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.
Chopin
P
P
Division of Neurobiology I, Centre de Recherche Pierre Fabre, Castres, France.
Briley
M
M
D000818:Animals; D014151:Anti-Anxiety Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D001007:Anxiety / Q000139:chemically induced / Q000523:psychology*; D001522:Behavior, Animal / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D005442:Flumazenil / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000819:agonists* / Q000037:antagonists & inhibitors*
D014151:Anti-Anxiety Agents; D011949:Receptors, Cholecystokinin; D005442:Flumazenil