状迷宫测试中产生了剂量依赖性的工作记忆损害。丙谷胺(1和10毫克/千克,皮下注射)、地伐西匹(一种选择性CCK - A受体拮抗剂;0.01和1毫克/千克,皮下注射),以及雨蛙素(0.01、0.1和1微克/千克,皮下注射)和CCK - 4(一种选择性CCK - B受体激动剂;25和50微克/千克,皮下注射)均无可靠效果。(摘要截短于250字)