IDENTIFYING DRUGS FOR THE TREATMENT OF BZ WITHDRAWAL

苯二氮卓类药物(BZ)的治疗剂量依赖性良好 已经成立了。长期戒断症状的发生率 苯二氮类药物使用者高达80%，其中焦虑症最多 经常报告的戒断症状。因为焦虑是原因 大多数患者开始服用苯二氮卓类药物，这是焦虑的反弹增加 在退出期间可能会干扰停止BZ的尝试 用法。BZ戒断症状的药物治疗是其中之一 帮助患者尝试停止治疗的机制 BZ治疗。我们最近开始研究一种动物模型，它是 对两者的增加和焦虑的减少都很敏感，这使得我们能够 研究BZ的主要作用以及戒断诱导的影响 会引起焦虑的作用。该型号是盖勒-塞夫特的改进型 冲突范例(一种渐进的冲突程序)。的目标是 这里提出的研究是为了测试潜在的治疗药物 减轻BZ戒断引起的焦虑增加的能力 (冲突前效应)。该项目的具体目标将是 检查5-羟色胺1A的辅助给药程度 受体激动剂丁螺环酮或三环类抗抑郁药丙咪嗪， 可以减轻当BZS被观察到的反弹撤退的严重性 停产。这些实验的第二个目标是确定 增量冲突范式对以下因素的抗焦虑作用很敏感 长期服用新型抗焦虑药物。

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.