Dependence Potential of GHB, GBL and 1,4-BD

GHB、GBL 和 1,4-BD 的潜在依赖性

• 批准号: 6668704
• 负责人: Elise M Weerts
• 金额: $ 32.7万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6668704
• 关键词: anesthetics; baboons; behavior test; behavioral /social science research tag; biological models; butyrolactone; catheterization; conditioning; diol; disease /disorder proneness /risk; dosage; drug addiction; drug addiction antagonist; drug adverse effect; drug withdrawal; gamma hydroxybutyrate; neuropsychology; psychometrics; psychomotor function; psychopharmacology; substance abuse related behavior

DESCRIPTION: (provided by applicant) Gamma-hydroxybutyrate (GHB) is currently under investigation as a potential treatment for narcolepsy and alcohol dependence. Although GHB is currently classified as a Schedule I substance under the controlled substances act, illicit use of GHB, and its precursors gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD), is on the rise. The ability of GHB and its precursors to produce physical dependence has not been evaluated in controlled studies in humans or laboratory animals. The goal of the proposed research is to evaluate the physical dependence potential of GHB, GBL and 1,4-BD. Two specific aims are proposed: Aim 1 is to characterize the behavioral effects of GHB, GBL, 1,4-BD after acute and chronic intragastric drug administration in baboons. Aim 2 is to characterize physical dependence and the withdrawal syndrome for GHB and its precursors GBL and 1,4-BD in baboons. First, GHB, GBL and 1,4-BD will be administered alone and then in combination with the GHB antagonist NCS-382. Changes in food-maintained behavior, observed behaviors, and fine motor coordination, when compared to controls, will be evaluated. Next a high dose of GHB, GBL or 1,4-BD will be administered chronically via continuous i.g. infusion and changes in food-maintained behavior, observed behaviors, and fine motor coordination, when compared to vehicle control, will be evaluated. Then, the GHB antagonist NCS-382 will be administered to baboons that have been chronically treated with GHB, GBL or 1,4-BD. Evidence for a precipitated withdrawal syndrome will be determined based on changes in food-maintained behavior, observed behaviors, and fine motor coordination when compared those same behaviors recorded during the vehicle baseline and following administration of the antagonist alone. Finally, chronic treatment with GHB, GBL or 1,4-BD will be abruptly discontinued. The presence and time-course of a spontaneous withdrawal syndrome will be determined based on comparison with the same behavioral measures determined during a) the vehicle baseline condition and b) during the chronic drug dosing condition. The results of these studies will provide critical information on the behavioral pharmacology and physical dependence potential of GHB and its precursors.

描述：（申请人提供） 伽马-羟基丁酸（GHB）目前正在调查中， 治疗嗜睡症和酒精依赖。虽然GHB目前 根据《管制物质法》被列为附表一的物质， 非法使用伽马-羟丁酸及其前体-丁内酯， 1，4-丁二醇（1，4-BD）的需求正在上升。伽马-羟丁酸及其前体 产生身体依赖性尚未在对照研究中进行评估， 人类或实验室动物。这项研究的目的是评估 GHB、GBL和1，4-BD的身体依赖性潜力。两个具体目标是 提出：目的1是表征GHB、GBL、1，4-BD的行为效应 狒狒急性和慢性胃内给药后。目标二是 描述伽马-羟丁酸的身体依赖性和戒断综合征及其 前体GBL和1，4-BD。首先，GHB、GBL和1，4-BD将被 单独给药，然后与GHB拮抗剂NCS-382联合给药。 食物维持行为、观察行为和精细运动的变化 将评价与对照组相比的协调性。接下来是高剂量的 GHB、GBL或1，4-BD将通过连续i.g. 输注和食物维持行为、观察到的行为和罚款的变化 当与载体对照比较时，将评价运动协调。然后， GHB拮抗剂NCS-382将被施用给已经 长期服用GHB、GBL或1，4-BD。有证据表明 戒断综合征将根据食物维持的变化来确定。 行为，观察到的行为，和精细运动协调相比， 在车辆基线和以下期间记录的相同行为 单独施用拮抗剂。最后，长期服用伽马-羟丁酸， GBL或1，4-BD将突然中断。A的存在和时间过程 自发性戒断综合征将根据与 在a）车辆基线条件下确定的相同行为测量 和B）在慢性药物给药条件期间。这些研究的结果 将提供关于行为药理学和物理学的重要信息， 伽马--羟丁酸及其前体的依赖潜力。