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

描述：(申请人提供) 伽马-羟基丁酸酯(GHB)目前正在接受研究，作为一种潜在的 治疗发作性睡病和酒精依赖。尽管GHB目前 根据《管制物质法》被归类为附表一物质， 非法使用GHB及其前体--γ-丁内酯和 1，4-丁二醇(1，4-BD)呈上升趋势。羟基丁酸及其前体的能力 在一项对照研究中尚未对产生身体依赖进行评估 人类或实验动物。拟议研究的目标是评估 GHB、GBL和1，4-BD的身体依赖性。两个具体目标是 建议：目标1是表征GHB、GBL、1，4-BD的行为效应 在急性和慢性灌胃给药后，狒狒。目标2是 GHB及其戒断症状与躯体依赖的特征 狒狒的前体是GBL和1，4-BD。首先，GHB、GBL和1，4-BD将 单独给药，然后与GHB拮抗剂NCS-382联合使用。 食物维持行为、观察到的行为和精细运动的变化 当与控制相比较时，将对协调进行评估。接下来是大剂量的 GHB、GBL或1，4-BD将通过连续静脉注射进行长期给药。 输液和食物维持行为、观察到的行为和罚款的变化 当与车辆控制相比较时，将对运动协调进行评估。然后, GHB拮抗剂NCS-382将用于已经被 长期使用GHB、GBL或1，4-BD治疗。关于沉淀物的证据 将根据饮食维持的变化来确定戒断综合征 行为，观察到的行为，以及精细的运动协调 在车辆基线和跟随过程中记录的相同行为 单独对敌手进行管理。最后，长期服用羟基丁酸， GBL或1，4-BD将突然停产。一种病毒的存在和时间进程 自然戒断综合症将根据与 在a)车辆基线状况期间确定的相同行为测量 以及b)在长期服药期间。这些研究的结果 将提供有关行为药理学和物理方面的重要信息 羟基丁酸及其前体的依赖势。

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.