LACK OF EFFECT OF CCKB RECEPTOR ANTAGONISTS IN ETHOLOGICAL AND CONDITIONED ANIMAL SCREENS FOR ANXIOLYTIC DRUGS

The effects of the CCKB receptor antagonists L-365,260, CI-988 and L-7 40,093, a new compound with improved bioavailability and CNS penetrati on, were assessed for anxiolytic-like effects in three rat anxiolytic screens sensitive to benzodiazepines, the elevated plus maze (EPM), co nditioned suppression of drinking (CSD) and conditioned emotional resp onse (CER) tests. In the EPM, L-740,093 (0.1-1.0 mg/kg), L-365,260 (0. 00001-10.0 mg/kg), and CI-988 (0.01-1.0 mg/kg) did not increase the ti me spent on the open arms of the maze or the number of entries onto th e open arms. In contrast, the benzodiazepine receptor partial agonist, bretazenil (0.3-10.0 mg/kg), significantly increased both the time sp ent on the open arms and the number of open arm entries. In the CSD an d the CER tests, L-740,093 (0.1-1.0 mg/kg) L-365,260 (0.0001-0.1 mg/kg ) and CI-988 (0.01-10.0 mg/kg) failed to increase suppression ratios c ompared to the vehicle-treated control rats, whereas, the benzodiazepi ne receptor partial agonist FG 8205 (10.0 mg/kg) (CSD) and bretazenil (0.3-3.0 mg/kg) (CER) both significantly increased suppression ratios compared to vehicle-treated control rats. In addition, L-365,260 (1.0- 50.0 mg/kg), CI-988 (0.1-10.0 mg/kg) and diazepam (0.1-1.0 mg/kg) were assessed in a squirrel monkey conflict procedure. Although diazepam s ignificantly increased suppressed lever pressing rates, L-365,260 and CI-988 were without effect. The present findings provide little suppor t for the hypothesis that CCKB receptor antagonists have anti-anxiety effects in animals.