Discriminative stimulus effects of GHB and GABAB agonists are differentially attenuated by CGP35348

The aim of this study was to examine the possible heterogeneity of mechanisms that contribute to the discriminative stimulus and rate-decreasing effects of γ-hydroxybutyrate (GHB). Dose effect curves were determined for GHB and two GABAB receptor agonists (baclofen and SKF97541) alone and together with the selective GABAB receptor antagonist CGP35348 in rats discriminating GHB. In a second study, GHB and SKF97541 dose effect curves were determined alone and together with baclofen. CGP35348 attenuated the discriminative stimulus and rate-decreasing effects of SKF97541 and baclofen to a greater extent than those of GHB. In the second study, baclofen enhanced the discriminative stimulus and rate-decreasing effects of GHB and SKF97541; however, the GHB dose effect curve was not shifted in a parallel manner. Taken together, these data suggest that multiple mechanisms, possibly including GHB receptors and GABAB receptor subtypes, are involved in the discriminative stimulus and rate-decreasing effects of GHB.