IDENTIFYING DRUGS FOR THE TREATMENT OF BZ WITHDRAWAL

确定治疗 BZ 戒断的药物

• 批准号: 2593402
• 负责人: RANDY S BARRETT
• 金额: $ 7.63万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 1999-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2593402
• 关键词: anxiety; benzodiazepines; buspirone; drug administration rate /duration; drug adverse effect; drug withdrawal; imipramine; injection /infusion; laboratory rat; tranquilizer

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.

对治疗剂量的苯二氮卓类药物（BZ）的依赖性一直很好 确立了习 长期服用海洛因者中戒断症状的发生率 苯二氮卓类药物使用者高达80%，其中焦虑最多 经常出现戒断症状。 因为焦虑是 大多数患者开始服用苯二氮卓类药物， 停药期间可能干扰尝试停用BZ 使用. BZ戒断症状的药物管理是一种 可以帮助患者尝试中断的机制 BZ治疗。 我们最近开始研究一种动物模型， 对两者都敏感会增加焦虑，这使我们能够 研究BZ的主要作用以及戒断诱导的 抗焦虑作用 这个模型是盖勒-塞弗特模型的改进型 冲突模式（增量冲突程序）。 的目标 这里提出的研究是测试潜在的治疗药物， 减弱BZ戒断诱导的焦虑增加的能力 （促冲突效应）。 该项目的具体目标是 检查连续给予5-羟色胺1A 受体激动剂丁螺环酮或三环类抗抑郁药丙咪嗪， 可以减轻BZ时观察到的反弹戒断的严重程度。 停止了。 这些实验的第二个目标是确定 增量冲突范式对焦虑的抗焦虑作用敏感， 新的抗焦虑药，当它们被长期施用时。