The CCK-B antagonist LY288513 blocks effects of diazepam withdrawal on auditory startle

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IN order to explore the potential clinical utility of CCK-B antagonists for the treatment of benzodiazepine with-drawal symptoms, the auditory startle reflex was examined in rats undergoing withdrawal from the chronic administration of diazepam. Animals were exposed to diazepam continuously for 12 days (2C mg kg-1 per day) via osmotic minipumps. After 12 days the pumps were removed and the animals were allowed to go through spontaneous withdrawal for 4 days. Acute pretreatment with either diazepam or the selective CCK-B antagonist LY288513 dose-dependently blocked withdrawal-induced increases in the auditory startle response. These results support the hypothesis that the selective CCK-B antagonist LY288513 may be an effective treatment for alleviating at least some benzodiazepine withdrawal symptoms in man.

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