Differentiating the discriminative stimulus effects of gamma-hydroxybutyrate and ethanol in a three-choice drug discrimination procedure in rats

Behavioral analyses of GHB: Receptor mechanisms

“…These data are consistent with GABA B receptor agonists occasioning greater GHB-appropriate responding and more GHB-appropriate responding across a larger range of GHB training doses, as compared to results obtained with compounds acting at GABA A receptors (Carter et al, 2003; Koek et al, 2006b). The finding that GHB, GHB precursors, and GABA B receptor agonists occasion similar levels of drug-appropriate responding in animals discriminating GHB and in animals discriminating baclofen, and that these compounds typically do not occasion drug-appropriate responding in animals discriminating diazepam or ethanol, further supports a predominant role for GABA B receptors in the discriminative stimulus effects of GHB in rats (Carter et al, 2004a; Baker et al, 2008). …”

“…Similar results were found in studies in which rats discriminated 300 mg/kg GHB ig. In these animals, baclofen, and to a lesser extent benzodiazepine positive modulators (e.g., diazepam, alprazolam, flunitrazepam), occasioned GHB-appropriate responding; however, in rats discriminating a larger dose of 700 mg/kg GHB ig, baclofen occasioned GHB-appropriate responding, and diazepam did not (Colombo et al, 1998b; Lobina et al, 1999; Baker et al, 2004; Baker et al, 2005; Baker et al, 2008). As the specificity of a drug’s discriminative stimulus generally increases with training dose (e.g., Koek et al, 2006b), these data suggested that while both GABA A and GABA B receptors appear to play a role in the effects of small doses of GHB, GABA B receptors appear to be predominantly involved in the discriminative stimulus effects of large doses of GHB.…”

“…GABA B receptor antagonists reliably attenuate the discriminative stimulus effects of GHB. In rats discriminating 300 or 700 mg/kg GHB ig from vehicle, CGP35348 attenuated the discriminative stimulus effects of GHB (Colombo et al, 1998b; Baker et al, 2005; Baker et al, 2008). In rats discriminating 200 mg/kg GHB, CGP35348 attenuated the discriminative stimulus effects of GHB, baclofen, and another GABA B receptor agonist SKF97541 (Carter et al, 2003; Carter et al, 2006a).…”

Preclinical assessment of abuse liability of biologics: In defense of current regulatory control policies

“…Although it has been claimed that GHB shares similar discriminative stimulus effects to that of ethanol, rats trained on a threeoperandum discrimination procedure were able to successfully discriminate between GHB (300 mg/kg), ethanol (1.0 or 1.5 g/kg), and vehicle (Baker et al, 2008). Additional substitution tests revealed full GHB-like substitution for two GHB precursors, gamma butyrolactone (GBL) and 1,4-butanediol (1,4-BD).…”

“…It is has been made abundantly clear, through the research conducted with rodents (Baker et al, 2008;Baker et al, 2005;Carter et al, 2004;Colombo et al, 1995), pigeons , and nonhuman primates (Woolverton et al, 1999), that GHB can function as a discriminative stimulus. Research examining the interactions of GHB and ethanol has been conducted in an attempt to discern the role of GHB in the treatment of alcohol dependence and withdrawal, as well as the potential unique stimulus properties of GHB.…”