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

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。为了在人类中开发一种GHB药物辨别程序，我们将在指导的新反应辨别程序下，检查GHB、GABAB激动剂巴氯芬、苯二氮卓激动剂三唑仑和甲基黄嘌呤中枢神经系统刺激剂咖啡因在人类中的效果，以区分0.32g/70公斤或1.8g/70公斤的GHB和安慰剂。高训练剂量和低训练剂量的GHB将根据来自非人类研究的证据进行检验，这些证据表明GHB的区别性刺激效应取决于训练剂量(Columbo等人，1995,1998 ab；Lobina等人，1999)。巴氯芬(5，10，20毫克)和三唑仑(0.125，0.25，0.5毫克)是基于非人类药物辨别数据选择的，GHB辨别刺激完全概括了训练为区分低剂量或高剂量GHB与安慰剂的大鼠的巴氯芬，但部分概括了训练为区分低剂量GHB与安慰剂的大鼠的GAAA激动剂安定(Columbo等人，1995年，1998ab；Lobina等人，1999年)。咖啡因(0,100,320,560毫克)在实验中被选为阴性对照，因为它的作用主要是通过不同的机制介导的，其中最重要的机制被认为是腺苷受体的竞争性拮抗(见Fredholm1985；Gould等人，1984；Snyder等人，1981)。

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).