Characterization of the discriminative stimulus effects of gammahydroxybutyric acid as a means for unraveling the neurochemical basis of gamma-hydroxybutyric acid actions and its similarities to those of ethanol

The present paper reviews the drug discrimination studies, both from the li terature and from this laboratory, conducted to investigate the pharmacolog ical profile of the discriminative stimulus effects of gamma-hydroxybutyric acid. Collectively, the results of these studies suggest that: (1) the dis criminative stimulus effects of gamma-hydroxybutyric acid are composed of d ifferent cues, each one bring the effect of gamma-hydroxybutyric acid on a specific receptor system: (2) the proportion of each component cue varies a s the training dose of gamma-hydroxybutyric acid is increased; (3) the gamm a-aminobutyric acid B-mediated cue is a major ingredient of the mixed stimu lus of gamma-hydroxybutyric acid, but it is more prominent at high training doses than at low training doses of gamma-hydroxybutyric acid; and (3) pos itive modulation of the gamma-aminobutyric acid A receptor is a relevant pa rt of the discriminative stimulus effects of low gamma-hydroxybutyric acid doses. Finally, data indicating symmetrical generalization between the disc riminative stimulus effects of a specific range of Jesus of gamma-hydroxybu tyric acid and those of ethanol are discussed in regard to their further su pport of the hypothesis that gamma-hydroxybutyric acid may exert its antial cohol effects through a substitution mechanism. (C) 2000 Elsevier Science I nc. All rights reserved.