IDENTIFYING DRUGS FOR THE TREATMENT OF BZ WITHDRAWAL

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Dependence on therapeutic doses of benzodiazepines (BZ) has been well established. The incidence of withdrawal symptoms among long-term benzodiazepine users is as high as 80%, with anxiety being the most frequently reported symptom of withdrawal. Since anxiety is the reason most patients began taking benzodiazepines, a rebound increase in anxiety during withdrawal is likely to interfere with attempt to discontinue BZ usage. Pharmacologic management of BZ withdrawal symptoms is one mechanism by which patients could be aide in their attempts to discontinue BZ treatment. We have recently begun working with an animal model that is sensitive to both increases an decreases in anxiety, which allows us to study both the primary effects of BZ as well as withdrawal-induced anxiogenic effects. This model is a modification of the Geller-Seifter conflict paradigm (an incremental conflict procedure). The goal of the research proposed here is to test potential therapeutic agents for their ability to attenuate BZ withdrawal-induced increases in anxiety (proconflict effects). The specific aim of this project will be to examine the extent to which adjunctive administration of the serotonin 1A receptor agonist, buspirone or the tricyclic antidepressant, imipramine, can attenuate the severity of the rebound withdrawal observed when BZs are discontinued. A second goal of these experiments is to determine if the incremental conflict paradigm is sensitive to the antianxiety effects of novel anxiolytics when they are administered chronically.