INVOLVEMENT OF GABA(A) AND GABA(B) RECEPTORS IN THE MEDIATION OF DISCRIMINATIVE STIMULUS EFFECTS OF GAMMA-HYDROXYBUTYRIC ACID

The present study was designed to further investigate the pharmacologi cal profile of;he discriminative stimulus effects of gamma-hydroxybuty ric acid (GHB). Drugs acting at the gamma-aminobutyric acid (GABA)(B) receptor (baclofen and CGP 35348), GABA(A)/benzodiazepine receptor com plex (diazepam), N-methyl-D-aspartate (NMDA) receptor complex (dizocil pine), and cannabinoid receptor (WIN 55,212-2) were tested for substit ution or blockade of the GHB interoceptive cue in rats trained to disc riminate either 300 or:OO mg/kg of GHB i.g. from water in a T-maze, fo od-reinforced drug discrimination paradigm. Baclofen completely substi tuted for both training doses of GHB; however, its potency in substitu ting for GHB increased as the training dose of GHB was increased. CGP 35348 partially and completely blocked the cue elicited by 300 and 700 mg/kg of GHB, respectively. In contrast, diazepam partially substitut ed for 300 mg/kg of GHB, while failing to produce a GHB-appropriate re sponse in the rat group trained to the higher GHB dose. Neither dizoci lpine nor WIN 55,212-2 substituted for GHB. Collectively, these data s uggest that: a.) GHB produces a compound stimulus; and b) GABA(B)- and GABA(A)-mediated cues are prominent components of the mixed stimulus of GHB. However, the quality (i.e., the proportion of the component cu es) of the stimulus varies as the training dose of GHB is increased; i ndeed, the contribution of the GABA(A)- and GABA(B)-mediated cues were smaller and greater, respectively, at 700 and 300 mg/kg of GHB traini ng doses. (C) 1998 Elsevier Science Inc.