DISCRIMINATIVE EFFECTS OF BENZODIAZEPINE WITHDRAWAL

描述：(改编自申请人的摘要) 苯二氮卓类药物是越来越多的化合物中的一员，这些化合物对许多 它们在γ-氨基丁酸(GABA)A上的作用 受体复合体。苯二氮卓类药物被广泛用于催眠和治疗 焦虑相关的障碍；然而，长期使用这些药物可能会 产生临床上显著的身体依赖。此外，还有 苯二氮卓类药物和其他药物共同滥用的证据越来越多 精神活性药物，特别是有精神分裂症病史的人 酒精或镇静剂/催眠药滥用。这个项目的一个主要目标是 开发一种研究歧视性刺激的程序 苯二氮卓类药物依赖和戒断的主观效应 恒河猴和，在最后一段支持期间，这样的程序 是发展起来的。在这个项目的继续期间，不同的小组 将使用安定治疗、唑吡坦治疗和未治疗的猴子 用药方式调查三个一般性问题 辨别、通风和神经内分泌活动。首先，GABAA 调节器将被用来检验关于药物选择性的假设 作用和疗效的变化。尽管人们已经知道了很多关于 GABAA调节剂在体外的分子作用，知之甚少 关于这些发现的临床后果。这些研究将 提供从分子研究到临床应用的桥梁，通过 使用非人类灵长类动物的主观药物效应和物理模型 依赖。第二，这些实验将扩大条件下的 哪些辨别程序可以用来研究依赖 在接受小说的猴子中建立氟马西尼的歧视 GABAA调节剂唑吡坦，一种广泛用于催眠的药物。 第三，“盲目”药物评价将在 CPDD。总的来说，这些研究将从根本上提供新的 GABAA调节剂和Will的体内药理信息 有助于确定药物和行为决定因素 对镇静催眠药的身体依赖。

DESCRIPTION: (Adapted From The Applicant's Abstract) Benzodiazepines are among a growing set of compounds that exert many of their effects by actions at the gamma-amino butyric acid (GABA)A receptor complex. Benzodiazepines are widely used for hypnosis and for anxiety-related disorders; however, long term use of these drugs can generate clinically-significant physical dependence. Moreover, there is increasing evidence for the co-abuse of benzodiazepines and other psychoactive drugs especially among individuals with a history of alcohol or sedative/hypnotic abuse. One major goal of this project is to develop a procedure for studying the discriminative stimulus (subjective) effects of benzodiazepine dependence and withdrawal in rhesus monkeys and, during the last period of support, such a procedure was developed. In the continuation of this project, separate groups of diazepam-treated, zolpidem-treated and untreated monkeys will be used to investigate three general issues using measures of drug discrimination, ventilation and neuroendocrine activity. First, GABAA modulators will be used to test hypotheses regarding selectivity of drug action and variations in efficacy. Although much is known about the molecular actions of GABAA modulators in vitro, very little is known about the clinical ramifications of those findings. These studies will provide a bridge from molecular studies to clinical applications by using a non-human primate model of subjective drug effects and physical dependence. Second, these experiments will expand the conditions under which discrimination procedures can be used to study dependence by establishing a flumazenil discrimination in monkeys receiving the novel GABAA modulator zolpidem, a drug that is widely prescribed for hypnosis. Third, "blind' drug evaluations will be conducted under the auspices of the CPDD. Collectively, these studies will provide fundamentally new information on the in vivo pharmacology of GABAA modulators and will help to identify the pharmacologic and behavioral determinants of physical dependence on sedative hypnotics.