THE DISCRIMINATIVE STIMULUS, SELF-REPORTED AND PHYSIOLOGICAL EFFECTS OF COMMON M

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。为了开发一个GHB药物的歧视程序在人类中，我们将检查GHB的影响，GABAB激动剂巴氯芬，苯二氮卓GABAA激动剂三唑仑，和甲基黄嘌呤中枢神经系统兴奋剂咖啡因的人训练区分0.32克/70公斤或1.8克/70公斤的GHB从安慰剂根据指示的新反应的歧视程序。将基于来自非人类研究的GHB辨别性刺激效应取决于训练剂量而不同的证据来检查GHB的高和低训练剂量（Columbo等人，1995，1998 ab; Lobina等人，1999年）。baclofen（5、10、20 mg）和三唑仑（0.125、0.25、0.5 mg）的选择是基于非人类药物辨别数据，即GHB辨别刺激在训练用于辨别低或高剂量GHB与安慰剂的大鼠中完全推广至巴氯芬，但在训练区分低剂量GHB与安慰剂的大鼠中部分地对GABAA激动剂地西泮有影响（Columbo等，1995，1998 ab; Lobina等人，1999年）。在实验中选择咖啡因（0、100、320、560 mg）作为阴性对照，因为其作用主要通过不同的机制介导，其中最重要的被认为是对腺苷受体的竞争性拮抗作用（参见Fredholm，1985; Gould等人，1984; Snyder等人，1981年）。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In order to develop a GHB drug discrimination procedure in humans, we will examine the effects of GHB, the GABAB agonist baclofen, the benzodiazepine GABAA agonist triazolam, and the methylxanthine CNS stimulant caffeine in humans trained to discriminate either a 0.32 g/70 kg or 1.8 g/70 kg of GHB from placebo under the instructed novel-response discrimination procedure. A high and low training dose of GHB will be examined based on evidence from nonhuman studies that the GHB discriminative stimulus effect differs depending upon the training dose (Columbo et al., 1995, 1998ab; Lobina et al., 1999). Baclofen (5, 10, 20 mg) and triazolam (0.125, 0.25, 0.5 mg) have been selected based on nonhuman drug discrimination data that the GHB discriminative stimulus generalizes fully to baclofen in rats trained to discriminate either a low or high dose of GHB from placebo, but partially to the GABAA agonist diazepam in rats trained to discriminate the low dose of GHB from placebo (Columbo et al., 1995, 1998ab; Lobina et al., 1999). Caffeine (0, 100, 320, 560 mg) has been selected as a negative control in the experiment because its actions are mediated primarily through different mechanisms, the most important of which is considered to be that of competitive antagonism at adenosine receptors (see Fredholm, 1985; Gould et al., 1984; Snyder et al., 1981).