The discriminative stimulus paradigm has been used as an in vivo assay of receptor-mediated activity and can be a useful tool to define the neurotransmitter systems that underlie the behavioral effects of a given dose and class of drugs (Holtzman 1990). Positive modulators of GABAA receptors, like benzodiazepines, barbiturates, and certain neuroactive steroids, all produce ethanol-like discriminative stimulus effects in water vs. ethanol discrimination in pigeons, mice, rats, gerbils, and cynomolgus monkeys (Grant 1999; Grant et al. 1996, 2008a; Shelton and Grant 2002). Recent studies have aimed to understand the contribution of different GABAA receptor subtypes to the discriminative stimulus properties of ethanol. Studies in non-human primates show that ethanol and zolpidem share similar discriminative stimulus effects suggesting that ethanol’s sedative-hypnotic actions may involve α1-GABAA receptors (Helms et al. 2008). However, zolpidem antagonism by Ro15-4513 may involve additional zolpidem-sensitive α2-/α3-/α5-GABAA receptor subtypes (Helms et al. 2008). In contrast, Platt and collaborators (Platt et al. 2005) reported a prominent role for the α5- but not the α1-GABAA receptors in the discriminative stimulus effects of ethanol and the ethanol-like effects of benzodiazepines
