BEHAVIORAL PHARMACOLOGY OF CHRONIC BENZODIAZEPINE USE

长期使用苯二氮卓类药物的行为药理学

• 批准号: 3211481
• 负责人: MARY JEANNE KALLMAN
• 金额: $ 12.44万
• 依托单位: UNIVERSITY OF MISSISSIPPI
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-01 至 1994-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3211481
• 关键词: albino rat; alprazolam; behavior modification; behavior test; benzodiazepines; buspirone; diazepam; drug abuse; drug administration rate /duration; drug adverse effect; drug tolerance; drug withdrawal; lorazepam; midazolam; operant conditionings; pharmacokinetics; psychological reinforcement; psychopharmacology; tranquilizer

The role of behavioral-environmental factors in the development of tolerance and drug withdrawal to benzodiazepines (BZs) will be investigated in six separate experiments with albino rats. An examination of both contingent and non-contingent components of operant responding are emphasized as potential modes for behavioral change during the development of tolerance and withdrawal. Two operant experiments will explore the development of tolerance and withdrawal produced by 30 days of pre and postsession exposure to modest doses of two BZs, midazolam (MZ) and diazepam (DZ), when reinforcement is dependent on the duration of the responses or the force of responses rather than rate of responding. Since duration of drug action is an important predictor of drug abuse and of behavioral tolerance phenomena, one experiment will compare the development of tolerance as assessed with the multiple FR:FI operant schedule to two intermediate-duration-of-action BZs, alprazolam (AP) and lorazepam (LP), which have dissimilar pharmacological profiles. AP is more efficacious clinically as an anxiolytic and LP is more efficacious as a muscle relaxant. The importance of duration of BZ activity in the development of behavioral tolerance and drug withdrawal will be further explored by manipulation of inter-drug interval in rats exposed to MZ (28 total drug exposures) as a model for drug "binging". With total cumulative dose being held constant, three different dosing regimens will be examined: continuous daily exposure, two days of exposure followed by five days of no exposure, and four days of exposure followed by three days of no exposure. Previous data on repetitive exposure to BZs will be extended to examine the importance of behavioral-environmental factors in repetitive exposure to two non-BZ anxiolytics, buspirone (BU) and gepirone (GP), which mediate their effects via 5-HT1A receptors. The final project will evaluate the importance of chronically experiencing MZ while responding in predicting long term alterations in sensitivity to BZs and the non-BZ anxiolytic buspirone (BU).

行为-环境因素在儿童精神分裂症发生发展中的作用 将调查对苯二氮类药物(BZS)的耐药性和停药情况 在六个单独的白化大鼠实验中。对两者的考察 操作型反应的偶然性和非偶然性成分包括 被强调为在发展过程中行为改变的潜在模式 宽容和退缩。两个可操作的实验将探索 30天的耐受性和戒断反应的发展 会后暴露于中等剂量的两种BZ、咪达唑仑(MZ)和 安定(DZ)，当加固取决于持续时间时 反应或反应的力量，而不是反应的速度。自.以来 药物作用的持续时间是药物滥用的重要预测指标 行为容忍现象，一项实验将比较 用多个FR：FI手术计划评估的耐受性为2 中效BZS、阿普唑仑(AP)和劳拉西潘(LP)， 它们有不同的药理特征。AP更有效 临床上，作为一种抗焦虑药物，LP作为一种肌肉更有效 松弛药。BZ活动持续时间在BZ发展中的重要性 行为耐受性和药物戒断将由 MZ染毒大鼠药物间隔的操纵(共28种药物) 暴露)，作为吸毒“狂欢”的典范。总累积剂量为 在保持不变的情况下，将检查三种不同的剂量方案： 每天连续暴露，暴露两天，然后不暴露五天 暴露，暴露四天，然后三天不暴露。 之前关于重复暴露于BZS的数据将扩展到检查 行为环境因素在重复暴露中的重要性 两种非BZ类抗焦虑药物丁螺环酮(BU)和吉培酮(GP) 它们通过5-HT1a受体发挥作用。期末项目将评估 应对时长期体验MZ在预测中的重要性 BZS和非BZ抗焦虑药的长期敏感性变化 丁螺环酮(BU)。