THE BENZODIAZEPINE ANTAGONIST FLUMAZENIL BLOCKS THE EFFECTS OF CCK RECEPTOR AGONISTS AND ANTAGONISTS IN THE ELEVATED PLUS-MAZE

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.