Chopin P, Briley M
Division of Neurobiology I, Centre de Recherche Pierre Fabre, Castres, France.
Psychopharmacology (Berl). 1993;110(4):409-14. doi: 10.1007/BF02244646.
Peripheral administration of the unsulphated cholecystokinin octapeptide (CCK-8us) led to an anxiogenic-like action in the elevated plus-maze model of anxiety in rats. Devazepide and L-365,260 showed potent anxiolytic-like effects at similar doses. The fact that devazepide is 1000 times more potent as a CCK-A receptor antagonist than L-365,260, whereas the two compounds are nearly equipotent at the CCK-B receptor subtype, suggests that CCK-B rather than CCK-A receptors are involved in these effects. Similar results were obtained in mice using the two-compartment test. In the elevated plus-maze, the benzodiazepine antagonist, flumazenil, which was inactive when given alone, significantly antagonized the anxiogenic-like activity of CCK-8us and the anxiolytic-like effects of devazepide and L-365,260. These results suggest a complex interaction between benzodiazepine and CCK receptor mechanisms in the regulation of anxiety states.
在大鼠焦虑的高架十字迷宫模型中，外周给予未硫酸化的胆囊收缩素八肽（CCK-8us）会产生类似焦虑的作用。地伐西匹和L-365,260在相似剂量下显示出强效的类似抗焦虑作用。地伐西匹作为CCK-A受体拮抗剂的效力比L-365,260强1000倍，而这两种化合物在CCK-B受体亚型上几乎等效，这一事实表明参与这些作用的是CCK-B而非CCK-A受体。在小鼠的双隔室试验中也得到了类似结果。在高架十字迷宫中，单独给药时无活性的苯二氮䓬拮抗剂氟马西尼，能显著拮抗CCK-8us的类似焦虑活性以及地伐西匹和L-365,260的类似抗焦虑作用。这些结果表明，在焦虑状态的调节中，苯二氮䓬和CCK受体机制之间存在复杂的相互作用。
