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).
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