The effects of CCKA and CCKB antagonists on activity in the black/white exploration model of anxiety in mice.
In view of evidence suggesting that cholecystokinin (CCK) may have a role in the mediation of human panic disorders, it was predicted that CCK receptor antagonists may have anxiolytic-like activity in an animal model of anxiety, the black/white exploration test. Data revealed that, in mice, the CCKA receptor antagonist, devazepide (formerly L-364,718, MK-329), produced a clear anxiolytic-like profile with an inverted U-shaped dose-response curve centered around 5 micrograms/kg. Similarly, L-365,031, a specific, but less potent, CCKA antagonist, also produced a profile consistent with weak anxiolysis but only at 5 micrograms/kg. By direct contrast, the potent and specific CCKB antagonist L-365,260 had no robust anxiolytic-like effects in this test. Therefore, these data suggest that devazepide has the greatest effects in this model, that L-365,031 is only marginally active, and that L-365,260 is without influence. These results suggest that CCKA receptor mechanisms are involved in the mediation of anxiolytic-like effects in the black/white model of exploration in mice.
Hendrie
C A
CA
Department of Psychology, University of Leeds, West Yorkshire, UK.
Neill
J C
JC
Shepherd
J K
JK
Dourish
C T
CT
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001007:Anxiety / Q000523:psychology*; D001570:Benzodiazepinones / Q000494:pharmacology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors; D020109:Devazepide; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*
D014151:Anti-Anxiety Agents; D001570:Benzodiazepinones; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C053649:L 365031; C058121:L 365260; D002766:Cholecystokinin; D020109:Devazepide