THE CCK-B ANTAGONIST LY288513 BLOCKS EFFECTS OF DIAZEPAM WITHDRAWAL ON AUDITORY STARTLE

IN order to explore the potential clinical utility of CCK-B antagonist s for the treatment of benzodiazepine withdrawal symptoms, the auditor y startle reflex was examined in rats undergoing withdrawal from the c hronic administration of diazepam. Animals were exposed to diazepam co ntinuously for 12 days (20 mg kg-1 per day) via osmotic minipumps. Aft er 12 days the pumps were removed and the animals were allowed to go t hrough spontaneous withdrawal for 4 days. Acute pretreatment with eith er diazepam or the selective CCK-B antagonist LY288513 dose-dependentl y blocked withdrawal-induced increases in the auditory startle respons e. These results support the hypothesis that the selective CCK-B antag onist LY288513 may be an effective treatment for alleviating at least some benzodiazepine withdrawal symptoms in man.